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  • 2005-2009
  • 1990-1994  (5)
  • calcium antagonist  (3)
  • cell volume  (2)
  • 1
    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
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  • 2
    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
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  • 3
    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
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    The journal of membrane biology 123 (1991), S. 33-41 
    ISSN: 1432-1424
    Keywords: eccrine ; sweat gland ; cell volume ; cholinergic ; Ca ; potassium ; chloride ; channels ; quinidine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary The goal of the present study was to elucidate the ionic mechanisms by which cholinergic stimulation induces cell shrinkage in eccrine clear cells. Dissociated Rhesus monkey eccrine sweat clear cells were prepared by collagenase digestion of freshly isolated secretory coils and immobilized on a glass slide in a perfusion chamber at 30°C. The cell was visualized by light microscopy with differential interference contract (DIC) and was recorded with a video system (15,000× total magnification). The cell volume was calculated from the maximal cross section of the cell. Methacholine (MCh)-induced cell shrinkage, which was as much as 30% of resting cell volume, was dose dependent and pharmacologically specific. MCh-induced cell shrinkage was persistent in some cells but tended to partially wane with time in others. MCh-induced cell shrinkage was dependent on the chemical potential gradient for KCl, i.e., increasing [K] in the bath ([K] o ) from 5 to 120mm caused MCh to induce cell swelling, whereas removing [Cl] o at 120mm K partially restored the MCh-induced cell shrinkage. The interpolated null [K] o (medium [K] where the cell volume did not change by MCh) of 71mm agreed with the predicted [K] o,null. MCh-induced cell shrinkage was inhibited completely by 1mm quinidine (K-channel blocker) and partially by 1mm diphenylamine-2-carboxylic acid (DPC, a Cl-channel blocker), but not by 0.1mm ouabain or 0.1mm bumetanide, suggesting that MCh-induced cell shrinkage may be due to activation of both K and Cl channels with the resultant net KCl efflux down the chemical potential gradient. That Ca/calmodulin may be involved in cholinergic regulation of Cl and K channels is suggested because 10 μm ionomycin also induced cell shrinkage, MCh failed to induce cell shrinkage in a Ca-free medium after the endogenous Ca store was depleted, and (6-aminohexyl)-5-chlorol-naphthalenesulfonamide (W-7, a putative inhibitor of calmodulin) also inhibited MCh-induced cell shrinkage in a reversible manner.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1424
    Keywords: eccrine sweat gland ; cell volume ; X-ray microanalysis ; acetylcholine ; potassium ; sodium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Chemistry and Pharmacology
    Notes: Summary Methacholine (MCh)-induced changes in intracellular concentrations of Na, K, and Cl ([Na]i, [K]i, and [Cl]i, respectively) and in cellular dry mass (a measure of cell shrinkage) were examined in isolated monkey eccrine sweat secretory coils by electron probe X-ray microanalysis using the peripheral standard method. To further confirm the occurrence of cell shrinkage during MCh stimulation, the change in cell volume of dissociated clear and dark cells were directly determined under a light microscope equipped with differential interference contrast (DIC) optics. X-ray microanalysis revealed a biphasic increase in cellular dry mass in clear cells during continuous MCh stimulation; an initial increase of dry mass to 158% (of control) followed by a plateau at 140%, which correspond to the decrease in cell volume of 37 and 29%, respectively. The latter agrees with the MCh-induced cell shrinkage of 29% in dissociated clear cells. The MCh-induced increase in dry mass in myoepithelial cells was less than half that of clear cells. During the steady state of MCh stimulation, both [K]i and [Cl]i of clear cells decreased by about 45%, whereas [Na]i increased in such a way as to maintain the sum of [Na]i+[K]i constant. There was a small (12–15mm) increse in [Na]i and a decrease in [K]i in myoepithelial cells during stimulation with MCh. Dissociated dark cells failed to significantly shrink during MCh stimulation. The decrease in [Cl]i in the face of constant [Na]i+[K]i suggests the accumulation of unknown anion(s) inside the clear cell during MCh stimulation. While the decrease in [K]i and [Cl]i may be instrumental in facilitating influx of ions via Na−K−2Cl cotransporters, the functional significance of MCh-induced cell shrinkage remains unknown.
    Type of Medium: Electronic Resource
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