[AdipoRon for the treatment of type 2 diabetes in mice and its possible mechanism of the liver].

OBJECTIVE: To observe the effect of AdipoRon for the treatment of type 2 diabetes (T2DM)in mice and its effect on the liver. METHODS: Forty male C57/BL6 mice (SPF) were randomly divided to normal control (NC) group and the experimental group. To establish the T2DM mice model, mice in the experimental group were fed with high fat and high glucose, combined with intraperitoneal injection of streptozotocin (STZ) in small doses, and mice were further subdivided into model control (DM) group, model control with low AdipoRon (DM+L) group and model control with high AdipoRon (DM+H) group (n=10). Serum indexes, such as levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) were detected biochemically and the morphological changes of liver cells were observed with HE staining and expression of liver carbohydrate related gene (PEPCK) were determined by real-time fluorescence quantitative PCR (real time FQ-PCR). RESULTS: Compared with mice in the DM group, levels of ALT, AST, ALP, triglyceride (TG), glucose (GLU) reduced in DM+L and DM+H group (P<0.05). Concentrations of serum free fatty acids (FFA) in DM+L and DM+H group reduced significantly (P<0.05). Besides, concentrations of liver glucose-6-phosphatase (G-6-P) in the mice of DM+L group reduced significantly, while there was no significant difference in the content of G-6-P between the mice of DM+H group and the mice of DM group. Furthermore, the expression of the liver phosphoenolpyruvate carboxylase (PEPCK) in the DM+H group reduced significantly (P<0.05). Compared with the DM group no significant change was found in the PEPCK expression between DM+L and DM group. CONCLUSIONS: The serum indexes such as levels of ALT, AST, ALP, TG, Glu, G-6-P and PEPCK were all reduced in DM mice treated with AdipoRon, indicating the obvious protecting effect of AdipoRon on the liver in DM mice.

[Effects of pirfenidone on hepatic fibrosis in mice induced by carbon tetrachloride].

OBJECTIVE: To investigate the effects of pirfenidone on CCl4-induced liver fibrosis in mice. METHODS: After 8-week feeding, 40 healthy male SPF ICR mice were randomly divided into 4 groups:liver fibrosis group (CCL4 group), low doses of Pirfenidone group (PFD-L group), high doses of Pirfenidone group (PFD-H group) and control group. The mice in CCL4 group, low doses of Pirfenidone group (PFD-L group), high doses of Pirfenidone group (PFD-H group) were injected intraperitoneally with 0.4 ml 10% CCL4 solution dissolved in soybean oil. Then the PFD-L and PFD-H groups were treated with 120 mg and 240 mg PFD via gastric gavage, respectively. Control group was injected with same volume of saline. Alanine aminotransferase(ALT), aspartate aminotransferase(AST), alkaline phosphatase(ALP) in serum were tested with automatic biochemistry analyzer and the pathologic changes of liver tissue were examined by HE staining. Furthermore, we identi-fied hyaluronic acids(HA), laminin(LN), collagentype IV(IV-C) in serum using radioimmunoassay and the expression of smooth muscle acti-nalpha(α-SMA) related gene in liver was tested by real-time fluorescence quantitative PCR. RESULTS: Compared with control group, hepatic lobules in CCL4 mice were damaged significantly, collagenous fiber was deposited obviously, and counterfeit hepatic lobules formed. The serum levels of ALT, AST, ALP were increased obviously (P<0.05) with the enhancement of HA, LN, IV-C in serum (P<0.05) and the ex-pression of α-SMA related gene (P<0.05). Compared to CCL4-treated mice, the serum levels of ALT, AST, ALP in PFD-L and PFD-H groups were decreased, HA, LN, IV-C in PFD-L and PFD-H mice went down obviously,and the expression of α-SMA related gene was con-trolled (P<0.05). From pathological observation, we found the degree of liver fibrosis in PFD-L mice was reduced and collagenous fiber was decreased, only a little counterfeit hepatic lobule could be found. Cell arrangement in PFD-H mice recovered, the structural of hepatic lobules disordered and no obvious counterfeit hepatic lobules were found. Therefore, the recovery of PFD-H group was better than PFD-L group. CONCLUSIONS: Pirfenidone has a protective role in improving the outcome of the liver fibrosis and it may become a new direction of early intervention in liver fibrosis.

Acupuncture therapy for sudden sensorineural hearing loss: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Acupuncture has commonly been used in China, either alone or in combination with Western medicine, to treat sudden sensorineural hearing loss (SSHL). The purpose of this systematic review is to assess the efficacy and safety of acupuncture therapy for patients with SSHL. METHODS: We searched PubMed, the Cochrane Library, Embase, China National Knowledge Internet (CNKI), Database for Chinese Technical Periodicals (VIP), and Chinese Biomedical literature service system (SinoMed) to collect randomized controlled trials of acupuncture for SSHL published before July 2014. A meta-analysis was conducted according to the Cochrane systematic review method using RevMan 5.2 software. The evidence level for each outcome was assessed using the GRADE methodology. RESULTS: Twelve trials involving 863 patients were included. A meta-analysis showed that the effect of manual acupuncture combined with Western medicine comprehensive treatment (WMCT) was better than WMCT alone (RR 1.33, 95%CI 1.19-1.49) and the same as the effect of electroacupuncture combined with WMCT (RR 1.33, 95%CI 1.19-1.50). One study showed a better effect of electroacupuncture than of WMCT (RR 1.34, 95%CI 1.24-1.45). For mean changes in hearing over all frequencies, the meta-analysis showed a better effect with the combination of acupuncture and WMCT than with WMCT alone (MD 10.85, 95%CI 6.84-14.86). However, the evidence levels for these interventions were low or very low due to a high risk of bias and small sample sizes in the included studies. CONCLUSION: There was not sufficient evidence showing that acupuncture therapy alone was beneficial for treating SSHL. However, interventions combining acupuncture with WMCT had more efficacious results in the treatment of SSHL than WMCT alone. Electroacupuncture alone might be a viable alternative treatment besides WMCT for SSHL. However, given that there were fewer eligible RCTs and limitations in the included trials, such as methodological drawbacks and small sample sizes, large-scale RCTs are required to confirm the current findings regarding acupuncture therapy for SSHL.

[Effects of pyrrolidine dithiocarbamate pretreatment on canine myocardial energy metabolism during cardiopulmonary bypass].

OBJECTIVE: To develop a technology for production of recombinant SAG1 of Toxoplasma gondii(T.g) in batches. METHODS: Twelve healthy mongrel dogs undergoing CPB were randomly allocated into control group (group C, n=6) and PDTC pretreatment group (group P, n=6). In group P, the dogs received intravenous injection of PDTC at 30 mg/kg before CPB, while in group C, normal saline was given instead. The myocardial tissues were obtained before CPB, 60 min after aortic cross-clamping (AC) and 60 min after declamping (DC) for determining the myocardial contents of adenine nucleotides (ATP, ADP, AMP, TAN, EC) and malondialdehyde (MDA) and evaluating the total anti-oxidation capacity (T-AOC) and mitochondrial swelling degree (MSD). The heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were monitored before CPB, 30 min and 60 min after DC. RESULTS: In both groups, the myocardial contents of ATP, TAN, EC and T-AOC decreased while MDA content and MSD increased after AC as compared to the values before CPB (P<0.01). In group C, ATP, TAN, EC and T-AOC decreased while MDA content and MSD increased after DC as compared to the values before CPB (P<0.01). At 60 min after DC, the dogs in group P showed no significant variation in the contents of ATP, TAN, EC, MDA, T-AOC or MSD (P>0.05). ATP, TAN, EC and T-AOC were significantly lowered while MDA and MSD increased at 60 min after AC and after DC in group P in comparison with the measurements in group C (P<0.01). HR, MAP and CO of group P recovered rapidly at 30 min and 60 min after DC as compared with those in group C (P<0.01). CONCLUSION: CPB can induce serious energy exhaustion and delay in the recovery of energy metabolism. PDTC pretreatment can substantially ameliorate myocardial energy depletion and protect the myocardial mitochondria to attenuate myocardial ischemia/reperfusion injury.

[Protective effect of pyrrolidine dithiocarbamate on erythrocytes during canine cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) on erythrocytes during canine cardiopulmonary bypass (CPB). METHODS: Twelve adult healthy dogs undergoing CPB were randomly divided into the control group (n = 6) and the PDTC group (n = 6). In the PDTC group, PDTC 30 mg/kg was administered intravenously before CPB. Dogs in the control group was intravenously administering with normal saline. The levels of interleukin (IL)-1beta, IL-8, malondiadehyde (MDA), free hemoglobin (F-HB) in plasma, erythrocyte adenosine triphosphate (E-ATP), and erythrocyte superoxide dismutase (E-SOD) were determined before CPB, 30 and 60 minutes after aortic cross-clamping (AC), and 30 and 60 minutes after declamping (DC). RESULTS: In the control group, plasma levels of IL-1beta and IL-8 significantly increased after CPB (P < 0.01). In the PDTC group, plasma levels of IL-1beta and IL-8 significantly increased after CPB (P < 0.05, P < 0.01). Plasma levels of MDA and F-HB significantly increased (P < 0.01) and the E-ATP level and E-SOD activity significantly decreased after CPB (P < 0.01) in both two groups. The E-ATP level and E-SOD activity in the PDTC group at 30 and 60 minutes after AC and 30 and 60 minutes after DC were significantly higher than those in control group (P < 0.01). However, the levels of IL-1beta, IL-8, MDA, and F-HB at 30 and 60 minutes after AC and 30 and 60 minutes after DC were significantly lower in the PDTC group than those in control group (P < 0.01). CONCLUSION: PDTC can protect erythrocytes by alleviating lipid peroxidation and inflammatory response during CPB.

[Effect of pyrrolidine dithiocarbamate on antioxidation of canine myocardium during ichemia/reperfusion injury].

OBJECTIVE: To assess the alterations in myocardial energy metabolism and lipid peroxidation during canine cardiopulmonary bypass (CPB), and to investigate the interventional effects of pyrrolidine dithiocarbamate (PDTC) pretreatment. METHODS: Twelve adult healthy dogs undergoing CPB were randomized into control group (Group C, n=6) and PDTC group(Group P, n=6). In Group P, 30 mg/kg PDTC was administered intravenously before CPB and in Group C animals were given physiological saline instead of PDTC. The contents of adenosine triphosphate (ATP), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), malondialdehyde (MDA) and mitochondrial swelling degree (MSD) of myocardium were determined before CPB, 60 min after aortic cross-clamping (AC) and 60 min after declamping (DC). Hemodynamics was monitored before CPB, 30 min and 60 min after DC. RESULT: Contents of ATP, SOD and GSH-PX in Group P at 60 min after AC and 60 min after DC were higher than those in Group C (P<0.01). MDA and MSD in Group P at 60 min after AC and 60 min after DC were significantly lower than those in Group C (P<0.01). Hemodynamics of Group P was recovered at 30 min and 60 min after DC. CONCLUSION: Pretreatment with PDTC is effective in improving antioxidation capacity of myocardium and ameliorates myocardial energy metabolism.

[Effect of reperfusion leukocyte-depleted blood on canine myocardial energy metabolism balance during cardiopulmonary bypass].

OBJECTIVE: To investigate the impact of myocardial energy metabolism of canine reperfused with leukocyte-depleted blood during cardiopulmonary bypass (CPB). METHODS: Eighteen adult healthy dogs undergoing CPB were randomly divided into 3 groups: the control group (group C, n=6), whole blood (group W, n=6) and the experimental group (group L, n=6) with use of the leukocyte depletion filter (LDF) on the bypass circuit. The contents of adenine nucleotide, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), myeloperoxidase (MPO), malondialdehyde (MDA) and mitochondrial swelling of myocardia were determined respectively before cross-clamping, at 40 min and 60 min after aortic cross-clamping (AC), 30 min and 60 min after declamping (DC) during CPB. RESULTS: Reperfused with leukocyte-depleted blood by LDF connected with bypass circuit, the dog hearts of group L at 60 min after AC, 30 min and 60 min after DC were much better in the recovery of myocardium energy metabolism, higher in contents of myocardium SOD and GSH-PX than those in group C and W (P < 0.01). The myocardium MPO, MDA and mitochondrial swelling degree at 60 min after AC, 30 min and 60 min after DC were distinctly lower in group L than those in group C and W (P < 0.01). CONCLUSION: Myocardium has serious energy exhaustion and deteriorated metabolism during CPB. Myocardial mitochondrial structure and function can be protected and myocardial energy depletion can be reduced by infusion of leukocyte-depleted blood to the heart before DC, which can distinctly attenuate myocardial ischemia/reperfusion injury.