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  • 1
    Electronic Resource
    Electronic Resource
    Comparison of Pf1 and Fd Gene 5 Proteins and Their Single-Stranded DNA Complexes by NMR Spectroscopy and Differential Scanning Calorimetry (1995)
    s.l. : American Chemical Society
    Biochemistry 34 (1995), S. 148-154 
    Details
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1021/bi00001a018
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  • 2
    Electronic Resource
    Electronic Resource
    The efficacy of leflunomide in S-antigen-induced autoimmune uveitis (1994)
    Springer
    Inflammation research 41 (1994), S. C274 
    Details
    ISSN: 1420-908X
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leflunomide (LEF), an isoxazole derivative under development for the treatment of rheumatoid arthritis, is a novel immunomodulator which has been reported to be efficacious in experimental models of transplantation and systemic autoimmune diseases. The ability of leflunomide to effect autoimmune eye disease was investigated in a model of ocular autoimmunity, experimental S-antigen (S−Ag)-induced autoimmune uveitis (EAU). Leflunomide or the reference compound, Cyclosporin A (CSA), were administered topically to one eye or orally each day beginning on the day of S−Ag injection. Drug efficacy was measured by the suppression of ocular inflammation. Both oral and topical treatment with LEF suppressed the ocular disease symptoms, retinal necrosis, and S−Ag antibody levels associated with EAU. LEF and CSA were both able to completely inhibit EAU disease onset. A comparison of the IC50 and IC90 values suggest that LEF is more potent than CSA in inhibiting EAU. These results indicate that leflunomide may be useful in treating ocular autoimmune diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01987667
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  • 3
    Electronic Resource
    Electronic Resource
    Leflunomide: Inhibition of S-antigen induced autoimmune uveitis in Lewis rats (1994)
    Springer
    Inflammation research 42 (1994), S. 167-172 
    Details
    ISSN: 1420-908X
    Keywords: Leflunomide ; Immunomodulator ; Uveitis Eye ; Cyclosporin-A
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Leflunomide (LEF) is a novel immunomodulator which has been reported to be efficacious in experimental models of systemic autoimmune diseases and in treating rheumatoid arthritis in man. Leflunomide's ability to ameliorate ocular disease processes was investigated in a model of autoimmune eye disease, experimental autoimmune uveitis (EAU). EAU was induced by the injection of retinal S-antigen (S−Ag) into the foot-pad of Lewis rats. Leflunomide, or the reference compound cyclosporin A (CSA), was administered orally or topically (to one eye) each day beginning on the day of S−Ag injection. Drug efficacy was measured by the suppression in clinical signs of ocular inflammation and confirmed by histology. Both oral and topical ocular treatment with LEF suppressed the ocular disease signs and symptoms and retinal necrosis and reduced the S−Ag antibody levels associated with EAU in a dose-dependent manner. Both LEF and CSA were able to inhibit totally the disease manifestations of EAU; however, a comparison of the IC50 and IC90 values indicate that LEF is more potent than CSA in inhibiting EAU. These results suggest that leflunomide may be useful for treating autoimmune diseases of the eye.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01983486
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  • 4
    Electronic Resource
    Electronic Resource
    Chronic low frequency electrical activation for one week corrects nerve conduction velocity deficits in rats with diabetes of three months duration (1989)
    Springer
    Diabetologia 32 (1989), S. 759-761 
    Details
    ISSN: 1432-0428
    Keywords: Diabetic neuropathy ; chronic electrical stimulation ; nerve conduction ; streptozotocin-diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study examined the effect of chronic electrical activation on conduction velocity deficits after three months of streptozotocin-induced diabetes. There were 30% and 20% reductions in conduction velocity in diabetic animals for tibialis anterior and saphenous nerves, respectively (p〈0.01). Unilateral electrical stimulation of the common peroneal nerve, which contains axons supplying tibialis anterior but not saphenous nerve, was carried out in a group of diabetic and a group of normal control rats. Stimulation was given over seven days, at 10 Hz for 8 h/day. Final experiments were carried out at least 17 h after the last stimulation session. In normal rats stimulation had no effect on conduction velocity in either nerve. In diabetic animals, however, tibialis anterior conduction was within the normal control range for the stimulated nerve. In contrast, the contralateral unstimulated nerve had reduced conduction velocity (p〈0.001), which was within the unoperated diabetic control range. There were no effects on saphenous nerve conduction, comparing stimulated and unstimulated legs. We conclude that chronic increases in nerve electrical activation promote mechanisms that reverse conduction deficits in diabetic rats.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00274538
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  • 5
    Electronic Resource
    Electronic Resource
    The effect of the calcium antagonist nifedipine on peripheral nerve function in streptozotocin-diabetic rats (1992)
    Springer
    Diabetologia 35 (1992), S. 1113-1117 
    Details
    ISSN: 1432-0428
    Keywords: Neuropathy ; nerve conduction ; ischaemia ; capillary density ; calcium antagonists ; streptozotocin ; diabetic rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Recent data suggests that reduced nerve blood flow is implicated in the aetiology of experimental diabetic neuropathy, which may be prevented by manipulations that reduce receptor-mediated vasoconstrictor activity. This investigation examines the effects of nifedipine, a voltage-sensitive calcium channel antagonist which has a direct vasodilatory effect on vessels, on nerve conduction, hypoxic resistance and capillary density in streptozotocin-induced diabetic rats. Treated and non-treated non-diabetic and diabetic groups were employed. Diabetes duration was 2 months. Treatment was preventive, groups received a nifedipine dietary supplement (40 mg · kg−1 · day−1) for 2 months from the start of the study. Conduction was measured in sciatic motor branches supplying tibialis anterior and gastrocnemius muscles, and sensory saphenous nerve. Diabetes resulted in a 23–28 % reduction in motor conduction velocity (p〈0.001), and a 15% deficit for sensory saphenous nerve (p〈0.001). In the nifedipine-treated diabetic group, motor and sensory conduction deficits were minimal compared with non-treated diabetes (p〈0.001). Nifedipine treatment had no significant effect on conduction velocity in nondiabetic rats. In vitro measurement of sciatic nerve hypoxic resistance revealed a 60 % increase in the time taken for compound action potential amplitude to reach half its initial value with diabetes (p〈0.001). This was not significantly affected by nifedipine treatment. Experimental diabetes or nifedipine treatment did not significantly alter sciatic nerve endoneurial capillary density. We conclude that nifedipine, a vasodilator which acts directly on vascular smooth muscle, prevents nerve conduction deficits in experimental diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00401363
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  • 6
    Electronic Resource
    Electronic Resource
    Contractile properties of cardiac papillary muscle in streptozotocin-diabetic rats and the effects of aldose reductase inhibition (1989)
    Springer
    Diabetologia 32 (1989), S. 365-370 
    Details
    ISSN: 1432-0428
    Keywords: Aldose reductase ; diabetic cardiomyopathy ; myocardial mechanics ; polyol pathway ; ponalrestat ; streptozotocin diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study examined the preventative effect of an aldose reductase inhibitor, ponalrestat, on contractile properties of heart left ventricular papillary muscles in rats having streptozotocin induced diabetes for 13 weeks. Both contraction and relaxation were slowed by diabetes. The time to reach peak twitch tension was increased by 21%, and the time to relax to half peak tension was increased by 29% (p〈0.01, respectively compared to normal control animals). With ponalrestat treatment, the increase in contraction time was only 11%, and relaxation was only slowed by 4% (p〈0.05 and p〈0.01, respectively compared to diabetic controls). Diabetes also reduced maximum rates of contraction (13%) and relaxation (19%) and prolonged the time taken to reach peak relaxation rate (36%, p〈0.01). Ponalrestat had no effect on maximum contraction rates but was particularly effective in normalising relaxation rates (p〈0.01). Deficiencies with diabetes were noted over a range of stimulation frequencies (0.1–4.0 Hz), and ponalrestat treatment was beneficial except at the highest rates. Diabetes and ponalrestat effects were observed over a temperature range of 25–37 °C. Ventricular sorbitol levels showed a 17-fold increase with diabetes (p〈0.01) and this was reduced by 67% with ponalrestat (p〈0.01). There were no changes in ventricular myo-inositol. It is possible that ponalrestat treatment prevented a defect in sarcoplasmic reticulum calcium handling which could be responsible in part for the deficits in contraction ability and mainly for the deficits in relaxation ability in diabetic cardiomyopathy, although this remains to be tested directly.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00277260
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  • 7
    Electronic Resource
    Electronic Resource
    Angiotensin converting enzyme inhibition prevents development of muscle and nerve dysfunction and stimulates angiogenesis in streptozotocin-diabetic rats (1992)
    Springer
    Diabetologia 35 (1992), S. 12-18 
    Details
    ISSN: 1432-0428
    Keywords: Neuropathy ; hypoxia ; ischaemia ; nerve conduction ; muscle contraction ; capillary density ; lisinopril ; angiotensin converting enzyme
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The effects of the angiotensin converting enzyme inhibitor lisinopril on slow and fast twitch muscle contractile properties, nerve conduction and hypoxic resistance, and muscle and nerve capillary density were examined in streptozotocin-diabetic rats. Prolongation of soleus contraction and relaxation were partially prevented by treatment (p〈0.01). A 22% deficit in fast twitch extensor digitorum longus tetanic tension production was also ameliorated (p〈0.01). Sciatic motor and sensory conduction velocity, 25% and 12% reduced by diabetes respectively, were 75% normalized by lisinopril (p〈0.01). There was a 47% increase in resistance to hypoxic conduction block with diabetes (p〈0.01). Lisinopril treatment resulted in normal hypoxic resistance. Capillarisation of nerve and muscle was little affected by diabetes; however, there was a 17% increase in capillary density in sciatic nerve, and a 40% increase in extensor digitorum longus muscle with lisinopril (p〈0.01). For soleus, a smaller treatment-induced increase in capillary density led to an elevated capillary/muscle fibre ratio (p〈0.01). These results suggest that lisinopril promoted angiogenesis. It was concluded that the beneficial effect of preventive lisinopril treatment is likely to depend upon a reduction of peripheral vascular resistance and improvement of tissue blood flow, which implicates relative hypoxia as an important factor in the development of myopathy and neuropathy in experimental diabetes.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00400846
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  • 8
    Electronic Resource
    Electronic Resource
    Use of the bomb radiocarbon chronometer for age validation in the blue grenadier Macruronus novaezelandiae (1997)
    Springer
    Marine biology 128 (1997), S. 557-563 
    Details
    ISSN: 1432-1793
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Accelerator mass-spectrometry was used to measure radiocarbon in the earliest formed portions of selected blue grenadier, Macruronus novaezelandiae, otoliths to provide a validation of fish-age estimates based on the quantification of opaque and translucent zones in otolith thin-sections. Δ14C data from blue grenadier otoliths were compared with previous estimates of Δ14C in seawater-dissolved inorganic carbon at similar latitutes, longitudes, and depths to link variation in otolith Δ14C to time. Minimum otolith Δ14C was −76.9 ± 7.7‰, indicative of pre-bomb radiocarbon levels below the surface mixed-layer at latitudes where juvenile blue grenadier are found. When plotted versus fish age estimated from otolith sections, the majority of the Δ14C data combined to define a curve reflecting the increase in bomb radiocarbon in temperate oceans of the Southern Hemisphere, indicating that age-estimation procedures based on otolith thin-sections are satisfactory for determining blue grenadier age. If otolith-section age estimates were correct, peak otolith Δ14C of 106.8 ± 7.9‰ occurred during the late 1960s, i.e. earlier than expected. This may be a manifestation of an increase in the mixed-layer depth associated with increased frequency of zonal westerly winds at this time.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002270050121
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  • 9
    Electronic Resource
    Electronic Resource
    Cerebrospinal fluid shunts in the management of behavioural problems in Sanfilippo syndrome (MPS III) (1998)
    Springer
    European journal of pediatrics 157 (1998), S. 653-655 
    Details
    ISSN: 1432-1076
    Keywords: Key words Sanfilippo disease ; Mucopolysaccharidosis ; Cerebrospinal fluid shunt ; Hyperactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Severe behavioural disturbance is a very common feature of Sanfilippo syndrome (mucopolysaccharidosis III, MPSIII), and one of the more difficult aspects of the disease to treat. We describe a series of six patients with MPS III who had cerebrospinal shunts inserted in an attempt to ameliorate behaviour that had proved refractory to conventional treatment. Symptoms improved significantly in all six but removal of the shunt was necessitated in one patient due to shunt blockage and infection. Conclusion Our experience suggests cerebrospinal fluid shunting should be formally evaluated as an adjunct to conventional forms of treatment of extreme behavioural disturbance in MPS III.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004310050904
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  • 10
    Electronic Resource
    Electronic Resource
    Methyldopa kinetics before and after ingestion of methyldopa for eight weeks (1995)
    Springer
    European journal of clinical pharmacology 48 (1995), S. 397-400 
    Details
    ISSN: 1432-1041
    Keywords: Methyldopa ; drug absorption ; drug excretion ; induction ; secretion ; drug transport
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Abstract Methyldopa urine and plasma levels and urine metabolite levels were assessed following intravenous (IV) and oral (PO) methyldopa before, and after ingestion of methyldopa (500 mg) daily for eight weeks. There was no increase in (estimated) methyldopa absorption (8.4%) or renal clearance (PO 13.9%, IV 2.33%) after the eight weeks of methyldopa ingestion. However, the initial methyldopa absorption and renal clearance values in this study were higher than in previous studies. There was an inverse relation between the initial methyldopa absorption and the change in absorption (r -0.605) and between the initial methyldopa renal clearance and the change in renal clearance (PO r -0.874, IV r -0.891). Overall, this study did not confirm our previous studies showing induction of methyldopa absorption and renal clearance, possibly due to prior up regulation of transporter function. Consistent with methyldopa inducing drug transporters, those with low initial absorption and renal clearance values had the greatest increases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00194957
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