To study the protective effect and the mechanism of asiatic acid (AA) from Potentilla chinensis on alcohol hepatic injury in rats. Male Wistar rats were randomly divided into six groups: the normal control group, the AA control group (8 mg · kg(-1) AA), the model group (5.0-9.0 g · kg(-1) alcohol) and high, medium and low-dose AA-treated groups (alcohol + 8, 4, 2 mg · kg(-1) AA). Each group was orally administered with the corresponding drugs once a day for 24 weeks. Approximately 1. 5 hours after the final administration, all rats were killed, and their blood samples and hepatic tissues were collected. The AST and ALT in rat serum and the contents of MPO, TNF-α, IL-1β, SOD, GSH-Px, GSH-Rd and MDA in hepatic tissues were detected. The expressions of NF-κB, TLR4, CD14, MyD88, TRIF and protein expression in hepatic tissues were measured by western blot. The pathological changes in liver tissues were observed by histological examination. The results showed that compared with the model group, the AA-treated groups showed significant decreases in serum ALT, AST and MDA and increases in the activities of SOD, GSH-Px, GSH-Rd and MPO. Moreover, AA markedly inhibited the expressions of TNF-α, IL-1β, TLR4, CD14, MyD88 and NF-κB. The histological examination showed alleviated hepatic issue ijury to varying degrees. In short, asiatic acid (AA) from P. chinensis could protect alcohol-induced hepatic injury in rats. Its mechanism may be related to the inhibition of NF-κB inactivation and the reduction of inflammatory response.
Animals ; Liver ; drug effects ; pathology ; Liver Diseases, Alcoholic ; prevention & control ; Male ; NF-kappa B ; physiology ; Pentacyclic Triterpenes ; pharmacology ; Potentilla ; chemistry ; Protective Agents ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; antagonists & inhibitors

Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.
Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; blood ; chemistry ; pharmacokinetics ; Biological Availability ; Camptothecin ; administration & dosage ; analogs & derivatives ; blood ; chemistry ; pharmacokinetics ; Delayed-Action Preparations ; Drug Delivery Systems ; Drug Stability ; Female ; Lipids ; chemistry ; Lung ; metabolism ; Mice ; Mononuclear Phagocyte System ; physiology ; Nanoparticles ; Particle Size ; Phagocytosis ; drug effects ; Polyethylene Glycols ; chemistry ; Tissue Distribution

Polymyxin E shows effective treatment of the infection induced by resistant gramnegative bacteria, but its nephrotoxicity severely limits the clinical application of this drug. In this work, methoxypolyethylene glycols 2000 (mPEG2K)-polymyxin E (PME) was synthesized via chemical grafting reaction and had been characterized. The antimicrobial activity and cytotoxicity of mPEG2K-PME in vitro were investigated on Escherichia coli and HK-2 cells, separately. Intra-abdominal infection model was further established in order to study the therapeutic effect and the toxic effect on kidney of mice. The results showed that mPEG2K-PME exhibited significant inhibitory effect on Escherichia coli and had a lower toxicity on HK-2 cells in vitro. At the same time, mPEG2K-PME had a good efficacy in the treatment of Escherichia coli infected mice in vivo. Moreover, nephrotoxicity caused by mPEG2K-PME was significantly reduced compared to free PME. mPEG2K-PME is promising in development of new preparations with high efficiency and low toxicity.
Animals ; Cell Line ; Colistin ; pharmacology ; toxicity ; Escherichia coli ; drug effects ; Escherichia coli Infections ; drug therapy ; Humans ; Kidney ; cytology ; drug effects ; Mice ; Polyethylene Glycols ; chemistry

OBJECTIVETo investigate whether myocardial bridging (MB) is independently associated with coronary atherosclerosis proximal to MB in the left anterior descending coronary artery (LAD) identified by computed tomographic coronary angiography (CCTA).

METHODSFrom March 2011 to December 2012, patients (n=9 862) with suspected coronary disease underwent CCTA using dual-source CT scanner. The baseline clinical characteristics (age, gender, smoking history, presence of hypertension, dyslipidemia, diabetes mellitus, family history of heart attack, and body mass index) and the results of CCTA were reviewed. Two radiologists evaluated the coronary artery for MB and coronary atherosclerosis stenosis (CAS) in LAD and made a diagnosis by consensus. Significant independent risk factors for CAS were investigated by multivariate logistic regression analysis.

RESULTSA total of 3 182 (32.3%) cases of MB and 3 359 cases of CAS of LAD were identified. No patient with CAS in the tunneled segment was found. The mean length of bridges and the mean thickness of the overlying myocardium was (17.3±5.2) mm and (1.2±0.9) mm, respectively. There were 1658 MB cases in 3 359 cases of LAD stenosis and 1 524 MB cases in 6 503 cases of no LAD stenosis (χ(2)=681.12, P<0.05). Logistic regression analysis showed that MB in the LAD were significantly associated with CAS in the proximal LAD (OR=3.07, 95%CI=2.81-3.37, P<0.001), and after final adjustment for age, gender, body mass index, family history of heart attack, smoking, hypertension, dyslipidemia, diabetes mellitus, and resting heart rate (OR=2.86, 95% CI=2.60-3.16, P < 0.001).

CONCLUSIONMB in the LAD is independently associated with CAS in the proximal segment to MB.

Adult ; Aged ; Aged, 80 and over ; Coronary Stenosis ; complications ; diagnostic imaging ; Female ; Humans ; Logistic Models ; Male ; Middle Aged ; Myocardial Bridging ; complications ; diagnostic imaging ; Risk Factors ; Tomography, X-Ray Computed

Objective To investigate the basic distribution of endemic areas in the type of drinking water arsenism and in Xiantao City,Hubei Province,and to offer a scientific basis for control and prevention.Methods According to"the Chinese Scheme of Implementing Surveillance of Distribution of Endemic Arsenism",considering with the special geography feature of Xiantao,both sampling and overall survey were used in 7 towns chosen.The water arsenic content was determined by half quantitative fast reagent-box method.We began to search for clues and patients according to the endemic areas and the families with high arsenic wells.Results High endemic arsenic water sources were distributed in 7 the towns(districts or farms).In 81 villages of Xiantao City,35 villages had drinking water arsenic content exceeding 0.05 mg/L,accounting for 43.21%(35/81).In 4020 screened wells,269 had arsenic content higher than the national standard,the detective rate of high arsenic wells(more than 0.05 mg/L)was 6.69%(269/4020),with the highest rate in Shahu Seed Plant being 13.56%(115/848).The population exposed to high arsenic was 1091,in a rate of 5.75%(1091/18 975),in which 281 children were exposed in a rate of 5.82%(281/4826).In Shahu Seed Plant,467 people including 129 children were exposed to high arsenic, accounting for 13.26%(467/3522)and 12.91%(129/999),respectively.Conclusions High arsenic sources widely exist in Xiantao City,especially in Shahu Seed Plant,where arsenic content,the exposed rate of population and children are high.Therefore,prevention and control should be carried out in the southeast as soon as possible,as well as in other places where situation is less serious.

Objective To observe the clinical efficacy of infrared laser combined with alpha-zinc sulfate for the treatment of diabetic peripheral neuropathy ( DNP).Methods A total of 106 patients with DPN were randomly divided into observation group ( n =53 ) and control group (n=53).Besides base hypoglycemic drug therapy, patients in the control group received alpha-zinc sulfate injection 0.6 g once a day.The patients in observation group were given the above treatment plus anodyne therapeutic apparatus treatment.The treatment period lasted for 12 days.The data of clinical symptoms, temperature, and nerve conduc-tion velocity of two groups were observed before and after treatment.Results The effective rate and total effective rate were 52.83% and 90.57%in the observation group, significantly better than 41.51%and 86.66%in control group ( P<0.05 ).The data of peroneal nerve and sural nerve conduction velocity in observation group were much signifi-cantly improved than before treatment(P <0.05).No significant adverse effect was observed.Conclusion Infrared laser combined with alpha-zinc sulfate is effective on the treatment of diabetic peripheral neuropathy.

OBJECTIVE: To evaluate the results of transcatheter closure for patent ductus arteriosus (PDA) by different devices in children. METHODS: Seventy-eight cases of PDA in children (7 months to 14 years old), diagnosed by physical examination and transthoracic 2-dimensional echocardiography (TTE), were included in the study. The examination included the cardiac catheterization, photograph of the thoracic aorta and conventional technique of PDA closure. Among these patients, 16 were treated with coils, 9 with Amplatzer duct occluder (ADO), and 53 with native produced PDA occluders. RESULTS: TTE examination on the next day of the operation showed that PDAs were completely occluded in 76 cases, while the other 2 cases treated by coil had minimal residual shunt. Sixty-four patients, who were detected enlargement of the left ventricle before the operation, showed obvious diminishment of the cardiac size. By the end of 3 months, TTE examination showed that the closure of PDA was complete, and the left ventricle size was normal in 77 cases, while one case treated with coil had minimal residual shunt, which persisted for more than 4 years. The 3 - 80 months follow-up showed that the closure of PDA was complete in 77 cases, the configurations of the left ventricle, the thoracic aorta,and the left pulmonary artery were all normal. The occluders were well remained in situ. CONCLUSION The usual procedures of transcatheter closure for PDA are effective and safe with ADO, native produced occluders and coil in children. Interventional method, which shows minute insult, few complications, and few adverse effects, can substitute the thoracic surgery.
Adolescent ; Cardiac Catheterization ; Cardiac Surgical Procedures ; methods ; Child ; Child, Preschool ; Ductus Arteriosus, Patent ; surgery ; Echocardiography ; Female ; Follow-Up Studies ; Humans ; Infant ; Male ; Prostheses and Implants ; Treatment Outcome

OBJECTIVETo assess the value of preoperative coronary computed tomographic angiography (CCTA) in the detection of coronary artery disease (CAD) in patients planned to undergo non-cardiac surgery at intermediate or high risk to avoid unnecessary invasive coronary angiography (ICA).

METHODSThe study protocol was approved by our institutional review board and informed consent was given. In this prospective study, 157 consecutive patients who underwent CCTA before undergoing non-cardiac surgery at intermediate or high risk was involved. The non-cardiac surgery included high-risk surgery (17 patients) and intermediate-risk surgery (140 patients). Follow-up was performed in 6-11 months to define cardiac events described as acute coronary syndrome (ACS) or death secondary to ASC, arrhythmias, cardiac revascularization, or cardiac failure. χ(2) test was performed to compare the differences in incidence of cardiac events among patients who had undergone or who had not undergone preoperative ICA.

RESULTSCCTA was of diagnostic value in 145 of 157 patients. Thirty-seven of 145 had no CAD, and 88 of 145 had no significant CAD (<50% stenosis), and non-cardiac surgery was performed in them without preoperative ICA. No patients in those patients had postoperative ischemic events at follow-up; 20 had significant CAD (≥50% stenosis) and underwent surgery after preoperative ICA. CCTA was non-diagnostic in 12 patients who were referred for preoperative ICA, and 4 of 12 underwent surgery after PCI or CABG. There were no differences in cardiac events between patients who had undergone preoperative ICA and those who had not (P=0.45).

CONCLUSIONSIn patients with planned non-cardiac surgery at medium or high risk of cardiovascular events, preoperative CCTA is an effective diagnostic tool for detecting CAD. Preoperative ICA can be safely avoided in patients with normal findings or with stenosis<50% in CCTA.

Adult ; Aged ; Aged, 80 and over ; Coronary Angiography ; methods ; Coronary Artery Disease ; diagnostic imaging ; Female ; Humans ; Male ; Middle Aged ; Perioperative Care ; Prospective Studies ; Tomography, Spiral Computed ; methods

This study aims to prepare lipid bilayer-coated calcium phosphate core-shell nanoparticles (LCAPNs), which can dissolve in an acidic environment to improve the tumor cell toxicity of antitumor drug. Paclitaxel (PTX) loaded lipid coated calcium phosphate nanoparticles (PTX-LCAPNs) were prepared by thin-film dispersion method. The morphology, particle size and in vitro release behavior were characterized. Meanwhile, the intracellular uptake, intracellular dissolution, cell toxicity of PTX-LCAPNs and intracellular accumulation of PTX were evaluated in human HCC cell line (Huh-7). The results suggested that the mean diameter of the spherical LCAPNs was 124.73±6.41 nm. The PTX-LCAPNs demonstrated little drug leakage in simulated normal physiological conditions, while a rapid release was observed in simulated intracellular condition in vitro. Moreover, the PTX-LCAPNs achieved 1.7 fold improvement in the intracellular PTX concentration leading to 5-fold reduction in half maximal inhibitory concentration (IC₅₀) values of PTX compared with calcium phosphate nanoparticles loaded with PTX (PTX-CAPNs), demonstrating a stronger cancer cell lethality.

This study aims to synthesize new phospholipids, 1,3-dipalmaminophospholipid(Pad-PC-Pad), and prepare shear-stress sensitive liposomes(SSSL). ¹H NMR and MS indicated that Pad-PC-Pad were fully synthesized successfully. SSSL were prepared by filming-rehydration method with Pad-PC-Pad, which loaded calcein with aggregation-caused quenching(ACQ)characteristics to evaluate shear-stress sensitivity of liposomes and release behavior of liposomes in vitro. The results showed that the particle size of liposomes was 106.91 ± 1.24 nm and liposomes had lenticular morphology under transmission electron microscope. The release of calcein was increased with ultrasonic power, which suggests that the liposomes is shear-stress sensitive. Moreover, the liposomes exhibited a releasing effect for obstructed region under high shear-stress in a model system. Therefore, we synthesized quick functional phospholipid Pad-PC-Pad and the liposomes made from Pad-PC-Pad was shear-stress sensitive, which may be used for treatment of thrombosis.