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Results for “comparative effectiveness”

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PubMed2026

Comparative Effectiveness of Pharmacogenomics for Treatment of Depression.

PURPOSE/BACKGROUND: Pharmacogenomics (PGx), or the use of genetic information to assess drug-gene interactions, is an important step toward precision medicine. It is unclear if clinician use of PGx yields better outcomes for their patients. This study compared the effectiveness of combinatorial PGx-guided plus guideline-informed treatment (PGx+GIT) with guideline-informed treatment (GIT) alone to improve well-being in individuals with major depressive disorder. METHODS/PROCEDURES: Eligible participants (N=201) were randomized to PGx+GIT or GIT alone. PGx was measured with the proprietary GeneSight combinatorial test. PGx+GIT participant clinicians received test results within 2 business days to inform decisions about medication changes. Participants completed the World Health Organization Well-Being Index (WHO-5), Patient Health Questionnaire (PHQ-9), and PROMIS Profile physical functioning and social roles and activity domains every 2 weeks for 2 months and then every 2 months for the remaining 10 months. Monthly medication changes operationalized as necessary clinical adjustments were tracked with the medication recommendation tracking form. FINDINGS/RESULTS: Both groups improved average well-being over the 12-month study period (model-based change in WHO-5 per log (week) [95% CI]: 4.1 [3.3, 5.0] PGx+GIT and 4.8 [4.0, 5.5] GIT). PGx+GIT did not result in superior improvement in well-being (model-based difference [95% CI]: -0.6 [-1.8, 0.5], P =0.270), or any secondary outcomes. The effect of randomized treatment on well-being was not moderated by depression severity, number of previous failed medications for major depressive disorder, or presence of a comorbid condition. IMPLICATIONS/CONCLUSIONS: These data suggest PGx+GIT was not superior to GIT alone, possibly due to a ceiling effect of GIT, or PGx did not yield better results.

Humans↗

PubMed2026

Comparative Effectiveness of Oral Ivermectin, 1% Permethrin Shampoo, and 4% Dimethicone Liquid Gel in Treatment of Pediculosis Capitis among School Children in Chachoengsao Province, Thailand.

Pediculosis capitis remains a persistent public health issue, especially in developing countries where resistance to standard neurotoxic pediculicides like permethrin is increasingly prevalent. This study aimed to compare the effectiveness of alternative treatment options against the standard care in a resource-limited setting. We conducted a single-blind randomized controlled trial involving three primary schools in Chachoengsao Province, Thailand (ClinicalTrials.gov: NCT06332872). Eighty-five female participants ages 6-13 years with active infestations were enrolled. Schools were randomly assigned to three treatment arms: 1) oral ivermectin (200 µg/kg) on Days 0 and 7; 2) 1% permethrin shampoo on Days 0 and 7, or 3) 4% dimethicone liquid gel as a single dose on Day 0. The primary outcome was the cure rate, defined as the absence of live lice and viable nits upon clinical assessment on Day 9. Of the 66 participants included in the final per-protocol analysis, oral ivermectin achieved a cure rate of 95.5% (21/22), which was significantly higher than that of the 1% permethrin standard of care (37.0%; 10/27) and the 4% dimethicone physical suffocant (29.4%; 5/17) (P <0.001). Although dimethicone achieved high initial parasitic clearance on Day 0 (88.2%), a rapid reinfestation rate of 58.8% was observed by Day 9, indicating that a single-dose protocol may be clinically insufficient. Adverse events were mild and temporary across all groups. Oral ivermectin appears significantly more effective than both 1% permethrin and single-dose 4% dimethicone in this population. These findings suggest that permethrin resistance is clinically prevalent and relevant in this area.

Humans↗

PubMed1992

Compared effects of serotonin on cervical and hypoglossal inspiratory activities: an in vitro study in the newborn rat.

1. Experiments were performed on the brain stem-spinal cord preparation of newborn rats, in which the phrenic and hypoglossal nerves continue to show rhythmic respiratory activity in vitro, in order to compare the effects of serotonin (5-HT) on both activities and to analyse the mechanisms responsible for the depression by 5-HT of the hypoglossal activity. 2. Under control conditions, simultaneous recordings of the inspiratory discharges of hypoglossal and cervical roots showed that the two bursts did not start simultaneously and had different patterns (time-to-peak and peak values); this suggests that both pools of motoneurons did not share the same central drive(s). 3. Adding 5-HT and related agents to the bathing medium delayed and depressed the hypoglossal inspiratory discharge via activation of 5-HT2 receptors since these effects were elicited by 5-HT2 agonists (alpha-methyl-5-HT and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-HCl (DOI)) but not by 5-HT1 agonists (RU 24969 and (+/-)-8-hydroxy-2-(di-N-propylamino)tetralin hydrobromide (8-OH-DPAT)). The 5-HT depression of the hypoglossal discharge was prevented by applying a pretreatment with a specific 5-HT2 antagonist (ketanserin). Parallel to the hypoglossal discharge decrease, 5-HT elicited a permanent cervical root discharge along with a persistent inspiratory bursting. Adding the 5-HT precursor L-tryptophan to the bathing medium depressed the hypoglossal (XII) discharge without affecting the cervical one. 4. Local application of 5-HT within the hypoglossal motor nucleus decreased the hypoglossal output, revealing that the 5-HT depression of the hypoglossal discharge was at least partly mediated by the 5-HT effects at the level of the motoneurons. Local application of 5-HT within the cervical motor nucleus elicited a permanent firing in the cervical root with a persistent inspiratory bursting. 5. Intracellular analysis confirmed the existence of differences in central respiratory drive between cervical and hypoglossal motoneurons under control conditions, as well as differences in response to 5-HT. All the hypoglossal motoneurons became silent under 5-HT bathing, and showed no change in the input membrane resistance, a moderate depolarization, and a delayed central respiratory drive with a decreased amplitude. The cervical motoneurons became more active during inspiration, despite a decrease in the amplitude of the central respiratory drive, which was compensated for by a large depolarization and an increased input membrane resistance. Some cervical motoneurons even fired at a low rate during expiration.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

Comparative effects of the aromatase inhibitor R76713 and of its enantiomers R83839 and R83842 on steroid biosynthesis in vitro and in vivo.

R76713 (6-[(4-chlorophenyl)(1H-1,2,4-triazol-1-yl)methyl]-1-methyl-1H- benzotriazole) is a selective, non-steroidal aromatase inhibitor containing an asymmetric carbon atom. In this paper, we compare the effects of R76713 (racemate) with its enantiomers R83839 (the levo-isomer) and R83842 (the dextro-isomer) on steroid biosynthesis in rat cells in vitro and in the rat in vivo. In rat granulosa cells, aromatase activity was inhibited by 50% at concentrations of 0.93 nM of R76713, 240 nM of R83839 and 0.44 nM of R83842, revealing a 545-fold difference in activity between both enantiomers. Up to 1 microM, none of the compounds had any effect on steroid production in primary cultures of rat testicular cells. Above this concentration all three compounds showed a similar slight inhibition of androgen synthesis with a concomitant increase in the precursor progestins, indicative for some effect on the 17-hydroxylase/17,20-lyase enzyme. In rat adrenal cells none of the compounds showed any effect on corticosterone synthesis. At concentrations above 1 microM there was an increase in the levels of 11-deoxycorticosterone pointing towards an inhibition of the 11-hydroxylase enzyme. This increase was more pronounced for R83839 than for R76713 and R83842. In vivo, in PMSG-primed rats, R83842 reduced plasma estradiol by 50%. 2 h after oral administration of 0.0034 mg/kg, whereas 0.011 mg/kg of R76713 and 0.25 mg/kg of R83839 were needed to obtain the same result. Oral administration of up to 20 mg/kg of the compounds did not significantly affect plasma levels of adrenal steroids in LHRH/ACTH-injected rats. Plasma testosterone was lowered at 10 and 20 mg/kg of R83842 and at the highest dose (20 mg/kg) of R76713 and R83839. In conclusion, the present study shows that the aromatase inhibitory activity of R76713 resides almost exclusively in its dextro-isomer R83842. R83842 exhibits a specificity for aromatase as compared to other enzymes involved in steroid biosynthesis of at least a 1000-fold in vitro as well as in vivo. This confirms the extreme selectivity previously found for the racemate.

Adrenal Cortex Hormones↗

PubMed1975

Comparative effects of tolamolol and propranolol on cardiac and peripheral circulatory function in patients with coronary artery disease.

In a clinical study comparing the cardiocirculatroy effects of intravenous tolamolol to those of propranolol, tolamolol, 16 mg, induced similar reduction in resting heart rate as 8 mg propranolol in 16 coronary patients. Tolamolol did not disturb cardiac pump performance and exerted less negative inotropic action than propranolol as assessed by mechanical contractility indices. Myocardial beta-one chronotropic and inotropic stimulation by exogenous epinephrine was blocked equally by tolamolol and propranolol. Tolamolol exerted less systemic vascular beta-two blockade than propranolol as assessed by the peripheral resistance and vasopressor responses to epinephrine infusion. Tolamolction than propranolol and is thereby suitable for careful extension of beta blockade therapy to certain patients with pulmonary and ventricular dysfunction.

Adult↗

PubMed1992

Comparative effects of thyroxine and/or retinoic acid treatment in vivo on growth hormone synthesis and release by pituitaries from thyroidectomized rats.

Thyroid hormones and retinoic acid (RA) coregulate growth hormone (GH) synthesis and release from cultured pituitary tumor cells by interacting with nuclear receptors that activate GH gene transcription. Whether these two compounds share overlapping GH regulatory activities in vivo is unclear. Therefore we compared the effects of in vivo replacement therapy with thyroxine (T4) and/or retinoic acid (RA) on GH synthesis and release in pituitaries from hypothyroid rats. Three weeks after thyroidectomy, male rats (100-150 grams, body weight) received 7 days of intraperitoneal T4 (20 ug/kg/day) and/or RA (500 ug/kg/day) or vehicle. Isolated pituitary fragments were incubated for 3 h with [14C]leucine followed by 2 h with [3H]leucine and 3 nM rat growth hormone-releasing hormone (GHRH). Basal synthesis, GHRH-induced release of stored [14C]GH, and GHRH-stimulated release of newly synthesized [3H]GH were assessed by specific immunopercipitation of media and tissue homogenates. T4 increased the synthesis of GH in the absence and presence of GHRH. T4, but not RA, increased the absolute amount of stored and newly synthesized GH released by GHRH. Neither T4 nor RA altered the percent of stored GH released by GHRH, however, both independently or additively decreased the percent of newly synthesized GH released by GHRH. In summary, treatment of hypothyroidism with T4 increased GH synthesis and absolute release. Interestingly the fractional release of GH was unchanged or decreased by T4 treatment. RA treatment had no effect on GH synthesis or absolute release, but like T4 it decreased the fractional release of newly synthesized GH. Thus T4 and RA did not share similar regulatory effects on GH synthesis and stored GH release but did have similar effects on the fractional release of newly synthesized GH in pituitaries from thyroidectomized male rats.

Analysis of Variance↗

PubMed1991

Comparative effects on psychomotor performance of the muscle relaxant afloqualone, alone and with ethanol.

The purpose of this study was to investigate the interaction between 40 mg afloqualone, a new centrally acting muscle relaxant and 0.5 g/kg ethanol using a double-blind three-way cross-over trial in which subjects were each given afloqualone with ethanol, ethanol alone and afloqualone alone. We first compared the effects of 40 mg oral afloqualone and 15 mg diazepam (considered as a reference drug) on the psychomotor and cognitive performance and muscular relaxation of 12 healthy male volunteers. Performance was assessed by six objective tests and eight visual analogue self-rating scales. All the above treatments were separated by a 2-week interval. Volunteers performed the objective tests 1 h after drug ingestion, and the self-rating scale evaluations before drug intake and 1, 3.5, 6 and 8 h thereafter. Afloqualone impaired psychomotor performance less than diazepam as shown by the number of correct answers in the digit symbol cancellation test and the time needed to complete this test. However, the measurement of the frontalis muscle action potential showed that the muscle relaxant activity of 40 mg afloqualone was equivalent to that of 15 mg diazepam. Furthermore, afloqualone given at an effective relaxant dose did not enhance the effects of a single dose of ethanol which predominated on either psychomotor performance or subjective feelings.

Administration, Oral↗

PubMedDate not supplied

Comparative effects of chronic ethanol and acetaldehyde exposure on myocardial function in rats.

This study was conducted to compare separately the chronic effects of high blood levels of ethanol and acetaldehyde on the metabolism of the heart. Levels of ethanol and acetaldehyde were altered by administration of either 4-methylpyrazole (4-MP), a potent alcohol dehydrogenase inhibitor, or pargyline (PAR), a monoamine oxidase inhibitor that markedly increases acetaldehyde levels in the blood following ethanol administration. Measurements were made in rats consuming ethanol for three to four weeks. Mitochondrial respiration, in vitro contractility of glycerinated heart muscle fibers, and myocardial protein synthesis were determined. As compared to animals receiving only ethanol, administration of either-4-methyl-pyrazole or pargyline plus ethanol resulted in more severe damage to mitochondrial respiration and myocardial protein synthesis. The data illustrate that both acetaldehyde and ethanol in high concentrations can cause severe damage to myocardial metabolism.

Acetaldehyde↗

PubMed1990

Compared effects of GnRH analogs and 4-hydroxytamoxifen on growth and steroid receptors in antiestrogen sensitive and resistant MCF-7 breast cancer cell sublines.

Antiestrogens, such as tamoxifen, have a direct antitumor action and are widely used in cancer therapy. The direct antitumor action of GnRH analogs has been documented in both in vitro and clinical studies. GnRH analog direct action could therefore provide an alternative approach in postmenopausal patients developing antiestrogen resistance, a frequent cause of relapse during hormonal treatment of breast cancer. This study was carried out to compare the effects of two GnRH analogs (the agonist Decapeptyl and the antagonist BIM 21009C) and the antiestrogen 4-hydroxy-tamoxifen (OH-TAM) on proliferation in antiestrogen-responsive or antiestrogen-resistant human breast cancer cell lines (MCF-7, MCF-7 LY2). Ineffective when used without estrogen stimulation, both of the GnRH analogs and OH-TAM inhibit the 17 beta-estradiol-stimulated growth of the estrogen-responsive cell line MCF-7. Compared with parental MCF-7 cell line responsiveness, the antiestrogen-resistant variant MCF-7 LY2 appears to be resistant to GnRH analogs. These findings indicate similarities between the two types of compounds with regard to their antiestrogenic effects on growth observed in vitro. However, since unlike OH-TAM, Decapeptyl displays no effect on steroid receptor levels of sensitive MCF-7 cells, the intracellular inhibitory mechanisms of these drugs are probably in part different. This study suggests that the direct effect of the studied GnRH analogs would not be a potent tool for treating antiestrogen-resistant breast tumors.

Antineoplastic Agents↗

PubMed1992

Comparative effects of BRL 38227, nitrendipine and isoprenaline on carbachol- and histamine-stimulated phosphoinositide metabolism in airway smooth muscle.

1. The ability of BRL 38227 and nitrendipine to affect muscarinic agonist and histamine-stimulated [3H]-inositol phosphate accumulation in slices of bovine tracheal smooth muscle has been studied and compared with the established inhibitory effects of isoprenaline on this pathway. 2. Pre-addition of BRL 38227 (5 microM), nitrendipine (1 microM) or isoprenaline (10 microM) significantly inhibited the subsequent inositol phosphate response to histamine at all concentrations studied (10- 1000 microM). BRL 38227 and nitrendipine also significantly inhibited the [3H]-inositol phosphate response to low (1 microM), but not high (100 microM) concentrations of carbachol. Isoprenaline had no effect at any concentration of carbachol studied. 3. Nitrendipine (IC50 = 95 nM) and BRL 38227 (IC50 = 322 nM) caused concentration-related inhibitions of the inositol phosphate response to histamine (100 microM). Similar maximal inhibitions were caused by each agent (55-58%). Inhibitory effect of BRL 38227 was reduced in potency (IC50 = 5.5 microM), but not magnitude, in the presence of glibenclamide (0.5 microM). 4. Time-course studies comparing the effects of BRL 38227 addition 15 min before, and 10 min after histamine challenge showed that for pre-addition a distinct (less than 2 min) lag occurred following histamine addition before the inhibitory effect of BRL 38227 was manifest. In contrast, when BRL 38227 was added 10 min after histamine, an inhibitory effect was immediately apparent. 5. Further evidence for an initial, 'protected' phase of inositol phosphate accumulation was provided by the finding that BRL 38227 pre-addition had no effect on the early (0-300 s) time-course of inositol 1,4,5-trisphosphate mass accumulation. 6. The inhibitory effect of BRL 38227, but not that of nitrendipine or isoprenaline, on histaminestimulated [3H]-inositol phosphate accumulation was completely prevented in the presence of an elevated extracellular K+ (65 mM) concentration. 7. The results demonstrate that membrane hyperpolarization, and/or blockade of voltage-operated Ca2"-channels can regulate agonist-stimulated phosphoinositide metabolism in airway smooth muscle. The possible contribution of this regulatory mechanism to the relaxant properties of these agents is discussed.

Animals↗

PubMed1990

Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease.

The aim of the study was to compare the pulmonary effects of four beta-blockers with different ancillary properties: propranolol (non-beta 1 selective without ISA), oxprenolol (non-beta 1 selective with ISA), atenolol (beta 1 selective), and celipropol (beta 1 selective with mild beta 2-agonist and alpha 2-antagonist activity) in hypertensive patients with chronic obstructive lung disease. Ten asthmatic patients, all males, aged 50-66 years were studied. Entry criteria were a) DBP greater than or equal to 95 mmHg and less than or equal to 115 mmHg; b) FEV1 less than 70% of the theoretical values; c) FEV1 increase of at least 20% after salbutamol inhalation (200 micrograms). After a 2-week washout period on placebo, each patient received propranolol (80 mg/day), oxprenolol (80 mg/day), atenolol (100 mg/day), and celiprolol (200 mg/day) for 1 week, according to a randomized, cross-over design. At the end of the washout and of each treatment period, airway function, assessed by FEV1, FVC, and FEV1%, was evaluated by spirometry both in the basal condition and after salbutamol inhalation. Unlike propranolol and oxprenolol, which significantly reduced FEV1 and inhibited the bronchodilator response to inhaled salbutamol, atenolol and celiprolol did not significantly affect respiratory function and did not antagonize salbutamol effects. Celiprolol more closely approached placebo in its respiratory effects than did atenolol, although the differences were not statistically significant.

Adrenergic beta-Antagonists↗

PubMed1991

Comparative effects of thrombopoietin and interleukin-6 on murine megakaryocytopoiesis and platelet production.

A thrombocytopoiesis-stimulating factor (TSF or thrombopoietin) derived from human embryonic kidney (HEK) cells is known to increase platelet production and to increase the number of morphologically unrecognizable early megakaryocytes, ie, small acetylcholinesterase-positive (SAChE+) cells in mice. Other recent studies have concluded that interleukin-6 (IL-6) also stimulates murine megakaryocytopoiesis both in vitro and in vivo. Some workers have suggested that IL-6 is thrombopoietin. Therefore, the purpose of this study was to compare the effects of TSF and IL-6 on percent 35S incorporation into platelets, platelet sizes, and the percentages of SAChE+ cells in C3H mice, and to determine if they produce the same or different responses. The results showed that two or four injections of a partially purified TSF (total dose of 2 or 4 units (U) over a 1- or 2-day period) increased percent 35S incorporation into platelets (P less than .005) and platelet sizes (P less than .005) of both normal and rebound-thrombocytotic mice when compared with values from other mice treated with human serum albumin, the carrier protein for both TSF and IL-6. In eight separate experiments, it was shown that IL-6 (40,000 U, 4 micrograms), when given to rebound-thrombocytotic mice in four injections over a 2-day period, produced a small but significant (P less than .005) increase in percent 35S incorporation into platelets. Additional studies showed that negative results were obtained when similar high doses of IL-6 were administered in two doses over a 1-day period. TSF, but not IL-6, stimulated an increase in platelet sizes of normal mice (P less than .005 to 0.0005); however, IL-6 increased platelet sizes of rebound-thrombocytotic mice when given in two of four injections (P less than .05 to .0005). Also, IL-6, but not TSF, caused anemia in normal mice (P less than .0005) that were given two injections and tested 3 days later. TSF stimulated an increase (P less than .005) in the percentage of SA-ChE+ cells; whereas IL-6, even at high doses, did not. Because of the observed differences in biologic responses of these two cytokines, we conclude that TSF and IL-6 are separate entities.

Acetylcholinesterase↗

PubMed1975

Multiple-myeloma bone disease. The comparative effect of sodium fluoride and calcium carbonate or placebo.

A randomized double-blind study was carried out in 26 patients with multiple myeloma to compare the therapeutic effect of sodium fluoride (50 mg twice daily) plus calcium carbonate (1 g four times daily) and placebo. All patients also received melphalan and prednisone for one week every six weeks. Bone biopsies for microradiography and histology, and videodensitometry as well as conventional roentgenograms, 99mTc-polyphosphate bone scans, and bone densitometry of the mid and distal radius, were done initially and one year after therapy. Microradiography and videodensitometry studies revealed significant increases in bone formation (P less than 0.01) and bone mass (P less than 0.005) in the fluoride-calcium group. Bone trabeculae appeared thickened on roentgenograms of six of 13 fluoride-calcium-treated patients (P less than 0.02). Technetium bone scans and bone densitometry determinations proved insensitive for detection of skeletal changes. Fluoride calcium should be considered a useful adjunct in the treatment for multiple myeloma.

Bone Diseases↗

PubMed1976

The comparative effect of prolonged feeding with raw and heated soybean mean on the growth response, pancreatic enlargement and pancreatic enzymes of chicks.

Prolonged feeding of chicks with raw soybean meal as the main protein source in the diet resulted in growth inhibition, pancreas enlargement, and increased content of pancreatic proteolytic enzymes. The effect of feeding with raw soybean meal as compared to heated soybean meal upon total intestinal enzymatic activities in chicks was tested. The tendency of chicks to overcome the effects of raw soybean meal is expressed mainly by the increase of biosynthesis and secretion of proteolytic enzymes in the pancreas.

Amylases↗

PubMed1990

Comparative effects of esmolol and verapamil in a model of a supraventricular tachydysrhythmia.

Supraventricular tachydysrhythmias are a commonly encountered clinical problem after cardiothoracic surgery. Current choices for acute drug therapy of these dysrhythmias include intravenous verapamil as well as esmolol, but no data yet exist comparing the relative negative dromotropic (atrioventricular [A-V] nodal blocking) and negative inotropic effects of these agents. The purpose of this study was to compare the effects of esmolol with those of verapamil on systemic hemodynamics, coronary blood flow, and cardiac contractility at doses that produce a similar ventricular response rate in an animal model of a supraventricular tachydysrhythmia. Rapid electrical stimulation (800 impulses/min) of the left atrium in 14 dogs resulted in a rapid and irregularly irregular ventricular rhythm. Esmolol or verapamil were administered by bolus and then infusion to incrementally slow the average ventricular rate. Regional myocardial contractility was measured using the end-systolic pressure-length relationship (Ees). At drug doses that produced similar decreases in ventricular rate, esmolol produced a greater decrease in contractility (Ees: 284 +/- 46 to 40 +/- 22 mmHg/mm, LV dp/dt: 2,400 +/- 450 to 1,360 +/- 450 mmHg/sec) compared with that following verapamil (Ees: 297 +/- 57 to 116 +/- 25 mmHg/mm, LV dp/dt: 2,040 +/- 580 to 1,950 +/- 520 mmHg/sec). This was accompanied by a modest decrease in cardiac output in the esmolol group (2,800 +/- 940 to 2,290 +/- 730 ml/min) compared with an unchanged cardiac output as ventricular rate slowed in verapamil-treated animals. Stroke volume increased significantly in the verapamil-treated animals (10.9 +/- 4.0 to 18.5 +/- 4.6 ml), but remained unchanged following esmolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1976

Comparative effects of acebutolol and practolol on the lipolytic response to isoprenaline.

1 The effects of beta-adrenoceptor blockade on the metabolic responses to isoprenaline have been studied in an in vitro system of isolated fat cells and in six normal subjects. 2 The inhibitory effects of varying concentrations of acebutolol, practolol and propranolol on free fatty acid (FFA) release produced by isoprenaline (10(-7) M) were compared in isolated fat cells prepared from rat epididymal adipose tissue. Acebutolol and practolol, at equimolar concentrations, showed a similar inhibitory effect whilst propranolol was approximately 100 times more potent then either drug. At 10(-5)M concentration of propranolol, lipolysis was virtually abolished whilst at the same molar concentration, acebutolol and practolol halved the response. 3 Six healthy volunteers received three successive 15 min intravenous isoprenaline challenges (0.03 mug kg-1 min-1) per individual experiment. The first acted as a control whilst the following two were given either after single oral doses of placebo, acebutolol or practolol. The mean (+/- s.e. mean) basal FFA level was 0.77 +/- 0.06 mE1/1 and subsequent resting values after the administration of placebo or beta-adrenoceptor blocker were not significantly different. 4 Acebutolol inhibited the respective mean rises in FFA, produced by both post-control isoprenaline challenges, by (mean +/- s.e. mean) 70 +/- 4% and 84% +/- 5%. The comparable figures for practolol were 33 +/- 15% and 24 +/- 20%. The higher serum concentration of acebutolol produced greater inhibition but correlation of log serum concentration of the drug with percentage inhibition of FFA rise did not achieve significance. 5 Administration of isoprenaline, acebutolol or practolol did not significantly alter serum glucose, triglyceride or cholesterol levels. 6 Acebutolol and practolol effectively blocked the isoprenaline-induced tachycardia. The degree of blockade produced by practolol was greater than its inhibitory effect on FFA release. The diatolic fall in blood pressure in response to isoprenaline was abolished by acebutolol suggesting that its beta-adrenoceptor blocking action encompasses peripheral vascular sites. The comparable effect with practolol was a partial inhibition of the diastolic fall.

Acebutolol↗

PubMed1978

Comparative effects of centrophenoxine on the picrotoxin convulsive-seizure threshold in non-irradiated and irradiated mice.

A comparative study is made of the effect of centrophenoxine (CP) on the picrotoxin convulsive-seizure threshold (PCST) in non-irradiated and irradiated 3 and 7 days previously male mice. It is found that the CP appliked intracerebroventricularly in doses of 200 and 400 micrograms/mouse (weight 18-22 g), increases PCST. In non-irradiated mice the PCST-increasing effect of CP occurs rapidly (5 min) and it is brief (it can be observed until the 15th min). When the irradiation is performed three days previously, the PCST-increasing effect of CP is prolonged (it is observed until the 6th hour after its application). When the irradiation is performed seven days previously the characteristic features of the PCST-increasing effect of CP are similar to those in the early stage (3 days), the only difference being that the duration of the effect is prolonged to 120 min. Generally, these specificities of the CP effect are valid for all three phases of the convulsive seizure (general excitation, clonic convulsive seizure and tonic convulsive seizure.

Animals↗

PubMed1976

Comparative effects of niridazole on spermatogenesis and reproductive capacity in the mouse, rat and Japanese quail.

Niridazole is an effective schistosomicidal compound which, at lower dose levels, affects schistosome gonads. Its antifertility and possible mutagenic effects after various courses of oral treatment were compared in mice, rats and Japanese quail (Coturnix coturnix japonica). In all three species the meiotic stage of spermatogenesis was particularly affected. In mice the highest dose rate (five daily doses of 100 mg/kg) produced sterility during the 4th week. Rats were more susceptible, the compound producing prolonged and, in some animals, permanent sterility against which HCG treatment offered no protection. In quail only a brief phase of sterility occurred. Niridazole appears to be non-mutagenic since dominant lethal mutations were not produced in dose-response studies. Minimal changes in testis histology occurred in the mouse, but in rats severe damage persisted even in animals which had recovered their fertility.

Animals↗