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  • 2005-2009
  • 1990-1994  (5)
  • calcium antagonist  (3)
  • Stratum corneum  (2)
  • 1
    Electronic Resource
    Electronic Resource
    The role of proteases in stratum corneum: involvement in stratum corneum desquamation (1994)
    Springer
    Archives of dermatological research 286 (1994), S. 249-253 
    Details
    ISSN: 1432-069X
    Keywords: Stratum corneum ; Desquamation ; Trypsin-like serine protease ; Chymotrypsin-like serine protease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of protease inhibitors on cell dissociation were studied in vitro in order to examine the involvement of proteases in stratum corneum desquamation. Stratum corneum sheet (peeled from human backs after sunburn) was incubated in a detergent mixture containing 8 mM N,N-dimethyldodecylamine oxide, 2 mM sodium lauryl sulphate and 60 Μg/ml kanamycin with or without protease inhibitors, and the number of released cells was counted after incubation for 48 h. Cell dissociation was inhibited strongly by antipain or aprotinin, but not at all by N-[N-(l-3-transcarboxyoxiran-2-carbonyl)-l-leucyl]-agmatin, N-ethylmaleimide or pepstatin, which suggests that only serine proteases are associated with desquamation. Furthermore, leupeptin and chymostatin each reduced cell dissociation about half as effectively as aprotinin or antipain, while a mixture of leupeptin and chymostatin prevented stratum corneum dissociation as potently as antipain or aprotinin. In addition, the activity of chymotrypsin-like protease in scaly skin was higher than that in normal skin, as we have previously found for trypsin-like protease. These results suggest that both trypsin-like and chymotrypsin-like serine proteases are involved in stratum corneum desquamation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00387596
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Detection and characterization of endogenous protease associated with desquamation of stratum corneum (1993)
    Springer
    Archives of dermatological research 285 (1993), S. 372-377 
    Details
    ISSN: 1432-069X
    Keywords: Stratum corneum ; Protease ; Desquamation ; Scaly skin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In order to identify the endogenous protease associated with stratum corneum (SC) desquamation, we examined properties of proteases in the stratum corneum of normal human skin. SC were obtained by tape stripping, washed in toluene and then dried. The proteolytic activity in SC was measured using peptidyl 4-methyl-coumaryl-7-amides (MCAs). The SC was dispersed uniformly in the reaction mixture with dimethylformamide and Triton X-100 and incubated with the peptidyl MCAs. The protease in the SC hydrolysed both Boc-Phe-Ser-Arg-MCA and Boc-Gln-Ala-Arg-MCA (substrates for trypsin) very effectively. The hydrolytic activity was inhibited by the serine protease inhibitors diisopropyl fluorophosphate (DFP), aprotinin, antipain and leupeptin, but not by chymostatin, a chymotrypsin inhibitor. These results show that one or more trypsin-like serine protease is present in the SC of normal human skin. Casein-acrylamide electrophoresis showed that the molecular weight of this serine protease was about 30 kDa. We have previously shown that cells dissociate from human SC sheets in a detergent mixture (N,N-dimethyldodecylamine oxide and sodium lauryl sulphate). This cell dissociation was inhibited by aprotinin and leupeptin. In addition, the proteolytic activity in the outer SC was higher than that in the inner SC, and the activity in the SC of scaly skin induced by SLS treatment was higher than that of untreated skin. These results strongly suggest that the trypsin-like serine protease described here is involved in SC desquamation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00371839
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    Paper (German National Licenses)
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  • 3
    Electronic Resource
    Electronic Resource
    Dose escalation trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage (1990)
    Springer
    Acta neurochirurgica 107 (1990), S. 11-15 
    Details
    ISSN: 0942-0940
    Keywords: Subarachnoid haemorrhage ; chronic cerebral vasospasm ; calcium antagonist ; AT877 ; HA 1077
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The initial dose-escalating clinical trial of a novel calcium antagonist, AT877, in patients with aneurysmal subarachnoid haemorrhage is reported. AT877 is characterized by its strong spasmolytic activity, its inhibition of intracellular calcium ion activity, and the inhibiton of several protein kinases. A total of 113 patients (Hunt and Hess grades I to IV) who had undergone surgery within 3 days of aneurysmal rupture entered the study. Patients were divided into 5 groups according to the total daily dose of AT877: I: 20 mg; II: 40 mg; III: 60 mg; IV: 90 mg; and V: 120–180 mg. AT877 was given by intravenous infusion over 30 min two or three times a day for 14 days after surgery. Although AT877 did not completely abolish angiographic vasospasm, severe vasospasm was seen less frequently in patients given higher doses. Vasospasm was the cause of a poor clinical outcome (Glasgow outcome scale rating 3 or greater) in 19%, 7%, 9%, 8%, and 6% of the patients in groups I to V, respectively. The results indicated a favourable clinical effect of AT877 at doses above 40 mg per day. Only mild hypotension was seen, even when 60 mg of AT877 was infused over 30 min. AT877 appears to be effective in patients with subarachnoid haemorrhage. Part of its effect may be attributable to protection of the brain from ischaemic insults due to chronic cerebral vasospasm. However, the drug still needs to be evaluated in a placebo-controlled double-blind trial (which is currently being carried out).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01402606
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    Paper (German National Licenses)
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  • 4
    Electronic Resource
    Electronic Resource
    The effects of HA1077 on the cerebral circulation after subarachnoid haemorrhage in dogs (1991)
    Springer
    Acta neurochirurgica 110 (1991), S. 185-188 
    Details
    ISSN: 0942-0940
    Keywords: HA1077 ; cerebral vasospasm ; subarachnoid haemorrhage ; cerebral blood flow ; calcium antagonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We examined the effects of the recently developed calcium antagonist HA1077 on cerebral haemodynamics during the chronic stage of the two-haemorrhage canine model system of vasospasm. Regional cerebral blood flow (rCBF), regional cerebral blood velocity and regional cerebral blood volume in the canine parietal cortex were measured by Laser-doppler flowmeter. On the 7th day after the initial injection of autogenous blood, subarachnoid haemorrhage (SAH) produced a significant decrease in rCBF (59% of control, p〈0.05) and Hood velocity (48% of control, p〈0.05), with no remarkable change in blood volume (108% of control). Bolus intravenous administration of HA1077 (0.1–0.3 mg/kg) dose-dependently increased the rCBF and blood velocity, without significantly changing the blood volume on Day 7 after SAH. HA1077 improves haemodynamic function manifested by an increase in rCBF and velocity in this SAH model, and may be suitable for the treatment of vasospasm in patients with SAH.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01400689
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    Paper (German National Licenses)
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  • 5
    Electronic Resource
    Electronic Resource
    Effects of prophylactic intrathecal administrations of nicardipine on vasospasm in patients with severe aneurysmal subarachnoid haemorrhage (1994)
    Springer
    Acta neurochirurgica 131 (1994), S. 19-25 
    Details
    ISSN: 0942-0940
    Keywords: Cerebral vasospasm ; cerebral aneurysm ; calcium antagonist ; nicardipine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Calcium antagonists are currently most widely used for chronic cerebral vasospasm after aneurysmal subarachnoid haemorrhage (SAH). However, the vasodilatory effects of systemically administered calcium antagonists can be limited secondary to hypotension. We previously compared intrathecal and intravenous routes of administration of nicardipine. Intrathecal administration of nicardipine significantly dilated spastic basilar arteries on day 7 in a two-haemorrhage canine model of vasospasm. In the present communication, the effects of prophylactic, serial administration of intrathecal nicardipine on vasospasm was examined in 50 patients. Patients were classified as Fisher SAH group 3 and all had their aneurysms clipped within 3 days of SAH. Following placement of a cisternal drain, 2 mg of nicardipine was injected, three times each day for an average of 10 days. The control group consisted of 91 similar patients with cisternal drainage not treated with nicardipine. Intrathecal administration of nicardipine decreased the incidence of symptomatic vasospasm by 26%, angiographic vasospasm by 20% and increased good clinical outcome at one month after the haemorrhage by 15%. Postoperative angiograms revealed that patients in the nicardipine group showed less vasospasm of major cerebral arteries, near the tip of a drain in the basal cistern, but vasospasm in the A2 and M2 segments was not decreased. Radio-isotope cisternography suggested that nicardipine might not reach the subarachnoid space around A2 and M2 segments. Nine patients complained of headache probably secondary to nicardipine induced vasodilation. Two patients suffered from mengingitis, both were successfully treated. Intrathecal administration nicardipine appears to be effective in the treatment of vasospasm, but side effects were significant.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01401450
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    Paper (German National Licenses)
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