Cognitive-behavioral and pharmacologic interventions for hyperactive boys: Comparative and combined effects.

Assessed the effects of 2 interventions—reinforcement and reinforced self-evaluation—on the positive social behavior of 24 8–13 yr old hyperactive males to test the hypothesis that reinforced self-evaluation would produce greater positive social behavior in Ss. Comparisons between Ss receiving methylphenidate (5–40 mg/day) and Ss receiving placebo were also conducted to clarify the effects of stimulant medication on Ss' social behavior. The primary outcome measures were direct observations of appropriate and negative social interactions. Results indicate that both methylphenidate and reinforced self-evaluation were superior to the contrast treatments. When the effects of the 4 treatment combinations were rank ordered, medication plus cognitive-behavioral self-evaluation proved optimal; placebo plus reinforcement alone was significantly worse than all other conditions. Medication enhanced the accuracy of Ss' self-evaluation. Findings are discussed in the context of the need for intervention with the social and interpersonal difficulties of hyperactive children. (46 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative study of antiradical effects of several antiglaucoma drugs

Studies of the in vitro inhibitory effects of drugs most often used in the treatment of primary glaucoma on the generation of the main active oxygen forms (hydroxyl radical, superoxide anion radical, singlet oxygen and radical products of hydrogen peroxide and peroxidase reaction) showed that antiradical activity is more intrinsic for thimolol and decreases in the following series: betoptic-pilocarpinclofelin. This once more validates the efficacy of beta-blockers in the treatment of glaucoma and prevention of cataract associated with it.     

Comparative study of the effects of ouabain and digoxin on blood pressure of rats

OBJECTIVE: To compare the effect of ouabain on the blood pressure of rats with that of digoxin to find the evidences of the relationship between endogenous ouabain (EO) and development of hypertension. METHODS: Sprague-Dawley rats, which were divided into 3 groups, were infused with ouabain (23 x 75 micrograms.kg-1/day, i.p.), digoxin (36 x 84 micrograms.kg-1/day, i.p.) and normal saline (NS) once a day respectively. Systolic blood pressure and body weight were recorded weekly. Five weeks later, rats of ouabain group were randomly assigned to three infusion subgroups: Oc group, continued with ouabain infusion; Od group, added digoxin (73 x 68 micrograms.kg-1/day, i.p.) and Os group, stopped administration of ouabain. Another week later, direct blood pressure was recorded in aorta. Systolic and diastolic cardiac function, plasma renin activity and aldosterone levels of all the rats were measured. RESULTS: After a latent period of one week, blood pressure of Ouabain group increased significantly [95.4 +/- 11.8 mmHg (1 mmHg = 0.133 kPa) at the beginning of the experiment vs 122.5 +/- 16.9 mmHg at the end of week 6, P < 0.05] with normal plasma renin activity and higher aldosterone (1.28 +/- 0.45 ng/ml vs 0.69 +/- 0.27 ng/ml, P < 0.05). The blood pressure decreased after either withdrawal of ouabain or addition of digoxin (116.3 +/- 14.4 mmHg vs 100 +/- 10.7 mmHg, P < 0.05; 123.9 +/- 13.9 vs 103.3 +/- 10.5 mmHg, P < 0.05, respectively). No difference of blood pressure was found between the digoxin and NS group. CONCLUSIONS: Our results suggested that EO might be one of the causes of the development of hypertension. Aldosterone might play some role in the mechanism of ouabain-induced hypertension. Digoxin can not induce hypertension. There is a great difference between the effect of ouabain and digoxin on the blood pressure. Moreover, digoxin can reverse the hypertension induced by ouabain.     

Comparative study of the effects of fluphenazine-depot and flupenthixol-depot in the treatment of schizophrenic psychoses

The influence of one-and two-sided regulated atmospheres with lower 02-and increased CO2-concentrations in comparison with air was studied on the growth and toxin-production of 4 different mycotoxin-producing molds (A. versicolor, P. expansum, P. urticae, B. nivea). Low O2-values in the atmosphere (2-0.5%) had scarely an influence on the development and toxinproduction in different nutrient media after 14 d at 25 degrees C. Only higher CO2-and lower O2-concentrations than that of the air (e.g. 40% CO2, 6% O2) reduced the sterigmatocystin-and patulin-production in nearly all cultures, whereas growth was only retarded insignificantly. Atmospheres with 90% CO2 and 10% air as well nitrogen atmospheres with 10% CO2 inhibited remarkably the growth of molds and prevented the toxin-production of nearly all strains. In pure N2-atmospheres most of the A. versicolor strains exhibited growth with toxic mycelia whereas only minimum growth of the patulin-producing species without any patulin synthesis had been observed.     

Comparative pharmacokinetic and pharmacodynamic studies of human insulin and analogues in chronic diabetic Yucatan minipigs

Pharmacokinetics and pharmacodynamics of insulin analogues were compared with human insulin in streptozotocin-induced chronic diabetic Yucatan minipigs. After overnight fasting, insulin or one of the insulin analogues (0.6 nmol/kg) in acid solutions (pH approximately 3.0) was administered to the minipigs s.c. The plasma insulin concentrations were then measured by radioimmunoassay at predetermined time intervals although blood glucose levels were monitored continuously. The mean (+/-S.E.) values of DeltaCmax (difference between peak and basal plasma insulin levels) were 598 (+/-21), 528 (+/-44), 176 (+/-21), 325 (+/-60) and 228 (+/-33) pM, respectively, for analogue AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaCmax values were statistically significant between AspB9GluB27 and insulin (P < .02), and between AspB9 and insulin (P < .01), but not between GluB27 or AspB28 and insulin. Moreover, the mean (+/-S.E.) values of DeltaAUC0-->6 (integrated area between plasma insulin concentration curve and basal level) were 1877 (+/-169), 1897 (+/-70), 485 (+/-36), 500 (+/-32) and 677 (+/-105) pM x hr, respectively, for AspB9GluB27, AspB9, GluB27, AspB28 and insulin. The differences in DeltaAUC0-->6 values were statistically significant between AspB9GluB27 and insulin (P < .05) and between AspB9 and insulin (P < .02), but not between GluB27 or AspB28 and insulin. However, there was no significant difference in the values of Deltanadir (difference between nadir and basal levels) and ABGC0-->12 (integrated area between blood glucose response curve and basal level) between insulin and various analogues. In conclusion, although the insulin analogues are different from human insulin in pharmacokinetics, they exhibit similar biological activity to human insulin in the streptozotocin-induced chronic diabetic minipigs.     

Pharmacokinetic/pharmacodynamic evaluation of systemic effects of flunisolide after inhalation

The pharmacokinetics and pharmacodynamics of flunisolide were studied in healthy volunteers after inhalation. In the morning on the day the study began, volunteers inhaled 0.5 mg of flunisolide with and without oral administration of charcoal, or 1 mg, 2 mg, and 3 mg of flunisolide with concomitant administration of charcoal. A placebo group was used to assess the endogenous cortisol, granulocyte, and lymphocyte baseline levels. Flunisolide plasma levels were determined by high-performance liquid chromatography using a tandem mass spectrometer as detector (HPLC/MS/MS). Cortisol plasma levels and differential white blood cell counts were obtained over 12 hours. An integrated pharmacokinetic/pharmacodynamic (PK/PD) model was applied to link the flunisolide plasma concentrations with the effects on lymphocytes, granulocytes, and cortisol. Maximum concentration levels of 3 to 9 ng/mL of flunisolide were observed after 0.2 to 0.3 hours for all of the investigated doses. The terminal half-life ranged from 1.3 to 1.7 hours. There was no statistical difference between treatments in the presence or absence of orally administered charcoal. The pharmacokinetic/pharmacodynamic (PK/PD) models satisfactorily described the time-courses of the effects on granulocytes, lymphocytes, and cortisol suppression. The resulting E50-values (concentrations to induce 50% of the maximum effect) concurred with the reported values of in vitro receptor binding affinities. The duration of the systemic effects were short because of the short half-life of the drug. Cumulative cortisol suppression increased with dose administration and ranged from 20% to 36%. The PK/PD simulations resulted in a smaller degree of cortisol suppression for the drug administered at 10 PM. The cumulative change from baseline was slightly smaller for the effects on granulocytes and lymphocytes than those on cortisol. This information promotes the comparison with other inhaled glucocorticoids.     

Comparative study on effects of pentoxifylline, prednisolone and colchicine in experimental alveolitis

Neutrophil alveolitis is a hallmark of cryptogenic fibrosing alveolitis (CFA), known for its poor prognosis. Corticosteroids, as the remedy of choice, are ineffective in a majority of patients. More and more evidence indicates that pentoxifylline (POF) could be an effective therapeutic alternative. Furthermore, colchicine has been proposed for therapy of CFA for many years now. We conducted an experimental study comparing the efficacy of these drugs in preventing neutrophil alveolitis in vivo. Alveolitis was induced in male rats by intratracheal instillation of bleomycin. Treatment consisted of daily injections of POF i.p., colchicine i.p., or prednisolone i.m. After 8 days the animals were sacrificed and body weights, cell differentials in BAL, amount of proliferating interstitial cells as determined by KI-67 staining of lung tissue, and collagen concentrations in lungs were determined. Bleomycin instillation was followed by a significant weight loss in the animals, a neutrophil alveolitis in BAL and an increased amount of proliferating cells in lung interstitium. POF significantly inhibited any of the parameters named, whereas prednisolone and colchicine had little effect. Data cannot be applied directly in human disease. There are however many similarities between CFA and bleomycin-induced lung injury and alveolitis. We conclude that POF is an effective inhibitor of neutrophil alveolitis, whereas neither colchicine nor prednisolone exerted significant influence in our model. We suggest POF effects should be further investigated regarding anti-inflammatory and anti-fibrotic properties.     

Pharmacokinetic and pharmacodynamic models of the antistaphylococcal effects of meropenem and cloxacillin in vitro and in experimental infection

The efficacies of meropenem (MPM) and cloxacillin (CLC) against two Staphylococcus aureus strains were established in vitro. A pharmacodynamic model equation, based on the concept that the killing rate depends on concentration and time, was fitted to the numbers of CFU. The parameters of the equation are maximum killing rate, time point of maximum killing, and 50% effective concentration (EC50). The EC50s for the two strains were 0.047 and 0.040 mg/liter, respectively, for MPM and 0.105 and 0.121 mg/liter, respectively, for CLC. Calculated values of the parameters were used to predict the numbers of CFU at exponentially decreasing concentrations in vitro as well as in an experimental infection model. The prediction for in vitro conditions gave a satisfactory fit (R2, between 0.862 and 0.894). In vivo the numbers were predicted with the assumption that killing rate in vivo is proportional to that in vitro (R2, between 0.731 and 0.973). The proportionality factor ranged between 0.23 and 0.42; this variation was due mainly to covariation with growth rates in control animals, without other significant differences between antibiotics or strains.     

Synthesis and pharmacologic study of 1,5-benzodiazepine-2,4-dithiones and their alkyl derivatives

Mutations of p16 and p15 suppressor oncogenes and the replication errors in six microsatellite loci in sporadic malignant melanomas were analyzed. Four (9.1%) homozygous deletions of both p16 and p15 genes and one point mutation (2.3%) in the p15 gene were detected among 44 primary melanoma samples. One mutation in each of the p16 and p15 genes was observed in ten metastatic lesions. Eight (18.2%) replication errors were detected in three microsatellite loci in the primary melanoma samples, but no replication error was detected in the metastatic samples. None of the samples showed the alteration of p16/p15 genes and the replication errors concomitantly. These results suggest that (1) the homozygous deletions of p16/p15 genes and the replication errors may occur in rather early stages of melanoma tumorigenesis, while the p16/p15 gene mutation may occur in later stages, and (2) the p16 and p15 gene mutations in sporadic malignant melanomas might not be induced by the defect in mismatch repair, implying that p16 as well as p15 gene alterations may play an important role in the pathogenesis of sporadic malignant melanomas.     

Pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel at a rate of 27 micrograms/24 hours: a pilot study

The pharmacokinetic and pharmacodynamic effects of vaginal rings releasing levonorgestrel (L-NOG) at an initial rate of 27 micrograms/24 h were studied in a group of 12 normally menstruating women during 90 days of continuous use (i.e., during three 30-day treatment segments). Blood samples were drawn immediately before insertion, 15 and 30 min, as well as 1, 2, 4, 8, 12 and 24 h after insertion of the rings, and thereafter three times weekly throughout the study for the analysis of L-NOG, estradiol, progesterone and sex hormone-binding globulin (SHBG). Endometrial biopsies were obtained for a morphometric analysis in a pre-treatment (control) cycle and in the 6th and 10th weeks of treatment. The peak of average L-NOG levels was reached within two hours after the insertion of rings. Until 24 h after insertion, the levels did not change significantly. Thereafter, a decrease at a rate of 0.2% per day was initiated. The L-NOG and SHBG levels were highly correlated. This was seen for both the pre-treatment SHBG vs L-NOG (r = 0.96) and the treatment SHBG vs L-NOG levels (r = 0.92). There was a significant (p < 0.001) decrease of SHBG levels due to treatment. During the total of 36 treatment segments, a normal ovarian function was seen in 47% of the segments. The women were anovulatory and had an inadequate lutal function in 28% and 25% of segments, respectively. No correlation between the L-NOG levels and ovarian reaction to treatment was found. The use of L-NOG induced significant changes in the endometrium; the number of glands/mm2 decreased after 6 (p < 0.02) and 10 weeks of use (p < 0.01). Also, the diameter of glands and the occurrence of vacuolated cells decreased significantly (p < 0.02 and p < 0.005, respectively). None of the endometrial parameters or dating was correlated with the ovarian reaction to treatment, indicating independent endometrial effects of L-NOG.     

Reversal of the sedative and sympatholytic effects of dexmedetomidine with a specific alpha2-adrenoceptor antagonist atipamezole: a pharmacodynamic and kinetic study in healthy volunteers

BACKGROUND: Specific and selective alpha2-adrenergic drugs are widely exploited in veterinary anesthesiology. Because alpha2-agonists are also being introduced to human practice, the authors studied reversal of a clinically relevant dexmedetomidine dose with atipamezole, an alpha2-antagonist, in healthy persons. METHODS: The study consisted of two parts. In an open dose-finding study (part 1), the intravenous dose of atipamezole to reverse the sedative effects of 2.5 microg/kg of dexmedetomidine given intramuscularly was determined (n = 6). Part 2 was a placebo-controlled, double-blinded, randomized cross-over study in which three doses of atipamezole (15, 50, and 150 microg/kg given intravenously in 2 min) or saline were administered 1 h after dexmedetomidine at 1-week intervals (n = 8). Subjective vigilance and anxiety, psychomotor performance, hemodynamics, and saliva secretion were determined, and plasma catecholamines and serum drug concentrations were measured for 7 h. RESULTS: The mean +/- SD atipamezole dose needed in part 1 was 104+/-44 microg/kg. In part 2, dexmedetomidine induced clear impairments of vigilance and psychomotor performance that were dose dependently reversed by atipamezole (P < 0.001). Complete resolution of sedation was evident after the highest (150 microg/kg) dose, and the degree of vigilance remained high for 7 h. Atipamezole dose dependently reversed the reductions in blood pressure (P < 0.001) and heart rate (P = 0.009). Changes in saliva secretion and plasma catecholamines were similarly biphasic (i.e., they decreased after dexmedetomidine followed by dose-dependent restoration after atipamezole). Plasma norepinephrine levels were, however, increased considerably after the 150 microg/kg dose of atipamezole. The pharmacokinetics of atipamezole were linear, and elimination half-lives for both drugs were approximately 2 h. Atipamezole did not affect the disposition of dexmedetomidine. One person had symptomatic sinus arrest, and another had transient bradycardia approximately 3 h after receiving dexmedetomidine. CONCLUSIONS: The sedative and sympatholytic effects of intramuscular dexmedetomidine were dose dependently antagonized by intravenous atipamezole. The applied infusion rate (75 microg x kg(-1) x min(-1)) for the highest atipamezole dose was, however, too fast, as evident by transient sympathoactivation. Similar elimination half-lives of these two drugs are a clear advantage considering the possible clinical applications.     

Phase I and pharmacologic study of topotecan in patients with impaired renal function

PURPOSE: To determine the toxicities, pharmacokinetics, and recommended doses of the topoisomerase I inhibitor, topotecan, in patients with varying degrees of renal excretory dysfunction. PATIENTS AND METHODS: Fourteen patients with normal renal function [creatinine clearance (CrCl) > or = 60 mL/min] and 28 patients with varying degrees of renal dysfunction were treated with topotecan 0.4 to 2.0 mg/m2/d as a 30-minute infusion for 5 consecutive days every 3 weeks. Plasma and urine samples were obtained to determine the disposition of topotecan. RESULTS: In patients with mild renal dysfunction (CrCl = 40 to 59 mL/min), dose-limiting hematologic toxicity was observed in three of eight patients receiving topotecan 1.0 mg/m2/d and in two of five patients receiving topotecan 1.5 mg/m2/d. In patients with moderate renal dysfunction (CrCl = 20 to 39 mL/min), dose-limiting hematologic toxicity was observed in three of eight patients who received topotecan 0.5 mg/m2/d, and in two of four patients receiving topotecan 1.0 mg/m2/d; these events were more frequently observed in extensively pretreated patients. Pharmacokinetic analyses showed significant correlations between CrCl and the plasma clearance of both total topotecan [Spearman's correlation coefficient (r2) = 0.65, P = .00001] and topotecan lactone (r2 = 0.65, P = .00003). Mean systemic plasma clearance of total topotecan was significantly reduced in patients with mild (P = .04) and moderate (P = .00006) renal dysfunction. There was no evidence of changes in the pharmacodynamic relationship between topotecan exposure (AUC) and myelotoxicity. CONCLUSION: Dose adjustments are required in patients with moderate, but not mild, renal impairment. For patients with moderate renal dysfunction, the recommended starting dose of topotecan is 0.75 mg/m2/d for 5 days every 3 weeks. Moreover, extensively pretreated patients need further dose reductions.     

Inhibition of antigen-induced airway and cutaneous responses by heparin: a pharmacodynamic study

We have previously shown that heparin attenuates the acute bronchoconstrictor response and immediate cutaneous reaction (ICR) to antigen in allergic sheep. In the present investigation, we studied the pharmacodynamics of the antiallergic action of heparin. Specific lung resistance (sRL) was measured in eight sheep, allergic to Ascaris suum antigen, before and 5 min after inhalation challenge with the antigen. On different experiment days, antigen challenge was repeated after pretreatment with 1) aerosol heparin (1,000 U/kg) administered < or = 20 min, 6 h, 12 h, and 24 h and 2) intravenous heparin (1,000 U/kg) administered < or = 20 min, 1 h, 6 h, and 12 h before antigen challenge. sRL increased by 374 +/- 116% (SE) above baseline with antigen alone. Both aerosol and intravenous heparin attenuated the antigen effects on sRL in a time-dependent fashion. Prolonging the lag time between pretreatment and antigen challenge decreased the inhibitory effect of aerosol heparin; delta sRL was 31 +/- 29, 99 +/- 38, 142 +/- 40, and 306 +/- 60% for < or = 20-min, 6-h, 12-h, and 24-h pretreatment protocols, respectively. In contrast, prolonging the lag time increased the inhibitory effect of intravenous heparin: delta sRL was 246 +/- 64, 66 +/- 26, and 76 +/- 32% for < or = 20 min, 1 h, and 6 h, respectively. In seven additional sheep pretreatment with intravenous heparin (1,000 U/kg) attenuated the ICR also in a time-dependent manner; the inhibitory effect of heparin on ICR to antigen was enhanced 60% by increasing the heparin pretreatment interval from 20 to 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of the effects of clozapine and clothiapine in different preparations of guinea pig and rat isolated organs

1. A study has been made to know the effects of clozapine and clothiapine on the responses of rat isolated vas deferens to norepinephrine, dopamine and potassium, those of the rat isolated uterus to serotonin and potassium, and that of guinea pig isolated ileum to histamine. 2. Clozapine was a noncompetitive antagonist to norepinephrine, dopamine, serotonin and histamine; it inhibited potassium-induced contraction in isolated rat uterus and vas deferens. 3. Clothiapine was a competitive antagonist to serotonin and a noncompetitive antagonist to norepinephrine, dopamine and histamine; it inhibited potassium-induced contractions in isolated rat uterus and vas deferens.     

Comparative study of the effects of auranofin and aurothiomalate on laboratory and clinical indicators in patients with rheumatoid arthritis

We studied the changes in the anticipatory postural adjustments (APAs), associated with dropping a load from extended arms and during fast bilateral shoulder flexion movements, when movements were performed in a self-paced manner and under a simple reaction-time instruction. The latter instruction applied time pressure and did not allow the regular pattern of APAs to be used. In particular, the following questions were asked: (1) are there changes in the relative timing of APAs under the reaction time condition; (2) are changes in the relative timing of APAs associated with changes in APAs themselves; (3) can different postural strategies be used to maintain stability under self-paced and reaction time conditions; and (4) are changes in APAs related to actual reaction time or to a change in the instruction? In particular, under reaction-time conditions, APAs occurred later in time, typically simultaneously with the initiation of the focal movement. Additional changes in electromyographic (EMG) patterns in postural muscles included an increase in the amplitude of EMG bursts and "speeding-up" some of the tri-phasic patterns in postural dorsal-ventral muscle pairs. This was accompanied by a smaller early shift of the center of pressure followed by its more rapid delayed displacement. There was considerable variability in the changes of EMG and dynamic characteristics across subjects. Some of the changes in the EMG patterns in postural muscles depended on actual reaction time, while others were related to a change in the instruction and occurred even if actual reaction times were long enough to allow for the typical self-paced APA patterns to occur. These findings can be interpreted as supporting the parallel control hypothesis for the focal movement and postural adjustments. Alternatively, they can be interpreted within a framework that implies the generation of a single control function, which is transformed into two components, one directed at the focal muscles/joints and the other directed at postural muscles/joints.     

Impaired wound healing in the cancer patient: effects of cytotoxic therapy and pharmacologic modulation by growth factors

This article reviews the experimental and clinical data regarding the effects of chemotherapy on wound healing. In addition, the role of growth factors in the normal wound healing process and their therapeutic potential to optimize wound healing in the cancer patient are discussed.     

Pharmacokinetics and pharmacodynamic effects of the angiotensin II antagonist valsartan at steady state in healthy, normotensive subjects

The Salford static knee instrument (SSKI) was developed to determine the quantitative assessment of the human knee joint in vivo by utilizing the technique of applied displacement and measurement of resistive load as proposed by Butler et al. (1). The instrument was used in parallel with the device developed by Al-Turaiki (2) which utilized the opposite method of assessment. The objective of the research was to examine which of the two techniques provided the more reliable and accurate method of knee assessment. Fourteen patients with suspected isolated rupture of the anterior cruciate ligament (ACL) were subjected to anterior-posterior drawer testing on both devices. The results showed that each instrument produced results which confirmed the clinical diagnosis by indicating a significant decrease in anterior stiffness when comparing the injured and uninjured knees. [SSKI device (p = 0.000) and Al-Turaiki (2) device (p = 0.002) statistical significant difference testing with Bonferonni Alpha correction p = 0.0125]. The results showed the Salford static knee instrument indicated a 58 per cent decrease in anterior stiffness and the Al-Turaiki (2) device a 35 per cent decrease when comparing the injured and uninjured knees. In conclusion it is suggested that the application of displacement and measurement of load as proposed by Butler et al. (1) may be the most appropriate technique for precise clinical diagnosis of pathological human knee joint instability.     

Comparative pharmacological effects of dl-amphetaminil and dl-amphetamine in the rat

The present investigation shows that amphetamine and amphetaminil produce identical pharmacological effects (increase in motility and body temperature, anorexia, stereotypic behaviour). There was neither a qualitative difference under "open field" conditions nor a difference in the capacity of modifying the reserpine induced syndrome. In isomolar doses amphetamine was somewhat more effective. Almost the same amounts of amphetamine were found in blood and brain following amphetamine or amphetaminil administration, with exception of somewhat higher peak levels after amphetamine. These results favor the hypothesis that amphetaminil effects are produced by the amphetamine molecule.