Validation of age- and sex-dependent association of uric acid and incident hypertension in rural areas.

BACKGROUND: A previous study based on urban areas suggested the age- and sex-dependent association of uric acid (UA) and incident hypertension. We aimed to investigate whether this association is valid even in rural areas with different lifestyle. METHODS: Data from the cardiovascular disease association study, a prospective cohort study based on rural residents, was analyzed. A total of 4,592 subjects (mean age, 60.1 ± 9.5 years; men, 37.7%) without hypertension were included. We first investigated whether UA was a risk factor for incident hypertension using Cox regression, and then compared the relative risk by stratification according to age and sex. RESULTS: During the follow-up period (mean, 2.0 years), 579 subjects (12.6%) were newly diagnosed with hypertension. The risk factors for incident hypertension were age (Hazard ratios [HR] for ≥ 65, 1.26), systolic blood pressure (HR per 1 mmHg increase, 1.07), and serum UA concentration (HR per 1 mmHg increase, 1.10). The risk of UA-related incident hypertension was higher in the non-elderly than in the elderly for both men and women (HR, 1.74 for non-elderly men; 1.88 for non-elderly women; 1.66 for elderly men; 1.10 for elderly women). Even after adjusting for multiple confounders, the risk of UA-related incident hypertension was significantly higher in non-elderly women (HR, 1.59; P < 0.05). CONCLUSIONS: Age- and sex-dependent association of UA with incident hypertension suggested in cohort study based on urban areas was consistently found in rural areas as well. In particular, non-elderly women were at a higher risk for UA-related incident hypertension.

Formulations of deoxycholic for therapy: a patent review (2011 - 2014).

INTRODUCTION: Deoxycholic acid (DOCA) is involved in many physiological functions and has been used in various fields of pharmaceutical formulations as a natural active solubilizing and permeation-enhancing agent. Although DOCA has been suggested to be a promoter of colon cancer, it has also been used extensively as a starting material to obtain new derivatives for potential therapeutic applications. AREA COVERED: In this review, we focus on patents and research reports from 2011 to 2014 related to pharmaceutical formulations and therapeutic applications using DOCA and its derivatives as surfactants or absorption enhancers, drug delivery carriers, and anti-cancer agents. EXPERT OPINION: In recent few years, DOCA and its derivatives have been used mostly as pharmaceutical excipients for solubilizing lipophilic compounds to improve their bioavailability. Other studies have expanded its applications to include enhanced drug permeability and have designed more effective drug carriers by conjugation with polymeric materials. Recently, a synthetic DOCA injection, ATX-101, has shown long-term efficacy in the non-surgical treatment of unwanted submental fat and acceptable tolerability in humans. Thus, it may be used for reducing specific localized fat accumulations. Additionally, DOCA has been a starting material for anti-cancer drugs, and some derivatives showed strong inhibitory activities against several carcinoma cells.

Use of MDLC-DIGE and LC-MS/MS to identify serum biomarkers for complete remission in patients with acute myeloid leukemia.

The response criteria for complete remission (CR) in acute myeloid leukemia (AML) are currently based on morphology and blood cell counts. However, these criteria are insufficient to establish a diagnosis in cases with poor quality bone marrow (BM) samples demonstrating a loss of cellular morphology. We investigated whether the sera of patients contained biomarkers that indicate disease response status. First, we performed multidimensional liquid chromatography-differential gel electrophoresis (MDLC-DIGE) to generate protein profiles of two pooled, paired serum samples from patients who had achieved CR; one collected at diagnosis (PreCR) and the other collected after chemotherapy (CR). Then, with the biomarker candidates found, ELISA was carried out for individual PreCR and CR samples, and for other verification sets including nonremission (NR) patients and normal samples. We selected two proteins, complement factor H (CFH) and apolipoprotein H (ApoH), with dye (Cy) ratios showing greater than 2.0-fold differences between the pooled samples. ELISA showed that CFH and ApoH are useful for distinguishing between the recovered (CR and normal) and nonrecovered (PreCR, PreNR, and NR) states in AML (p <0.001). We successfully applied a protein profiling technology of MDLC-DIGE and LC-MS/MS to discover two biomarkers for CR which needs further validation for a clinical setting.

Results of a phase III, 8-week, multicenter, prospective, randomized, double-blind, parallel-group clinical trial to assess the effects of amlodipine camsylate versus amlodipine besylate in Korean adults with mild to moderate hypertension.

BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.