Discovery of novel non-peptide CCR1 receptor antagonists

Ligands for the CCR1 receptor (MIP-1alpha and RANTES) have been implicated in a number of chronic inflammatory diseases, most notably multiple sclerosis and rheumatoid arthritis. Because these ligands share a common receptor, CCR1, we sought to discover antagonists for this receptor as an approach to treating these disorders. A novel series of 4-hydroxypiperidines has been discovered by high throughput screening (HTS) which potently inhibits the binding of MIP-1alpha and RANTES to the recombinant human CCR1 chemokine receptor. The structure-activity relationships of various segments of this template are described as the initial HTS lead 1 was optimized synthetically to the highly potent receptor antagonist 6s. This compound has been shown to have at least 200-fold selectivity for inhibition of CCR1 over other human 7-TM receptors, including other chemokine receptors. In addition, data obtained from in vitro functional assays demonstrate the functional antagonism of compound 6s and structurally related analogues against the CCR1 receptor in a concentration dependent manner. The discovery and optimization of potent and selective CCR1 receptor antagonists represented by compound 6s potentially represent a novel approach to the treatment of chronic inflammatory diseases.     

Alterations of striatal monoamine metabolites in young rats following pre- and postnatal lead exposure

Dam rats were given lead (0, 0.58, 1.76, and 5.27 mmol/l) containing water ad lib from day 16 of gestation to weaning of the offspring on day 21 postpartum. The pups continued drinking the same lead containing water until the postnatal day 30. At the 30th day postpartum, the pups in each lead treated group were divided into four groups. The first group contains six male pups (PN30M). The second, third, and fourth groups contain six female pups (PN30F, PN60a, PN60b), respectively. The six female pups from control group formed the fifth group (PN60c). PN60a continued drinking the same lead-containing water until the postnatal day 60. PN60b were dosed with distilled water instead of lead-containing water from the 30th day to the 60th day postpartum. PN60c began to expose to 5.27 mmol Pb/l from the 30th day to the 60th day postpartum. The rats in PN30M and PN30F were decapitated on the 30th day postartum, whereas PN60a, PN60b, and PN60c were decapitated on the 60th day postpartum. The contents of metabolites of monoamine neurotransmitters: homovanillic acid (HVA), dihydroxyphenylacetic acid (DOPAC), 3-methoxy-4-hydroxyphenylglycol (MHPG), and 5-hydroxyin-doleacetic acid (5-HIAA) in striatum were determined using high performance liquid chromatography with electrochemical detection (HPLC-ECD). There were significant increases in the concentrations of HVA (1.58 ± 0.30 vs. 1.17 ± 0.12 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.01; and 1.44 ± 0.08 vs. 1.17 ± 0.10 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) and DOPAC (2.39 ± 0.25, 2.47 ± 0.28, 2.39 ± 0.44 vs. 1.82 ± 0.24 ng/mg wet tissue in three lead treated groups of PN60a, p < 0.05). The significant decreases in the concentration of MHPG (37.33 ± 5.53, 32.02 ± 6.87, 33.31 ± 2.41 vs. 43.85 ± 4.93 ng/mg wet tissue in the 0.58 mmol Pb/l group of PN60a, p < 0.05; in the 1.76 and the 5.27 mmol Pb/l group of PN60a, p < 0.01) and 5-HIAA (0.23 ± 0.04 vs. 0.38 ± 0.05 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30M, p < 0.05; 0.26 ± 0.09 vs. 0.45 ± 0.09 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN30F, p < 0.05; 0.31 ± 0.08 vs. 0.44 ± 0.08 ng/mg wet tissue in the 5.27 mmol Pb/l group of PN60a, p < 0.05) were observed. No significant changes in the concentration of monoamine metabolites were observed either in rats of PN60b or PN60c. The results demonstrated the disturbances of monoamine metabolism in the striatum of developmental lead exposed rats.     

Another CT sign of sinonasal polyposis: truncation of the bony middle turbinate

In order to study the features of sinonasal polyposis (SNP) on CT, 100 consecutive coronasal sinus CT examinations done for chronic inflamamtory sinonasal disease were reviewed. The CT findings of the 27 fully documented SNPs were analyzed. All our SNPs were bilateral. There was a strong tendency for extensive involvement. Nasal polyps were seen in 22 of 27 (81%); bony trabecular deossification in 23 of 27 (85%); widening of infundibulum in 26 of 27(96%). We discovered a new sign truncation of the bony middle turbinate, where the bulbous part of bony middle turbinate was missing, in 51 of 26 (58 %) of SNP patients without a previous history of middle turbinectomy, 12 of 15(80%) were bilateral. The one SNP patient (1 of 27) with previous middle turbinectomy was not regarded to be real truncation. Truncation of the bony middle turbinate is a characteristic and easily recognizable ancillary sign, and is not seen in other patterns of sinusitis. Together with other features on coronal sinus CT, this adds diagnostic confidence in diagnosing sinonasal polyposis. Correspondence to: E. Y. Liang     

A discussion of jaws relation in complete denture restoration]

We studied jaws relation of 8 edentulous patients after complete denture restoration by using Digital Sirognathograph (D-SGG).The results indicated that the maximum intercuspation occlusion (i.e.CO or MCP) is not commonly coincident with the CRO,and the discrepancy is statistically significant.The CO is anterior to the CRO by 0.72+/-0.39mm,and it may vary significantly in different closures of the same patient. This implies that the termination of the occlusion with neuromusculature is not strictly precise and constant,but alters in a corresponding range.So,it seems reasonable to develop a "freedom of centric" in the range of 0.72+/-0.39mm anterior to the CRO.The physiological functional occlusion,therefore,is restricted to neither of the CO nor the CRO, but is guided between the two.     

Evaluation of facial fat distribution using magnetic resonance imaging

Magnetic resonance imaging (MRI) provides noninvasive images of facial and neck fat for a variety of conditions. It accurately maps the soft tissues pre- and postoperatively, enabling surgeons to precisely and objectively assess results of soft tissue facial contouring and fat transplantation. The risks of MRI are few. It has the potential to provide aesthetic surgeons with a more scientific means of comparing various techniques of fat contouring.     

The measurement of visual refraction of pupils]

The ocular refraction was measured by applying 1% atropine eye-drops for 3 days in 5,458 eyes (male 2,944, female 2,514) of the pupils aged 7-17 in rural areas. The results were as follows: the majority of the pupils had hyperopia (male 84.71%, female 80.55%); the frequency of the measurements was not in normal distribution; the degree of far-sight began to recede and gradually become converted to myopias with advancing age but varying greatly between age-groups. The myopias began to appear at the age of 9 and increased rapidly at the age of 14 for girls and 15 for boys. From then on the rate of conversion continued to increase with schoolgirls more than schoolboys and, as a result, formed "the dangerous stage of myopia", the values of physiological visual refraction were shown as follows: pupils aged 7-9 + 2.00 D- + 2.50 D, aged 10-13 + 1.50 D- + 1.75 D, aged 14-17 + 1.00 D- + 1.25 D. The possibility of pathological hyperopia was greater if the pupils aged 7-9 and the value of visual refraction over +3.75 D, aged 10-13 had the value over +3.00 D and aged 14-17 had the value +2.50 D. The possibility of developing myopia was great in those pupils aged 7-9 whose value was under +1.00 D and in those aged 10-17 whose value was under +0.50 D. The deprived vision of the pupils should be routinely corrected by skiascopy.     

罗通定中降解物巴马汀限量检测方法

目的：研究解决罗通定及硫酸罗通定注射液中降解物巴马汀的检测方法。方法：用薄层色谱法和紫外分光光度法限量检查样品中的巴马汀。结果：与对照品斑点大小、荧光强度比较和用吸收度限值控制均可对样品中的巴马汀进行限量检查，结果与原标准一致。结论：两方法均灵敏，专属，简便，快速。     

小儿肺炎电超导治疗的研究

目的 评价电超导辅助治疗小儿肺炎的临床疗效。方法 所有144例，治疗组84例，对照组64例，对照组应用抗生素，同时止咳，化痰，平喘对症处理，治疗组在以照组的基础上超导辅助治疗，疗程一周。结果 治疗组总有效率100％，总痊愈率92．86％。而对照组总有效率仅为71．67％。结论 在原有治疗基础上加用电超导，可明显提高治愈率及总有效率。     

药敏纸片的质量控制研究

目的：探讨和研究药敏纸片质量控制的方法。方法：以克拉霉素药敏纸片为例，参照美国临床实验室标准化委员会(NCCLS)和联邦法规全书(CFR)的方法，建立一套药敏纸片质量控制的指标，包括鉴别、检查及含量测定。结果：采用专属性较强、灵敏度较高的TLC法进行鉴别，最低检出量为50μg；制订纸片的的直径、重量差异、含量均匀性及干燥失重作为检查项，采用短小芽孢杆菌(Bacillus pumilus)[CMCC(B)63202]作为检定菌，进行含量测定。结论：建立的克拉霉素药敏纸片质量标准能够控制其质量，可作为其他抗生素药敏纸片建立质量标准的参考。