OBJECTIVETo investigate uptake and accumulation of gentamicin by cells in the guinea pig inner ear after intratympanic injection using a fluorescent probe--gentamicin-Texas-red conjunction (GTTR).

METHODSAdult guinea pigs (n = 80) were administered a single dose of GTrR to the middle ear cavity through the intact membrane and survived for 12 h, 24 h, 48 h, 3 d, 4 d, 7 d, 14 d and 28 d. The distribution of GTTR in the cochlear and vestibular cells was observed after staining with phalloidin-alexa-488. Texas Red and DMSO were injected into the tympanum as control.

RESULTSDiffuse staining of gentamicin in the labyrinth was observed initially after local drug administration. At later time point the outer hair cells and sensory cells of vestibular organ were staining more densely than the support cells in the inner ear. The peak level of fluorescent density was reached 3 days after local injection. The GTTR was observed in the infracuticular zone.

CONCLUSIONSGTTR was a potential fluorescent probe to investigate the pharmacokinetics and mechanisms of gentamicin accumulation in local application.

Animals ; Anti-Bacterial Agents ; administration & dosage ; pharmacokinetics ; toxicity ; Ear, Inner ; metabolism ; Fluorescent Dyes ; Gentamicins ; administration & dosage ; pharmacokinetics ; toxicity ; Guinea Pigs ; Hair Cells, Auditory ; metabolism

OBJECTIVETo establish a rabbit model of intervertebral disc degeneration by puncturing the anulus fibrosus through an approach between the longissimus dorsi muscle and obliquus externus abdominis.

METHODSThe L(4/5) and L(5/6) intervetebral discs of 6 New Zealand white rabbits were punctured by an 18-gauge pin in the anterolateral annular fibrosus through an approach between the longissimus dorsi muscle and the obliquus externus abdominis with the right transverse processes of L(5) and L(6) resected; the L(2/3) discs were used as the control without exposure or needle stab, and the L(3/4) discs were subjected to sham operation with the discs exposed but not punctured after resecting the right transverse process of L(4). X-ray and magnetic resonance imaging (MRI) were performed preoperatively and at the 4th week after puncture. At 4 weeks after the operation, histological and immunohistochemical analyses of the discs were carried out.

RESULTSX-ray of the punctured discs at 4 weeks after the operation presented a significant decrease of disc height, osteophytosis formation, and end-plate stiffness; an obvious decrease of signal intensity on T(2)-weighted images was found in the puncture group but not in the control or sham-operated groups. Gross morphological inspection showed atrophy of the nucleus pulposus, which became loose, soft, and fragile with a light yellow color. Histological and immunohistochemical analyses showed a significant decrease of notochordal cells and type II collagen in the nucleus pulposus in the puncture group as compared to the control and sham-operated groups.

CONCLUSIONPuncture through the approach between the longissimus dorsi muscle and the obliquus externus abdominis allows the establishment of a reliable animal model for studying intervertebral disc degeneration.

Animals ; Disease Models, Animal ; Female ; Intervertebral Disc Degeneration ; Lumbar Vertebrae ; physiopathology ; Male ; Rabbits

Objective To investigate the uptaking and accumulation of gentamicin by mouse hair cells in vitro.Methods Cochlear explants were prepared from the microdissected neonatM mouse cochlea. Cochlear explants were cultured with gentamicin-Texas-red conjunction (G1TrR) for difierent time.Laser confocal microscopy was used to observe the distribution of GTYR in the cochlear sensoty ceUs after labeling with phalloidin-alexa-488.ResulIs Soon after culture,there was diffuse red staining all tissue cells in the explants.At later time the hair cells were more staining tllan other cells in the explants.There was no obviously accumulation of GTTR in the supporting cells.The peak level of fluorescent density was reached at 24 hours culture.The GTTR was seen in the infracuticular zone of the hair cells.There was still accumulation of GTTR in the hair cells of the explants after 7 days culturing.Conclusions GTTR and Cochlea explants were useful methods to investigate the pharmacokinetics and mechanisms of gentamicin accumulation over time.

Through the markets investigations and literature surveying, this paper investigates and analyzes the qualitative characteristics and commodity condition of Panax notoginseng. And the samples collected from market and origin were analyzed in order to revise the commodity specification and grade standard of P. notoginseng combined with production practice. In this paper, the authors divide the P. notoginseng into 4 commodity specification which are root (including Cunqi and Dongqi ), Rhizome and rootlet according to different parts and harvest time. And the root were divided into 8 grade which are 20, 30, 40, 60, 80, 120, countless and substandard. The density and internal components between the different commodity specification and grade of P. notoginseng were also compared. As well as the effect of different producing area, cultivation years and harvesting time on the commodity specification and grade of P. notoginseng were researched. On this basis, we revise and improve the commodity specification and grade standard of P. notoginseng. Moreover, we suggest the quality control indexes of P. notoginseng should be developed according to the different medicinal part and commodity specification in CHP. In order to guide the standardized production of traditional Chinese medicine and ensure the quality of medicinal materials, the cultivation years and density of each medicinal materials should also be indicated in CHP.

The solubility of nebivolol hydrochloride was determined in acidic aqueous media in the absence and presence of different concentration of NaCl, NaBr, or NaI at 37 ℃ in order to facilitate proper selection of dissolution media that have adequate discriminating power for enhancing the likelihood of a generic drug product to successfully pass in-vivo bioequivalence test. In the range of pH 5.0 to pH 1.0, the solubility of nebivolol hydrochloride decreased with the decrease in the pH of aqueous solution, and the solubility of nebivolol hydrochloride further decreased with the increase in the concentration of added sodium chloride. The solubility decrease of a few weakly basic drug molecules in acidic media and in higher concentration of added chloride was published previously by other researchers, and the observed decrease in the solubility in the presence of higher chloride concentration was interpreted in terms of common-ion effect. However, the results in this paper showed that the solubility of nebivolol hydrochloride also decreased when sodium chloride was replaced with sodium bromide or iodide. The approach described in this paper (i.e. substituting sodium chloride with sodium bromide or iodide) provides an effective method to verify whether common-ion effect is the true (or at least the sole) driving force behind the observed decrease in the solubility of nebivolol hydrochloride in the presence of sodium chloride. The solubility decrease reported in this paper can be interpreted in terms of salting-out effect of sodium chloride, bromide, and iodide. For hydrochloride salt of a weakly basic drug molecule like nebivolol hydrochloride, its solubility in an acidic dissolution medium can be purposely decreased to the lower end of sink condition by adding sodium chloride to make the resulting medium more discriminating. As shown in this paper, a medium at pH 1.2 with added sodium chloride is discriminating and this medium is shown to be bio-relevant to the in-vivo data collected under fasting condition (in-vivo study protocol was approved by Institutional Review Board).

The study is aimed to clarify the spatial distribution of Epimedium koreanum( Ek) high-quality production areas. Through visiting and field investigation,collecting the distribution information of Ek samples,and based on the four kinds of flavonoids in Ek,the high-quality production areas and distribution of Ek distribution of the main environmental factors were drawn using GIS technology,the maximum entropy model( MaxEnt),geographical detector statistical analysis method,and the statistical significance of regression equation were obtained. Considering the content of 4 main flavonoids in Ek,the results of this study showed that the main environmental factors,such as precipitation,annual precipitation variation coefficient,annual average temperature and clay content exhibited the greatest influence on the growth suitability of Ek. Ek materials quality concentrated distribution in southeastern Jilin province Changbai mountain hinterland and northeastern Liaoning province. Ek with high content of epimedine A and epimedine C are mainly distributed in the southeastern Jilin province and northeastern Liaoning province,Ek with high epimedine B is distributed in eastern Liaoning province; high icariin Ek was found in most area of northeastern Liaoning province,a small amount distributed in the southeast of Jilin province. This study predicted the climate suitability distribution of Ek,and provided reference for the rational planning and establishment of the standardized cultivation base of Ek.
China ; Climate ; Drugs, Chinese Herbal ; Epimedium/chemistry* ; Flavonoids/analysis* ; Geography ; Plants, Medicinal/chemistry* ; Soil/chemistry* ; Temperature