In the face of escalating problems with pathogen control, the development of proper formulations of existing antibiotics is as important as the development of novel antibiotics. Daptomycin is a lipopeptide antibiotic with potent activity against Gram-positive bacteria. Currently, only injectable solution of daptomycin has been approved for clinical use. In the present study, the formulation of PEGylated liposomal daptomycin (PLD) was prepared and optimized, and its efficacy against methicillin-resistant Staphylococcus aureus (MRSA252) strains was investigated. The obtained PLD had a mean vesicle diameter of (111.5 +/- 15.4) nm and a mean percent drug loading of (5.81 +/- 0.19) % with high storage stability. Potent activity of PLD against MRSA was demonstrated in vitro with a more sustained effect than that of conventional liposomal daptomycin and daptomycin solution. In addition, intravenous administration of a single dose (equal to human use) of PLD significantly increased the survival of mice in a MRSA252 systemic infection model compared with other formulations. Drug distribution in the lung was significantly enhanced following administration of PLD, and no measurable tissue lesions or pathological changes were detected during PLD treatment. Taken together, PEGylated liposomes loaded with daptomycin may represent a promising approach to reduce MRSA252 infections, especially those involving bloodstream dissemination, such as hematogenous pulmonary infection.
Animals ; Anti-Bacterial Agents ; pharmacology ; Daptomycin ; pharmacology ; Liposomes ; Methicillin-Resistant Staphylococcus aureus ; drug effects ; Mice ; Staphylococcal Infections ; drug therapy

OBJECTIVETo observe therapeutic effect and safety of acupuncture at the five-zangshu for treatment of perimenopausal syndrome (PMS).

METHODSForty cases of PMS were randomly divided into a treatment group and a control group, 20 cases in each group. The treatment group were treated with acupuncture at the five-zangshu and the control group with oral administration of Premarin tablets. The therapeutic effects and changes of Kupperman scores, and serum estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH) levels before and after treatment were observed.

RESULTSThe total effective rate was 90. 0% in the treatment group which was better than 65.0% in the control group (P<0. 05). After treatment, serum E2 level significantly increased (P<0.01), with a significant difference between the two groups (P<0.05), and with a significant difference between the two groups in Kupperman symptom score index (MI) after treatment (P<0.05).

CONCLUSIONTherapeutic effect of acupuncture at the five-zangshu is better than that of Premarin for treatment of perimenopausal syndrome.

Acupuncture Points ; Acupuncture Therapy ; methods ; Estradiol ; blood ; Female ; Follicle Stimulating Hormone ; blood ; Humans ; Luteinizing Hormone ; blood ; Middle Aged ; Perimenopause ; blood

Objective To detect the influence of fluoride on the expression TM9SF1 mRNA and Ras mRNA of osteoblasts. Methods The third generation of primary cultured osteoblasts were exposed to a series concentrations of 0,2.5,5.0, 10.0,20.0 mg/L fluoride for 10 days. The influence of different doses of fluorine on the expression of TM9SF1 mRNA and Ras mRNA of osteoblasts cultured in vitro was investigated by SYBR Green I methods. Results The osteoblasts of the control group and the 2.5 mg/L group were in the shape of long spindle, triangle or irregular polygon and had processes, and the cytoplasm was translucent, adjacent cells affixed to each other under light microscope. Those of the 20.0 mg/L group shaped as long spindle or irregular polygon, and some vacuolization and granular materials appeared in cytoplasm. The number of the cells decreased and the volume increased significantly. After exposed to fluoride for 10 days, osteoblasts of 2.5 mg/L group morphologically proliferated. There were statistical siguificances between each groups of TM9SF1 mRNA in human osteoblasts(F = 322.82, P < 0.01). The highest in the 2.5 mg/L group(9326.0 ± 115.97), the expression of TM9SF1 mRNA decreased along with the increasing dose of fluorine. There were statistical significances between 5.0, 10.0,20.0 mg/L groups(6495.0 ± 323.9, 4387.5 ± 545.2, 5962.5 ± 536.7) and control group(9221.0 ± 107.5, all P< 0.01). There was a statistical significance between each groups of Ras mRNA in human osteoblasts(F = 703.28, P < 0.01). The highest in the control group, the expression of Ras mRNA decreased along with the increasing of dose of fluorine. There were statistical significance between 2.5, 5.0, 10.0, 20.0 mg/L groups(6144.5 ± 270.82,5603.5 ± 88.39,3181.0 ± 159.81,4067.5 ± 37.4) and control group(6571.0 ± 196.58). Conclusion The influence on TM9SFI mRNA and Ras mRNA expression in osteoblasts correlates with the dose of fluorine.

Adult ; Arsenic ; pharmacology ; Chromosome Aberrations ; chemically induced ; Dose-Response Relationship, Drug ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged

OBJECTIVETo establish the steriod-induced osteoporosis model with the type of Kidney-Yin deficiency.

METHODSTotally 45 female Kunming mice were randomly divided into normal group,model group and Liuwei Dihuang pills(Chinese character: see text)group. The model was established by intramuscular injecting of Dexamethasone. Liuwei Dihuang pills (Chinese character: see text) group was administered orally with Liuwei Dihuang pills (Chinese character: see text). The signs and symptoms of mice were observed dynamically. All the animals were sacrificed at the end of the 6th weeks. The level of ACTH, cAMP, cGMP, TSH and E2 in serum were detected to evaluate deficiency of Kidney-Yin. Morphological changes and bone density were observed to evaluate osteoporosis.

RESULTS(1) Compared with control group, mice in model group appeared obvious Kidney-Yin deficiency symptoms, including hair dry, restlessness, excitability, hard stool, and yellow. (2) Compared with control group,the weight of mice in model group gained slower (P<0.01); the index of adrenal gland,liver and spleen decreased (P<0.01, P<0.01 ,P<0.01); the level of ACTH and TSH increased (P<0.01 ,P<0.01), the level of E2 decreased (P<0.01) and the ratio of cAMP/cGMP increased (P< 0.05). (3)Compared with control group,the bone density of lumbar vertebra and femur in model group were significantly decreased (P<0.01, P<0.05); HE staining revealed osteoporosis in model group mice. (4)However, the Liuwei Dihuang pills (Chinese character: see text) group can partly antagonize the inhibition of the HPA axis, alter the disordered sex hormone and the ratio of cAMP/cGMP, and reverse the osteoporosis partly.

CONCLUSIONthe model of osteoporosis with type of Kidney-Yin deficiency could be established by Dexamethasone intramuscular injection. With less interference, it wight be a stable and reliable modeling method for integration of disease and syndrome in TCM.

Animals ; Bone Density ; Dexamethasone ; toxicity ; Disease Models, Animal ; Female ; Kidney Diseases ; etiology ; Medicine, Chinese Traditional ; Mice ; Osteoporosis ; chemically induced ; Yin Deficiency ; complications

The content of the asarone submicro emulsion injection was determind by HPLC method, and thereby a quality evaluation method was established based on indexes of pH value, particle size, peroxide value, methoxy aniline values, free fatty acid, lysophosphatidylcholine, visible foreign substances, insoluble particle, sterility, bacterial endotoxin and impurities, etc. The results showed that the injection exhibited uniform physical appearance and all the products were in milkwhite liquid. The content of the three batches products were respectively 102.9%, 100.8%, 97.70% of the labeled amount, with mean particle size of 210-250 nm, and other indexes all met with the standards. The reserved samples showed no obvious change in terms of detection indexes and indicated good stability after the accelerated stability test and long-term stability for 12 months. The quality evaluation method established in this study could be applied to quality control and stability investigation of asarone submicron emulsion injection, which laid a basis for further clinical research and application.
Anisoles ; chemistry ; Chromatography, High Pressure Liquid ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; Emulsions ; chemistry ; Particle Size ; Quality Control

Chronic osteomyelitis is one of the most common disorder in clinic. In recent years due to diabetes, peripheral vascular disease and trauma induced disease increased, the prevalence rate increased. With the development of magnetic resonance imaging and CT imaging technology, it greatly improved the accuracy of clinical diagnosis of chronic osteomyclitis and ability to describe the infection characteristics, and provide a reliable basis for clinical treatment. The current research on chronic osteomyelitis mainly concentrated on the aspects of imaging applications and ways of using antibiotic optimization control inflammation, defect restoration and reconstruction of blood supply and treatment. But the best time to the antibiotic therapy and the use of program is still uncertain, for after debridement, bone grafting time and defect repair function of fast recovery still need further research.
Anti-Bacterial Agents ; therapeutic use ; Chronic Disease ; Humans ; Osteomyelitis ; diagnosis ; therapy

OBJECTIVETo observe effects of serum Bushen Huoxue prescription(Chinese characters) on classic Wnt/β-catenin signaling pathways of osteoblasts, and explore mechanism of Bushen Huoxue prescription (Chinese characters) for preventing osteoporosis.

METHODSTwenty health female rats were randomly divided into two groups, including Bushen Huoxue (Chinese characters) group and saline group,10 in each group. Bushen Huoxue (Chinese characters) group and Saline group were gavaged Bushen Huoxue and saline every day for 1 week. Bushenhuoxue containing serum and saline containing serum were got according to methods of serum preparation of drug-containing. The osteoblasts was cultured with neonatal rat skull according to Enzyme Consumer Law, and was identified by Wright-Giemsa staining (R-J) and alkaline phosphatase staining (ALP). The third generation of osteoblasts was divided into three groups, including saline group, normal group,Bushen Huoxue (Chinese characters) group. Each group were added to 15% appropriate medium. ALP activity of osteoblasts and osteoblasts proliferation rate were tested, mineralized nodules were observed, the expression of β-catenin, Runx2, Osx mRNA of osteoblasts were tested by RT-PCR.

RESULTSThere was blue granules in cytoplasm, cell nucleus was flint with 1 to 3 nucleoli showed by R-J staining, morphology of osteoblasts were cultured. ALP staining showed cytoplasm with purple granules, the results showed that the cultured cell was osteoblasts. The content of ALP in Bushen Huoxue (Chinese characters)group was (6.272±0.131) ,appreciation rate was (0.81? 0.172), and could significantly improve differentiation and proliferation activity of osteoblasts compared with Saline group (P< 0.01). There were four different size orange nodules, the Maximun nodule was 1.0 x 1.0 cm in Bushen Huoxue (Chinese characters) group after Alizarin red staining, the results showed Bushen Huoxue (Chinese characters)group could obviously improve mineralization of osteoblasts. The expression of mRNA of β-catenin, Runx2 and Osx in Bushen Huoxue (Chinese characters)group were (1.782±0.944), (1.935±0.994) and (1.610±0.811) by RT-PCR,it was significantly increased compared with saline group (P<0.01), but there was no difference between Bushen Huoxue (Chinese characters)group and normal group (P>0.05).

CONCLUSIONBushen Huoxue (Chinese characters)group could obviously promote differentiation, proliferation and mineralization of osteoblasts through activation of Wnt, β-catenin signaling pathway. It suggested that the mechanism of action of Bushen Huoxue (O'f f Il.t)particle clould prevent osteoporosis through the activation of Wnt, β-catenin signaling pathway.

Animals ; Cell Differentiation ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; Osteoblasts ; cytology ; drug effects ; metabolism ; Osteoporosis ; drug therapy ; genetics ; metabolism ; physiopathology ; Rats ; Rats, Sprague-Dawley ; Wnt Proteins ; genetics ; metabolism ; Wnt Signaling Pathway ; drug effects ; beta Catenin ; genetics ; metabolism

Background:Besides typical gastroesophageal reflux symptoms,some reflux esophagitis( RE)patients also complain“morning sour taste in mouth”,but related studies are rare. Aims:To study the pathophysiology of RE with sour taste in mouth. Methods:Fifty-two RE patients with typical regurgitation symptom and confirmed by endoscopy from Mar. 2013 to Oct. 2013 at Tianjin Medical University General Hospital were enrolled. Patients were divided into two groups according to whether there was an existence of morning sour taste in mouth. Results of esophageal manometry and 24-hour esophageal impedance-pH monitoring were analyzed. Nine healthy volunteers who had esophageal manometry performed were served as controls. Results:Length of lower esophageal sphincter( LESL)was shortened and LES pressure( LESP)and effective peristalsis of esophageal body were decreased in both RE groups when compared with controls( P ﹤ 0. 05 ). Upper esophageal sphincter pressure( UESP)was significantly lower and more nocturnal reflux episodes occurred in RE group with sour taste than those without( P ﹤ 0. 05 );however,no significant differences in other manometric and reflux parameters were found between RE groups with and without sour taste(P﹥0. 05). Conclusions:Esophageal motility and reflux events in RE patients with morning sour taste in mouth are somewhat different from those without sour taste. Decrease in UESP might be an important pathophysiological mechanism of sour taste in mouth in RE patients.

Objective To determine the relationship between visual signal intensity and quantitative signal intensity of HCC assessed with DWI and histopathological differentiation of HCC.Methods The MR examinations including MRI plain scan,LAVA dynamic enhanced scan and DWI (1.5T,b value:0 and 600 s/mm2) of 224 patients who had surgically resected HCCs were retrospectively reviewed.Histopathological examinations revealed that there were 31 well-,169 moderately-,and 24 poorly-differentiated HCCs.The incidence of each visually evaluated signal intensity and quantitative signal intensity of HCC assessed with DWI signal intensity and the relationship between signal intensity and histopathological differentiation were assessed for each sequence.Results (1) On DWI,56.7％ of HCCs appeared as obviously hyperintense,24.1％ tumors appeared as moderate hyperintense,and 19.2％ tumors appeared as isotense or slight hyperintense to the surrounding hepatic parenchyma.There was a significant difference between isotense/slight hyperintense and obvious hyperintense and histopathological differentiation (P ＜ 0.05).There was no significant difference between isotense/slight hyperintense and moderate hyperintense and histopathological differentiation (P ＜ 0.05).There was no significant difference between moderate hyperintense and obvious hyperintense and histopathological differentiation (P ＞ 0.05).Visually evaluated signal Intensity of HCC showed an inverse correlation with histopathological differentiation (r =-0.324,P ＜ 0.05).On DWI,the tumors tended to show a brighter signal with decreasing histopathological differentiation.(2) There was a significant difference in DWI signal intensity value among the well,moderately and poorly differentiated HCCs (P ＜ 0.05).The SI value of well differentiated HCCs was lower than that of moderately differentiated HCCs and poorly differentiated HCCs (P ＜ 0.05).The SI value of moderately differentiated HCCs was lower than that of poorly differentiated HCCs.However,there was no significant difference between the SI value of the moderately and poorly differentiated HCCs (P ＞ 0.05).ROC analysis showed that the optimal cutoff point of SI value in diagnosing well differentiated HCCs was 66.5.A cutoff SI value equal to or less than 66.5 was used to differentiate well-differentiated HCC from moderately-and poorly-differentiated HCC with a sensitivity of 90.1％ and a specificity of 71.9％.Conclusions On DWI,the tumors tended to show a brighter,visually evaluated signal intensity and higher quantitative signal intensity with decreasing histopathological differentiation (P ＜ 0.05).The quantitative signal intensity of HCC assessed with DWI signal intensity could only predict well differentiated HCC.It was limited in predicting histopathological differentiation of HCC using evaluating signal intensity and quantitative signal intensity of HCC assessed with DWI.