ABSTRACT
Objective To investigate the incidence and influencing factors of aldosterone escape in patients with non-diabetic nephropathy by RASI-therapy. Methods A total of 104 patients with non-diabetic nephropathy were treated with ARB or combination therapy of ACEI and ARB in a mean follow-up period of 12 months. Aldosterone escape was determined according to the change of plasma aldosterone concentration before and after treatment during 6-month and 12-month ACEI/ARB treatment, while the influencing factors of aldosterone escape in patients with non-diabetic nephropathy was also analyzed after therapy with RASI . Results In 12 months, the incidence of aldosterone escape was significantly higher than that in 6 months (26.92% vs. 14.42%, P = 0.007). After 12-month treatment, the difference was statistically significant in incidence of aldosterone escape among different stages of CKD (P = 0.027). Compared with 6-month incidence of aldosterone escape in the losartan group, 12-month incidence increased evidently (P = 0.020). The Ald level was positively correlated with urinary protein excretion and the Scr level (r = 0.431, P = 0.003 and r = 0.336, P = 0.009, respectively), and negetively correlated with levels of the eGFR (r = -0.275, P = 0.006). Univariate Logistic regression demonstrated that risk factors of aldosterone escape included pre-treatment values of the urinary protein excretion (OR = 3.671, P = 0.028) and the eGFR (OR = 0.972, P = 0.019). Multivariate Logistic model revealed pre-treatment values of the eGFR was positively associated with aldosterone escape (OR = 0.970, P = 0.012). Conclusion The incidence of the aldosterone escape increases along with the time of treatment. Renal function has correlated with aldosterone escape and pre-treatment value of the eGFR is an independent risk factor of aldosterone escape.
ABSTRACT
BACKGROUND: Osthol is a simple coumarin from Cnidium monnier (L.)Cusson which has been long used of in China as a herbal medicine for arthritis. We have previously observed protective effects of osthol on Ca2+antagonism, oxidative stress and inflammation. And other researches reported that it could inhibit increase of serum xanthine oxidase induced by liver tumor.OBJECTIVE: To investigate the protective effect of osthol on carbon tetrachloride (CCl4)-induced liver injury of mice.DESIGN: Completely randomized controlled study.SETTING: Department of Pharmacology, Gannan Medical College; Physical Education, Gannan Normal College.MATERIALS: A total of 40 Kunming mice were of both genders and weighing (20±2) g. Osthol was provided by Chengdu Longquan High-Tech Natural Pharmaceutical Co. Ltd.METHODS: The experiment was performed at Department of Pharmacology, Gannan Medical College from March to July 2005. Forty mice were randomly divided into control, model, osthol (ip 50 g/kg) and osthol (ip 100 g/kg) groups with 10 in each. Separately once a day for 15 consecutive days, the control and model groups were equalized injected intraperitoneally with 10 mL/kg saline and osthol groups injected intraperitoneally with 50 and 100 g/kg osthol, respectively. On 15 day just after treatment,they, except the control, were challenged with CCl4 (ip 1 g/L peanut oil solution 10 mL/kg). Then all mice were free access to water but fast food.At specified time points 16 hours after the injection of CCl4, all mice were sacrificed and blood was collected in centrifuge tubes. The serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver malondialdehyde (MDA) were determined, and the pathological examination of liver was observed.MAIN OUTCOME MEASURES: Contents of serum ALT, AST, MDA and pathological examination.RESULTS: Forty mice were involved in the final analysis. ① At 16 hours after CCl4 induction, contents of ALT and AST were higher in model group than those in control group (P ＜ 0.001). The increase in the contents of ALT and AST was inhibited by osthol in a dose-dependent manner, especially in 100 mg/kg osthol group (P ＜ 0.05). Both 50 mg/kg and 100 mg/kg osthol could inhibit the increase of AST induced by CCl4 (P ＜ 0.01-0.001).② Content of MDA in model group was increased (P ＜ 0.05), and content of MDA in 100 mg/kg osthol group was similar to that in control group.100 mg/kg osthol could decrease content of MDA, 50 mg/kg osthol could increased the content; however, it still had the tendency of decrease. ③Effect of osthol on histopahtological changes, the livers of CCl4intoxicated mice showed massive fatty change, gross necrosis, broad infiltration of the lymphocytes, and Kupffer cells around the central vein, loss of cellular boundary. The histological pattern of the livers of the mice treated with 100 mg/kg and 50 mg/kg osthol showed a mild degree of fatty change,necrosis and lymphocyte infiltration. In contrast, the inhibitory potency of 100 mg/kg osthol on the histological changes significantly higher than those models.CONCLUSION: Osthol can protect against CCl4-induced hepatotoxicity in mice through decreasing activities ALT and AST and contents of MDA.
ABSTRACT
BACKGROUND: As a plant in valerianaceae, patrina villosa juss, which characterizes by acrid and bitter in taste and cold in nature, has been proved that its extract has effect on central inhibition.OBJECTIVE: To observe the effect of patrina villosa juss extract on hypoxia tolerance of mice and acknowledge whether it has dosage-dependence or not.DESIGN: Randomized controlled animal study.SETTING: Pharmacological Department and Pathological Department of Gannan Medical College.MATERIALS: The experiment was completed at the Laboratory of Scientific Research Center of Gannan Medical College from March to April 2005. A total of 100 healthy adult Kunming mice were selected in three hypoxia experiments.METHODS: ① Hypoxia tolerance experiment under normal pressure:Forty mice were randomly divided into 4 groups. Mice were injected intravenously with 2 μL/g saline in saline group, with 0.02 mg/g propranolol solution (10 g/L) in propranolol group, with 0.02 mg/g patrina villosa juss extract in 0.02 mg/g patrina villosa juss group, and 0.04 mg/g patrina villosa juss extract in 0.04 mg/g patrina villosa juss group, respectively. Twenty-five minutes later, mice were put into wide mouthed bottle with the volume of 250 mL and the bottle was enclosed to observe the survival time. ② Rapid decapitation experiment: Thirty mice were randomly divided into 3 groups. Mice were injected intravenously with 2 μL/g saline in saline group, with 0.02 mg/g patrina villosa juss extract in 0.02 mg/g patrina villosa juss group, and 0.04 mg/g patrina villosa juss extract in 0.04 mg/g patrina villosa juss group, respectively. Twenty-five minutes later, heads of mice were cut rapidly to record the time from decapitation to the last gasp. ③ Experiment for ligating bilateral common carotid artery: Thirty mice were randomly divided into 3 groups. Mice were perfused with 2 μL/g saline in saline group, with 0.01 mg/g patrina villosa juss extract in 0.01 mg/g patrina villosa juss group, and 0.015 mg/g patrina villosa juss extract in 0.015 mg/g patrina villosa juss group, respectively, once a day for 7 days in total. Seven days later, bilateral common carotid artery was ligated to observe time of respiratory arrest.MAIN OUTCOME MEASURES: ① Survival time of hypoxia tolerance;② time from decapitation to the last gasp; ③ time from ligating bilateral common carotid artery to respiratory arrest.RESULTS: A total of 100 mice were involved in the final analysis. ① Survival time of hypoxia tolerance under normal pressure: Time in 0.02 mg/g and 0.04 mg/g patrina villosa juss groups was longer than that in saline group [(57.8±4.6), (76.2±4.9), (42.5±3.6) minutes, P ＜ 0.05, 0.01], but there was no significant difference from that in propranolol group (P ＞ 0.05).The higher the dosage was, the longer the survival time was. ② Gasping time of decapitation mice: Time in 0.02 mg/g and 0.04 mg/g patrina villosa juss groups was longer than that in saline group [(22.1 ±1.6),(25.3±2.2), (18.6±0.8) s, P ＜ 0.05, 0.01], and the higher the dosage was, the longer the survival time was. ③ Time of respiratory arrest: Time in 0.01 mg/g and 0.015 mg/g patrina villosa juss groups was longer than that in saline group [(123.4±25.1),(142.2±30.2), (86.0±12.8) s, P ＜ 0.05, 0.01], and the higher the dosage was, the longer the survival time was.CONCLUSION: Patrina villosa juss extract can improve symptom of myocardial hypoxia induced by cerebral hypoxia, whole-body hypoxia and increase of myocardial oxygen consumption; moreover, the higher the dosage is, the more remarkable the effect is. The mechanism is of possibility that patrina villosa juss extract can improve myocardial and cerebral oxygen consumption.