Current Issue : July - September Volume : 2014 Issue Number : 3 Articles : 6 Articles
In this article the importance of blood proteins for drug dosing regimes is discussed.\nA simple mathematical model is presented for estimating recommended drug doses\nwhen the concentration of blood proteins is decreased. Practical guidance for drug\ndosing regimes is discussed and given in the form of a figure. It is demonstrated\nthat correction of drug dosing regimes is needed only for when there is a high level\nof drug conjugation with blood proteins and a high degree of hypoalbuminaemia.\nAn example of the use of this model is given....
This study tested whether a low dose (40% less than the pharmacological dose of 17-?? estradiol) would be as effective as the\npharmacological dose to improve cardiovascular parameters and decrease cardiac oxidative stress. Female Wistar rats (?? =\n9/group) were divided in three groups: (1) ovariectomized (Ovx), (2) ovariectomized animals treated for 21 days with low dose\n(LE; 0.2mg), and (3) high dose (HE; 0.5mg) 17-?? estradiol subcutaneously. Hemodynamic assessment and spectral analysis for\nevaluation of autonomic nervous system regulation were performed. Myocardial superoxide dismutase (SOD) and catalase (CAT)\nactivities, redox ratio (GSH/GSSG), total radical-trapping antioxidant potential (TRAP), hydrogen peroxide, and superoxide anion\nconcentrations were measured. HE and LE groups exhibited an improvement in hemodynamic function and heart rate variability.\nThese changes were associated with an increase in the TRAP, GSH/GSSG, SOD, and CAT. A decrease in hydrogen peroxide and\nsuperoxide anion was also observed in the treated estrogen groups as compared to the Ovx group. Our results indicate that a low\ndose of estrogen is just as effective as a high dose into promoting cardiovascular function and reducing oxidative stress, thereby\nsupporting the approach of using low dose of estrogen in clinical settings to minimize the risks associated with estrogen therapy....
Selective serotonin reuptake inhibitor medications are one of the most common treatments for mood disorders. In humans,\nthese medications are taken orally, usually once per day. Unfortunately, administration of antidepressant medications in rodent\nmodels is often through injection, oral gavage, or minipump implant, all relatively stressful procedures. The aim of the present\nstudy was to investigate how administration of the commonly used SSRI, fluoxetine, via a wafer cookie, compares to fluoxetine\nadministration using an osmotic minipump, with regards to serum drug levels and hippocampal plasticity. For this experiment,\nadult female Sprague-Dawley rats were divided over the two administration methods: (1) cookie and (2) osmotic minipump and\nthree fluoxetine treatment doses: 0, 5, or 10mg/kg/day. Results show that a fluoxetine dose of 5mg/kg/day, but not 10mg/kg/day,\nresults in comparable serum levels of fluoxetine and its active metabolite norfluoxetine between the two administration methods.\nFurthermore, minipump administration of fluoxetine resulted in higher levels of cell proliferation in the granule cell layer (GCL) at\na 5mg dose compared to a 10mg dose. Synaptophysin expression in the GCL, but not CA3, was significantly lower after fluoxetine\ntreatment, regardless of administration method. These data suggest that the administration method and dose of fluoxetine can\ndifferentially affect hippocampal plasticity in the adult female rat....
Poison-induced cardiogenic shock (PICS) as a result of beta-blocker (�Ÿ-blocker) or calcium channel blocker (CCB)\noverdose is a common and potentially life-threatening condition. Conventional therapies, including fluid resuscitation,\natropine, cardiac pacing, calcium, glucagon, and vasopressors often fail to improve hemodynamic status. High-dose\ninsulin (HDI) is an emerging therapeutic modality for PICS. In this article, we discuss the existing literature and highlight\nthe therapeutic success and potential of HDI. Based on the current literature, which is limited primarily to case\nseries and animal models, the authors conclude that HDI can be effective in restoring hemodynamic stability, and\nrecommend considering its use in patients with PICS that is not responsive to traditional therapies. Future studies\nshould be undertaken to determine the optimal dose and duration of therapy for HDI in PICS....
Background. Traumatic brain injuries (TBIs) are a major health care problem worldwide. Approximately 1.5 million new TBI cases\noccur annually in the United States, with mortality rates ranging between 35% and 40% in severe patients. Despite the incidence\nof these injuries and their substantial socioeconomic implications, no specific pharmacological intervention is available for clinical\nuse. Several studies have indicated that 300mg/kg or 400mg/kg of valproate (VPA) exhibits neuroprotective effects in animal\nmodels.However, humans cannot tolerate high doses of VPA. This study aims to investigate whether 30mg/kg of VPA administered\nto rats affects TBIs. Methods. We used a rat model to test the effects of 30mg/kg of VPA on TBIs. Molecular identifications for\nhistone acetylation and phosphorylation of cAMP response element-binding protein (CREB) and phosphorylated extracellular\nsignal regulated kinase (ERK)were performed. Results.Theresults indicated that treating adult rats with VPAafter TBIs significantly\ndecreased the contusion volume and recovery of contusion-related skilled forelimb reaching deficits. Applying VPA also increased\nhistone acetylation, p-ERK, and p-CREB expression in the brain. Furthermore, applying VPA reduced inflammation, glial fibrillary\nacidic protein activation, and apoptosis. Conclusion. This study found that 30mg/kg of VPA assists in treating TBIs in rat models....
Resealed erythrocyte loaded antiviral agent have potential effective therapy against modified tuberculosis pathogens. The advantages over the administration of rifampicin, includes less dose, decreased toxicity and lower systemic dose which can produce sustained delivery of the rifampicin at peak concentration to the intracellular site of microbial replication and increased therapeutic efficacy. In this research, the entrapment of Rifampicin by rat’s erythrocyte prepared using dilutional haemolysis and preswell dilutional haemolysis methods were studied. The effect of drug concentration and methods of encapsulation on the entrapment efficiency of rifampicin were determined. The hematologic parameters and osmotic fragility of rifampicin loaded erythrocyte carriers were measured. The entrapment of rifampicin by erythrocyte carriers was dependent on the method of encapsulation and amount of drug used. Difference in the osmatic fragility profile between native and drug loaded erythrocytes were observed, which were dependent on method of drug loaded. Mean hematological parameters were evaluated and compared with native erythrocytes. The mean corpuscular volume (MCV) of rifampicin loaded erythrocyte was significantly similar with native forms. The cell recovery of drug loaded erythrocytes were small than native cells. Rifampicin proved a sustained release from loaded erythrocytes over 48 h periods, which suggested an active use of the erythrocyte as a slow systemic release for treatment of tuberculosis infections....
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