高效液相色谱法测定右旋儿茶素血浆浓度及药代动力学参数

本文建立了体液中右旋儿茶素的RP-HPLC测定方法。采用C_(18)键合相硅胶为填料的固相提取柱进行样品预处理,右旋儿茶素的提取回收率为79.8%.应用二极管阵列检测器对色谱峰纯度进行鉴定。该法精密度好,方法回收率近100%,日内、日间的变异系数为2.4～5.6%,血浓69.6～1160 ng/ml范围内呈线性关系,r=0.9993。家兔静注右旋儿茶素18mg/kg,其药代动力学过程符合二室模型,分布相半衰期为0.129 h,消除相半衰期为1.19h。     

Cyclophosphamide in treatment of systemic lupus erythematosus: 7 years’ experience

This paper describes our experience with cyclophosphamide in the treatment of systemic lupus erythematosus. Since 1965, 42 such patients have been treated either singly with cyclophosphamide or in combination with steroid. Serious complications have been rare except for amenorrhoea, which occurred in 14 out of 32 patients within the reproductive period. Our experience suggests that cyclophosphamide has an important, though not primary, part to play in the therapy of this disease.     

T cell immunodeficiency in dyskeratosis congenita.

Dyskeratosis congenita has been found to be associated with abnormal immune function. In this study we report a patient with this association. He developed Pneumocystis carinii interstitial pneumonia, and impaired cell mediated immunity was confirmed by the presence of depressed lymphoproliferative responses to in vitro stimulation with mitogen. Enumeration of T cell subsets showed a severely depressed CD4:CD8 ratio (0.38), which is the likely cause for impaired cell mediated immunity. The T cell activation pathway appeared intact, as his T lymphocytes were able to express activation markers (CD25 and HLA-DR) after mitogen stimulation.     

Responses against complex antigens in various models of CD4 T-cell deficiency

The most common models of CD4 T-cell deficiency are mice exogenously injected with anti-CD4 antibody (Ab), CD4 knockout (CD4^−/−) and major histocompatibility complex (MHC) class II knockout (class II^−/−) mice. We recently described the anti-CD4 Ab transgenic mouse (GK) as an improved CD4 cell-deficient model. This review compares this new GK mouse model with the widely available class II^−/− and CD4^−/− mice, when exposed to complex antigens (foreign grafts and during bacterial or viral infection). We highlight here the cytometric and functional differences (including Ab isotype, viral or bacterial clearance, and graft survival) among these CD4 cell-deficient models. For example, whereas grafts are generally rejected in class II^−/− and CD4^−/− mice as quickly as in wild-type mice, they survive longer in GK mice. Also, CD4^−/− mice produce IgG against both simple model and complex antigens, but class II^−/− and GK mice produce small amounts of IgG2a against complex antigens but not simple model antigens. These differences harbinger the caveats in the use of these various mice.     

The UTX gene escapes X inactivation in mice and humans

We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.      

L1 knockout mice show dilated ventricles, vermis hypoplasia and impaired exploration patterns

L1 is a neural cell adhesion molecule mainly involved in axon guidance and neuronal migration during brain development. Mutations in the human L1 gene give rise to a complex clinical picture, with mental retardation, neurologic abnormalities and a variable degree of hydrocephalus. Recently, a transgenic mouse model with a targeted null mutation in the L1 gene was generated. These knockout (KO) mice show hypoplasia of the corticospinal tract. Here we have performed further studies of these KO mice including magnetic resonance imaging of the brain, neuropathological analysis and behavioral testing. The ventricular system was shown to be abnormal with dilatation of the lateral ventricles and the 4th ventricle, and an altered shape of the Sylvius aqueduct. Additionally, the cerebellar vermis of the KO mice is hypoplastic. Their exploratory behavior is characterized by stereotype peripheral circling reminiscent of that of rodents with induced cerebellar lesions.      

Prevalence and Associated Factors of Sarcopenia in Singaporean Adults—The Yishun Study

ObjectivesTo describe the normative values of sarcopenia among community-dwelling adults (≥21 years of age); compare the prevalence of sarcopenia using Asian Working Group for Sarcopenia criteria, 2014 (AWGS2014), Asian Working Group for Sarcopenia criteria, 2019 (AWGS2019), and European Working Group on Sarcopenia in Older People criteria, 2018 (EWGSOP2) guidelines; and identify factors associated with sarcopenia.DesignParticipants were recruited through random sampling. Sarcopenia assessments were performed using a dual-energy x-ray absorptiometry scan (muscle mass), handgrip test (muscle strength), and usual walking test (physical performance). Questionnaires were administered to evaluate lifestyle and cognition.Setting and ParticipantsIn total, 542 community-dwelling Singaporeans were recruited (21?90 years old, 57.9% women).MethodsWe assessed anthropometry, body composition, and questionnaire-based physical and cognitive factors, and estimated sarcopenia prevalence according to the AWGS2014, AWGS2019, and EWGSOP2 recommendations, and examined associations using logistic regression.ResultsAccording to AWGS2019, the Singapore population-adjusted sarcopenia prevalence was 13.6% (men 13.0%; women 14.2%) overall, and 32.2% (men 33.7%, women 30.9%) in those aged 60 years and above. The cut-offs derived from young adult reference group for low appendicular lean mass index were 5.28 kg/m2 for men and 3.69 kg/m2 for women (lower than AWGS recommended cut-off); for gait speed it was 0.82 m/s, (AWGS2019 recommended cut-off 1.0 m/s, AWGS2014 cut-off was 0.8 m/s); and for handgrip strength it was 27.9 kg/m2 for men and 16.7 kg/m2 for women (close to AWGS2019 recommendation). Age, sex, marital status, alcoholism, physical activity, body mass index, waist circumference, and global cognition were associated with sarcopenia (P < .05).Conclusions and ImplicationsThis is the first study to provide reference values of muscle mass, strength, and gait speed across the adult lifespan of Singaporeans. Using AWGS2019 criteria, sarcopenia is prominent in older age (32.2% in ≥60 years old), but it is already nontrivial (6.9%) among young and middle-age persons. Multidomain lifestyle modifications addressing muscle strength, cognition, and nutrition over the adult lifespan are important to delay the development of sarcopenia.