褶合光谱-PLS法同时测定安痛定注射液3组分含量

通过褶合变换获得褶合光谱,以此为基础,结合应用偏最小二乘(PLS)法,同时测定安痛定注射液中氨基比林、安替比林及巴比妥的含量,方法简便,结果满意。平均回收率和RSD依次分别为:99.84%,0.15%;99.87%,0.21%及100.27%,0.39%。     

An animal model for Norrie disease (ND): gene targeting of the mouse ND gene

In order to elucidate the cellular and molecular processes which are involved in Norrie disease (ND), we have used gene targeting technology to generate ND mutant mice. The murine homologue of the ND gene was cloned and shown to encode a polypeptide that shares 94% of the amino acid sequence with its human counterpart. RNA in situ hybridization revealed expression in retina, brain and the olfactory bulb and epithelium of 2 week old mice. Hemizygous mice carrying a replacement mutation in exon 2 of the ND gene developed retrolental structures in the vitreous body and showed an overall disorganization of the retinal ganglion cell layer. The outer plexiform layer disappears occasionally, resulting in a juxtaposed inner and outer nuclear layer. At the same regions, the outer segments of the photoreceptor cell layer are no longer present. These ocular findings are consistent with observations in ND patients and the generated mouse line provides a faithful model for study of early pathogenic events in this severe X-linked recessive neurological disorder.      

Reduced collagen VI causes Bethlem myopathy: a heterozygous COL6A1 nonsense mutation results in mRNA decay and functional haploinsufficiency

We have identified a new pathogenic mechanism for an inherited muscular dystrophy in which functional haploinsufficiency of the extracellular matrix protein collagen VI causes Bethlem myopathy. The heterozygous COL6A1 mutation results in a single base deletion from the mRNA and a premature stop codon. The mutant mRNA is unstable, subject to nonsense- mediated mRNA decay, and is almost completely absent both from patient fibroblasts and skeletal muscle, resulting in haploinsufficiency of the alpha1(VI) subunit and reduced production of structurally normal collagen VI. This is the first example of a muscular dystrophy caused by haploinsufficiency of a structural protein or member of the dystrophin-glycoprotein complex, and identifies collagen VI as a critical contributor to cell-matrix adhesion in skeletal muscle.      

An abnormal digastric muscle with three bellies

Summary During the gross anatomy dissection of the submental region, an anatomical variation of the right digastric muscle was found. This muscle had three bellies. Whereas the anterior and posterior bellies had their normal origin and course and were joined by an intermediate tendon, the accessory anterior belly originated from the digastric fossa and a thin tendon together with the anterior belly was inserted onto the hyoid bone. This kind of variation can easily be confused with pathological conditions. For this reason, knowledge of the muscular anatomy and variations of the floor of the mouth is helpful when evaluating the base of the skull with CT and MR imaging.

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Un muscle digastrique anormal à trois ventres

Résumé Au cours de la dissection macroscopique de la région submentale, une variation anatomique touchant le m. digastrique droit a été trouvée. Ce muscle avait trois ventres. Alors que les ventres antérieur et postérieur avaient une origine et un trajet normaux et étaient reliés par un tendon intermédiaire, le ventre antérieur accessoire naissait de la fosse digastrique par un fin tendon, commun au ventre antérieur, et se terminait sur l'os hyoïde. Ce type de variation peut aisément être confondu avec des situations pathologiques. Pour cette raison, la connaissance de l'anatomie musculaire et des variations du plancher oral est utile dans l'exploration du crâne en tomodensitométrie et en IRM.

     

An open-label study of repeated use of diazepam rectal gel (Diastat) for episodes of acute breakthrough seizures and clusters: safety, efficacy, and tolerance. North American Diastat Group

PURPOSE: To assess safety of diazepam rectal gel (DZPRG) for control of acute seizures in epilepsy patients and to evaluate tolerance with repeated use of DZPRG at intervals of > or =5 days. METHODS: Subjects were persons with epilepsy, age 2 years or older, with seizure clusters or prolonged seizures. Onset of a treatable episode was defined; caregivers were trained to administer DZPRG and to monitor respiration, seizures, and adverse effects (AEs). DZPRG was dispensed in a single-use, prefilled syringe; dosage was determined by age and weight. Maximal use was > or =5-day intervals, < or =5 times/month. After use, caregivers returned data booklets and syringe. Caregivers and physicians completed global ratings yearly. RESULTS: In 149 subjects treated, 77% of 1,578 administrations resulted in seizure freedom for the next 12 h. One hundred twenty-five received two or more treatments (two to 78; median, 8), 0.03-4.3/month (median, 0.4). To evaluate tolerance, subjects with two or more episodes were divided into low (two to seven episodes) and high use (eight to 78 episodes treated). There was no difference in proportion seizure free 12 h after the first administration versus last administration, for either infrequent or frequent administration. Sedation occurred in 17%, attributed to DZPRG in 9%. No respiratory depression was attributable to DZPRG. Three subjects withdrew because of AEs attributable to (agitation) or possibly attributable to DZPRG (chest pain, rash). Five subjects withdrew because of AEs unrelated to DZPRG. Caregiver and physician global ratings were highly positive at both 12 and 24 months. CONCLUSIONS: DZPRG is safe and effective in children and adults with epilepsy with breakthrough seizures. Neither tolerance nor significant medication-related AEs were seen with repeated DZPRG administration at intervals > or =5 days.     

Diabetes-specific genetic effects on obesity traits in American Indian populations: the Strong Heart Family Study

Background

The prevalence of genotypes of the 677C>T polymorphism for the MTHFR gene varies among humans. In previous studies, we found changes in the genotypic frequencies of this polymorphism in populations of different ages, suggesting that this could be caused by an increase in the intake of folate and multivitamins by women during the periconceptional period. The aim was to analyze changes in the allelic frequencies of this polymorphism in a Spanish population, including samples from spontaneous abortions (SA).

Methods

A total of 1305 subjects born in the 20th century were genotyped for the 677C>T polymorphism using allele specific real-time PCR with Taqman^® probes. A section of our population (n = 276) born in 1980–1989 was compared with fetal samples (n = 344) from SA of unknown etiology from the same period.

Results

An increase in the frequency of the T allele (0.38 vs 0.47; p < 0.001) and of the TT genotype (0.14 vs 0.24; p < 0.001) in subjects born in the last quarter of the century was observed. In the 1980–1989 period, the results show that the frequency of the wild type genotype (CC) is about tenfold lower in the SA samples than in the controls (0.03 vs 0.33; p < 0.001) and that the frequency of the TT genotype increases in the controls (0.19 to 0.27) and in the SA samples (0.20 to 0.33 (p < 0.01)); r = 0.98.

Conclusion

Selection in favor of the T allele has been detected. This selection could be due to the increased fetal viability in early stages of embryonic development, as is deduced by the increase of mutants in both living and SA populations.     

Smad2 and Smad6 as predictors of overall survival in oral squamous cell carcinoma patients

Background  

To test if the expression of Smad1-8 mRNAs were predictive of survival in patients with oral squamous cell carcinoma (SCC).     

应用血管脱细胞方法构建人股动脉同种异体移植材料

目的:运用自行建立的血管脱细胞方法,制备人股动脉同种异体血管移植材料。方法:实验于2004-09/2005-09在空军总医院临床实验中心完成。①取材:股动脉供者为急性外伤后右下肢截肢患者,男,26岁,患者及家属同意捐献截除的右下肢,并经过医院伦理道德委员会许可。右下肢离体至取材时间为6h,取材在无菌条件下进行。②人股动脉血管脱细胞化学萃取:①无离子水(低渗)12h→②10g/LTriton24h→③磷酸盐缓冲液洗涤3次后,无离子水4h→④10g/LSDS24h→⑤用磷酸盐缓冲液洗涤3次后,无离子水4h,用含抗生素的Hanks溶液漂洗2次,4h/次。上述各步中均加入蛋白酶抑制剂苯甲基磺酰氟5μmol/L。③力学特性测量及组织学观察:选择其中两根脱细胞血管测量二维爆破压。并通过苏木精-伊红、V-W等染色方法观测细胞脱出情况和脱细胞后胶原和弹性纤维情况,并通过扫描电镜观察脱细胞股动脉的内膜超微结构。结果:①经去垢剂10g/LTritonX-100,10g/LSDS等多步骤脱细胞方法处理后,人股动脉血管的细胞基本脱除,剩余成分主要为维持血管张力的胶原蛋白和弹性蛋白,细胞外基质和血管的弹性、韧性保持完好,可在正常张力下行常规的血管缝线吻合。②两根脱细胞血管的二维爆破压分别为950mmHg(1mmHg=0.133kPa)和>1000mmHg;远高于人体血压,可以满足移植的需要。③脱细胞血管的内膜表面内皮细胞已不复存在,断面上可见纤维组织排列疏松不够整齐,组织之间可见细小间隙。结论:经去垢剂TritonX-100,SDS加低渗溶液和蛋白酶抑制剂处理的多步脱细胞法可以脱除人股动脉血管的细胞成分,细胞外基质和血管的弹性、韧性保持完好,制备出的人脱细胞股动脉可以作为同种异体血管移植材料。     

An evaluation of the safety and immunogenicity of a five-component acellular pertussis, diphtheria, and tetanus toxoid vaccine (DTaP) when combined with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine (PRP-T) in Taiwanese infants

OBJECTIVE: Immunologic interference particular to the Haemophilus influenzae type b (Hib) response has been observed with previous acellular pertussis-Hib combination vaccines. To test this hypothesis a clinical trial to assess the safety and immunogenicity of a five-component (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], and fimbriae 2 and 3 [FIM]), pertussis vaccine combined with diphtheria and tetanus toxoids (DTaP) when given simultaneously with a lyophilized Hib-tetanus toxoid conjugate vaccine (PRP-T) in infants at 2, 4, 6, and 18 months of age was conducted. The study compared two methods of administration: both vaccines combined in a single syringe and administered as a single injection, or both vaccines administered concurrently but at separate sites of injection. METHODS: Healthy 2-month-old infants were enrolled at the National Taiwan University Hospital. DTaP, PRP-T, and oral poliomyelitis vaccine (OPV) were given at 2, 4, 6, and 18 months. Reaction information was collected by telephone 2 days after each vaccination. Serum was collected at 2, 6, 7, 18, and 19 months of age. RESULTS: One hundred thirty-five healthy infants were enrolled in Taiwan, of which 127 (94%) completed the 18-month booster: 68 received the combined vaccine and 67 the separate vaccines. All vaccines were well tolerated. No differences in rates of local and systemic reactions were seen between the two methods of administration. No serious adverse events were reported. Serologic responses were comparable between the groups. Pertussis responses (enzyme-liked immunoabsorbant assay units [EU]/mL) at 7 months were, for combined versus separate, PT (131 vs 105), FHA (116 vs 116), PRN (100 vs 77), and FIM (922 vs 702). At 19 months, pertussis results were, for combined versus separate, PT (216 vs 182), FHA (203 vs 200), PRN (263 vs 197), and FIM (892 vs 732). Only the 7-month PT response in the combined group was significantly higher (combined 131 EU/mL vs separate 105 EU/mL). After the third dose (age 6 months), all subjects achieved serologic serum antibody levels indicative of protection against Hib, diphtheria, tetanus, and poliovirus types 1, 2, and 3. In fact, 96% of children had anti-PRP levels indicative of protection (>/=0.15 microgram/mL) against Hib after only two doses. At 7 months, anti-PRP geometric mean titer values were 11.8 micrograms/mL in the combined group compared with 13.0 micrograms/mL in the separate group. The anti-PRP geometric mean titers after the 18-month booster were 58.5 micrograms/mL in the combined group versus 55.3 micrograms/mL in the separate group. CONCLUSION: The five-component DTaP vaccine may be combined with PRP-T vaccine without clinically significant immunologic interaction when given in a 2-, 4-, 6-, and 18-month schedule.     

雷公藤红素对IL—1和IL—2活性及PGE2释放的抑制作用

雷公藤红素0.1～1.0μg/ml在试管内能降低LPS诱导的小鼠腹腔巨噬细胞外和细胞内白细胞介素-1(IL-1)的活性,也能抑制ConA诱导的小鼠脾细胞产生白细胞介素-2(IL-2).动态观察表明,雷公藤红素经预处理8h和3h后已能分别抑制IL-1和IL-2的产生。此外,雷公藤红素能降低A23187刺激家兔滑膜细胞释放前列腺素E_2(PGE_2)。