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To study the protective effect of oxyphenamone, a novel inodilator against myocardial ischemia-reperfusion injury.
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Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology.
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Thrombin-induced increase in [Ca²⁺](i) was significantly inhibited by pretreatment of platelets with R59949, while thapsigargin-induced increase in [Ca²⁺](i) was comparable in platelets with and without R59949 pretreatment. Thapsigargin-induced increase in [Ca²⁺](i) was markedly attenuated in the presence of SKF-96365. In the presence of SKF-96365, thrombin-induced increase in [Ca²⁺](i) was significantly attenuated, and additional treatment with R59949 caused a further decrease in [Ca²⁺](i) . Pretreatment of platelets with 1-butanol significantly attenuated thrombin-induced increase in [Ca²⁺](i) , while thrombin-induced increase in [Ca²⁺](i) was augmented in the presence of propranolol. mRNA expression of DGK-α and DGK-γ, which are known to be inhibited by R59949, in platelets was confirmed by RT-PCR analysis.
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Hemangiomas are common vascular birthmarks that usually present a predictable pattern of proliferation and ultimate involution. Most do not require any treatment. When intervention is clinically indicated, medical and surgical options exist. Historically, corticosteroids have been used and have been shown to slow or stop the growth of a majority of hemangiomas; however, growth concerns and infectious complications have complicated their use. In 2008, a letter to the editor in The New England Journal of Medicine described another serendipitous observation of the effect of the nonselective beta-blocker, propranolol, on hemangiomas in 9 cases. This finding has been expanded by the authors of this original observation as well as others.
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Concomitant movement disorders, such as dystonia, are common among patients with childhood-onset ET, which supports the concept that ET is a heterogeneous disorder. Treatment strategies used for adult patients with ET seem to be effective also for children with ET, although controlled therapeutic trials in this population of patients with ET are lacking.
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Intractable fever in cancer patients is problematic and the causes of this fever can be diverse. Paroxysmal persistent hyperthermia after sudden mental change or neurologic deficit can develop via autonomic dysregulation without infection or any other causes of fever. Paroxysmal hyperthermic autonomic dysregulation is a rare disease entity. It manifests as a form of paroxysmal hypertension, fever, tachycardia, tachypnea, pupillary dilation, agitation and extensor posturing after traumatic brain injury, hydrocephalus, brain hemorrhage or brain neoplasm. We recently experienced a case of paroxysmal hyperthermia following intracerebral hemorrhage along with brain neoplasm. Extensive fever workups failed to show an infectious or inflammatory source and/or hormonal abnormality. Empirical treatments with antibiotics, antipyretics, morphine, steroid and antiepileptic agents were also ineffective. However, Propranolol, a lipophilic beta-blocker, successfully controlled the fever and stabilized the patient. Fever in cancer patients is a common phenomenon, but a central origin should be considered when the fever is intractable. Propranolol is one of the most effective drugs for treating paroxysmal hyperthermia that is due to autonomic dysregulation.
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This study evaluated the safety and effects of propranolol as a premedication before cataract surgery and compared them with the usual combination doses of fentanyl and ketamine. Among all reffered patients to Feiz Hospital of Esfahan for cataract surgery, 122 patients between Mar to Sep 2010 were enrolled in this study and randomly allocated into one of the following equal groups: 40 mg propranolol, 2 hours before surgery and combination of 15 mg ketamine and 50 µg fentanyl l. 5 min before surgery. The ability to control of hemodynamic instabilities caused by stress and to gain patients satisfaction was compared between two groups. Also, the efficacy of each premedication to control of hemodynamic changes during surgery were evaluated and compared. No significant differences were seen in the patients satisfaction and controlling of stress induced hemodynamic changes between two groups (P>0.05). However, patients in ketamine + fentanyl group showed more nausea and less pain during and after surgery. Moreover, no significant adverse effects were reported during and after the surgery. Our results demonstrated that propranolol can be used safely as a premedication in cataract surgery in the comparable efficacy to ketamine plus fentanyl premedication.
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Given its improved safety profile compared with systemic corticosteroids, propranolol has become the mainstay treatment of infantile haemangioma (IH) worldwide. There is evidence, mainly from adult volunteer studies, that propranolol use is associated with central nervous system (CNS) effects. Impairment to short- and long-term memory, psychomotor function, sleep quality and mood with relatively low doses and durations of treatment have been reported. The exact magnitude of CNS effects resulting from propranolol use, especially in the early developmental stages and for prolonged periods of use, is not currently known. These effects may not be readily recognizable and require specialized assessment of cognitive function not routinely performed. Furthermore, there may be a delay between exposure and cognitive defects. The evidence to date provides a strong rationale to proceed with caution when prescribing propranolol for IH: treatment should be used only when indicated (in the presence of ulceration, impairment of a vital function or risk of permanent disfigurement) and for a limited duration, and the benefits of treatment should be weighed carefully against potential adverse events before treatment is initiated. This narrative review describes the evidence for an effect of propranolol use on CNS function from volunteer and patient studies, including IH.
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An investigation of the optimal acquisition parameters for quantitation was conducted for propranolol, reserpine, leucine enkephalin and neurotensin from mouse plasma samples. The lower limits of quantitation were demonstrated to be 1-3 nM while the quantitation linear dynamic range extends to four orders of magnitude. This level of performance is sufficient for most bioanalytical applications in drug discovery.
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The sorption of three polychlorinated biphenyls (PCBs) in single-solute and bi-solute systems in the presence of propranolol was studied on biochars at pyrolyzing temperatures of 200°C (BC200) and 700°C (BC700). Hydrophobicity and molecular planarity played a major role in PCB sorption onto BC200 and BC700, respectively. The steric hindrance caused by non-planarity made the strong specific sorption sites on BC700 less accessible to nonplanar PCBs. In bi-solute systems for BC200, propranolol monomers at an initial concentration (Cinit) of 0.8mg/L inhibited the sorption of PCB4 by competing for sorption sites. Propranolol at Cinit larger than 1.2mg/L could form hemimicelle structures on the biochar surface, providing a favorable phase for PCB4 partitioning, thereby increasing Koc up to 1.15 times. For BC700, propranolol prohibited PCB4 sorption mainly by pore-blocking, with the log Koc being reduced from 4.92 to 3.94. This study informs the application of biochar in mixture-contaminated environment.