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Recently pharmaceuticals have become significant environmental pollutants in aquatic ecosystems, that could affect primary producers such as microalgae. Here we analyzed the effect of pharmaceuticals on the photosynthesis of microalgae commonly found in freshwater-two species of Chlorophyceae and a member of the Eustigmatophyceae, via PAM fluorometry. As pharmaceuticals, three medicines often consumed in households were chosen: (i) fluoxetine, an antidepressant, (ii) propranolol, a β-blocker and (iii) ibuprofen, an anti-inflammatory and analgesic medicine. The EC50 for the quantum yield of photosystem II in phytoplankton acclimated to inorganic phosphorus (Pi)-replete and Pi-limited conditions was estimated. Acute toxicity experiments over a 5 h exposure revealed that Nannochloropsis limnetica was the least sensitive to pharmaceuticals in its photosynthetic yield out of all species tested. Although the estimation of sub-lethal effects can be vital in contrast to that of LC50s, the EC50 values in all species and for all medicines were orders of magnitude higher than concentrations found in polluted surface water. Chlamydomonas reinhardtii was the most sensitive to fluoxetine (EC50 of 1.6 mg L(-1)), and propranolol (EC50 of 3 mg L(-1)). Acutodesmus obliquus was most sensitive to ibuprofen (EC50 of 288 mg L(-1)). Additionally, the sensitivity to the pharmaceuticals changed under a Pi-limitation; the green algae became less sensitive to fluoxetine and propranolol. In contrast, Pi-limited algal species were more sensitive to ibuprofen. Our results suggest that the sensitivity of algae to pharmaceuticals is (i) highly compound- and species-specific and (ii) dependent on the cellular P status.
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To study the regular pattern and mechanism of positive inotropic effect after washout of ACh (rebound of myocardial contractile force) in isolated rabbit hearts.
BACKGROUND Acute beta-adrenergic blockade increases aortic-wave reflection in young women. However, it is not known whether this effect extends to postmenopausal women. We therefore examined the effect of systemic beta-adrenergic blockade on aortic wave reflection in 14 postmenopausal women with a mean age of 58±2 years. METHODS Aortic pressure waveforms were synthesized noninvasively from high-fidelity radial pressure waveforms obtained through applanation tonometry before and during systemic beta-blockade with propranolol given in a bolus dose of 0.25mg/kg, followed by a continuous infusion at 0.004mg/kg/min. To further examine the effects of acute beta-blockade on aortic-wave reflection in postmenopausal women, we compared the changes in hemodynamics and indices of aortic-wave reflection with published data from a previous study with a protocol identical to that in the present study but which involved young women. RESULTS Acute beta-blockade increased the aortic augmentation index (AIx) in postmenopausal women (32±2% vs. 35±2%, P < 0.01). However, AIx adjusted for a heart rate of 75 bpm (AIx75) was unchanged (25±2% vs. 24±2%, P > 0.05). The changes in AIx, AIx75, and the amplitude of reflected waves (augmented aortic pressure) during beta-blockade were all substantially smaller in postmenopausal women than in their younger counterparts (P < 0.05). Conclusions As compared with those in our previously published study involving young women, indices of aortic-wave reflection were significantly less affected by acute systemic beta-adrenergic blockade in the postmenopausal women in the present study. Taken together, our data suggest that the negative effects (i.e. increased aortic wave reflection) of nonselective beta-adrenergic blockade are less pronounced in postmenopausal than in young women.
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The cell surface glycoprotein CD44 is proposed as a main participant in cell adhesion and migration. We studied the function, expression, and distribution of CD44 in the invasive and metastatic F3II murine carcinoma cell line during adhesion, spreading, migration, and invasion. A mAb anti-CD44 (KM 201) dramatically blocked F3II cell adhesion on both plastic and hyaluronic acid coatings, as well as spreading on uncoated plastic surfaces (P < 0.01). KM201 mAb significantly inhibited F3II cell migration and invasion in Transwell chambers. Immunocytochemistry of spreading cells revealed that CD44 distributed in bands on the cell surface, particularly in the tip of leading edges and in the perinuclear zones of the cell membrane. CD44 antigen was never detected in filopodia or lamellipodia nor in focal adhesion-like structures, but was also detectable as strong interlamellar bands. Fully spread cells showed a decreased CD44 signal compared to cells in early stages of spreading. This decrease correlated with a reduced expression of CD44 as detected by Western blot. We also investigated the signals that may regulate CD44 expression in F3II cells. Treatment of F3II cells, with phorbol myristate acetate (PMA) or phosphatidic acid (PA, the product of PLD-dependent hydrolysis of phosphatidylcholine), significantly enhanced CD44 expression. Conversely, the treatment of F3II cells with H7, a specific PKC inhibitor, or propranolol, which blocks PA conversion to DAG, significantly decreased CD44 expression levels. These results suggest the involvement of PKC and PLD pathways in CD44 expression. These results demonstrate that CD44 plays an important role during F3II cells adhesion, spreading, migration, and invasion. In addition we provide information linking the PLD- and PKC-dependent pathways with the regulation of CD44 expression.
The spectral and morphological indicators and, independently, those derived from the analysis of normalized energy regions of interest provide a reliable approach to the evaluation of the complexity of ventricular fibrillation as an alternative to complex mapping techniques.
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A timed non-invasive determination of cardiac function is potentially important for safety pharmacology and toxicity studies. The objectives of this study were to evaluate the accuracy of real-time three-dimensional (RT3D) echocardiography measurements of the left ventricular (LV) volume and LV function and to investigate the effects of some drugs on LV function in cynomolgus monkeys.
We describe a case of pulmonary hypertension and high-output heart failure in a 61-year-old woman suffering from relapsing Graves disease. The patient experienced prompt hemodynamic and symptomatic recovery after normal thyroid function was restored. Possible mechanisms for the development of pulmonary arterial hypertension due to hyperthyroidism include damage to pulmonary vascular endothelium due to high cardiac output or an autoimmune process or increased metabolism of intrinsic pulmonary vasodilators. Another possible mechanism is vascular vasoconstriction due to decreased cholinergic output.
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Capillary hemangioma is one the most common tumors of eyelid and orbit reported in pediatric age group. Oral propranolol therapy is latest addition to the armamentarium of treatment options available to ophthalmologists in treating capillary hemangiomas. We report the successful response to propranolol therapy to a 5-year-old child with capillary hemangioma involving lids, orbit, and the paranasal sinuses. A long-term follow-up is necessary for the prognostic efficacy of the therapy.
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To investigate the role of adrenoceptor subtypes in regulating the spontaneous contractile activity of the inner lining of the urinary bladder (urothelium/lamina propria).
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Variations of mean arterial pressure (MAP) were observed after icv injection of endomorphine-1 in rats. The effects of i.v. or icv of various blockers, naloxone, phentolamine, propranolol, atropine and N omega-nitro-L-arginine, on the variation of MAP caused by endomorphin-1 were observed.
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Experiments were carried out to determine whether central administration of beta-adrenergic antagonists blocks antidepressant-like effects produced by peripheral administration of the beta(2)-adrenergic agonist clenbuterol.
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We examined whether various widely prescribed beta2-adrenoceptor agonists differ in anti-inflammatory mechanisms.
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To study the absorption of coptisine chloride (COP) and berberrubine (BRB) as chemical constituents of some traditional Chinese medicines in human intestinal epithelial.
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The present study was designed to further investigate the effect of amitriptyline, a classical tricyclic antidepressant, on carrageenan-induced paw edema in rats.
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1 We examined bone-marrow in mice receiving subcutaneous implants of heat-coagulated egg white, which are known to present chronic eosinophilic inflammation at the implant site. Egg white implants (EWIs) induced marked bone-marrow eosinophilia, and increased bone-marrow cell responses to granulocyte-macrophage colony-stimulating factor and interleukin-5 in culture. These effects were observed as early as 24 h and lasted for, at least, 30 days in implant recipients. 2 We found, however, that increased eosinophil production was also observed in control mice which underwent surgery but received no EWI (sham-implanted mice), up to 15 days post-surgery. As this suggests an important contribution of nonspecific stress mechanisms to eosinopoiesis, we further evaluated the role of stress hormones produced by the adrenal glands in the bone-marrow eosinophilia of sham-implanted mice. 3 Bone-marrow eosinophilia in mice undergoing surgery was dissociated from increases in other haemopoietic lineages. Surgery by itself increased circulating corticosterone levels by 24 h, and the increase was prevented by inhibition of adrenal glucocorticoid production by metyrapone. The effect of surgery on bone-marrow eosinophilia was prevented by pretreatment with both the glucocorticoid receptor antagonist, mifepristone, and metyrapone, and by surgical adrenalectomy. 4 By contrast, cathecolamine receptor antagonists (propranolol, prazosin and yohimbine) were ineffective, indicating that cathecolamine release from the adrenal glands was not responsible for the effects on bone-marrow. 5 These results highlight a critical role for stress-induced glucocorticoid hormones in selectively upregulating bone-marrow eosinopoiesis in mice submitted to surgery.
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Isolated frog corneas, with the endothelium scraped off, were mounted as a partition between Ussing-type hemichambers. Unidirectional diffusional water fluxes (Jdw) were measured by adding 3H2O to one hemichamber and sampling from the other. Electrical parameters were measured simultaneously. Jdw was determined in control isosmotic conditions and after either changes in osmolarity of the bathing solutions or the additions of amphotericin B, epinephrine, Ca2+ ionophore, and other agents.
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The effects of aging and diabetes on the distribution of beta-adrenoceptor subtypes in the gut were investigated in the BB rat. [125I]Cyanopindolol binding to 10-micron sections was evaluated using film autoradiography. Cyanopindolol binding to beta-, beta 1-, and beta 2-adrenoceptors was displaced by 1 microM propranolol, 50 nM ICI-89-406, and 100 nM ICI-118-551, respectively. beta-Adrenoceptor binding was highest in the circular muscle of proximal colon and lowest in the pylorus of 4- to 5-month-old rats. Aging (8- to 10-month-old vs. 4- to 5-month-old rats) was associated with increased beta-adrenoceptor binding in the pylorus and reduced binding in the proximal colon. Diabetes had a time-dependent effect on the level of beta-adrenoceptor binding. It was increased in the antral and pyloric stomach but longer periods of diabetes caused a reduction in beta-adrenoceptor binding in the pylorus. Those in the intestine were reduced time-dependently and involved beta 1- or beta 2-adrenoceptors or both.
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After preparing a script of a negative disturbing memory, participants were instructed to imagine this event 1 week later after ingestion of either 35 mg cortisol, 80 mg propranolol, or a placebo. Physiological responding to the script-driven imagery was recorded. Another week later, after washout, the imagery was repeated again. During all three sessions as well as 8 months later, subjective emotional reactions to the memories were assessed.
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Our findings are in sharp contrast with the currently pharmacological and cognitive behavioral treatments for anxiety and related disorders. The β-adrenergic blocker was only effective when the drug was administered upon memory reactivation, and a modification in cognitive representations was not necessary to observe a change in fear behavior. A new wave of treatments that pharmacologically target the synaptic plasticity underlying learning and memory seems to be within reach.
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Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease leading to cirrhosis and cholangiocellular carcinoma. Inhibitors of the renin-angiotensin system or the sympathetic nervous system delay liver fibrogenesis in animal models.
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The study was undertaken considering that: i) androgens affect β2-adrenoceptor (AR)-mediated catecholamine (CA) action in many tissues; and ii) peripubertal changes in both circulating androgen and thymic CA levels are implicated in rat thymic involution. Its aims were to: i) explore putative effects of the late prepubertal orchidectomy on thymic CA:β2-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:β2-AR complex from those elicited secondarily through altered influence of this complex components on each other's availability. Upon showing that prepubertal orchidectomy augmented the efficacy of thymopoiesis through increasing the thymocyte surface density of Thy-1, whose expression is negatively regulated by β2-AR-mediated signaling, we examined the effects of orchidectomy and 14-day-long propranolol (PROP) treatment in orchidectomized (ORX) and sham-ORX rats on thymic norepinephrine (NE) concentration and metabolism and β2-AR expression. Orchidectomy, despite an increase in the average NE amount per thymocyte and total thymocyte NE content, diminished thymic NE concentration. This decrease reflected the diminished density of CA-synthesizing nerve fibers, CD68+ macrophages, cortical (aminopeptidase A+), and medullary (UEA-1+) thymic epithelial cells (TECs) and their CA content (probably due to lessened TH expression accompanied by increased MAO-A expression). Moreover, orchidectomy decreased the surface β2-AR expression on thymocytes, CD68+ macrophages and OX-62+ dendritic cells, but increased its expression on the TECs. In sham-ORX rats, PROP reduced thymic NE concentration by diminishing TH expression in the thymic cells. Additionally, PROP in thymocytes and thymic stromal cells diminished and enhanced the β2-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):β2-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to β-AR blockade by altering thymic NE and β2-AR availability. Collectively, the results showed that testicular hormones contribute to alterations in thymus/thymopoiesis during the critical peripubertal period by shaping modulatory sympathetic influence and CA autocrine/paracrine action within the organ.