The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The harmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability was compared using the pharmacokinetic parameters, peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC0-t). AUC0-t was significantly higher in formulation F2 group (5.201±0.511) ng·mL-1·h and formulation F3 group (5.174±0.498) ng·mL-1·h than that in formulation F4 group (3.013±0.623) ng·mL-1·h. Also, Cmax was significantly higher in formulation F2 group (1.524±0.125) ng·mL-1 and formulation F3 group (1.513±0.157) ng·mL-1 than that in formulation F4 group (0.939±0.089) ng·mL-1. Further analysis of the data showed a statistically significant difference between F2 and F4 (P<0.01) as well as F3 and F4 (P<0.01) with regard to the values of AUC0-∞ and Cmax for three SEDDS formulations, but not between those of F2 and F3 (P>0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.

Pneumococcal meningitis is one of the most common infectious diseases of the central nervous system in pediatric period which is characterized by acute fever,unconvulsions,consciousness,in-creased intracranial pressure and meningeal irritation and cerebrospinal fluid pus changes in clinic. With the advent of antibiotics and pneumococcal vaccination,the morbidity and mortality of the disease decline signifi-cantly. But due to the appearance of drug-resistant bacteria and the relative lag of research and development speed of clinical new antibacterial drugs,it still has high mortality and morbidity which are promoting resear-ches of pathogenesis and adjuvant therapy. In this paper,researches of pathogenesis and adjuvant therapy for preumococcal meningitis were reviewed in recent years.

Objective To investigate the protective effects of midazolam on noise-induced hearing loss in guinea pigs by testing reactive oxygen species (ROS) level in the cochlea and plasma SOD and MDA. Methods Totally forty male pigmented guinea pigs were randomly divided into four groups: control (C) , midazolam (M), normal saline (S) and noise-induced deafened (D) groups, with ten guinea pigs in each. Groups M, S and D were exposed to a continuous noise (4kHz , octave band, 100dB SPL) 3h every day for 3 consecutive days. Group M was treated with midazolam, which was administered intramuscularly (0.1mg/kg) 24h before noise exposure, and immediately upon and during noise exposure. Group S was exposed to noise and treated with the same volume of normal saline intramuscularly, the time of injection was the same as that of Group M. Group C was not exposed to noise, but was treated with midazolam intramuscularly, the time of injection and the dosage were the same as those of Group M. Group S was exposed to noise and treated with normal saline intramuscularly ,the time of injection was same with that of Group M.Group D was exposed to noise only. All animals received auditory brainstem response (ABR) threshold recording before and immediately after noise exposure. Blood was collected when the guinea pigs were killed after the last ABR threshold recording, and serum SOD activity and MDA content were detected. Both the cochleae were removed and prepared for ROS assay. Results After noise exposure, ABR threshold shift (1.6±1.5) and ROS content [(291.10±2.30)u/mL] in Group M were significantly lower than those in Groups S and D [41.7±3.3, 44.3±3.9; (348.52±3.60)u/mL, (315.56±6.70)u/mL, P<0.05]. Serum SOD activity and MDA content were significantly increased in Group M, but the amplitude was less than that in Groups S and D.Conclusion Midazolam can prevent noise-induced hearing loss by reducing the increased ROS level in the cochlea after noise exposure.

Objective To evaluate the effect of dexmedetomidine on noise-induced hearing loss in guinea pigs.Methods Twenty-four adult male guinea pigs,aged 3 months,weighing 400-500 g,were randomly divided into 3 groups (n =8 each) using a random number table:dexmedetomdine group (group D),noise-induced hearing loss group (group N) and dexmedetomidine + noise-induced hearing loss group (group DN).A loading dose of dexmedetomidine 5 μg/kg was infused over 5 min,followed by 135 min of infusion at a rate of 10 μg· kg-1 · h-1.The equal volume of normal saline was infused in group N.Groups N and DN were exposed to noise of 4 kHz center frequency and 118-122 dB SPL for 120 min starting from 20 min of administration.Mean arterial pressure (MAP) and cochlear blood flow (COBF) were recorded before administration and every 5 min during drug administration.The changing rate of COBF was calculated.Arterial blood samples were collected for determination of plasma concentration of noradrenaline (NE) by high performance liquid chromatography at 20 and 140 min of administration.Auditory brainstem response (ABR) threshold was recorded before administration and at 1 and 72 h and 10 days after the end of administration.Results Compared with group N,MAP was significantly decreased,the changing rate of COBF was increased at 5-10 min and 30-140 min of administration,ABR threshold was decreased at 1 and 72 h and 10 days after the end of administration,and the plasma concentration of NE was decreased at 140 min of administration in D + N group (P ＜ 0.05).Conclusion Dexmedetomidine can attenuate noise-induced hearing loss in guinea pigs possibly through inhibiting activation of sympathetic nerves and increasing COBF.

Objective To detect the change of brain activity under different depth of anesthesia (DOA)noninvasively. Methods The Lempel-Ziv complexity C(n) was used to analyze EEG and its four components (delta,theta, alpha, beta), which was recorded from SD rats under different DOA. The relationship between C(n) and DOA was studied. Results The C(n) of EEG will decrease while the depth of anesthesia increasing and vice versa. It can be used to detect the change of DOA sensitively. Compared with power spectrum, the change of C(n) is opposite to that of power spectru,. Only the C(n) of delta rhythm has obvious variations induced by the change of DOA, and the variations of delta is as similar as the EEG's. Conclusion The study shows that the desynchronized EEG is replaced by the synchronized EEG when rat goes into anesthesia state from awake, that is just the reason why complexity and power spectrum appear corresponding changes under different DOA. C(n) of delta rhythm dynamic change leads to the change of EEG, and the delta rhythm is the dominant rhythm during anesthesia for rats.

Objective To investigate the distribution and drug resistance of bacteria in 1 -6 months infants with lower respiratory infection(LRI).Methods Induced sputum was extracted from 326 infants with LRI who were 1 -6 months.Antibiotic susceptibility tests were performed after bacteria had been identified.Results 61 cases were detected pathogenic bacteria and the detection rate of bacteria was 18.71%.5 cases were detected two kinds of bacte-ria.66 bacterial strains were isolated among which gram -positive bacteria(33 strains)accounted for 50.00% and gram -negative bacteria(33 strains)accounted for 50.00%.Staphylococcus aureus was the most common gram -pos-itive bacteria and Streptococcus pneumoniae was the second.13 strains were methicillin -resistant Staphylococcus au-reus(MRSA).Hemophilus influenzae was the most common gram -negative bacteria,followed by Klebsiella pneumo-nia and Escherichia coli among which ESBL positive Klebsiella pneumonia were 5 cases and ESBL positive Escherich-ia coli were 4 cases.The common gram -positive bacteria had higher rate of penicillin resistance.MRSA had higher rate of penicillin,oxacillin,erythomycin and clindamycin resistance.Resistant strains to vancomycin and rina thiazole amine were not found.The common gram -negative bacteria had higher rate of ampicillin,ampicillin/shu tan,cefazo-lin and ceftriaxone resistance and had lower rate of cefepime,ceftazidime,piperacillin/he azole temple and imipenem resistance.Conclusion The common pathogenic bacteria in 1 -6 months infants with lower respiratory infection were Staphylococcus aureus,Hemophilus influenzae,Streptococcus pneumoniae,Klebsiella pneumonia and Escherichia coli. We should pay attention to the common antibiotic resistance.MRSA and ESBL positive bacteria were the common mul-tiple drug resistant bacterias.Reasonable selection of antibiotics should be based on susceptibility results earlier.

Objective To explore the relationship between urinary activin A and neonatal hypoxic-ischemic encephalopathy(HIE).Methods 50 full-term neonatal with HIE were selected as the observation group,48 normal full-term neonatal in the same period were selected as the normal control group randomly.Within 7 days after birth,the observation group was divided into the group of 30 patients with mild HIE and the group of 20 patients with moderate and severe HIE,according to diagnostic criteria and clinical grading of neonatal HIE.The levels of urinary activin A in two groups after birth at different time(2,12,24,48,72h)was determined by using ELISA method.Results The levels of urinary activin A in moderate and severe HIE group was significantly higher than than in the normal control group(P＜0.01)and mild HIE group(P＜0.01);The levels of urinary activin A in the normal control group and mild HIE group showed no significant differences(P＞0.05).Urinary activin A level＞70 ng/L for the critical value to determine the occurrence of moderate and severe HIE,the sensitivity and specificity of 2 h urinary activin A levels were separately 86％ and 99％;The sensitivity and specificity of 12～72 h urinary activin A levels were separately 100％ and 98％.Conclusion The correlation between the level of urinary activin A and the severity of HIE was positive,the level of urinary activin A had a high degree of sensitivity and specificity for determine the incidence of moderate and severe HIE,it provided an important basis for diagnosis of moderate and severe HIE.

Objective To compare broth microdilution and agar dilution methods for in vitro testing of activities of fluconazole,ketoconazole and itraconazole against clinical Malassezia isolates.Methods Broth microdilution and agar dilution methods were used to determine the minimal inhibitory concentration(MIC)of fluconazole,ketoconazole and itraconazole for 27 clinical strains(5 species)of Malassezia.Results The minimal inhibitory concentration(MIC)ranges of fluconazole,ketoconazole and itraconazole were 0.25-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.125 mg/L respectively as shown by broth microdilution method,2-≥64 mg/L,≤0.03-0.5 mg/L and ≤0.03-0.25 mg/L respectively as revealed by agar dilution method.Both methods demonstrated that itraconazole possessed the strongest activity against Malassezia species,followed by ketoconazole and fluconazole.The agreement rate in MICs between the two methods was 78.8％,85.2％ and 88.9％,respectively for fluconazole,ketoconazole and itraconazole,with the intraclass correlation coefficients (ICCs)being 0.88,0.80 and 0.76 respectively.Conclusions Fluconazole,ketoconazole and itraconazole are highly active against Malassezia species in vitro,and itraconazole is the most active.Broth microdilution and agar dilution method coincide well in,and are applicable for,the antifungal susceptibility testing of Malassezia species in vitro.

Objective To study dosimetric characteristics of helical tomotherapy (HT) by comparing its treatment plans with linear accelerator-based step-and-shoot intensity modulated radiation therapy (IMRT) for nasopharyngeal carcinoma(NPC). Methods Targets on CT images of 10 NPC patients were delineated and transferred to HT and IMRT treatment plan systems. The prescription dose was 70 Gy/33 f for pGTV and GTVnd,60 Gy/33 f for FTV1 ,and 54 Gy/33 f for PTV2. The limit dose of organ at risk was parotid V35 ＜50% ,brain-stem＜54 Gy,spinal cord ＜45 Gy and lens ＜9 Gy. Data of the two groups were compared by paired t-test. Results The dose distribution, conformality and homogeneity were good in both groups.But the homogeneity index(HI) and Dmean of PTV1 in HT group were better than IMRT group( P ＜ 0.01 ).The Dmean of PTV1 in HT group(63.84 Gy)was lower than IMRT group(70.30 Gy). The Dmean, V35 and V30 of parotids,and the Dmax of larynx-esophagus were lower in HT group than IMRT group. Conclusions Helical tomotherapy treatment plan has a better homogeneity, steeper dose gradient, and a better protection for organs at risk.

Objective To investigate the risk factors of cerebral palsy in newborns with periventricular leukomalacia(PVL).Methods Sixty-one infants with sequela of cerebral palsy among 806 neonates born at the Second People'S Hospital of Liaocheng,Shandong,China,during December 2000 to November 2005 were studied for its etiology.Diagnosis of cerebral palsy in 26 of the 61 infants was established by type B ultrasonic scanning or magnetic resonance imaging(MRI)for the head at least twice and excluded of other diseases.Thirty-five infants without PVL hospitalized at the same hospital were enrolled as control group during the same period.Logistic regression analysis was performed for the risk factors of PVL. Results Twenty-six infants were diagnosed as PVL.accounting for 42.6％of those with cerebral palsy.Main high-risk factors of PVL included severe asphyxia(x3),low gestational age(x1),intraventricular hemorrhage(x14)and low blood pressure(x8),with odds ratios of 2.843,3.575,3.268 and 1.947,respectively,and a fitted regression model as logistic(P)=β0+0.7952 x3-1.428x1-1.328 x14+0.8256x8.Pregnant hypertension,neonate respiratory distress syndrome(NRDS),and intrauterine infection could also affect occurrence of PVL,all with statistical significance(P＜0.05).Conclusion PVL is one of main causes of cerebral palsy,with severe asphyxia,low gestational age,intraventricular hemorrhage and low blood pressure as main high-risk factors.