Objective To investigate the clinical effects of lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease.Methods 120 patients with nonalcoholic fatty liver disease were selected,and they were randomly divided into control group (60 patients used glutathione alone) and observation group (60 patients received lactobacillus acidophilus on the basis of control group).The clinical efficacy,liver function index,blood lipid index and the ultrasonography grading of fatty liver before and after treatment of the two groups were compared.Results The clinical total effective rates of the control group and the observation group were 76.67％,91.67％,respectively.The total effective rate of the observation group was significantly higher than that of the control group(x2 =10.52,P ＜ 0.05).The levels of AST,ALT and GGT of the observation group after treatment were significantly lower than those of the control group and before treatment [(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L,(36.89 ±7.14) U/L vs.(49.36 ± 11.08) U/L,(45.91 ± 10.24) U/L,(90.28 ± 20.70) U/L;(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L,(36.89 ± 7.14) U/L vs.(92.90 ± 24.3) U/L,(81.11 ± 17.37) U/L,(147.27 ± 34.19) U/L,t =2.88,2.54,2.91;3.01,3.36;3.18,3.48;3.41,3.87;all P ＜0.05).The levels of TG,TC,HDL-C and LDL-C of the observation group after treatment were significantly better than those of the control group and before treatment [(1.66 ± 0.42) mmol/L,(4.05 ± 0.77) mmol/L,(1.69 ± 0.60) mmol/L,(2.44 ± 0.38) mmol/L vs.(2.13 ± 0.80) mmol/L,(4.64 ± 0.94) mmol/L,(1.45 ± 0.48) mmol/L,(2.97 ± 0.57) mmol/L;(1.66 ± 0.42) mmol/L,(4.05 ± 0.77) mmol/L,(1.69 ± 0.60) mmol/L,(2.44 ± 0.38) mmol/L vs.(2.71 ± 1.33) mmol/L,(5.42 ± 1.27) mmol/L,(1.08 ± 0.36) mmol/L,(3.49 ± 0.71) mmoL/L,t =2.43.2.13,2.55,2.07;3.02,3.41;3.11,3.65;2.81,3.30;2.87,3.15;all P ＜ 0.05).In the control group,normal in 6 cases,mild in 24 cases,moderate in 21 cases and severe in 9 cases as fatty liver degree;in the observation group,normal in 13 cases,mild in 30 cases,moderate in 13 cases and severe in 4 cases as fatty liver degree.The ultrasonography grading of fatty liver of the observation group after treatment were significantly better than those of control group and before treatment (U =3.74,5.20,all P ＜ 0.05).Conclusion Lactobacillus acidophilus combined with glutathione in the treatment of nonalcoholic fatty liver disease can efficiently promote the recovery process of liver function,regulate blood lipid levels and is helpful to improve the imaging grading.

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.
Drug Carriers ; chemistry ; Fluorescence ; Kinetics ; Micelles ; Particle Size ; Poloxamer ; chemistry ; Solubility ; Stilbenes ; chemistry ; Water

BACKGROUND: Antigene RNAs (agRNAs) could be a useful tool to downregulate beta arrestin 2 (Arrb2) gene expressions, and realize gene knock-out effect in cell levels. OBJECTIVE: To observe the effects of agRNAs on DAMGO-induced mu-opioid receptor (MOR) desensitization in C17.2 cells by using agRNAs complementary to transcription start sites of beta arrestin 2 (Arrb2) to downregulate the gene expression in mouse C17.2 cells. METHODS: Mouse neural stem cells C17.2 was cultured in Dulbecco's minimal essential medium containing 10% fetal bovine serum, 10 mg/L penicillin and 10 mg/L ampicillin with 5% CO_2 at 37 ℃. The cells were passaged every 5 to 6 days after digestion with 0.25% trypsin when cells were 80% confluent. The expression of MOR on mouse C17.2 cells was detected by RT-PCR and immunocytochemical method. AgRNAs which could silence the expression of Arrb2 was transfected into C17.2 cells with Lipofectamine. The expression of green fluorescent protein gene was observed by fluorescence microscopy 24 hours after transfection. [~(35)S]GTPγS binding was assessed by autoradiography to examine the ability of the MOR to couple to G proteins on stimulation with selective agonist DAMGO.RESULTS AND CONCLUSION: The expression of MOR on C17.2 cells was confirmed by RT-PCR. The receptors were expressed on cell membrane and in plasma determined by immnocytochemistry. The expression of green fluorescent protein gene could be observed in C17.2 cells transfected with plasmid pGPU6/GFP/Arrb9 using fluorescent microsocpe. The results of [~(35)S]GTPγS binding showed that the stimulation ratio in cells with and without DAMGO stimulation or transfected with agRNAs were (113±14)%, (253±17)% and (239±15)% respectively. This indicated that agRNAs could downregulate the expression of beta-arrestin 2 and inhibit the desensitization of MOR.

OBJECTIVETo compare the difference in depression relief in the treatment of depressive disorder at the acute stage between the combined therapy of acupuncture and 5-HT (5-hydroxytryptamine) selective serotonini reuptake inhibitors (SSRIs) and the single application of SSRIs and explore the impact on the imbalance of 5-HT and TH1/TH2.

METHODSNinety cases of depressive disorder at the acute stage were randomized into a combined therapy group and a medication group, 45 cases in each one. In the medication group, SSRIs were prescribed forl oral administration, once or twice a day, continuously for 4 weeks. In the combined therapy group, on the basis of treatment as the medication group, acupuncture was combined. The main acupoints were Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), Fengchi (GB 20), Dazhui (GV 14) and Sishencong (EX-HN 1), once every two. days, continuously for 4 weeks. Before treatment, and after the 1st, 2nd and 4th weeks of treatment, the Hamilton depression scale (HAMD) was used to evaluate the depression severity. Separately, before and after the 4 weeks of treatment, the levels of serum 5-HT, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-10 (IL-10) were determined and compared with those in 45 cases of the healthy group.

RESULTSHAMD score was reduced in the 1st, 2nd and 4th weeks of treatment as compared with that before treatment in the combined therapy group (all P<0 01). HAMD score was reduced in the 2nd and 4th weeks of treatment as compared with that before treatment in the medication group (all P<0. 01). HAMD scores in the combined therapy group were lower than those in the medication group in the 1st, 2nd and 4th weeks of treatment (all P< 0. 01). Before treatment, in the combined therapy group and the medication group, the levels of serum 5-HT, IL-4 and IL-10 were all lower than those in the healthy group (all P<0. 01); the levels of IL-1β and IL-6 were higher than those in the healthy group (all P<0. 01). In the combined therapy group and the medication group, the levels of 5-HT, IL-4 and IL-10 in 4 weeks of treatment were all increased as compared with those before treatment (all P<0. 01), and the levels of IL-1β and IL-6 were lower than those before treatment (all P<0. 01). In the combined therapy group, the levels of IL-1β and IL-6 in 4 weeks of treatment were lower than those in the medication group, and the levels of 5-HT, IL-4 and IL-10 were higher than those in the medication group (P<0. 01, P< 0. 05).

CONCLUSIONThe combined therapy of acupuncture and SSRIs achieves much quicker and more effective re-' sult for relieving depression in the patients of depressive disorder as compared with simple oral administration of' SSRIs, and much more contributes to adjust the imbalance of serum 5-HT and TH1/TH2.

Acupuncture Points ; Acupuncture Therapy ; Adolescent ; Adult ; Antidepressive Agents ; administration & dosage ; Combined Modality Therapy ; Depressive Disorder ; blood ; drug therapy ; therapy ; Female ; Humans ; Interleukin-10 ; blood ; Interleukin-1beta ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Male ; Middle Aged ; Serotonin ; blood ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Young Adult

Objective To evaluate the efficacy of alendronate sodium combined with dietary and exercise intervention in postmenopausal osteoporosis. Methods 88 postmenopausal osteoporosis patients were enrolled and treated with alendronate sodium and Vitamin D combined with dietary and exercise intervention for 12 months. Bone mineral density (BMD) of lumber spine and femur neck were measured before and after the treatment. Results Medication combined with dietary and exercise intervention significantly increased bone mineral density of postmenopausal osteoporosis patients, and the serum levels of bone alkaline phosphatase (BLAP), alkaline phosphatase (AKP) and tartrate resistant acid phosphatase (TRACP) were significantly higher than those pre-treatment, with significant differences (P<0.05). Conclusion Compared to simple medication treatment, medication combined with dietary and exercise intervention is more effective to enhance medication efficacy and BMD level.

Objective To study the role of ligustrazine injection on collagen-Ⅲ(Col-Ⅲ) and laminin(LN) in pulmonary fibrosis rats induced by bleomycin A5.Methods Seventy Wistar rats were divided into 5 groups at random:normal group,model group,large-dose group,middle-dose group,little-dose group.The other groups were injected bleomycin A5 in intratrache except for normal group.From the second day,large-dose group,middle-dose group,little-dose group were given ligustrazine injection by intraperitoneal injection to 28th day,the dose was dividedly:250,150,40 mg/(kg?d).Col-Ⅲ and LN in serum were detected in 14th,28th days and the content of them in lung tissue homogenate in 28th day were also detected.HE staining was detected on lung tissue.Results The contents of Col-Ⅲ and LN of lung tissue and serum in pulmonary fibrosis rats were significantly upgraded compared with that of normal group(P

Background Intracameral or intracorneal administration of amphotericin B (AMB) can achieve significant therapeutic efficacy in the treatment of recalcitrant fungal keratitis in cases that do not respond to conventional antifungal therapy. However, the ocular pharmacokinetics of the two routes of administration is unclear.Objective The goal of this study was to investigate the level of amphotericin B in cornea and aqueous humor of rabbits after administration of AMB via three different routes. Methods Forty-five healthy domestic rabbits were randomly divided into three groups. 1% amphotericin B of 10 μg was intrastromally or intracamerally injected into 15 rabbits, respectively,in group A and group B. Topical 0. 25% amphotericin B was topically administered to the eyes with corneal epithelial debridement (group C). Experimental animals were sacrificed and the corneas and aqueous humor samples were obtained for the detection of levels of amphotericin B at 30 minutes,6 hours, 1 day,3 and 7 days by high-performance liquid chromatography (HPLC). Results Calibration curves were linear over the range of 0. 10-100. 00 mg/L. The concentration of 0. 10 mg/L was the lowest quantifiable limit. The recovery of amphotericin B ranged from 89. 1% -95.7% from aqueous humor samples and 81.4% -83.6% from the cornea samples. After a single injection,effective drug levels were achieved and maintained for 7 days in cornea in group A, exceeding the minimum inhibitory concentration at which 90% of isolates are inhibited (MIC90) for a wide spectrum of fungi and molds with significant differences in comparison with group B and group C ( P＜0. 05 ). Effective drug levels were achieved in the aqueous humor in group B at 30 minutes after a single injection, but drug levels decreased dramatically within 6 hours. The evident differences were found between group B and group A or group C (P＜ 0.05). A considerable amount of amphotericin B was detected in the cornea and aqueous humor in group C within 1 day.Conclusion Effective high drug levels can be reached in rabbit cornea and aqueous humor after intrastromal and intracameral injection, respectively. Penetration of topical amphotericin B was greatly elevated after epithelial debridement.

OBJECTIVETo propose a simple and practical method for preparing a mouse model of oligo-astheno-terato-spermia/azoospermia, and to offer a methodological suggestion for the studies on the related mechanism of spermatogenesis and evaluation of medication efficacy by observing the early changes of testis morphology after 5-fluorouracil treatment.

METHODSMice were injected with a single dose of 5-flourouracil at 250 mg/kg via the tail vein, and their testes were harvested and paraffin sections prepared before and 3, 7, 11 and 14 d after the injection to be observed for the morphological changes by hematoxylin and eosin staining.

RESULTSThe numbers of spermatocytes/spermatids were progressively reduced inside the testis seminiferous tubules of the mice at 3, 7 and 11 d after the 5-fluorouracil injection, and the tubule walls became thinner, which reached the nadir at 11 d, with evident swelling and crazing of the seminiferous tubules. At 14 d, the swelling almost disappeared and spermatocytes became repopulated, while the flaws still existed in the seminiferous tubules and no mature sperm were seen.

CONCLUSIONOne-dose injection of 5-fluorouracil via the tail vein might be a simple and effective method for preparing the animal model of reproductive function damage induced by chemotherapeutic medication.

Animals ; Fluorouracil ; pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Testis ; anatomy & histology ; drug effects

OBJECTIVETo evaluate pathologically the effect of the single or combined application of UDP-glucose, GDNF and memantine on the improvement of white matter injury in neonatal rats with periventricular leukomalacia (PVL) under light and electron microscopy.

METHODSA five-day-old neonatal rat model for PVL was established by ligation of the lateral common carotid artery following 120-minute hypoxia. Rats were randomly divided into six groups (30 rats in each group): sham-operated, PVL, UDP-glucose (UDP-glucose 2000 mg/kg intraperitoneally after PVL), GDNF (GDNF 100 μg/kg intracerebrally after PVL), tmemantine (memantine 20 mg/kg intraperitoneally after PVL), and a combination administration of three drugs (UDP-glucose, GDNF and memantine). The rats were sacrificed 7 or 21 days after PVL for assessment of pathological changes in the white matter under both light and electron microscopy. The number and thickness of the myelin sheath in the white matter were measured under electron microscopy, and both of pathological grading and scoring were undertaken under light microscopy.

RESULTSThere was rare and sparse myelinogenesis with a loose arrangement of nerve fibers in the white matter under electron microscopy in the PVL group at 7 and 21 days after PVL. The number and thickness of the myelin sheath in the PVL group were significantly less than in the sham-operated, UDP-glucose, GDNF, memantine and combination administration groups (P<0.01). The results of pathological grading of white matter under light microscopy showed that all rats in the PVL group manifested either mild injury (38%-50%) or severe injury (50%-62%) at 7 and 21 days after PVL. The majority of rats (50%-88%) in the four drug administration groups had normal white matter at 7 and 21 days after PVL. The pathological scores at 7 and 21 days after PVL in the PVL group were the highest, and they were significantly higher than in the other five groups (P<0.05).

CONCLUSIONSThe single or combined application of UDP-glucose, GDNF and memantine may significantly improve pathological changes in the white matter of rats with PVL. The favorable effect is inferred to be closely correlated with the improvement of brain microenvironment and the enhancement of nerve regeneration promoted by the three drugs.

Animals ; Brain Ischemia ; drug therapy ; pathology ; Cerebral Ventricles ; pathology ; ultrastructure ; Female ; Glial Cell Line-Derived Neurotrophic Factor ; administration & dosage ; therapeutic use ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; drug therapy ; Male ; Memantine ; administration & dosage ; therapeutic use ; Microscopy, Electron ; Rats ; Rats, Sprague-Dawley ; Uridine Diphosphate Glucose ; administration & dosage ; therapeutic use

OBJECTIVEIt is known that Siglec-8 is selectively expressed on human eosinophils at a high level and mediates eosinophil apoptosis when crosslinked with its antibody. The aim of our review is to elucidate the molecular and biological characteristic of Siglec-8 and then discuss the function and possible mechanisms of Siglec-8 in eosinophils. Thereby, we will expand our understanding to the regulation of eosinophil apoptosis, and provide important clues to the treatment of asthma and other hyper-eosinophilic diseases.

DATA SOURCESMost articles were identified by searching of PubMed online resources using the key term Siglecs.

STUDY SELECTIONMainly original milestone articles and critical reviews written by major pioneer investigators in the field were selected.

RESULTSSiglec-8 is selectively expressed on human eosinophil and can specifically induce eosinophil apoptosis.

CONCLUSIONThe restricted expression of Siglec-8 on human eosinophil and the rapid progress in understanding its role as cell signaling and activation of death receptors have made it an attractive target for treatment of asthma and other hyper-eosinophilic diseases.

Apoptosis ; genetics ; physiology ; Asthma ; metabolism ; therapy ; Eosinophils ; cytology ; metabolism ; Humans ; Sialic Acid Binding Immunoglobulin-like Lectins ; metabolism