Epidemiology of endogenous uveitis in north-eastern Italy. Analysis of 655 new cases

PURPOSE: To report the results of a retrospective analysis among endogenous uveitis patients in the north-eastern area of Italy. METHODS: The authors reviewed a series of 655 new cases treated between October 1986 and December 1993. The incidence of endogenous uveitis was calculated based on a 100,000 patient population. RESULTS: The average incidence was 11.40/100,000. The majority of patients were between the ages of 20 and 70 years (74.43%). A probable diagnosis was determined in 55.57% of cases; anterior uveitis was diagnosed in 58.01% of cases, posterior uveitis in 26.11%, panuveitis in 12.98%, and intermediate uveitis in 2.9% of cases. The authors observed recurrences in 25.49% of cases. While the first cases are almost equally distributed in the various months, the recurrences seem to be significantly more frequent in the cold (from November to February; mean air temperature <8 degrees) and transitional months (October and from March to May; mean air temperature from 8 degrees C to 18 degrees C) than in the warm months (from June to September; mean air temperature >18 degrees C). Respectively p=0.003 and p=0.029. CONCLUSION: The incidence in this series is lower than in other European and American studies. Despite the high rate of idiopathic cases in this study, the authors support that the presentation of single case experiences may allow improved multi-centric analysis and a greater understanding of the epidemiology of uveitis.     

Tumour necrosis factor-alpha and leukotriene B(4) mediate the neutrophil migration in immune inflammation.

1. We investigated the mediators responsible for neutrophil migration induced by ovalbumin (OVA) in immunized mice and the mechanisms involved in their release. 2. OVA administration promoted dose- and time-dependent neutrophil migration in immunized, but not in non-immunized mice, which was mediated by leukotriene B(4) (LTB(4)) and tumour necrosis factor (TNF)alpha, since it was inhibited by LTB(4) synthesis inhibitor (MK 886) or by LTB(4) receptor antagonist (CP 105,696), by dexamethasone and by antiserum to TNFalpha (82, 85, 63 and 87%, respectively). Confirming TNFalpha involvement, OVA challenge in immunized p55 TNF receptor deficient mice (p55(-/-)) did not promote neutrophil migration (control: 2.90 +/- 0.68; p55(-/-): 0.92+/-0.23 x 10(6) neutrophils cavity(-1)). 3. OVA-stimulated peritoneal cells from immunized mice released a neutrophil chemotactic factor which mimicked, in naive mice, neutrophil migration induced by OVA. 4. Supernatant chemotactic activity is due to TNFalpha and LTB(4), since its release was inhibited by MK 886 (93%) and dexamethasone (90%), and significant amounts of these mediators were detected. 5. TNFalpha and LTB(4) released by OVA challenge seem to act through a sequential mechanism, since MK 886 inhibited (88%) neutrophil migration induced by TNFalpha. Moreover, peritoneal cells stimulated with TNFalpha released LTB(4). 6. CD(4)(+) T cells are responsible for TNFalpha release, because the depletion of this subset prevented the release of TNFalpha (control: 400 +/- 25; immunized: 670 +/- 40; CD(4)(+) depleted: 435 +/- 18 pg ml(-1)). 7. In conclusion, neutrophil migration induced by OVA depends on TNFalpha released by CD(4)(+) cells, which acts through an LTB(4)-dependent mechanism.     

CYP450s体外重组技术及在药物代谢和安全性评价中的应用

药物代谢是在代谢酶催化下完成的 ,它决定着药物的药理学和毒理学特性。根据动物实验来预测人体的药物代谢时 ,代谢酶的种属差异性会使这项研究工作变得非常困难。本文对含有人体代谢酶系的重组技术模型的应用进行了介绍和评价。从而有助于预测新药在人体中的代谢机制     

苯诱导小鼠卵母细胞及1细胞合子雌原核染色体非整倍体的研究

目的：研究苯对卵母细胞和1细胞合子雌原核染色体非整倍体率的影响。方法：成年雌性NIH小鼠,1次灌胃（942、1881和3762mg/kg)与多次吸入（706、1992和4864mg/m^3)染毒,灌胃后雌雄鼠以1：1同笼过夜,收集卵母细胞和1细胞合子作细胞遗传学分析,测定非整倍体率。结果小鼠吸入染毒3个剂量组的每2次减数分裂中期（MⅡ）卵母细胞非整倍体率分别为7．06％、7．50％和9．76％,明显高于对照组（1．30％）,有剂量－效应关系,同时也观察到第1次减数分裂中期（MⅠ）卵母细胞减数分裂停滞,MⅠ卵母细胞频率分别为1．16％、3．61％和5．75％,高于对照组（0．00％）,有剂量－效应关系,在灌胃组仅见剂量组MⅡ卵母细胞非整倍体率增高,1细胞合子雌原核非整倍体率未见效应关系,在灌胃组仅见高剂量组MⅡ卵母细胞非整倍体率增高,1细胞合子雌原核非整倍体率未见增高。结论：吸入或灌胃给小鼠高剂量苯,可诱导MⅡ卵母细胞非整体倍率增高。     

An Investigation into the Surface Deposition of Progesterone on Poly (d,l-) Lactic Acid Microspheres Using Micro-Thermal Analysis

Pharmaceutical Research -     

Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens

Understanding structural requirements for a chemical to exhibit estrogen receptor (ER) binding has been important in various fields. This knowledge has been directly and indirectly applied to design drugs for human estrogen replacement therapy, and to identify estrogenic endocrine disruptors. This paper reports structure-activity relationships (SARs) based on a total of 230 chemicals, including both natural and xenoestrogens. Activities were generated using a validated ER competitive binding assay, which covers a 10(6)-fold range. This study is focused on identification of structural commonalities among diverse ER ligands. It provides an overall picture of how xenoestrogens structurally resemble endogenous 17beta-estradiol (E(2)) and the synthetic estrogen diethylstilbestrol (DES). On the basis of SAR analysis, five distinguishing criteria were found to be essential for xenoestrogen activity, using E(2) as a template: (1) H-bonding ability of the phenolic ring mimicking the 3-OH, (2) H-bond donor mimicking the17beta-OH and O-O distance between 3- and 17beta-OH, (3) precise steric hydrophobic centers mimicking steric 7alpha- and 11beta-substituents, (4) hydrophobicity, and (5) a ring structure. The 3-position H-bonding ability of phenols is a significant requirement for ER binding. This contributes as both a H-bond donor and acceptor, although predominantly as a donor. However, the 17beta-OH contributes as a H-bond donor only. The precise space (the size and orientation) of steric hydrophobic bulk groups is as important as a 17beta-OH. Where a direct comparison can be made, strong estrogens tend to be more hydrophobic. A rigid ring structure favors ER binding. The knowledge derived from this study is rationalized into a set of hierarchical rules that will be useful in guidance for identification of potential estrogens.     

Host pathogenesis in urinary tract infections

Urinary tract infections (UTIs) are the result of an interaction between bacterial virulence and host defense factors that compete to invade or protect the host, respectively. Research over the past 30 years has demonstrated that vaginal colonization with uropathogens precedes most UTIs. Receptivity of the vaginal mucosa for uropathogens is an essential initial step in vaginal mucosa colonization. When vaginal and buccal epithelial cells were collected from patients susceptible to reinfection and compared with such cells obtained from controls resistant to UTIs, the strains that caused cystitis adhered much more avidly to the epithelial cells from susceptible women. These genotypic traits for epithelial cell receptivity may be a major susceptibility factor in UTIs. The presence or absence of blood group determinants on the surface of uroepithelial cells may influence an individual's susceptibility to UTIs. The protective effect in women with the secretor phenotype may be due to fucosylated structures at the cell surface which decrease the availability of putative receptors for Escherichia coli. Susceptibility among women who do not secrete blood group antigens may be due to specific E. coli-binding glycolipids that are absent in women who secrete blood group antigens. Recent studies have shown that the vaginal fluid, which forms an interface between uropathogens and epithelial cells, also influences vaginal colonizations.