Eudesmanolides from <Emphasis Type="Italic">Taraxacum mongolicum</Emphasis> and their inhibitory effects on the production of nitric oxide

A new eudesmanolide, 1β,3β-dihydroxy-eudesman-11(13)-en-6α,12-olide (1) was isolated and identified from Taraxacum mongolicum, together with two known compounds, 1β,3β-dihydroxyeudesman-6α,12-olide (2) and loliolide (3). The structure of 1 was established by analysis of its physical and spectroscopic data. 1 was found to have an inhibitory activity on nitric oxide production with an IC₅₀ of 38.9 μM in activated RAW 264.7 cells.     

Korean Red Ginseng Water Extract Restores Impaired Endothelial Function by Inhibiting Arginase Activity in Aged Mice

Cardiovascular disease is the prime cause of morbidity and mortality and the population ages that may contribute to increase in the occurrence of cardiovascular disease. Arginase upregulation is associated with impaired endothelial function in aged vascular system and thus may contribute to cardiovascular disease. According to recent research, Korean Red Ginseng water extract (KRGE) may reduce cardiovascular disease risk by improving vascular system health. The purpose of this study was to examine mechanisms contributing to age-related vascular endothelial dysfunction and to determine whether KRGE improves these functions in aged mice. Young (10±3 weeks) and aged (55±5 weeks) male mice (C57BL/6J) were orally administered 0, 10, or 20 mg/mouse/day of KRGE for 4 weeks. Animals were sacrificed and the aortas were removed. Endothelial arginase activity, nitric oxide (NO) generation and reactive oxygen species (ROS) production, endothelial nitric oxide synthase (eNOS) coupling, vascular tension, and plasma peroxynitrite production were measured. KRGE attenuated arginase activity, restored nitric oxide (NO) generation, reduced ROS production, and enhanced eNOS coupling in aged mice. KRGE also improved vascular tension in aged vessels, as indicated by increased acetylcholine-induced vasorelaxation and improved phenylephrine-stimulated vasoconstriction. Furthermore, KRGE prevented plasma peroxynitrite formation in aged mice, indicating reduced lipid peroxidation. These results suggest KRGE exerts vasoprotective effects by inhibiting arginase activity and augmenting NO signaling and may be a useful treatment for age-dependent vascular diseases.     

Nicardipine versus nitroprusside infusion as antihypertensive therapy in hypertensive emergencies

This prospective study compared the efficacy of nicardipine and nitroprusside for treating hypertensive emergencies by measuring haemodynamic indices and serum catecholamine levels. Patients admitted to the emergency department with a hypertensive crisis and acute pulmonary oedema received intravenous infusions of nitroprusside (starting dose 1 microgram/kg per min, n = 20) or nicardipine (starting dose 3 micrograms/kg per min, n = 20). Both groups experienced significant declines in systolic and diastolic blood pressure after treatment, but there were no significant time-dependent differences between the groups. Heart rate decreased in the nicardipine group and increased in the nitroprusside group, but neither change was significant. Respiration rate decreased and capillary oxygen saturation rate increased after treatment in both groups. Adrenaline and noradrenaline levels decreased significantly after treatment in both groups; noradrenaline levels were significantly decreased in the nicardipine-treated group compared with the nitroprusside-treated group. Injectable nicardipine is easy to use and as effective as nitroprusside for treating hypertensive crisis with acute pulmonary oedema.     

Clinical evaluation of incadronate in korean patients with malignancy-associated hypercalcemia: An open-label, multicenter study

Abstract

Background:

Incadronate has been found to lessen the increase in corrected serum calcium levels in malignancy-associated hypercalcemia (MAH) in a Phase III study in Japan. The drug is currently used to treat MAH in Japan.

Objective:

The purpose of this study was to assess the clinical usefulness of incadronate in patients with MAH.

Methods:

This open-label study was conducted at 3 medical institutions in Korea. Korean patients with MAH (corrected serum calcium levels ≥11.0 mg/dL) were given a single 10-mg IV infusion of incadronate over 2 to 4 hours in 500 to 1000 mL of normal saline. Corrected calcium levels were determined and subjective symptoms and objective findings (ie, bone pain, spontaneous pain, pain from contusion, tenderness, other pain, loss of appetite, nausea and/or vomiting, thirst, constipation, fatigue, and disturbance of consciousness) were used to monitor the effectiveness of the drug for 6 days after the infusion. Symptoms were evaluated using a 4-point scale (0 = none to 3 = severe). Adverse events (AEs) were identified by patients'' reports, and adverse drug events (ADEs) were assessed by the investigators throughout the study.

Results:

Twenty-four Korean patients (18 [75%]male, 6 [25%]female; mean age, 56.5 years) were included in the study; data from 22 and 24 patients were used to assess effectiveness and tolerability, respectively. Corrected serum calcium level was significantly decreased on day 6 after treatment compared with pretreatment on day 0 (baseline) (9.51 [0.89] mg/dL vs 11.83 [0.89] mg/dL; P < 0.001). The antihypercalcemic effect of incadronate became apparent as an inhibition of bone absorption a few days after infusion. Corrected serum calcium level was significantly decreased on days 2 to 6 (P < 0.001) after treatment compared with pretreatment at baseline. Evaluation of symptoms showed significant improvement in the incadronate-treated group (mean total score [range] at baseline, 8 [1–23] and day 6, 5.5 [1–17]; P = 0.001). Eight (33.3%) of the patients were found to have ADEs. Some of the 8 patients experienced >1 ADE (mild and transient fever [13 events], chills [3], headache [1], and myalgia [1]). AEs were observed in 19 (79.2%) of 24 patients. The most frequently reported AE was fever (14 events).

Conclusion:

In this small, open-label study, Korean subjects with MAH treated with incadronate experienced significant improvement in symptoms and calcium levels from baseline.Key Words: incadronate, bisphosphonate, malignancy-associated hypercalcemia, Korea     

Relationship between chronic kidney disease and risk of coronary heart disease in Korean men

There have been many epidemiological researches of chronic kidney disease (CKD), accompanied by an increase in the incidence of coronary heart disease (CHD). However, as far as we know, little research has been done to examine the extent of the relationship between CKD and CHD as estimated by Framingham risk score (FRS) in Korean men. CKD was defined as either proteinuria or an eGFR of < 60 mL/min per 1.73 m(2). The FRS has been used to predict the 10-yr risk of coronary events and usually divided into three levels of risk < 10% (low), 10%-19% (intermediate) and ≥ 20% (high). We defined FRS ≥ 10% as more-than-a-moderate CHD risk group and FRS ≥ 20% as a high CHD risk group, respectively. After adjusting for covariates, multivariable-adjusted logistic regression analyses showed a strong statistical significant relationship between CKD and high risk of CHD (adjusted OR, 1.95 [95% CI, 1.32-2.87]). Dipstick urinalysis and eGFR can be readily measured in most clinical settings. The measurement of kidney function may represent a relatively inexpensive and efficient way to identify individuals at higher risk for CHD.