High blood pressure. Causes, symptoms, treatments

Anticoagulant and Anti-thrombotic Treatments in the Management of Hematological Malignancies in a Home Care Program.

2017-05-29

We have recently found that isolation-reared mice show hyperactivity during an encounter with an intruder. However, it is not known whether encounter-induced hyperactivity may model some aspects of psychiatric disorders. The present study examined the pharmacological profile of encounter-induced hyperactivity in isolation-reared mice. Encounter-induced hyperactivity was reduced by acute administration of various antidepressants including the tricyclic antidepressant desipramine (10 mg/kg), the selective serotonin (5-HT) reuptake inhibitors fluvoxamine (10 mg/kg) and paroxetine (10 mg/kg), the 5-HT/noradrenaline reuptake inhibitors venlafaxine (10 mg/kg) and duloxetine (10 mg/kg), the antipsychotic drug risperidone (0.01 mg/kg), the 5-HT2 antagonist ritanserin (1 mg/kg), and the glucocorticoid receptor antagonist RU-43044 (30 mg/kg). The α2 adrenoceptor agonist clonidine (0.03 mg/kg) and the 5-HT4 receptor agonist BIMU8 (30 mg/kg) also reduced encounter-induced hyperactivity. The effect of desipramine was blocked by the α2 adrenoceptor antagonist idazoxan (0.3 mg/kg). The effect of fluvoxamine was blocked by the 5-HT4 receptor antagonist GR125487 (3 mg/kg), but not the 5-HT1A receptor antagonist WAY100635 (1 mg/kg), the 5-HT3 receptor antagonist azasetron (3 mg/kg), or the 5-HT6 receptor antagonist SB399885 (3 mg/kg). The effect of venlafaxine was blocked by the simultaneous administration of idazoxan (0.3 mg/kg) and GR125487 (3 mg/kg), but not by either compound alone. These findings suggest that encounter-induced hyperactivity in isolation-reared mice is a robust model for testing the pharmacological profile of antidepressants, although the range of antidepressants tested is limited and some non-antidepressants are also effective. The present study also shows a key role of α2 and 5-HT4 receptors in the antidepressant effect in this model.

The objective of this analysis was to evaluate the cost-effectiveness of duloxetine when considered as an additional treatment option for UK-based patients suffering from diabetic peripheral neuropathic pain.

A novel dispersive liquid-liquid microextraction method based on solidification of floating organic droplets (DLLME-SFO) technique was developed for the determination of duloxetine in human plasma samples by high performance liquid chromatography with fluorescence detection (HPLC-FLD). During the extraction procedure, plasma protein was precipitated by using a mixture of zinc sulfate solution and acetonitrile. After the protein precipitation step, duloxetine in an alkaline sample solution was quickly extracted by DLLME-SFO with 50 μL of 1-undecanol (extractant). Disperser was unnecessary because the small amount of remaining acetonitrile, which acts as a protein precipitating reagent, was also employed as a disperser; therefore, organic solvent consumption was reduced as much as possible. The emulsion was centrifuged and then fine droplets were floated to the top of the sample solution. The floated droplets were solidified in an ice bath and easily transferred. Various DLLME-SFO parameters such as extractant type, extractant amount, ionic strength, pH and extraction time were optimized. The chromatographic separation of duloxetine was carried out using ethanol as mobile phase. Validation of the method was performed with respect to linearity, intra- and inter-day accuracy and precision, limit of quantification (LOQ), and recovery. Calibration curves for duloxetine showed good linearity with correlation coefficients (r²) higher than 0.99. The method showed good precision and accuracy, with intra- and inter-assay coefficients of variation less than 15% (LOQ: less than 20%) at all concentrations. The recovery was carried out following the standard addition procedure with yields ranging from 59.6 to 65.5%. A newly developed environmentally friendly method was successfully applied to the pharmacokinetic study of duloxetine in human plasma and was shown to be an alternative green approach compared with the conventional solid-phase microextraction (SPME) and dispersive liquid-liquid microextraction (DLLME) techniques.

Five clusters were identified, from "worst" (high pain levels and severe mental/physical impairment) to "best" (low pain levels and nearly normal mental/physical function). For patients with moderate overall severity, mental and physical symptoms were less correlated, resulting in 2 distinct clusters based on these 2 symptom domains. Three key variables with threshold values were identified for classification of patients: Brief Pain Inventory (BPI) pain interference overall scores of <3.29 and <7.14, respectively, a Fibromyalgia Impact Questionnaire (FIQ) interference with work score of <2, and an FIQ depression score of ≥5. Patient characteristics and frequencies per baseline category were similar between treatments; >80% of patients were in the 3 worst categories. Duloxetine patients were significantly more likely to improve after 12 weeks than placebo patients. A sustained effect was seen with continued duloxetine treatment.