Repetitive brief ischemia: Intermittent reperfusion during ischemia ameliorates the extent of injury in the perfused kidney

Acute renal failure commonly follows reduced renal perfusion or ischemia. Reperfusion is essential for recovery but can itself cause functional and structural injury to the kidney. The separate contributions of ischemia and of reperfusion were examined in the isolated perfused rat kidney. Three groups were studied: brief (5 min) ischemia, 20 min ischemia, and repetitive brief ischemia (4 periods of 5 min) with repetitive intervening reperfusion of 5 min. A control group had no intervention, the three ischemia groups were given a baseline perfusion of 30 min before intervention and all groups were perfused for a total of 80 min. In addition, the effects of exogenous (NO)-N-. from sodium nitroprusside and xanthine oxidase inhibition by allopurinol were assessed in the repetitive brief ischemia-reperfusion model. Brief ischemia produced minimal morphological injury with near normal functional recovery. Repetitive brief ischemia reperfusion caused less functional and morphological injury than an equivalent single period of ischemia (20 min) suggesting that intermittent reperfusion is less injurious than ischemia alone over the time course of study. Pretreatment with allopurinol improved renal function after repetitive brief ischemia-reperfusion compared with the allopurinol-untreated repetitive brief ischemia-reperfusion group. Similarly, sodium nitroprusside reduced renal vascular resistance but did not improve the glomerular filtration rate or sodium reabsorption in the repetitive brief ischemia-reperfusion model. Thus, these studies show that the duration of uninterrupted ischemia is more critical than reperfusion in determining the extent of renal ischemia-reperfusion injury and that allopurinol, in particular, counteracts the oxidative stress of reperfusion.

Allowance for thermodynamic non-ideality in the characterization of protein self-association by frontal exclusion chromatography: hemoglobin revisited

This investigation re-examines theoretical aspects of the allowance for effects of thermodynamic non-ideality on the characterization of protein self-association by frontal exclusion chromatography, and thereby provides methods of analysis with greater thermodynamic rigor than those used previously. Their application is illustrated by reappraisal of published exclusion chromatography data for hemoglobin on the controlled-pore-glass matrix CPG-120. The equilibrium constant of 100/M that is obtained for dimerization of the (02 species by this means is also deduced from re-examination of published studies of concentrated hemoglobin solutions by osmotic pressure and sedimentation equilibrium methods. (C) 2003 Elsevier Science B.V. All rights reserved.

Thermodynamic non-ideality as an alternative source of the effect of sucrose on the thrombin-catalyzed hydrolysis of peptide p-nitroanalide substrates

The inhibitory effect of sucrose on the kinetics of thrombin-catalyzed hydrolysis of the chromogenic substrate S-2238 (D-phenylalanyl-pipecolyl-arginoyl-p-nitroanilide) is re-examined as a possible consequence of thermodynamic non-ideality-an inhibition originally attributed to the increased viscosity of reaction mixtures. However, those published results may also be rationalized in terms of the suppression of a substrate-induced isomerization of thrombin to a slightly more expanded (or more asymmetric) transition state prior to the irreversible kinetic steps that lead to substrate hydrolysis. This reinterpretation of the kinetic results solely in terms of molecular crowding does not signify the lack of an effect of viscosity on any reaction step(s) subject to diffusion control. Instead, it highlights the need for development of analytical procedures that can accommodate the concomitant operation of thermodynamic non-ideality and viscosity effects.

gl(2 vertical bar 2) current superalgebra and non-unitary conformal field theory

Motivated by application of current superalgebras in the study of disordered systems such as the random XY and Dirac models, we investigate gl(2\2) current superalgebra at general level k. We construct its free field representation and corresponding Sugawara energy-momentum tensor in the non-standard basis. Three screen currents of the first kind are also presented. (C) 2003 Elsevier B.V. All rights reserved.

Non-compact generalized variational inequalities for quasi-monotone and hemi-continuous operators with applications

Some results are obtained for non-compact cases in topological vector spaces for the existence problem of solutions for some set-valued variational inequalities with quasi-monotone and lower hemi-continuous operators, and with quasi-semi-monotone and upper hemi-continuous operators. Some applications are given in non-reflexive Banach spaces for these existence problems of solutions and for perturbation problems for these set-valued variational inequalities with quasi-monotone and quasi-semi-monotone operators.

Relative importance of female-specific and non-female-specific effects on variation in iron stores between women

Women have lower iron stores than men because of iron loss during their reproductive years. However, variation between women could result from differences in iron loss, aspects of iron homeostasis common to men and women, or a combination of both. We compared the effects of age, menopause, menstrual blood loss and the number of pregnancies (sex-specific factors), and the effects of genetic variation, on markers of iron stores. We assessed how much the same genes or other familial factors influence iron status in both men and women. Data from 2039 female twins who participated in studies of reproductive health and iron status were used to estimate the proportions of variation that could be ascribed to genes, environment and measured factors. Significant effects of age, menopausal status and magnitude of menstrual blood loss were demonstrated, accounting for up to 18% of variance in serum ferritin in this sample, but number of children had no significant effect. Genetic effects were more than twice as great as sex-specific effects. The within-pair similarity of ferritin values in dizygotic female twin pairs was greater than for dizygotic opposite-sex pairs, but this difference was not quite significant, consistent with a minor role for sex-specific factors; and the opposite-sex within-pair differences did not diminish significantly with age. We conclude that the contribution of genetic differences between women to variation in iron stores outweighs the comparatively small effects of interindividual variation in iron loss through variation in menstruation and number of pregnancies.

Back to (non)-Basics: Recent developments in neutral and charge-balanced glycosidase inhibitors

Certain glycosidase inhibitors possess potent antiviral, antitumour and antidiabetic properties. Glyconic acid lactones, the earliest glycosidase inhibitors identified, have planar anomeric carbons that mimic the transition state of glycoside hydrolysis. Other classes include lactams, glycals, epoxides, halides and sulfonium ions, the latter based on the natural product salacinol from an antidiabetic herb.

Acquired myasthenia gravis associated with a non-invasive thymic carcinoma in a dog

An 8 1/2-year-old neutered male Beagle was diagnosed with acquired myasthenia gravis associated with a non-invasive thymic carcinoma. The thymic mass was surgically excised and the dog was treated with pyridostigmine, prednisolone and azathioprine. Serial acetylcholine receptor antibody titres were increased initially but slowly declined to normal values over a period of 24 weeks. Improved exercise tolerance was seen following therapy, however, oesophageal dysfunction persisted. The dog was euthanased 26 weeks after initial presentation due to a complicating illness. A necropsy showed no regrowth or metastasis of the thymic carcinoma.

Evaluation of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital

Background: The heavy usage of coxibs in Australia far outstrips the predicted usage that was based on the treatment of patients with risk factors for upper gastro-intestinal adverse events from conventional anti--inflammatory agents. This raises questions regarding the appropriateness of prescribing. Aims: To determine: (i) the relationship between prescriptions for cyclooxygenase 2 (COX-2) inhibitors and objective evidence of inflammatory arthritis, (ii) prior experience with paracetamol and/or conventional non-steroidal anti-inflammatory drugs (NSAIDs), and (iii) contraindications to the use of NSAIDs. Methods: Drug utilization evaluation and rheumato-logical assessment was conducted on 70 consecutive patients admitted on COX-2 inhibitors to a 480-bed metropolitan hospital. The main outcome measures were: the indication for COX-2 inhibitor; objective -evidence of inflammatory arthritis; previous trial of -paracetamol or conventional NSAIDs; and patient -satisfaction. Results: Only 11 patients (16%) had symptoms or signs of an inflammatory arthropathy, and met Pharmaceut-ical Benefits Schedule criteria for prescribing a COX-2 inhibitor. Fifty-nine patients (84%) had chronic osteo-arthritis, degenerative spinal disease, injury or malignancy, without overt active inflammation. Fourteen patients (20%) had trialled regular paracetamol prior to using any NSAID treatment. Conventional NSAIDs had been previously used by 51 patients (73%). Eleven patients (16%) reported previous adverse gastrointestinal effects from conventional NSAIDs. On the basis of significant renal impairment (creatinine clearance 5/10). Conclusions: Drug utilization data indicate that COX-2 inhibitors are frequently used first line for degenerative osteoarthritis in the absence of overt inflammation, without prior adequate trial of paracetamol and with disregard for the cautions and contraindications of these agents. These findings may explain the unprecedented Pharmaceutical Benefits Schedule expenditure on COX-2 inhibitors in Australia.

Electropalatographic assessment of tongue-to-palate contacts exhibited in dysarthria following traumatic brain injury: Spatial characteristics

Consonant imprecision has been reported to be a common feature of the dysarthric speech disturbances exhibited by individuals who have sustained a traumatic brain injury (TBI). Inaccurate tongue placements against the hard palate during consonant articulation may be one factor underlying the imprecision. To investigate this hypothesis, electropalatography (EPG) was used to assess the spatial characteristics of the tongue-to-palate contacts exhibited by three males (aged 23-29 years) with dysarthria following severe TBI. Five nonneurologically impaired adults served as control subjects. Twelve single-syllable words of CV or CVC construction (where initial C = /t, d, S, z, k, g/, V=/i, a/) were read aloud three times by each subject while wearing an EPG palate. Spatial characteristics were analyzed in terms of the location, pattern, and amount of tongue-to-palate contact at the frame of maximum contact during production of each consonant. The results revealed that for the majority of consonants, the patterns and locations of contacts exhibited by the TBI subjects were consistent with the contacts generated by the group of control subjects. One notable exception was one subject's production of the alveolar fricatives in which complete closure across the palate was demonstrated, rather than the characteristic groove configuration. Major discrepancies were also noted in relation to the amount of tongue-to-palate contact exhibited, with two TBI subjects consistently demonstrating increased contacts compared to the control subjects. The implications of these findings for the development of treatment programs for dysarthric speech disorders subsequent to TBI are highlighted.

EMA analysis of tongue function in children with dysarthria following traumatic brain injury

Primary objective : To investigate the speed and accuracy of tongue movements exhibited by a sample of children with dysarthria following severe traumatic brain injury (TBI) during speech using electromagnetic articulography (EMA). Methods and procedures : Four children, aged between 12.75-17.17 years with dysarthria following TBI, were assessed using the AG-100 electromagnetic articulography system (Carstens Medizinelektronik). The movement trajectories of receiver coils affixed to each child's tongue were examined during consonant productions, together with a range of quantitative kinematic parameters. The children's results were individually compared against the mean values obtained by a group of eight control children (mean age of 14.67 years, SD 1.60). Main outcomes and results : All four TBI children were perceived to exhibit reduced rates of speech and increased word durations. Objective EMA analysis revealed that two of the TBI children exhibited significantly longer consonant durations compared to the control group, resulting from different underlying mechanisms relating to speed generation capabilities and distances travelled. The other two TBI children did not exhibit increased initial consonant movement durations, suggesting that the vowels and/or final consonants may have been contributing to the increased word durations. Conclusions and clinical implications : The finding of different underlying articulatory kinematic profiles has important implications for the treatment of speech rate disturbances in children with dysarthria following TBI.

Geometric nonlinear analysis of thin plates by a refined nonlinear non-conforming triangular plate element

Based on the refined non-conforming element method for geometric nonlinear analysis, a refined nonlinear non-conforming triangular plate element is constructed using the Total Lagrangian (T.L.) and the Updated Lagrangian (U.L.) approach. The refined nonlinear non-conforming triangular plate element is based on the Allman's triangular plane element with drilling degrees of freedom [1] and the refined non-conforming triangular plate element RT9 [2]. The element is used to analyze the geometric nonlinear behavior of plates and the numerical examples show that the refined non-conforming triangular plate element by the T.L. and U.L. approach can give satisfactory results. The computed results obtained from the T.L. and U.L. approach for the same numerical examples are somewhat different and the reasons for the difference of the computed results are given in detail in this paper. © 2003 Elsevier Science Ltd. All rights reserved.