Time-dependent modelling and asymptotic analysis of electrochemical cells

A (time-dependent) model for an electrochemical cell, comprising a dilute binary electrolytic solution between two flat electrodes, is formulated. The method of matched asymptotic expansions (taking the ratio of the Debye length to the cell width as the small asymptotic parameter) is used to derive simplified models of the cell in two distinguished limits and to systematically derive the Butler–Volmer boundary conditions. The first limit corresponds to a diffusion-limited reaction and the second to a capacitance-limited reaction. Additionally, for sufficiently small current flow/large diffusion, a simplified (lumped-parameter) model is derived which describes the long-time behaviour of the cell as the electrolyte is depleted. The limitations of the dilute model are identified, namely that for sufficiently large half-electrode potentials it predicts unfeasibly large concentrations of the ion species in the immediate vicinity of the electrodes. This motivates the formulation of a second model, for a concentrated electrolyte. Matched asymptotic analyses of this new model are conducted, in distinguished limits corresponding to a diffusion-limited reaction and a capacitance-limited reaction. These lead to simplified models in both of which a system of PDEs, in the outer region (the bulk of the electrolyte), matches to systems of ODEs, in inner regions about the electrodes. Example (steady-state) numerical solutions of the inner equations are presented.     

Gait function in spastic hemiparetic patients walking barefoot, with firm shoes, and with ankle-foot orthosis

Cortical spreading depression is a wave of electrical and biochemical changes that spreads across the cerebral cortex. It has been hypothesized to be an important underlying cause of the visual disturbances occurring during the migraine aura, but this is difficult to test in animals or humans. We created a computational model of cortical spreading depression and found that during the wave of biochemical changes the spatial pattern of neural activity broke up into irregular patterns of lines and small patches of highly activated elements. The corresponding visual disturbances that would be produced by these patterns of neural activity resemble the hallucinations reported during the migraine aura, providing strong support for the cortical spreading depression hypothesis of migraine. The model also makes the testable prediction that these hallucinations move at an exponentially increasing speed across the visual field.     

Hindshaker, a novel myelin mutant showing hypomyelination preferentially affecting the spinal cord

Animals with spontaneous mutations affecting myelin formation have provided useful information about the genetic and cellular mechanisms regulating normal and abnormal myelination. In this paper we describe a novel murine mutation termed hindshaker (hsh), which is inherited in an autosomal recessive manner. Affected mice are characterised by a variable tremor of the hind end which commences at about 2 weeks of age and largely disappears in animals older than 6 weeks. There is hypomyelination affecting predominantly the spinal cord, although the optic nerves and brain are involved to a much lesser degree. The defect of thinly myelinated and naked axons is maximal at 20 days of age and largely resolves with time so that in the adult most axons are myelinated. The myelin structure appears normal and immunostains for the major proteins. Although the distribution of oligodendrocytes in the spinal cord is similar to normal during the period of hypomyelination, there are fewer mature cells. The hsh mutation appears to delay the maturation of oligodendrocytes, particularly in the spinal cord. Additionally, there is a considerable variation in phenotypic expression and in penetrance when the mutation is expressed on different genetic backgrounds, suggesting the hsh locus is subject to the influence of modifying gene(s). Identification of the hsh gene should identify a factor important in the development of oligodendrocytes, particularly those in the spinal cord.     

Does the gender of a patient or the gender of a therapist affect the treatment of patients with major depression?

The role of gender was examined in the process and outcome of therapy in the treatment of depressed outpatients seen in the National Institute of Mental Health Treatment of Depression Collaborative Research Program. Patients received either interpersonal therapy, cognitive-behavioral therapy, imipramine plus clinical management, or placebo plus clinical management. None of the therapist-patient by gender groupings (i.e., therapist gender, therapist-patient gender matching vs. mismatching, or patients' beliefs about whether a male or female therapist would be more helpful) were significantly related to measures of treatment process and outcome, controlling for type of treatment and severity of pretreatment depressive symptoms. Findings were duplicated when examining the effects of gender within only the psychotherapeutic modes of treatment for the groupings of therapist gender and therapist-patient gender matching versus mismatching.     

Influence of the major histocompatibility complex on age at onset of chronic lymphoid leukaemia

Goodpasture syndrome is an often fatal autoimmune disease associated with glomerulonephritis and/or pulmonary hemorrhage. The clinical manifestations of this disease correlate well with the presence of circulating antiglomerular basement membrane (GBM) autoantibodies. The primary target antigen in glomerular and alveolar basement membranes is thought to be the alpha 3 chain of type IV collagen. Nearly all that is known about anti-GBM antibodies in humans comes from work on unbound circulating antibody. We recently had the unique and rare opportunity to obtain early postmortem antibody and tissues from a patient who died with catastrophic Goodpasture syndrome. The specificity of circulating, kidney-bound and lung-bound autoantibodies from this patient was evaluated against a variety of purified basement membrane constituents. The results indicate that the primary target for the circulating and tissue-bound autoantibodies is the NC1 domain of the alpha 3(IV) chain of type IV collagen. Additionally, all the antibodies recognize a cryptic epitope/s on the alpha 3(IV)NC1 hexamer. Furthermore, tissue-bound and circulating antibodies compete with one another for overlapping epitopes on the antigen. These findings demonstrate that circulating autoantibodies in Goodpasture syndrome are highly representative of those bound to organ tissues, strengthening the notion that pathogenic autoantibodies are targeted to the alpha 3(IV)NC1 collagen, and that previous reports of findings in the circulation may be applicable to tissue injury.     

Time-dependent differential changes of immune function in rats exposed to chronic intermittent noise

Noise is a highly relevant environmental and clinical stressor. Compared to most other experimental stressors, noise is a modest activator of neuroendocrine pathways that mimic the situation in human health where neuroendocrine activation by environmental stressors is often absent or difficult to establish. Little is known about the effects of noise exposure on the immune system. In the present work, the effects of a low-intensity chronic intermittent unpredictable noise regimen on various parameters of immune function was studied. Male wistar rats were exposed to a randomized noise protocol (white noise, 85 dB, 2-20 kHz) for 10 h per day, 15 min per h over a total period of 3 weeks. Control animals were exposed to ambient sound only. Immune function was monitored after 24 h, 7 days, and 21 days of noise exposure. Noise induced several significant changes in immune function in a time-dependent differential pattern involving both immunosuppression and immunoenhancement. After 24 h, serum IgM levels were increased and peripheral phagocytic activity was decreased. Splenic lymphocytic proliferation to mitogens was significantly decreased after 7 days, but slightly elevated after 3 weeks. The activity of splenic NK cells was increased significantly after 24 h and 7 days, but suppressed after 3 weeks. These results show that various parameters of immune function are affected differentially over time in a period of chronic mild noise stress, possibly due to sequential activation of different physiological mechanisms.     

Effect of polyethylene on osteocalcin, alkaline phosphatase and procollagen secretion by human osteoblastic cells

BACKGROUND AND STUDY AIMS: Anastomotic leakage is a severe complication in gastric surgery and it is associated with a high rate of mortality. Conservative treatment sometimes is not sufficient to stem the leakages and, even when it is sufficient, it takes a long time. The present study describes the first experience in the treatment of anastomotic leakages with endoscopic clipping. PATIENTS AND METHODS: From May 1995 to December 1996, seven patients with postoperative anastomotic leakages after gastric surgery were prospectively treated in our Endoscopy Service. Metallic endoclips (MD 850, Olympus Corp., Tokyo, Japan) with prongs 12 mm long and 6 mm wide were applied, controlling the closure of the leakage by endoscopy, using radiographs to confirm the closure 24 hours later. RESULTS: Complete closure of the leakage was obtained in all seven cases. A single session of endoscopic clipping was needed for five patients while two other required, respectively, two and three sessions. The median time of leakage closure after endoscopic clipping was 2.3 days (range 1-5 days). The clips spontaneously dislodged within 1 month in five patients and within the second month in the other two patients. CONCLUSION: Endoscopic treatment of anastomotic leakages by metallic clips represents a safe and easily repeated method and, compared to conservative treatment, it seems to offer several time and cost advantages. Further studies involving a larger number of patients are needed to verify this finding.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.