OBJECTIVETo study the protective effect of Ligustrazine Injection (LI) against cisplatin-induced ototoxicity and to explore its mechanism.

METHODSThirty healthy adult guinea pigs were randomly divided into three groups, 10 in each group, i.e., the normal control group, the cisplatin group, and the LI group. Guinea pigs in the normal control group were intraperitoneally injected with normal saline at 3 mL/kg for 7 consecutive days. Those in the cisplatin group were intraperitoneally injected with cisplatin at 3 mg/kg for 7 consecutive days. Those in the LI group were intraperitoneally injected with LI at 140 mg/kg for 7 days, but cisplatin (3 mg/kg) was intraperitoneally injected from the opposite side starting from the 4th day. Brainstem auditory evoked potential (BAEP) was performed in all animals before and after injection. All animals were sacrificed after the final testing under anesthesia and their cochleas collected. Half the cochleas of each group were collected for silver nitrate staining of cochlear basilar membrane stretched. The other half the cochleas of each group made into paraffin sections to observe the apoptosis of cochlea cells by TUNEL method and the expression levels of c-Jun detected by immunohistochemistry.

RESULTSThere was no statistical difference in the difference of BAEP threshold among the 3 groups before injection (P > 0.05), but the BAEP threshold increased in the cisplatin group and the LI group (P < 0.05). Besides, it was higher in the cisplatin group (P < 0.05). In the cisplatin group, most hair cells were missing, spiral ganglion cells obviously decreased, more TUNEL positive cells occurred, and the expression of c-Jun was stronger. But the aforesaid impairment in the LI group was obviously lessened (P < 0.05).

CONCLUSIONSLI showed certain antagonist effect on cisplatin-induced ototoxicity. Its mechanism might be associated with scavenging oxygen radicals of the cochlea tissue, improving the microcirculation, and fighting against apoptosis.

Animals ; Apoptosis ; drug effects ; Cisplatin ; toxicity ; Cochlea ; drug effects ; metabolism ; pathology ; Evoked Potentials, Auditory, Brain Stem ; Guinea Pigs ; Pyrazines ; pharmacology ; Reactive Oxygen Species ; metabolism

Objective: To investigate the protective effects of Ginsenoside Rg1 against cisplatin (CDDP)-induced ototoxicity and its mechanisms. Methods: Eighty guinea pigs were randomly divided into five groups with ten rats in each group, namely control group, cisplatin group, 5 mg/kg Rg1 + CDDP group, 10 mg/kg Rg1 + CDDP group, and 20 mg/kg Rg1 + CDDP group. Animals in the control group were administered with normal saline (NS, 3 mL/kg) via intraperitoneal (ip) route for 7 consecutive days. Cisplatin group were injected with cisplatin alone (3 mg/kg, ip) for 7 consecutive days. Rg1 + CDDP groups were given 3 consecutive days of Rg1 (5 mg/kg, 10 mg/kg, and 20 mg/kg ip respectively for each group) ahead of the application of Rg1 + cisplatin (3 mg/kg, ip) for 7 consecutive days. For the 7 consecutive days of co-treatment of Rg1 with cisplatin, Rg1 was injected peritoneally 1 hour before the injection of CDDP at the contralateral side. Auditory brainstem response (ABR) test was used to evaluate the auditory function of rats in each group before and after administration of CDDP. Stretched preparation of cochlear basilar membrane was examined for morphological changes of outer hair cells (OHC). The general case of diet, loss of hair, and activity status of guinea pigs were observed every day. HE staining techniques and optical microscopy were used to evaluate the lesions of spiral ganglion neurons (SGN). The levels of malondiadehyde (MDA) and superoxidedismutase (SOD) activities in cochlear tissues were detected by biochemical assay kits. The protein expressions of Caspase-3, p53, p-Akt, and Nrf2 were determined by western blotting. Results: Compared with CDDP group, Rg1 co-treatment significantly lowered the CDDP-induced ABR threshold elevation (P < 0.05) in a dose dependent manner. The severe damages of cochlear OHCs and SGNs exhibited in CDDP group were also markedly attenuated by co-treatment with Rg1 in the Rg1 + CDDP groups. In CDDP group, the MDA levels were significantly increased while the SOD activity was decreased in cochlear tissue after CDDP injection. Rg1 treatment evidently reduced the level of MDA and enhanced the SOD activity (P < 0.05). Western blot results indicated that Rg1 treatment significantly attenuated CDDP-induced pro-apoptotic protein expressions (Capase-3 and p53). Furthermore, treatment with Rg1 resulted in an increased expression of p-Akt and intranuclear Nrf2 in cochlear tissue compared to the CDDP group. Conclusion: Ginsenoside Rg1 protects auditory functions from cisplatin-induced ototoxicity via the Akt/Nrf-2 pathway in guinea pigs.

Objective To obtain antibiotic-resistant mutants producing metabolites with antitumor activity from wild-type actinomycete strains without antitumor activity. Methods An actinomycete strain L35-1 was used as an initial strain for obtaining antibiotic-resistant mutants, which is a marine-derived wild-type strain without antitumor activity with an inhibition rate of 2.8% at the 1000 μg/ml of high sample concentration on K562 cells. The antibiotic-resistant mutants both from auto-mutagenesis and chemical mutagen-induced mutagenesis were selected by single colony isolation on antibiotic-containing plates according to the method for obtaining drug-resistant mutants in ribosome engineering. The antitumor activity was assayed by the MTT method using K562 cells for the mutants with aqueous acetone extracts of the whole broth of their fermentation.Results A total of 114 neomycin-resistant (ner) and 68 streptomycin-resistant (str) mutants, all from auto-mutagenesis, was obtained on drug-containing plates. Among them, the 7 ner and 3 str mutants appeared to be bioactive with an inhibition rate above 20% at the 100 μg/ml sample concentration on K562 cells. On the other hand, 41 str and 32 ner mutants from DES-induced mutagenesis and 46 ner mutants from NTG-induced mutagenesis were obtained by mutagen-induced mutation coupled with the single colony isolation on antibiotic-containing plates, among which, one str mutant from DES-induced mutagenesis and one ner mutant from NTG-induced mutagenesis were bioactive with an inhibition rate over 20% at the 100 μg/ml sample concentration on K562 cells. Conclusions The present result has revealed that the wild-type actinomycete strains without bioactivity might become a great source initial strains to obtain bioactive mutants by drug-resistant mutation technique.

0.05 indicating no statistical difference.However,the noise measurements for the L and C groups were 30.05 and 27.80,respectively,with P

The quantitative identification and enrichment of viable regulatory T cells (Treg) requires reliable surface markers that are selectively expressed on Treg. Foxp3 is the accepted marker of natural Treg, but it cannot be used to isolate cells for functional studies. CD127 is a new surface marker expressed in Treg cells. In this study, two populations of Treg, including CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+)T cells, and profiles of the Foxp3 expression in CD4(+)CD25(+)CD127(low/-) cells were compared to evaluate which population is better. The peripheral blood cells were collected and spleen suspension of BALB/C mice were prepared, and using triple staining CD4, CD25, CD127 and CD4, CD25, Foxp3. The profiles of Treg, including CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+) were detected by flow cytometry. The quadruple staining CD4, CD25, Foxp3 and CD127 were used to determine the CD127 expression in CD4(+)CD25(+)Foxp3(+) cells. The results showed that on T cell subset the median expression levels of CD4(+), CD4(+)CD25(+) were 39.02%, 5.35% in peripheral blood and 23.49%, 3.86% in spleen. On CD4(+) T cell subset, the median expression level of CD4(+)CD25(+)CD127(low/-) and CD4(+)CD25(+)Foxp3(+)T cells were 7.13%, 3.97% in peripheral blood and 12.8%, 8.23% in spleen. The ratio of CD4(+)CD25(+)CD127(low/-) T cells was higher than that of CD4(+)CD25(+)Foxp3(+) cells in both peripheral blood and spleen cells (P < 0.01). The CD4(+)CD25(+)CD127(low/-) cells highly expressed Foxp3, while the CD4(+)CD25(+)Foxp3(+)T cells lowly expressed CD127. It is concluded that compared with the CD4(+)CD25(+)Foxp3(+) populations, CD4(+)CD25(+)CD127(low/-) T cells better fit the definition of naturally occurring regulatory T cells in peripheral blood cells and spleen of BALB/C mice. CD127(low/-) is a characteristic marker on surface of CD4(+)CD25(+) Treg cells, and has been confirmed to be more specific marker for quantitatively sorting Treg cells.
Animals ; Biomarkers ; blood ; Female ; Interleukin-7 Receptor alpha Subunit ; analysis ; Mice ; Mice, Inbred BALB C ; Spleen ; cytology ; T-Lymphocytes, Regulatory ; metabolism

OBJECTIVETo observe the clinical manifestations of bullous retinal detachment and analyze the etiological factors.

METHODSA retrospective analysis of the clinical data was conducted in 22 patients with multifocal retinal pigment epitheliopathy (DRPE) and big bullous retinal detachment (BBRD), who were admitted between 2003 and 2008 in Zhongshan Ophthalmic Center with the diagnoses established by ocular fundus examination, fundus fluorescein angiography (FFA) and/or indocyanine green angiography (ICGA).

RESULTSThe patients included 15 men (68%) and 7 women (32%), with a mean age at the initial visit of 42 years, ranging from 25 to 64 years. Four patients (18%) received previously systemic corticosteroid therapy, and 2 of them used corticosteroids before retina detachment, 1 suffered progression of retinal detachment after corticosteroid therapy, and the other developed retinal detachment in the healthy eye during the therapy. Multifocal bullous retinal detachment was diagnosed as diffuse pigment epitheliopathy (DRPE) in 9 cases. Most of the 13 cases of big bullous retinal detachment had poor vision after operation and laser therapy.

CONCLUSIONBullous retinal detachment occurs most frequently in mid-life and more often in men than women. Abnormal retinal pigment epithelium (RPE) and hyperpermeability of the choroid vessels are associated with its occurrence. Systemic corticosteroid therapy and mental stress may induce and aggravate this disease. Early medication and laser therapy are effective, and surgical intervention may save only part of the vision in advanced cases.

Adult ; Female ; Fundus Oculi ; Humans ; Male ; Middle Aged ; Retinal Detachment ; diagnosis ; etiology ; pathology ; therapy ; Retrospective Studies

OBJECTIVETo explore the possibility of using an endovascular microcoil as a gene delivery system.

METHODSAnti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of platinum microcoil. These antibodies were used to tether adenovirus encoding green fluorescent protein (Ad-GFP). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution.

RESULTSIn cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface. After 7 days, GFP was detected on the harvested platinum coil and in the organizing thrombus within the CCA according to fluorescence microscopy and immunohistochemistry. Morphometric analyses revealed that (13.3 +/- 2.0)% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney.

CONCLUSIONSGene delivery endovascular microcoils represents an interventional device-based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.

Adenoviridae ; genetics ; immunology ; Aneurysm ; surgery ; Animals ; Antibodies, Viral ; chemistry ; metabolism ; Biological Availability ; Carotid Artery, Common ; drug effects ; metabolism ; surgery ; Cells, Cultured ; Drug Delivery Systems ; instrumentation ; Embolization, Therapeutic ; methods ; Endothelial Growth Factors ; therapeutic use ; Genetic Therapy ; instrumentation ; methods ; Genetic Vectors ; administration & dosage ; chemistry ; Green Fluorescent Proteins ; analysis ; Muscle, Smooth, Vascular ; cytology ; Platinum ; chemistry ; Rats ; Rats, Sprague-Dawley ; Recombinant Proteins ; therapeutic use ; Transduction, Genetic ; instrumentation ; methods

OBJECTIVEImpact of the presence of bacteria associated with a marine dinoflagellate, Alexandrium tamarense CI01, on the growth and toxin production of the algae in batch culture was investigated.

METHODSPronounced changes in the activities of the algal culture were observed when the culture was treated with different doses of a mixture of penicillin and streptomycin.

RESULTSIn the presence of antibiotics at the initial concentration of 100 u/mL in culture medium, both algal growth and toxin yield increased markedly. When the concentration of antibiotics was increased to 500 u/mL, the microalgal growth was inhibited, but resumed in a few days to eventually reach the same level of growth and toxin production as at the lower dose of the antibiotics. When the antibiotics were present at a concentration of 1 000 u/mL, the algal growth was inhibited permanently.

CONCLUSIONSThe results indicate that antibiotics can enhance algal growth and toxin production not only through their inhibition of the growth and hence competition for nutrients, but also through their effects on the physiology of the algae.

Animals ; Anti-Bacterial Agents ; pharmacology ; Bacteria ; Dinoflagellida ; microbiology ; pathogenicity ; Eutrophication ; Marine Toxins ; biosynthesis ; Penicillins ; pharmacology ; Saxitoxin ; Streptomycin ; pharmacology

OBJECTIVEThis study was performed to evaluate the relationship between the stent fracture and restenosis after drug-eluting stent implantation.

METHODSThe study enrolled 536 patients with angiographies during stenting procedure and follow-up, the patients were divided into DES group (n=397) and BMS group (n=139). The coronary angiography images were analyzed to detect restenosis and stent fracture.

RESULTSRestenosis rate was significantly lower in DES group (31/397, 7.8%) compared that in BMS group (30/139, 21.6%, P<0.05). Stent fracture (n=5) was found only in DES group and not in BMS group (P<0.05). Restenosis were found in all stent fracture segments. The stent fracture developed at the angulated tortuosity lesions.

CONCLUSIONStent fracture is one of the causes of restenosis after drug-eluting stents implantation and related to implantation of long DES stent at the location of angulated tortuosity lesions.

Aged ; Angioplasty, Balloon, Coronary ; Coronary Restenosis ; diagnostic imaging ; etiology ; Drug-Eluting Stents ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Prosthesis Failure ; Radiography ; Retrospective Studies ; Ultrasonography

Objective To investigate the CT findings of Madelung's disease in the head and neck region,and to evaluate the value of CT in demonstrating the Madelung's disease in the head and neck region.Methods CT findings of Madelung's disease in the head and neck region in 7 cases were analyzed retrospectively.All were males,with the age from 36 to 60 years,mean 51 years.All patients were underwent CT native scan,and enhanced CT scan was performed on 3 of them.Results CT images in the neck of all patients showed accumulation of nonencapsulated fat within the subcutaneous tissue and(or) deep to the platysma,and(or)within the spaces between the muscles.The fat deposits were ill-defined and symmetrical.In most cases the fat deposits involved the anterior part of the neck(infrahyoid and suprahyoid),submandibular region,the subcutaneous tissue of the nape and deep to the stenomastoid muscles.Conclusions Madelung's disease in the head and neck region have characteristic CT findings,and CT has great value in qualitative and quantitative diagnosis in Madelung's disease.