The effect of rifaximin and lactulose treatments to chronic hepatic encephalopathy rats: An [18F]PBR146 in-vivo neuroinflammation imaging study.

INTRODUCTION: Hepatic encephalopathy (HE) is a severe neuropsychiatric complication of liver diseases characterized by neuroinflammation. The efficacies of nonabsorbable rifaximin (RIF) and lactulose (LAC) have been well documented in the treatment of HE. [18F]PBR146 is a translocator protein (TSPO) radiotracer used for in vivo neuroinflammation imaging. This study investigated anti-neuroinflammation effect of RIF or/and LAC in chronic HE rats by [18F]PBR146 micro-PET/CT. METHODS: Bile duct ligation (BDL) operation induced chronic HE models, and this study included Sham+normal saline (NS), BDL+NS, BDL+RIF, BDL+LAC, and BDL+RIF+LAC groups. Behavioral assessment was performed to analyze the motor function, and fecal samples were collected after successfully established the chronic HE model (more than 28 days post-surgery). In addition, fecal samples collection and micro-PET/CT scans were performed sequentially. And we also collected the blood plasma, liver, intestinal, and brain samples after sacrificing the rats for further biochemical and pathological analyses. RESULTS: The RIF- and/or LAC-treated BDL rats showed similar behavioral results with Sham+NS group, while the treatment could not reverse the biliary obstruction resulting in sustained liver injury. The RIF or/and LAC treatments can inhibit IFN-γ and IL-10 productions. The global brain uptake values of [18F]PBR146 in BDL+NS group was significantly higher than other groups (p < .0001). The brain regions analysis showed that the basal ganglia, hippocampus, and cingulate cortex had radiotracer uptake differences among groups (all p < .05), which were consistent with the brain immunohistochemistry results. Sham+NS group was mainly enriched in Christensenella, Coprobacillus, and Pseudoflavonifractor. BDL+NS group was mainly enriched in Barnesiella, Alloprevotella, Enterococcus, and Enterorhabdus. BDL+RIF+LAC group was enriched in Parabacteroides, Bacteroides, Allobaculum, Bifidobacterium, and Parasutterella. CONCLUSIONS: RIF or/and LAC had anti-neuroinflammation in BDL-induced chronic HE rats with gut microbiota alterations. The [18F]PBR146 could be used for monitoring RIF or/and LAC treatment efficacy of chronic HE rats.

Bandwidth broadening for stripline circulator.

This work provides a detailed analysis and simulation to demonstrate how to broaden the operating bandwidth of a circulator. A double-Y junction circulator is designed, and the shape of the central stripline is optimized with the knowledge of a modified equation. The equation predicts two resonant conditions. The overlapping of the two resonant conditions jointly constitutes the broad bandwidth. The bias magnetic field is simulated and then used in full electromagnetic-wave simulation. The designed circulator was fabricated in the S-band for communication purpose. The measured results agree very well with simulation. The overall operation range is from 1643 to 2027 MHz with the insertion loss less than 0.35 dB, reflection, and isolation better than 20 dB. The mechanism will be discussed.

Efficacy and safety of aranidipine enteric-coated tablets compared with amlodipine in Chinese patients with mild to moderate essential hypertension: a multicenter, randomized, double-blind, parallel-controlled clinical trial.

This is a multicenter, randomized, double-blind, parallel-controlled study, conducted in Chinese patients with mild to moderate essential hypertension. After a 2-week washout period, 236 eligible patients were randomly to receive aranidipine 5-10 mg/d (n = 118) or amlodipine 5-10 mg/d (n = 118) for 10 weeks. The blood pressure and heart rate were evaluated in outpatient clinics, and ambulatory blood pressure monitoring was performed in 24 patients in each group. The blood pressure was significantly decreased in both groups. Compared with amlodipine, the patients who received aranidipine had less response in blood pressure (P < 0.01). The trough/peak ratios of diastolic blood pressure in aranidipine and amlodipine groups were 0.57 ± 0.20 and 0.68 ± 0.19, respectively (P = 0.119). Adverse events occurred at 11.86% and 7.63% in the aranidipine and amlodipine groups, respectively (P = 0.348). Headache was observed at an incidence of >3.0% in both groups, and the serum glucose and lipid profile had no significant change in the amlodipine group. In conclusion, once-daily administration of aranidipine (5-10 mg) effectively controlled blood pressure, and the short-term treatment might result in it being less effective than amlodipine. It had a stable action over 24-hour period, and the mechanism of that is not yet clear. Aranidipine had a good safety similar to that of amlodipine.

Inhibiting effects of Leflunomide metabolite on overexpression of CD147, MMP-2 and MMP-9 in PMA differentiated THP-1 cells.

Recent studies have reported elevated expression of cluster of differentiation (CD) 147 on CD14(+) monocytes of the peripheral blood of patients with active rheumatoid arthritis and a correlation of CD147 expression with Disease Activity Score. Thus, CD147 may be a new target for treatment of rheumatoid arthritis. Leflunomide is a disease-modifying antirheumatic drug that is commonly used to treat rheumatoid arthritis. The effect of leflunomide in blocking the up-regulation of CD147 and in blocking the down-regulation of metalloproteinases (MMP)-2 and MMP-9 in active macrophages has not yet been established. In this study we investigated the effect of A771726, the active metabolite of leflunomide, on expression of CD147 and on the gelatinolytic activity of MMP-2 and MMP-9 in phorbol myristate acetate (PMA) differentiated THP-1 cells. The expression of CD147, MMP-2, and MMP-9 mRNAs were determined by real-time quantitative reverse transcription PCR, the levels of cellular surface expression of CD147 were determined by flow cytometry, and the gelatinolytic activity of MMP-2 and MMP-9 were determined by zymography. Our results showed that A771726 significantly inhibited the expression of CD147 on the cell surface of activated THP-1 cells in a dose-dependent manner (P<0.01), inhibited the expression of MMP-2 and MMP-9 mRNAs in a dose-dependent manner (P<0.01), and inhibited the gelatinolytic activity of MMP-2 and MMP-9 at concentration of 15 µg/ml and 45 µg/ml (P<0.01). Our results indicate that A771726, the active metabolite of leflunomide, inhibited CD147 expression at the protein level and inhibited gelatinolytic activity of MMP-2 and MMP-9 in PMA-differentiated THP-1 cells.

[Start-up of high solid anaerobic digestion process for treating straw with sludge cake as nitrogen additive].

Straw co-digestion with sludge cake as nitrogen additive from wastewater treatment plant (WWTP) can solve the pollution problems of improper treatment of straw and sludge. Moreover the products, including biogas and organic manures, can relieve the problems of energy supply and soil infertility in countryside. The properties of the start-up periods of two anaerobic digestors were studied. The result showed that the efficiency of the anaerobic digestors rose after pre-treating the straw by NaOH and adjusting C/N by adding 5% sludge. The start-up period lasted 930 h. The anaerobic bacteria activity has recovered and was acclimated in the start-up period. The solid content of the feeding was 12%-16% and the biogas-production rate was 0.15-0.18 L/h at the end of start-up period. The total solid and volatile solid degradation rates were 54% and 65% in the 1st reactor, and 67% and 75% in the 2nd reactor, respectively. During the start-up period, COD concentration and NH4+ -N concentration were rather low, which were 1000-6000 mg/L and 200-600 mg/L, respectively.

[Effects of pravastatin on myocardial connexin 43, IFN-gamma and IL-10 expressions in a murine model of viral myocarditis induced by Coxsackievirus B3].

OBJECTIVE: To observe the effects of pravastatin on myocardial connexin 43 (Cx43), IFN-gamma and IL-10 expressions in a murine model of viral myocarditis (VMC) induced by Coxsackievirus B3. METHODS: Four-week-old male Balb/c mice were inoculated intraperitoneally with Coxsackievirus B3 and then randomly received saline (group A, n = 12), low dose pravastatin (40 mg.kg(-1).d(-1), group B, n = 12) and high dose pravastatin (80 mg.kg(-1).d(-1), group C, n = 12) for 14 days. Another group of mice were injected with Eagle's solution and treated with saline (group D, n = 12) or high dose pravastatin (80 mg.kg(-1).d(-1), group E, n = 12). After 14 days treatments, serum IFN-gamma, IL-10 were assayed using ELISA, myocardium IFN-gamma, IL-10 and Cx43 mRNA levels were measured by real-time PCR, myocardium expression of Cx43 was also determined by immunohistochemistry staining method on cardiac myocytes. RESULTS: Pravastatin dose-dependently upregulated Cx43 proteins on membrane of myocardial cells (group A: 0.16 +/- 0.06, group B: 4.55 +/- 0.73 and group C: 5.21 +/- 0.42, P < 0.01 vs. group A) and Cx43 mRNA expression (group A: 1.000 +/- 0.127, group B: 1.320 +/- 0.096, group C: 1.550 +/- 0.126, P < 0.05 vs. group A), IL-10 mRNA expression (group A: 1.000 +/- 0.031, group B: 1.810 +/- 0.029, group C: 2.140 +/- 0.032, P < 0.05 vs. group A) while down-regulated IFN-gamma mRNA (group A: 1.000 +/- 0.061, group B: 0.603 +/- 0.063, group C: 0.333 +/- 0.071, P < 0.01 vs. group A). Serum IFN-gamma, IL-10 concentrations changed in the same direction as myocardial mRNA levels of IFN-gamma, IL-10 post pravastatin treatments. CONCLUSION: Pravastatin treatments upregulated expressions of Cx43 at mRNA and protein levels and improved the INF-gamma/IL-10 balance which might be the working mechanisms for pravastatin-mediated anti-VMC and anti-arrhythmia effects in this VMC model.

[Research on single phase high solid anaerobic digestion of organic fraction of municipal solid wastes].

Under mesophilic condition (35 degrees C), a bench-scale experiment based on high solid anaerobic digestion process was conducted in a fed-batch single phase reactor to treat the OFMSW. The experiment has lasted for more than half a year and significant results were obtained. At the start-up stage, acidification occurred and showed large inhibition to gas production and the gas production rate once dropped to 0. After pH conditioning, the system has recovered and began to stably running. In this period, gas production rate reached 746.33 L/kg volatile solids (VS) [3.69 L/(L x d)] when the total solids (TS) content of the feeding waste was 24.79% and the VS content was 23.06%. The organic loading rate and hydraulic retention time(HRT) was 4.94 kg/(m3 x d) and 47 d respectively. However, with time went by, accumulated ammonia exceeded its limited value, which is deduced as 2000 mg/L, and the gas production rate dropped below half of the maximum value. By adding chemicals to diminish the amount of ammonia and adjusting the C/N of the feeding, inhibition was relaxed and gas production rate increased gradually.

[Experimental investigation of the straw pre-treatment to enhance its high solid anaerobic digestion].

The straw contains a high content of lignin, which cannot be well utilized by anaerobic bacteria in high solid anaerobic digestion process. This paper presents the experimental investigation of the straw pre-treatment, which aims to destroy the complex structure of the lignin to enhance its high solid anaerobic digestion. The straw is pre-treated in different solutions including NaOH, ammonia, H2SO4, and carbamide. The pre-treating effects are expressed by COD concentration dissolved in the solutions and the 14-day biogas generation in the enhanced aerogenic experiment. Different affecting factors, such as the concentration of the chemical solution, the species of the straw, the pre-treatment reaction time, the reaction temperature and the size of the straw, are investigated. The results show that NaOH solution is the most effective pre-treatment chemical among the four different solutions. The experimental results still indicate that the accumulative biogas production can be 1 500 mL (10 g straw) in 14 days after pre-treatment in 4 mg/L NaOH solution and the dissolved COD in the solution reaches 39 000 mg/L after 24 hours. In addition, the experiment shows that the lignin content in the straw is reduced from 28% to 19% after pre-treatment in 1.5% (in weight) NaOH solution, and it can improve the straw treatment efficiency using high solid anaerobic digestion process.

[Start-up research of single phase high solid anaerobic digestion technology for organic waste].

Under mesophilic condition (35 degrees C), a bench-scale experiment based on high solid anaerobic digestion process was conducted in a fed-batch single phase reactor. At the start-up stage, the feeding amount of organic waste was modified with the variation of pH value and gas production. The results of this stage showed that 705.77 L of gas production per kg VS added was obtained while the total solids content of the feeding waste was 24.79% and the VS content was 93.04% of TS. After 30 days of the start-up, the pH value ranged between 6.9 and 7.3 in the reactor, and after 50 days the organic loading rate (VS) reached 6.98 kg/(m3 x d) with an HRT of 35 days.

[Effects of antidepressant therapy in patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression].

OBJECTIVE: We observed the therapeutic effectiveness and safety of different antidepressants as well as the correlation between symptomatic improvement of depression and improvement of chest pain in patients with susceptible "angina pectoris" and negative coronary angiogram complicating comorbid depression. METHODS: In this double-blinded randomized study, a total of 123 eligible patients were allocated into three groups: (1) Group F: fluoxetine 20 mg QN (n = 41); (2) Group P: Placebo 1 tablet QN (n = 40); (3) Group F + O: fluoxetine 20 mg + olanzapine 2.5 mg QN for the former 2 weeks and only fluoxetine 20 mg QN for the latter 2 weeks (n = 42). The total therapy duration was 4 weeks. HAMD, HAMA and self-evaluation table of chest pain were obtained before therapy, at the end of 1 and 2 weeks after therapy. RESULTS: Baseline HAMD and HAMA scores and self-evaluation score of chest pain were similar among 3 groups and all scores were significantly improved post various therapies in the order of group F + O > group F > group P. The rate of score decrease were seen after 1 week treatment in group F + O and after 2 week treatment in group F. There was a significant positive correlation between the rates of self-evaluation chest pain score decrease and HAMD (r = 0.867, P < 0.001) and HAMA (r = 0.854, P < 0.001) score decreases after 4 weeks therapies (P < 0.05). During the whole course of treatment, no serious adverse reaction was found in all patients. CONCLUSION: In patients with suspected "angina pectoris" and negative coronary angiogram complicating comorbid depression, the antidepressants were safe and significantly improved the symptoms of depression and anxiety and chest pain. Low dose fluoxetine plus short term olanzapine regimen was superior to fluoxetine alone regimen in terms of stronger and quicker symptom improvement.