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Biomedical subjects

J Koo

Publications and source records attributed to J Koo.

At least 73 records · Page 4Linked to original sources

Cyclosporine: what clinicians need to know.

Cyclosporine is known to be highly efficacious for the treatment of psoriasis as well as several other dermatologic conditions. Because of its profound anti-inflammatory properties and a side-effect profile that differs from other agents, such as methotrexate, the availability of cyclosporine confers certain advantages in meeting the challenges of treating recalcitrant psoriasis. In short-term use, cyclosporine can induce dramatic improvements in psoriasis, especially patients who present with intense inflammation. Because of nephrotoxicity and the possible development of hypertension, however, its utility in long-term usage, especially continuous usage beyond 1 year, is still to be defined. With contemporary attempts to use combination and rotational therapies to maximize therapeutic efficacy and minimize risk of long-term side effects, cyclosporine is definitely a welcome addition to our current armamentarium in the treatment of psoriasis.

Cyclosporine↗

Coriolis effects are principally caused by gyroscopic angular acceleration.

A cause of nausea evoked by cross-coupled rotation (termed Coriolis stimulus) was determined. Subjects were provided with two types of cross-coupled rotations: neck-forward flexion (Neck Flx) and upper body-forward flexion (Body Flx) during horizontal whole body rotation at a constant angular velocity. These Coriolis stimuli were given alternatively in an experimental sequence, and the severity of the nausea they evoked was compared by the subjects. The results indicated that the same quality of nausea was evoked by a slightly higher angular velocity during Body Flx (100.5 degrees/s) than during Neck Flx (90 degrees/s). While Body Flx generated Coriolis linear acceleration several times larger than Neck Flx, both the stimuli generated a similar magnitude of gyroscopic angular acceleration in this condition. Therefore, it was inferred that the nausea evoked by a Coriolis stimulus is principally caused by gyroscopic angular acceleration.

Acceleration↗

Solubility of calcium salts and carrageenan used in infant formulas did not influence calcium absorption in rats.

Calcium absorption from tricalcium phosphate (TCP) was compared to that from calcium chloride, CaCl2, in the presence and absence of carrageenan in the rat model. There was no difference in percent calcium absorption as indicated by femur uptake of TCP or CaCl2 intrinsically labeled with 45Ca given by gavage (78.4 +/- 9.6 vs. 80.0 +/- 5.9, respectively). Thus, the difference in solubility of the two salts did not influence calcium absorption. When TCP was delivered by gavage in a solution containing 1% carrageenan, calcium absorption was not decreased compared to that of a control without carrageenan. In this model, calcium from TCP in the presence of up to 1% carrageenan is well absorbed.

Animals↗

Ongoing ischemic pain as a workload indexed by P3 amplitude and latency in real-versus feigned-pain conditions.

We tested four independent groups: real pain, real pain/tracking, feigned pain, and feigned pain/tracking. After baseline (auditory oddball task only, .8/.2), the real pain groups had an ischemia cuff applied, which generated intense pain after 14 min. The pain feigners were instructed to simulate pain. The oddball task was repeated during low pain (6 min following cuff application) and during high pain (7-15 min following application). Real pain ratings were affected by low versus high pain and by tracking (reporting pain regularly), which elevated ratings. Nontracking feigned- and real-pain subjects differed in oddball-evoked P3 amplitude and latency during high pain. Oddball P3 amplitude decreased and latency increased from real low pain to high pain. Tracked but not untracked real low pain affected oddball P3 amplitude. Real and feigned pain-tracking subjects did not differ in P3 amplitude. P3 latency differed between real-pain and feigning subjects during low-pain tracking. A 91% individual hit rate (real vs. feign) obtained.

Adolescent↗

Secretion of erythropoietin from microencapsulated rat kidney cells: preliminary results.

Rat kidney epithelial cells were microencapsulated within alginate-poly(L)lysine-alginate membrane. The microencapsulated cells were incubated using a culture media containing cobalt and another without cobalt. The viability was measured by trypan blue exclusion test. Secretion of erythropoietin (EPO) was measured by radioimmunoassay (RIA). Viability of free cells was 53%. The viability of microencapsulated cells increased to 72% after 12 days of incubation and remained at this level. Samples of the culture media were collected every 2 days for RIA. Samples within the microcapsules were collected by breaking the microcapsules open. RIA of these samples showed the following for the media containing cobalt. Between day 16 and day 32 the concentrations of EPO were 5.3 mU/ml inside and 18.3 mU/ml outside the microcapsule. The medium from the same number of free cells contained 21.2 mU/ml of EPO. Culture media without cobalt collected during the same period contained 1.8 mU/ml inside and 9.9 mU/ml outside the microcapsules. The free cell culture with this media during the same period contained 8.3 mU/ml.

Alginates↗

Human pharmacokinetics of ibuprofen enantiomers following different doses and formulations: intestinal chiral inversion.

The influences of absorption rate and dosage size on the pharmacokinetics of ibuprofen (IB) enantiomers were studied in six healthy subjects. Rapidly absorbed solutions (50, 100, 200, 400, 600, and 1200 mg) and regular 600-mg tablets of racemic IB were given orally, and plasma concentration-time courses of the enantiomers were followed. Solutions were absorbed faster (tmax less than 0.25 h) than the tablet (tmax = 2.17 +/- 1.17 h). While the S:R AUC ratios were unaffected by increasing the dose, they were significantly greater after the tablet (1.35 +/- 0.14) as compared with the solutions (1.15 +/- 0.16 to 1.24 +/- 0.26). This indicates a greater extent of chiral inversion for the tablet, perhaps due to a longer residence time in the gut, thereby allowing more presystemic inversion. To test this hypothesis, R-IB was incubated at 37 degrees C in the presence of excised segments of human ileum and colon obtained from three patients. Chiral inversion was evident in all segments. After 3 h, the extent of inversion ranged from 20.0 to 33.0%. In addition, incubation resulted in the formation of up to 23.3 and 13.0% of acylglucuronides of S- and R-IB, respectively. In all subjects, the AUC-dose relationships were nonlinear, indicating a gradual increase in the clearance of both enantiomers due, perhaps, to a parallel saturation of plasma protein binding sites. In humans, the chiral inversion of IB is not influenced by the dosage size but is enhanced by prolongation of the residence time in the intestine.

Administration, Oral↗

Gross and histologic effects of topical misoprostol on canine gastric mucosa.

This study reports the histological effects of topical misoprostol, a synthetic PGE1 analog, administered in varying dosages on the resting canine gastric mucosa. Misoprostol did not macroscopically or microscopically damage the mucosa but its presumed permeability effects on the gastric vasculature induced marked edema of the mucosa and submucosa. Consistent features included increased thickness of both layers, dilated interglandular regions of the lamina propria, marked subepithelial edema, reduced depth and width of gastric foveolae, vasodilation of the vascular channels, reduced height of surface epithelial cells, swelling of their basolateral intercellular spaces, and increased amounts of surface adherent mucus. It is speculated that the mucosal edema, in addition to an increased mucus layer, may be important in the mechanism of gastric cytoprotection by increasing the distance of penetration or absorption for a mucosal-damaging agent, diluting its concentration, and disseminating any focal accumulations of red blood cells.

Administration, Topical↗

Cobalt as a gastric juice volume marker: comparison of two methods of estimation.

We investigated the use of cobalt-EDTA, a novel, nonabsorbable liquid phase marker, in the estimation of secretory volumes during topical misoprostol (synthetic PGE, analog) administration in the canine chambered gastric segment. We compared atomic absorption spectrophotometry (AAS) and instrumental neutron activation analysis (INAA) in the estimation of [Co]. Mucosal bathing solutions containing cobalt-EDTA were instilled into and recovered from the chamber by gravity every 15-min period as follows: (i) basal--60 min; (ii) misoprostol periods--150 min (plus 0.1-, 1-, 10-, 100-, and 1000-micrograms doses of misoprostol for two periods per dose). The recovered solutions were analyzed for [Co] by AAS and INAA. Total cobalt recovery by AAS after chamber washout was 102.97 +/- 0.98%. Mean +/- SE volumes (12.14 +/- 0.33 and 13.24 +/- 0.60 ml/15 min) obtained respectively from AAS and INAA were significantly higher (P less than 0.001) than the recovered mean volumes (10.51 +/- 0.17 ml/15 min). The percentage error in volume collection increased (range: 9.3-52.7%) with the volume of secretion. Values of [Co] obtained by the two techniques were comparable and not significantly different from each other (P greater than 0.05). INAA-estimated mean +/- SE [Co] showed consistently higher coefficients of variation. Spectra obtained for all samples during INAA measurements showed significant Compton background activity from 24Na and 38Cl. Cobalt-EDTA did not grossly or histologically damage the gastric mucosa. We conclude that cobalt is not adsorbed, absorbed, or metabolized, and is a suitable and reliable volume marker in this model.(ABSTRACT TRUNCATED AT 250 WORDS)

Activation Analysis↗

Ionic fluxes induced by topical misoprostol in canine gastric mucosa.

We studied the dose response of ionic fluxes in canine chambered gastric segment mucosa to increasing doses of topical misoprostol (0.1, 1, 10, 100, and 1000 micrograms). The fluxes were also correlated with the simultaneous changes in focal gastric mucosal blood flow measured by laser-Doppler flowmetry. After misoprostol administration, there was a dose-dependent increase in focal gastric mucosal blood flow (Emax = 8.23 +/- 3.25 V at 10 micrograms; ED50 = 1.05 micrograms), pH, and the outputs of ions (Na+, K+, Cl-, and HCO3-) and fluid (Emax for pH and fluxes greater than or equal to 1000 micrograms). ED50 values for these outputs ranged from 215.40 to 340 micrograms (mean +/- SE = 279.08 +/- 24.27 micrograms). H+ output showed a dose-dependent decrease to zero at the 10-micrograms dose, the dose at and after which net HCO3- secretion became obvious. The slopes of the dose-response curves for the fluxes of fluid, Na+, K+, Cl-, and HCO3- were significantly different (p less than 0.01) from the slope of the curve for mucosal blood flow changes. There were no correlations between the changes in these fluxes and blood flow changes. Na+ and Cl- were the predominant cation (98.84%) and anion (98.19%), respectively, in the misoprostol-induced secretion. Misoprostol stimulates a composite alkaline gastric nonparietal secretion, predominantly Na+ and Cl-, but also containing K+ and HCO3-. Our results suggest different mechanisms for the effects on nonparietal secretion and focal gastric mucosal blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Alprostadil↗

The dose-response of canine focal gastric mucosal blood flow to misoprostol.

We studied the dose-response of focal gastric mucosal blood flow measured simultaneously by laser-Doppler flowmetry and hydrogen gas clearance in the canine chambered gastric segment to topical misoprostol (0.1, 1.0, 10, 100, and 1000 micrograms in 10 ml of 150 mM NaCl for two 15-min periods per dose). Simultaneously obtained mucosal blood flow values showed a highly significant linear correlation (r = 0.63, n = 20, p less than 0.01) in the basal but not misoprostol periods between the two techniques. Laser-Doppler flowmetry measured a dose-dependent increase in blood flow (Emax = 6.4 +/- 2.8 V at the 100-micrograms dose; equivalent to 92.8% increase above the basal mean blood flow value; ED50 = 1.0 micrograms). Peak increase in blood flow by laser-Doppler flowmetry after dosing was attained in 6.1 +/- 0.7 min and maintained for 1.9 +/- 0.3 min. In contrast, hydrogen gas clearance showed a gradual decline in blood flow after misoprostol administration throughout all experiments. The duration of each hydrogen gas clearance measurement was 13.1 +/- 0.1 min. In conclusion, misoprostol dose-dependently and transiently increases focal gastric mucosal blood flow. However, only laser-Doppler flowmetry is sensitive enough to detect it. Although it can measure steady-state blood flow, owing to the duration of one measurement, hydrogen gas clearance is incapable of detecting rapid flow changes.

Alprostadil↗

Gastric mucosal blood flow in misoprostol pretreated aspirin-induced ulceration.

To determine whether topical misoprostol (a synthetic PGE analog) pretreatment will increase or prevent a decrease in gastric mucosal blood flow (GMBF) during topical aspirin administration, we studied focal GMBF simultaneously by hydrogen gas clearance in a split canine gastric chamber model with one side as control. In the test chamber, immediately after topical misoprostol, there was a transient and significant increase (18%) in GMBF (55.71 +/- 7.80 to 65.84 +/- 6.12 mL/min/100 g; p less than 0.05). After 15 minutes, GMBF returned to premisoprostol levels and then showed a graded drop throughout the aspirin and postaspirin periods. No grossly visible mucosal lesions were observed. In the control chamber, mucosal lesions were observed 45 minutes after aspirin administration accompanied by a graded drop in GMBF throughout the experiments. Misoprostol neither produced a sustained increase in GMBF nor prevented the subsequent reduction in GMBF induced by aspirin. Therefore, maintenance of GMBF may not be important in cytoprotection by misoprostol. The sustained nonparietal secretion induced by this synthetic PGE1 analog may be important in gastric cytoprotection.

Alprostadil↗

Focal gastric mucosal blood flow by laser-Doppler and hydrogen gas clearance: a comparative study.

We compared focal gastric mucosal blood flow (GMBF) values simultaneously obtained by laser-Doppler flowmetry (LDF) and hydrogen gas clearance (HGC) from the same point in a chambered segment model of the gastric corpus in two sets of experiments (Experiments 1 and 2) involving nine anesthetized dogs (weighing 20-30 kg). We also investigated the feasibility of obtaining a conversion factor for LDF signal to absolute flow values. The GMBF values showed a highly significant linear correlation within individual experiments and for the combined data in experiments 1 (r = 0.7132, P less than 0.0001, n = 37) and 2 (r = 0.5660, P less than 0.0001, n = 61). The combined data did not corroborate a common regression line hypothesis in both experiments (Experiment 1: F = 6.59, P less than 0.0005; Experiment 2: F = 10.57, P less than 0.0005). There was a statistically significant difference between the slopes of the 5 and 4 linear regression lines obtained in Experiments 1 (F = 13.15, P less than 0.0005) and 2 (F = 21.14, P less than 0.0005), respectively. The LDF signal was stable and optical coupling is not a problem in this experimental model. HGC and GMBF values were reliable and highly reproducible within dog measurements. We conclude that LDF and HGC are comparable in the measurement of focal GMBF. Our data, however, did not suggest the existence of a conversion factor for LDF signal to absolute flow values from experiment to experiment. Conversion will have to be within individual experiments. Thus, LDF may only be useful in situations where qualitative changes in focal blood flow are investigated.

Animals↗

Focal gastric mucosal blood flow in aspirin-induced ulceration.

Focal gastric mucosal blood flow was studied during aspirin injury by hydrogen gas clearance in a chambered segment model of canine gastric corpus. Measurements were made simultaneously every 15 minutes at ulcerated and nonulcerated areas 1.5 hours before, during (20 mM of aspirin in 150 mM of HCl for 1 hour), and 2 hours after exposure of the mucosa to topical aspirin. There was a highly significant decrease (p less than 0.001) in flow at the ulcerated areas 30 minutes after exposure to aspirin, coinciding with the appearance of focal mucosal pallor followed by subsequent hemorrhagic foci and ulceration. This was not followed by recovery to basal flow values. Blood flow to the non-ulcerated areas was significantly but less severely reduced than in the ulcerated areas (p less than 0.05) 90 minutes after exposure to aspirin. This was followed by recovery to basal levels. It is proposed that aspirin induces reduction of focal mucosal blood flow of varying degrees and that mucosal areas with flow reduced to below a "critical value" develop gross damage.

Acute Disease↗

Skin potential reflex corresponding to transient motion discomfort.

The qualitative and quantitative correspondence between the degree of motion discomfort and the skin potential reflex (SPR) was examined in four subjects. Head movement was provided three times during body rotation at three different angular velocities (Coriolis stimulus) to induce motion discomfort, and at rest as a control. SPRs were caused in the arousal sweat area by head movement. The wave form, latency, time-to-peak, and amplitude of SPR were analyzed. The amplitude of the depolarizing response (P response) of SPR increased proportionally to the angular velocity of body rotation and decreased in the course of repetitive Coriolis stimulation. It was revealed that the amplitude of P response of SPR in the arousal sweat area corresponds to the degree of transient motion discomfort.

Adult↗