[Urinary metabolomics study of the effects of Scutellaria baicalensis Georgi ethanol extract on D-galactose-induced rats].

The purpose of this study is to evaluate the anti-aging effects and reveal the underlying mechanism of Scutellaria baicalensis Georgi ethanol extract (SBG) in D-galactose-induced rats. Fifty rats were randomly divided into five groups: vehicle control group, D-galactose group, and D-galactose combined with 50, 100, 200 mg x kg(-1) SBG. A rat aging model was induced by injecting subcutaneously D-galactose (100 mg x kg(-1)) for ten weeks. At the tenth week, the locomotor activity (in open-field test) and the learning and memory abilities (in Morris water maze test) were examined respectively. The urine was collected using metabolic cages and analyzed by high-resolution 1H NMR spectroscopy combined with multivariate statistical analyses. The SBG at doses of 50, 100 and 200 mg x kg(-1) treatments groups could significantly ameliorate aging process in rats' cognitive performance. The 50, 100, 200 mg x kg(-1) SBG regulated citrate, pyruvate, lactate, trimethylamine (TMA), pantothenate, ß-hydroxybutyrate in urine favorably toward the control group. These biochemical changes are related to the disturbance in energy metabolism, glycometabolism and microbiome metabolism, which is helpful to further understanding the D-galactose induced aging rats and the therapeutic mechanism of SBG.

[Efficacy of low-dose interferon therapy for treating chronic hepatitis C patients who cannot tolerate standard treatment].

OBJECTIVE: To investigate the therapeutic efficacy of interferon (IFN) therapy and risk of long-term administration for chronic hepatitis C (CHC) patients who cannot tolerate the standard treatment. METHODS: Forty-six CHC patients who had proven intolerant to standard treatments were treated with low-dose IFN (non-pegylated IFN: 60 to 300MIU QOD, or pegylated IFN: 50 to 90 mug/w) plus ribavirin (RBV; 0.6g to 0.9 g/d) for 72 weeks. RESULTS: Forty-three (93.5%) of the patients were able to tolerate the long-term treatment with low-dose IFN plus RBV. Only three patients experienced severe side effects (low white blood cell and platelet counts) that required treatment withdrawal. The virology response rates over treatment time were: rapid virologic response (RVR): 10.9%; early virus response (EVR): 30.4%; 24 week virologic response: 45.7%; and, 48 week virologic response: 47.8%. B-sonographic imaging revealed that three patients experienced improved liver morphology through the treatment course. The patients who achieved RVR, EVR, or 24 weeks virologic response also attained higher 48 week virologic response. The 24 week virologic response had the strongest predictive value of good prognosis. CONCLUSIONS: Our study demonstrated that long-term treatment with low-dose interferon plus ribavirin is effective for patients who are otherwise intolerant to standard treatment. In these patients, low-dose IFN plus RBV can obtain a high virologic response rate at 48 week. Furthermore, the 24 week virologic response is sufficiently predictive of treatment success. As with any treatment regimen, it is important for healthcare workers to monitor the disease status and potential side effects throughout the course of therapy.

[Analysis of thyroid dysfunction and influencing factors in chronic hepatitis C patients treated with peg-IFNa-2a and ribavirin].

OBJECTIVE: To analyze the frequency of thyroid dysfunction and determine its influencing factors in chronic hepatitis C (CHC) patients treated with pegylated-interferon alpha (peg-IFNa)-2a and ribavirin (RBV) combination therapy. METHODS: A total of 194 CHC patients were treated with peg-IFNa-2a and RBV for 48 weeks. Development of thyroid dysfunction was recorded. Clinical and biological factors from pre-treatment (baseline) to post-treatment were statistically analyzed to determine correlation with thyroid dysfunction in this patient population. RESULTS: Fifty-two (26.80%) of 194 peg-IFNa-2a/RBV-treated patients developed thyroid dysfunction. Dysfunction severity ranged from hyperthyroidism (n = 1, 0.52%) and hypothyroidism (n = 10, 5.15%) to subclinical hyperthyroidism (n = 4, 2.06%) and subclinical hypothyroidism (n = 37, 19.07%). The dysfunction rate was significantly higher after peg-IFNa-2a/RBV treatment (26.80% vs. 12.37% at baseline, x2 = 12.829, P less than 0.05, odds ratio (OR) = 0.386, 95% confidence interval (CI): 0.226-0.657), in females (33.00% vs. 20.21% in males, P less than 0.05, 95% CI: 1.016-3.040), and in thyroid auto-antibody positive patients (64.29% vs. 23.89% in negative patients, P less than 0.05, 95% CI: 1.681-36.183). Early virological response did not have any significant effect on dysfunction rate (23.00% vs. 30.85% no early virological response, x2 = 1.522, P more than 0.05) nor did end of treatment response (27.19% vs. 26.25% no response at end of treatment, x2 = 0.021, P more than 0.05). Patients who developed thyroid dysfunction had higher interleukin (IL)-6 at baseline (i.e. before peg-IFNa-2a/RBV treatment) (27.08+/-14.90 vs. 11.65+/-5.46 in patients who maintained normal thyroid function, t = 3.127, P less than 0.05, 95% CI: 5.28-25.58). IL-6 levels were not significantly different between the two groups at 24 weeks (6.30+/-2.47 vs. 6.81+/-2.80, t = 0.352, P more than 0.05). IL-6 levels before and after 48 weeks of treatment in normal thyroid function patients were 27.08+/-14.90 and 6.30+/-2.47, t = 3.632, P less than 0.05, and in thyroid dysfunction patients were 11.65+/-5.46 and 6.81+/-2.80, t = 1.997, P more than 0.05. CONCLUSION: Peg-IFNa-2a/RBV combination therapy may cause thyroid dysfunction, especially hypothyroidism, in CHC patients. Female sex and thyroid auto-antibody positivity may put CHC patients at higher risk of developing thyroid dysfunction during peg-IFNa-2a/RBV therapy. Elevated IL-6 may be a predictive marker of peg-IFNa-2a/RBV-induced thyroid dysfunction.

Variations in blood pressure and heart rate in conscious rats with cervical lymphatic blockade.

The possible effects of cervical lymphatic blockade (CLB) on a series of parameters in conscious freely moving rats were analysed. Blood pressure (BP) and heart rate (HR) for conscious male Sprague-Dawley rats at 1, 3, 7, 11, 15 and 21 days after a CLB or a sham operation were monitored continuously for 24 hours with a computerized recording system. Since BP and HR were subjected to spontaneous variations, blood pressure variability (BPV) and heart rate variability (HRV) were expressed as the standard deviation of beat-to-beat BP and HR values. The baroreflex sensitivities (BRS) were determined by measuring the heart period (HP = 60,000/HR) prolongation in response to the elevation in BP induced by an intravenous administration of phenylephrine at 1, 7, 15 and 21 days after the CLB or sham operation. Compared with those in sham-operated rats, the values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial blood pressure (MAP), HR and BRS in CLB rats were significantly lower, whereas the values of BPV and HRV were markedly raised in CLB rats at different time points. Furthermore, the impaired ultrastructure in the dorsomedial nucleus of the solitary tract (dmNTS) including degeneration, apoptosis and necrosis in neurons and gliacytes, were apparent from the 1st to 15th day but the changes were most significant at 7th day after CLB operation. Structural changes appeared to be closely related to functional changes of the dmNTS at each time point. Thus, in CLB conscious rats, a significant decline in blood pressure accompanied by dysfunction in its regulation might be due to the impaired structure in the dmNTS.

Changes of nitric oxide, oxide free radicals, and systolic arterial blood pressure in rats with experimental lymphatostatic encephalopathy.

The model of lymphatostatic encephalopathy was established by occluding and removing profound cervical nodes in rats, and the kinetic alteration of nitric oxide (NO), maleic dialdehyde (MDA), free radical scavenger (CuZn-SOD) and arterial systolic blood pressure were determined on different days after the blockage. The results showed that the level of NO significantly decreased at 1 day (P<0.05) and further decreased at 3, 5 and 7 day (P<0.01). The levels of MDA at 1, 3, 5 and 7 day significantly increased, but the contents of CuZn-SOD significantly decreased compared with the control (P<0.01). There was negative correlation between the levels of MDA and CuZn-SOD, but there was no relationship between MDA an NO. Arterial systolic blood pressure decreased progressively after cervical lymphatic blockage. The results showed that NO, oxide free radicals and the disturbances of the cardiovascular regulation may play important roles in lymphatostatic encephalopathy.