Theory of charge transport in diffusive normal metal / unconventional singlet superconductor contacts

We analyze the transport properties of contacts between unconventional superconductor and normal diffusive metal in the framework of the extended circuit theory. We obtain a general boundary condition for the Keldysh-Nambu Green's functions at the interface that is valid for arbitrary transparencies of the interface. This allows us to investigate the voltage-dependent conductance (conductance spectrum) of a diffusive normal metal (DN)/ unconventional singlet superconductor junction in both ballistic and diffusive cases. For d-wave superconductor, we calculate conductance spectra numerically for different orientations of the junctions, resistances, Thouless energies in DN, and transparencies of the interface. We demonstrate that conductance spectra exhibit a variety of features including a $V$-shaped gap-like structure, zero bias conductance peak (ZBCP) and zero bias conductance dip (ZBCD). We show that two distinct mechanisms: (i) coherent Andreev reflection (CAR) in DN and (ii) formation of midgap Andreev bound state (MABS) at the interface of d-wave superconductors, are responsible for ZBCP, their relative importance being dependent on the angle $\alpha$ between the interface normal and the crystal axis of d-wave superconductors. For $\alpha=0$, the ZBCP is due to CAR in the junctions of low transparency with small Thouless energies, this is similar to the case of diffusive normal metal / insulator /s-wave superconductor junctions. With increase of $\alpha$ from zero to $\pi/4$, the MABS contribution to ZBCP becomes more prominent and the effect of CAR is gradually suppressed. Such complex spectral features shall be observable in conductance spectra of realistic high-$T_c$ junctions at very low temperature

Theory of charge transport in diffusive normal metal / conventional superconductor point contacts

Tunneling conductance in diffusive normal metal / insulator / s-wave superconductor (DN/I/S) junctions is calculated for various situations by changing the magnitudes of the resistance and Thouless energy in DN and the transparency of the insulating barrier. The generalized boundary condition introduced by Yu. Nazarov [Superlattices and Microstructures 25 1221 (1999)] is applied, where the ballistic theory by Blonder Tinkham and Klapwijk (BTK) and the diffusive theory by Volkov Zaitsev and Klapwijk based on the boundary condition of Kupriyanov and Lukichev (KL) are naturally reproduced. It is shown that the proximity effect can enhance (reduce) the tunneling conductance for junctions with a low (high) transparency. A wide variety of dependencies of tunneling conductance on voltage bias is demonstrated including a $U$-shaped gap like structure, a zero bias conductance peak (ZBCP) and a zero bias conductance dip (ZBCD)

Sub-chronic administration of the dopamine D1 antagonist SKF 83959 in bilaterally MPTP-treated rhesus monkeys: stable therapeutic effects and wearing-off dyskinesia

Item does not contain fulltextRationale: SKF 83959 acts as a D1 antagonist in vitro but has been claimed to induce anti-parkinsonian effects after acute administration in MPTP-treated marmosets. Objective: The aim of the present study was to evaluate the therapeutic and undesired effects of subchronic administration of SKF 83959 in bilaterally MPTP-treated rhesus monkeys and to compare these effects with the effects of L-dopa and the dopamine agonist SKF 82958. Methods: MPTP was given in the left carotid artery (2.5 mg) and 6 weeks later, the right carotid artery (1.25 mg). The monkeys (n=4) had previously been treated chronically with L-dopa (22 days, 10 mg/kg) and SKF 82958 (22 days, 1 mg/kg). Three months after the last administration of SKF 82958, SKF 83959 was given in a dose of 0.5 mg/kg from day 1 to day 15 and in a dose of 1.0 mg/kg from day 16 to day 18. Results: SKF 83959 increased goal-directed limb movementsin all animals, including those unresponsive to L-dopa. This therapeutic effect did not diminish during treatment. With respect to body displacement and undesired effects, a large variation in the response to SKF 83959 was found: a large increase in body displacement co-occurred with oro-facial dyskinesia (n=2), whereas a small increase in body displacement co-oc-curred with dystonia (n=2). In contrast to the undesired effects of L-dopa, the dyskinetic effects of SKF 83959 were primarily limited to the first treatment day. Unlike L-dopa and SKF 82958, SKF 83959 did not induce epileptoid behaviour. Conclusion: sub-chronic administration of SKF 83959 induced both clear-cut therapeutic effects that remained stable in time, and a limited number of dyskinetic effects that wore off during the treatment. The dopamine D1, antagonist SKF 83959 may be considered as an alternative treatment in Parkinson's disease, especially in those patients who do not respond to L-dopa

Priming of 6-hydroxydopamine-lesioned rats with 1-DOPA or quinpirole results in an increase in dipamine D1 receptor-dependent cyclic AMP production in striatal tissue

Priming with a dopamine agonist greatly enhances the behavioral effectiveness of dopamine D1 receptor agonists in rats with 6-hydroxydopamine lesions of the nigrostriatal pathway. The present study investigated the influence of priming on cyclic AMP production in striatal slices. Stimulation of dopamine D1 receptors with dopamine or the dopamine D1 receptor agonist, 1-phenyl-6-Cl-7,8-diol-2,3,4,5-tetrahydro-(1H)-3-benzazepine (SKF 81297), increased cyclic AMP production in the lesioned striatum of rats primed with l-3,4-dihydroxyphenylalanine (l-DOPA) by 329% and 405%, respectively, whereas in drug-naive rats the increase was 183% and 187%, respectively. Priming with quinpirole produced similar results. It is suggested that priming with either l-DOPA or a dopamine D2 receptor agonist results in increased effectiveness of dopamine D1 signal transduction, apparently not only related to previous stimulation of D1 receptor

The alleged dopamine D1 receptor agonist SKF 83959 is a dopamine D1 receptor antagonist in primate cells and interacts with other receptors.

So far, no clear correlation has been found between the effects of dopamine D1 receptor agonists on motor behavior in primate models of Parkinson's disease and their ability to stimulate adenylate cyclase in rats, the benzazepine SKF 83959 (3-methyl-6-chloro- 7,8-hy-droxy-1-[3-methylphenyl]-2,3,4,5-tetrahydro-]H-3-benzazepine) being the most striking example. Since this discrepancy might be attributed to: (A) the different species used to study these effects or (B) the interaction of SKF 83959 with other catecholamine receptors, the aims of this study were: (1) to study the ability of SKF 83959 to stimulate adenylate cyclase in cultured human and monkey glial cells equipped with dopamine D1 receptors and (2) to evaluate the affinity for and the functional interaction of SKF 83959 with other catecholamine receptors. Binding studies revealed that SKF 83959 displayed the highest affinity for the dopamine D1 receptor (pKi=6.72) and the a2-adrenoceptor (pKi=6.41) and moderate affinity for the dopamine D2 receptor and the noradrenaline transporter. In monkey and human cells, SKF 83959 did not stimulate cyclic adenosine monophosphate (cAMP) formation to a significant extent, but antagonized very potently the dopamine-induced stimulation of cAMP formation in both cell types. The compound stimulated basal dopamine outflow and inhibited depolarization-induced acetylcholine release only at concentrations > 10 uM. Finally, SKF 83959 concentration dependently increased electrically evoked noradrenaline release, indicating that it had a2-adrenoceptor blocking activity and interfered with the noradrenaline transporter. In conclusion SKF 83959 is a potent dopamine D1 receptor and a2-adrenoceptor adenylate cyclase in a stimulatory way

Assessing the potential of biochar and charcoal to improve soil hydraulic properties in the humid Ethiopian Highlands: The Anjeni watershed

Biochar has shown promise for restoring soil hydraulic properties. However, biochar production could be expensive in the developing world, while charcoal iswidely available and cheap. The objective of this study is therefore to investigate whether some of the charcoal made in developing countries can also be beneficial for improving soil hydraulic properties, and explore whether charcoal could potentially restore the degraded African soils. Laboratory and field experiments were conducted in the Anjeni watershed in the Ethiopian highlands, to measure soil physical properties including soil moisture retention and infiltration rates. Soils were dominantly clayey with pH in the acidic range, low organic carbon content, and steady infiltration rates ranging between 2 and 36 mm/h. Incorporation of woody feedstock (Acacia, Croton, and Eucalyptus) charcoals significantly decreased moisture retention at lower tensions (10 and 30 kPa), resulting in an increase in relative hydraulic conductivity coefficients at these tensions. While wood (oak) biochar decreased moisture retention at low tensions, corn biochar increased retention, but effects were only slight and not significant. Surprisingly, available water content was not significantly affected by any of the amendments. Overall findings suggest that wood charcoal amendments can improve soil hydraulic properties of degraded soils, thereby potentially reducing runoff and erosion

Differential sensitivity to hydrogen peroxide of dopaminergic and noradrenergic neurotransmission in rat brain slices.

Oxidative stress, induced by hydrogen peroxide, has been implicated in the pathogenesis of Parkinson's disease. Only scarce information is available if and how hydrogen peroxide, a side product of catecholamine (CA) breakdown, interferes with CAergic neurotransmission. Therefore, we investigated the effect of hydrogen peroxide on the release of

The predictive validity of the drug-naive bilaterally MPTP-treated monkey as model of Parkinson's disease: effects of L-DOPA and the D1 agonist SKF 82958.

Item does not contain fulltextThe aim of this study was twofold: (1) to study the predictive validity of the drug-naive, bilaterally MPTP-treated monkey as an animal model of Parkinson's disease (PD), and (2) to investigate the therapeutic and undesired effects of the D1 agonist SKF 82958 as compared to L-DOPA treatment, in drug-naive and L-DOPA pretreated monkeys. A detailed ethogram was used, allowing the separation of therapeutic and undesired effects. Eight weeks after bilateral intracarotid MPTP administration, SKF 82958 (1mg/kg, n = 4, SKF 82958, naive group) or methyl-L-DOPA + carbi-dopa (10 + 2.5 mg/kg, n = 4, L-DOPA group) was administered intramuscularly for 22 days. After a drug-free period of eight weeks, the L-DOPA group was treated with SKF 82958 for 22 days (SKF 82959, 1 mg/kg, n=4, pretreated). All drug treatments increased the parameters used classically to evaluate dopaminergic drugs, namely body displacement, dyskinesia and dystonia.However, the new detailed analysis revealed that L-DOPA, but not SKF 82958, had therapeutic effects, reflected by an increase in goal-directed fore-limb use. SKF 82958, but not L-DOPA, induced additional undesired effects; including epileptoid behaviours in both drug-naive and drug-pretreated monkeys. In one L-DOPA-unresponsive monkey, SKF 82958 did not induce minor therapeutic effects, as well as indesired effects. Although the effects of SKF 82958 on fore-limb movements, rotational behaviours and body displacement were comparable in the naive and pretreated group. SKF 82958 re-initiated undesired effects in the L-DOPA pretreated group from day one. It is concluded that the bilaterally MPTP-treated monkey is an animal model with predictive validity for PD: it adequately predicts the therapeutic effects and undesired effects of L-DOPA. Furthermore, it is concluded that SKF 82958 is less effective than L-DOPA in the treatment of PD, because it did not induce therapeutic effects, but instead elicited several undesired effects