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C Harakal

Publications and source records attributed to C Harakal.

34 records · Page 2Linked to original sources
PubMed1978

The relationship between pharmacokinetics and pharmacodynamic action as applied to in vivo pA2: application to the analgesic effect of morphine.

When the pA2 of an antagonist is determined in vivo, administered doses are used rather than the peak or steady-state tissue concentrations. The present report examines the error which can arise in this method and also presents a method for determining the pA2 from data obtained at times after peak. We applied this time-dependent analysis to time-dose-response data obtained with morphine-naloxone in the rat, using tail compression as the nociceptive stimulus. Good agreement between pA2 values was found: 8.0 with peak effect data, and 8.1 with the time-dependent method. Further, this analysis yielded 20 minutes as the half-life of naloxone. It is concluded that the time-dependent method provides a check on the pA2 in vivo and confirms the utility of this constant in classifying receptors. The appendix contains methodology for application to other agonist-antagonist combinations classified according to their kinetics.

Analgesics↗
PubMed1975

An instrument to assess staff time utilization in a community mental health center.

The Daily Staff Log is an empirically refined instrument to assess staff hours spent in direct patient and collateral contact, clinical backup time, consultation, education, and administration. Its primary uses as a management tool include description of staff activities, comparisons by discipline or clinic, pre- and postcomparisons following administrative policy change, and cost-effectiveness studies. Conditions for successful use include a firmly committed administrative interest, in-service education on the value of log data for decisionmaking to improve delivery of care, and positive feedback when logs indicate service goals are being met. Following the introduction of logging it was possible to document improvements in clinical and financial efficiency.

Administrative Personnel↗
PubMedDate not supplied

Role of sulfhydryl groups in aortic responses using N-ethylmaleimide.

This study examines the effects of N-ethylmaleimide (NEM) 10(-7) M on agonist-induced contraction, and the relaxation following drug washout of vascular smooth muscle (VSM) segments. 45Ca flux, cyclic 3':5'-adenosine-monophosphate (cAMP), and cyclic 3':5'-guanosine-monophosphate (cGMP) were analyzed in an attempt to understand the observed physiological modifications with NEM. Cyclic nucleotides were measured by 125I-radioimmunoassay. Contractile responses to norepinephrine (NE) 5.9 x 10(-7) M, angiotensin II (AT) 9.8 x 10(-8) M, and potassium chloride (KCl) 2.2 x 10(-2) M were significantly depressed when VSM segments were exposed to NEM prior to agonist challenge. An inhibition of relaxation occurred when NEM was added after the development of a maximal contractile response to NE, AT, or KCl. VSM relaxation was significantly inhibited when compared to controls. Altered 45Ca efflux, increased cGMP, and decreased cAMP levels were all associated with an inhibition of relaxation of VSM. These results suggest a regulatory role of sulfhydryl (SH) groups in contraction and relaxation of VSM involving both the control of Ca2+ flux and cAMP and cGMP metabolism.

Animals↗
PubMedDate not supplied

Calcium fractions in aortic segments from hypertensive rabbits.

The rate constants (-k) of Ca2+ from cellular compartments of intact smooth muscle cells of thoracic aorta of normotensive, renal hypertensive, and cadmium hypertensive rabbits were studied by 45Ca efflux and by employing norepinephrine (NE, 5.9 X 10(-7) M). Tissues from hypertensive animals showed an increased rate of release of 45Ca over a 5-h unloading period when compared to normotensive controls. Three exchangeable compartments were found to contribute to the total kinetic efflux curve for all groups. The Ca2+ fraction in compartments I and II showed an increased rate of Ca2+ release for the hypertensive subgroups. Although the rates were slowed for tissues treated with NE prior to efflux, the rates of the hypertensive subgroups were increased compared to the normotensive group. Pretreatment of aortic segments with NE caused an overall increase in 45Ca activity of the incubation medium and may explain the slowed rates attained in the efflux analyses. Influx studies showed that tissues from hypertensive animals had a greater uptake of 45Ca than did the normotensive controls. Such data may represent a larger exchangeable component in aortae from the hypertensive subgroups. These findings indicate differences in the rates of Ca2+ release from intact smooth muscle cells of hypertensive rabbits.

Animals↗
PubMedDate not supplied

Effects of calcium antagonists on isolated bovine cerebral arteries: inhibition of constriction and calcium-45 uptake induced by potassium or serotonin.

The purpose of this study was to determine the mechanisms by which organic calcium channel blockers inhibit cerebral vasoconstriction. Isolated bovine middle cerebral arteries were cut into rings to measure contractility or into strips to measure radioactive calcium (45Ca) influx and efflux. Calcium channel blockers (10(-5) M verapamil or 3.3 X 10(-7) M nifedipine) and calcium-deficient solutions all produced near-maximal inhibition of both potassium- and serotonin-induced constriction. In calcium-deficient solutions containing potassium or serotonin, verapamil and nifedipine each blocked subsequent calcium-induced constriction in a competitive manner. Potassium and serotonin significantly increased 45Ca uptake into cerebral artery strips during 5 minutes of 45Ca loading; for potassium 45Ca uptake increased from 62 to 188 nmol/g, and for serotonin from 65 to 102 nmol/g. Verapamil or nifedipine had no effect on basal 45Ca uptake but significantly blocked the increase in 45Ca uptake induced by potassium or serotonin. Potassium, and to a lesser extent serotonin, each induced a brief increase in the rate of 45Ca efflux into calcium-deficient solutions. Verapamil or nifedipine had no effect on basal or potassium-stimulated 45Ca efflux. The results demonstrate that verapamil and nifedipine block 45Ca uptake through both potential-operated (potassium) and receptor-operated (serotonin) channels in bovine middle cerebral arteries.

Animals↗