Many openers of ATP-dependent potassium channels (KATP channel openers) cause bronchorelaxation, whereas only a few of them have been claimed to reverse airways hyperreactivity. We investigated whether the antihyperreactive effect is a general feature of KATP channel openers and whether this property is linked to their ability to relax airways smooth muscle. For this purpose, the potency of the four KATP channel openers, bimakalim, rilmakalim, levcromakalim and SDZ PCO 400 ((-)-(3S,4R)-3,4-dihydro-3-hydroxy-2,2-dimethyl-4-(3-oxo-cyclopent -1 -enyloxy)-2H-1-benzopyran-6-carbonitrile), to inhibit bombesin- or histamine-induced bronchoconstriction and to reverse immune complex-induced airways hyperreactivity to histamine in guinea pigs, was compared to salbutamol, following intratracheal administration to minimize pharmacokinetic differences. Total lung resistance (RL) was determined in anaesthetized, ventilated guinea pigs. Bronchoconstriction, measured as increase in RL, was elicited in normoreactive animals by i.v. infusion of bombesin (100 ng/kg/min) or by i.v. injection of histamine (1.8-10 micrograms/kg). Airways hyper-reactivity was induced by acute i.v. administration of preformed immune complexes. I.v. bolus injections of histamine were used to define the sensitivity of the airways prior to and after the exposure to immune complex. Levcromakalim (ED50 = 150 micrograms/kg), bimakalim (ED50 = 4 micrograms/kg), rilmakalim (ED50 = 40 micrograms/kg) and SDZ PCO 400 (ED50 = 280 micrograms/kg) reverse bombesin-induced bronchoconstriction with lower potency than salbutamol (ED50 = 1 microgram/kg). The four KATP channel openers and salbutamol also reversed immune complex-induced airways hyperreactivity to histamine with ED50 values which were markedly lower than those for reversal of bombesin-induced bronchoconstriction; the rank order of potency was rilmakalim (ED50 = 0.2 microgram/kg) > bimakalim (ED50 = 0.5 microgram/kg) > SDZ PCO 400 (ED50 = 3.2 micrograms/kg) > levcromakalim (ED50 = 22 micrograms/kg). Salbutamol (ED50 = 0.008 microgram/kg) was the most potent compound in this test. Bimakalim, levcromakalim and SDZ PCO 400 did not inhibit histamine-induced bronchoconstriction in normoreactive guinea pigs at doses which completely reversed immune complex-induced airways hyperreactivity to histamine. For rilmakalim and salbutamol, 60-130 times higher doses were needed for protection against histamine-induced bronchoconstriction in normoreactive guinea pigs than for reversal of airways hyperreactivity. There was a poor correlation between the ED50 values for inhibition of histamine- or bombesin-induced bronchoconstriction in normoreactive guinea pigs and the reversal of immune complex-induced airways hyperreactivity. It is thus concluded that the ability of KATP channel openers to reverse immune complex-induced airways hyperreactivity is independent of their ability to reverse or prevent bronchoconstriction and thus from their ability relax airway smooth muscle.

Albuterol↗

PubMedDate not supplied

The benefit of multislice CT in the emergency room management of polytraumatized patients.

The early treatment of polytraumatized patients needs an effective and standardized approach. Reducing time requirements for the primary diagnostic evaluation is a major concern in the early phase of polytrauma management. Multislice-CT (MSCT) is a quick and reliable method for the initial diagnostic evaluation. Computed tomography provides more detailed and more consistent information than conventional radiography. It has the great advantage of allowing rapid examination of the head, vertebral column, chest, abdomen and pelvis during one single examination. The CT-suite needs to be adequately equipped for resuscitation and reanimation, which is done parallel to the radiological investigations. Since polytrauma management is based on a multidisciplinary approach characterized by a coordinated interaction between trauma surgeons, anaesthesiologists and radiologists, members of all involved disciplines need adequate teaching. Guidelines and algorithms contribute to optimize the early management.

Humans↗

PubMedDate not supplied

How LSD originated.

Explore the source record for details and available documents.

Autobiographies as Topic↗

PubMedDate not supplied

Calcium antagonist PY 108-068: demonstration of its efficacy in various types of experimental brain ischemia.

The protective properties of PY 108-068 against ischemic disturbances in the brain were investigated in vitro and in vivo. The calcium antagonistic effects were demonstrated on isolated, calcium-loaded arterial rings of feline cerebral arteries. Determination of brain tissue oxygenation with pO2 microelectrodes showed that PY 108-068 improved oxygen supply in the cortex of cats subjected to epicerebral arterial occlusion. In a model of cerebral vasospasm induced by autologous blood superfusion, PY 108-068 reversed the spastic state of cortical microvessels. In a chronic stroke model (microsphere embolization in rats) PY 108-068 led to a significant reduction in mortality and in the severity of neurological symptoms, whereby the peroral efficacy of the drug could be demonstrated. The efficacy of PY 108-068 in a variety of ischemic insults makes this drug a promising aid in the treatment of cerebrovascular accidents.

Animals↗

PubMedDate not supplied

Annexins: from structure to function.

Annexins are a family of calcium-dependent phospholipid-binding proteins. They are abundant in the eukaryotic kingdom. Though structurally well investigated in the last twenty years the in vivo function of the annexins is still unclear. The determination of the crystal structure of human annexin V was the first milestone in the structural investigation of this protein family. Succeedingly, a variety of three-dimensional structures of annexin crystals as well as of membrane bound annexins were solved. They should provide tools to understand the in vivo function of the annexin family. Based on the structural knowledge mutagenesis studies and biophysical investigations were started to elucidate possible functions of annexins like membrane binding and ion channel activity.

Animals↗