Epidemiological aspects of prenatal exposure to high doses of vitamin a in Spain

Reports of the human teratogenicity of retinoids have raised concern about the potential human teratogenicity of high doses of vitamin A. Nevertheless, there are few human case reports of excess intake of vitamin A during pregnancy and defective outcomes. No epidemiological studies have been carried out on this subject. Here we present the results of an epidemiological study of prenatal exposure to high doses of vitamin A in Spain, using data from the Spanish hospital-based, case-control registry. Although it is difficult to reach conclusions with such a very low exposure level (1.3 per 1,000 livebirths), our results suggest that a teratogenic effect might exist for exposures to high doses of vitamin A (OR = 0.5, p = 0.15 for less than 40,000 FU and OR = 2.7, p = 0.06 for 40,000 1U or more). As we might expect, this effect also seems to be related to the organogenetic status (OR = 5.4, p = 0.1 for 1^st –2^nd month, OR = 1.8, p = 0.4 for 3^rd onwards) at the time of exposure.     

The management of Darier's disease

Darier's disease (keratosis follicularis) is a rare, dominantly inherited condition which is characterised by the presence of warty papules and plaques on the trunk, scalp and flexures. Diagnostic nail changes are present in most patients. Suprabasal clefting, acantholysis and dyskeratosis are present in involved skin and the diagnosis may be confirmed by a skin biopsy. The disease never remits. Exacerbating factors such as heat, sweating and ultraviolet light should be avoided. Topical therapy with emollients, moderately potent corticosteroids and antimicrobials may provide some symptomatic relief, but have no effect on the progress of the disease. Oral retinoids are effective in most patients. Complications such as cutaneous infections, blistering and salivary gland obstruction may occur in some patients.     

I269S Mutation in horse liver alcohol dehydrogenase S isoenzyme and its reactivity for steroids and retinoids

Ile-269 in horse liver alcohol dehydrogenase isoenzyme S(HLADH-S) was mutated to serine by phosphorothioate-based site-directed mutagenesis in order to study the role of the residue in coenzyme binding. The specific activity of the mutant(I269S) enzyme to ethanol was increased 49-fold. All turnover numbers of I269S enzyme toward 9 primary alcohols were increased. The mutant enzyme showed 3.6, 4.6, 11.6-fold higher catalytic efficiency for 5β-androstane-3,17-dione, 5β-cholanic acid-3-one and retinal than wild-type, respectively. The reaction mechanism of I269S enzyme was ordered bi bi as wild-type's. These results indicate that the hydrophobic interaction of Ile-269 residue with coenzyme plays an important role in dissociation of coenzyme from enzyme-coenzyme complex, which has been known as the rate limiting step of ADH reaction.     

In Vitro Effects of Retinoids on the Proliferation and Differentiation Features of Epstein-Barr Virus-Immortalized B Lymphocytes

Retinoids have been shown to be effective in the chemoprevention and treatment of certain human malignancies. In this review, we will summarize our recent results concerning the effects of retinoids on the proliferation and differentiation of Epstein-Barr virus (EBV)-immortalized lymphoblastoid B-cell lines (LCLs), an in vitro model of EBV-related lymphoproliferative disorders arising in immunosuppressed hosts. Retinoids proved to be powerful inhibitors of the proliferation of EBV-infected LCLs in vitro, with 13-cis-retinoic acid (RA), all-trans-RA, and 9-cis-RA being the most effective compounds. Of note, retinoid-induced growth arrest in vitro appears irreversible at drug concentrations (10-^-6 mol/L) which may be reached in man after oral systemic therapy. The antiproliferative activity exerted by retinoids on LCLs is a generalized phenomenon usually associated with a progressive accumulation in G₀/G₁ phases of treated cells. The strong upregulation of p27^Kipl invariably observed in cells exposed to retinoids may contribute to the decreased number of cycling cells, probably by inhibiting the transition from the G₁ to S phase. Moreover, we obtained evidence indicating that the antiproliferative effects of retinoids are not dependent on the induction of terminal differentiation of EBV-immortalized B lymphocytes. In fact, the modifications induced by retinoids relative to LCL morphology, phenotype (downregulation of CD19, HLA-DR, and s-Ig, and upregulation of CD38 and c-Ig), and IgM production were highly variable among the lines tested and often only slightly relevant. Finally, the antiproliferative activity exerted by retinoids on LCLs is not mediated by a direct modulation of viral latent antigens, since EBNA-2 and LMP-1 downregulation was a late event detected only in some cell lines. These results indicate that retinoids may be useful in the medical treatment of EBV-related lymphoproliferative disorders of immunosuppressed patients, particularly in the earlier phases of these diseases.     

维甲类化合物Ro13-7410对HL-60细胞的作用

目的：探讨合成的第三代维甲类化合物（Ｅ）４［２５，６，７，８ｔｅｔｒａｈｙｄｒｏ５，５，８，８ｔｅｔｒａｍｅｔｈｙｌ２ｎａｐｈｔｈａｌｅｎｙｌ１ｐｒｏｐｅｎｙｌ］ｂｅｎｚｏｉｃａｃｉｄ（Ｒｏｌ３７４１０）对白血病细胞ＨＬ６０的影响。方法：采用ＮＢＴ还原能力测定检测细胞分化，电镜和程序性细胞死亡检测试剂盒（ＰＣＤａｓａｙｋｉｔ）鉴别凋亡细胞，Ｆｕｒａ２／ＡＭ荧光法测定胞浆内Ｃａ２＋浓度，ＰＣＲＥＬＩＳＡ试剂盒检测端粒酶活性，流式细胞术测定细胞周期分布。结果：Ｒｏｌ３７４１０诱导ＨＬ６０细胞分化的同时伴随细胞凋亡的发生。在ＨＬ６０细胞凋亡和分化的过程中胞浆内Ｃａ２＋浓度增高，端粒酶活性明显受抑，多数细胞被阻止在Ｇ２／Ｍ期。结论：Ｒｏｌ３７４１０可诱导ＨＬ６０细胞凋亡和分化的同时发生。胞浆内Ｃａ２＋浓度的增高，端粒酶活性的降低以及细胞周期的阻止与细胞凋亡和分化的诱导有关     

维甲酸致胎鼠骨骼畸形模型的建立

目的利用维甲酸胎鼠模型,观察其骨骼畸形出现的情况,探讨骨骼畸形的发生机制。方法于孕期第10天经胃管给SD母鼠注入125 mg/kg体重全反式维甲酸,对照组仅予载体溶液。分娩前24 h剖腹取出胎鼠,实验组和对照组分别随机各取20只和10只胎鼠去除软组织,行骨软骨双重染色法,显微镜观察骨骼情况。结果实验组胎鼠体重(4．294±0．670)g与对照组(4．743±0．542)g比较,差异有统计学意义(P＜0．05)。对照组未见骨骼畸形。维甲酸组有18只(90%)胎鼠可见明显的全身骨骼畸形,最常见的畸形分别是长骨畸形(80%)、腕掌跗跖骨缺如(80%)、胸廓外形异常(80%)、椎体畸形(75%)、骨盆畸形(70)和脊椎裂(65%)。结论维甲酸有较强的胎鼠骨骼致畸作用,这种作用是多部位的。维甲酸大鼠是研究骨骼先天性畸形的实用工具模型。     

Inhibitory effects of retinoids on development of squamous metaplasia in rat mammary epithelial organoids cultured in Matrigel

Squamous metaplasia (SQM) developed in cultures of rat mammary organoids in reconstituted basement membrane, Matrigel, under either a complete hormone medium (CHM) or a serum-free mammary epithelium growth medium (MEGM). Organoids cultured in CHM gave rise to fewer such SQM (˜5%) than those in MEGM (˜16%). Formation of SQM was completely suppressed when retinoids were added to CHM. However, a few SQM were still observed in cultures in MEGM with added retinoids. Addition of 5% fetal bovine serum suppressed development of SQM cultured in MEGM. Delayed addition of retinoids also inhibited further development of SQM. Development of SQM from mammary epithelial cells is not common, and regulatory molecules other than retinoids apparently are involved in their formation and prevention.     

维胺酯治疗痤疮类皮肤病的临床观察

<正> 维甲酸类(retinoids)在皮肤科临床上的应用,即在痤疮、银屑病、各种角化异常性皮肤病以及某些癌前或癌性疾病的治疗上,均取得了令人鼓舞的治疗效果。口服维甲酸类药物在皮肤科的应用,已有较详细的介绍。本文就国产维甲酸类衍生物维甲酯在痤疮类皮肤病中的疗效及其毒副作用作以下介绍。维胺酯的化学名称为N-(4-氧碳基苯基)维生素甲酰胺N-(ethoxycarbephenyl)-retinamide。分子式C_(29)H_(37)NO_3其化学结构式如下。     

新维甲类联合γ干扰素对急性单核细胞白血病细胞增殖分化作用的体外研究

目的探讨新研制的维甲类查尔酮酸Ｒ９１５８和ＹＳ９０４０１２联合γ干扰素（ＩＦＮγ）在急性单核细胞白血病分化疗法中的应用价值。方法应用细胞形态学、四氮唑蓝（ＮＢＴ）还原反应和非特异酯酶乙酸萘酚（ＤＣＥ）、细胞分化免疫表型ＣＤ１４和ＣＤ６８、ＣＦＵＬ集落形成抑制率等变化，体外研究其对６例急性单核细胞白血病患者白血病细胞的增殖分化作用。结果经ＹＳ９０４０１２联合ＩＦＮγ处理后，单核细胞由原始阶段变成较成熟的单核细胞，ＮＢＴ还原反应阳性率和ＤＣＥ分别由２３．４％和２５０％上升到６１．５％和５２．０％，ＣＤ１４和ＣＤ６８表达增强，ＣＦＵＬ集落增殖明显受抑。通过比较，ＹＳ９０４０１２联合ＩＦＮγ诱导细胞分化和抑制集落形成活性优于Ｒ９１５８和全反式维甲酸联合用药组（Ｐ＜０．０１）。结论ＹＳ９０４０１２联合ＩＦＮγ诱导分化治疗单核细胞白血病可能有一定临床实用价值。