朝藿素D的分离和结构

从朝鲜淫羊藿(Epimedium koreanum)地上部分分离得到一新黄酮成分(I)和一已知化合物(II)。经光谱解析,证明I的结构为5,7,3',4'-tetrahydroxy-5'-prenylflavone,命名为朝藿素D(epimedokoreanin D);II为2-hydroxy-3,4,6,7-tetramethoxy-9,10-dihydrophenanthren。     

A cross-sectional study of the forearm bone mineral density in long-term current users of the injectable contraceptive depot medroxyprogesterone acetate

Background

One of the well-established effects of the use of depot medroxyprogesterone acetate (DMPA) contraception is on bone mineral density (BMD). However, little evidence assesses the skeletal impact of long-term DMPA use. The objective of this study was to assess BMD on a cohort of women who used DMPA uninterruptedly between 1 and 15 years.

Study Design

A cross-sectional study with 232 users of DMPA matched to a group of 232 copper intrauterine device (IUD) users by age (±1) (range 20–53 and 20–51 years for DMPA and IUD group, respectively), body mass index (BMI; kg/m²) (±1) (range 17.4–44.5 and 18.5–40.2 for DMPA and IUD group, respectively) and years of use (1–15 years) was performed. The women underwent forearm BMD evaluation using dual-energy X-ray absorptiometry. The women were divided into five groups (1–5) according to the length of DMPA use: 1–3, 4–6, 7–9, 10–12 and 13–15 years of use.

Results

The mean (±SEM) age was 38.3±0.5 and 38.1±0.57 years and the mean (±SEM) BMI (kg/m²) was 26.4±0.3 and 26.3±0.3 for the entire group of women in the DMPA and IUD group, respectively. Women who used DMPA or IUD for a short time were younger and had lower BMI (kg/m²) than the women who used either contraceptive method long term. White women were significantly more frequent among IUD users (p<.040) than DMPA users. In addition, parity (p<.053) and physical activity (p<.012) were significantly greater among IUD users, whereas the prevalence of washing clothes by hand (p<.025) was significantly greater among DMPA users. There was no significant difference in BMD measurements between the current users of DMPA and those who had used the IUD either at the distal or ultra-distal sections of the forearm. However, women who had used DMPA for 13–15 years showed significantly lower BMD at the distal and ultra-distal radius when compared to IUD users (p<.041 and .042, respectively). Otherwise, all other differences in BMD values between DMPA and IUD users were nonsignificant at the distal and ultra-distal radius. For both DMPA and IUD users, we noted a direct correlation between higher BMD and BMI (kg/m²) and an inverse correlation between BMD and age for distal and ultra-distal radius.

Conclusions

Our study did not detect a deleterious effect on measurements of forearm BMD among long-term DMPA users with less than 13 years of use; however, a significantly lower BMD was observed at 13–15 years of use in DMPA users when compared to IUD users. Bone mineral density was inversely correlated to older age and directly correlated to BMI (kg/m²).     

Hungarian adaptation of a questionnaire for determining depression-specific quality of life

INTRODUCTION: The Quality of Life in Depression Scale (QLDS) is a widely used outcome measure available in a large number of languages. No measure of quality of life was available for use with depressed patients in Hungary and a decision was taken to adapt the QLDS for this purpose. The adaptation of a questionnaire for use in a new language involves three stages; translation, testing for face and content validity and assessment of the translated measure's psychometric properties. OBJECTIVES: To adapt the QLDS for use in Hungary and to evaluate its psychometric properties. METHOD: The dual panel method was used to translate the QLDS into Hungarian. The translation was tested for face and content validity by interviews conducted with depressed patients. Finally, a test-retest postal survey was conducted to determine internal consistency, reproducibility and construct validity. RESULTS: Interviews conducted with 25 patients indicated that the QLDS was an appropriate measure and that it was well accepted and completed. The postal survey ( n = 50) showed that the measure had good internal consistency (Cronbach's alpha-coefficients were 0.95 at both administrations) and that the test-retest reliability (0.89) indicated good reproducibility with limited random measurement error. Correlations of QLDS scores with those for the Nottingham Health Profile sections were as expected, providing evidence of convergent and divergent validity. CONCLUSION: Given the acceptability of the Hungarian version of QLDS to depressed patients and the excellent psychometric properties of the adapted questionnaire it is concluded that the adaptation was successful. The measure is suitable for use in clinical practice and studies involving depressed patients in Hungary.     

Receptor Tyrosine Kinase Fusions and BRAF Kinase Fusions are Rare but Actionable Resistance Mechanisms to EGFR Tyrosine Kinase Inhibitors

Introduction

We analyzed a large set of EGFR-mutated (EGFR+) NSCLC to identify and characterize cases with co-occurring kinase fusions as potential resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs).

c-src structure in human cancers with elevated pp60c-src activity.

We used RNAase protection and restriction fragment length polymorphism assays to detect activating mutations of c-src in a spectrum of human tumours. No mutations were detected at codons 98, 381, 444, and 530. We conclude that mutational activation is not the mechanism of enhancement of pp60c-src-specific kinase activity found in a number of human cancer types.     

In vivo metabolism of the anti-inflammatory agent 2-(5-ethylpyridin-2-yl)benzimidazole

The metabolic fate of anti-inflammatory agent 2-(5-ethylpyridin-2-yl)benzimidazole (KB-1043) was studied in rats after oral administration. An average of 12.2 +/- 1.5% of the dose was excreted in the urine in the course of 0-48 h; 56.7 +/- 2.6% with feces. Two metabolites were also detected in the urine and isolated by reverse phase HPLC. Structures have been given after identification by comparison with authentic samples. The more abundant metabolite proved to be 2-(5-(1-hydroxyethyl)pyridin-2-yl)benzimidazole, a benzylic oxidation product, which was also excreted as glucuronic acid conjugate; the other metabolite was confirmed to be 2-(5-acetylpyridin-2-yl)benzimidazole. Carrageenin edema and gastric ulcerogenic activity were also tested for the two identified metabolites.     

Intracellular transport and neuronal activation of phospholipid and glycoprotein synthesis during axonal regeneration of cranio-spinal nerves

In the present work, the hypothesis that the increased rapid intracellular transport of newly-synthesized material along the axons of a regenerating system is sustained by an alteration of the transport of proteolipid complexes through subcellular compartments of a neuronal cell body was tested by a biochemical methodology. The motoneurons of spinal cord ventral horn, 4 wk after unilateral lesion (crush) of cervico-thoracic nerves of the rabbit at the level of brachial plexus, were chosen as the model system of regeneration. A time-staggered procedure of in vivo and in vitro double labeling with metabolic precursors, such as [³H]-choline, [¹⁴C]-choline, [³H]-fucose, and [¹⁴C]-fucose, was used. Subcellular fractions (RER, SER, Golgi apparatus, and plasma membranes) of ventral horn tissue, taken from spinal cord hemisections (regenerating and contralateral side), were further isolated. Twenty-eight days after axotomy, we did not observe any change of intracellular transport kinetics (¹⁴C/³H ratio) of newly-synthesized choline-phospholipids and glycoproteins in regenerating motoneurons compared to controls. However, associated with regenerating phenomenon in Golgi apparatus, we observed an increase of labeled choline-phospholipid and glycoprotein material that could contribute to the increased fast axonal transport and delivery of membrane proteolipid complexes to plasma membrane and axonal compartments. The increase of glycoprotein labeling was more pronounced in the SER portion (vesicles and elements of smooth membranes). This result is in favor of the hypothesis that membrane-bound proteins are transported from the Golgi to the axon through the perikaryal SER.     

CD5 positive B lymphocytes in seronegative juvenile arthritis.

We investigated the levels of circulating CD5+ B cells in 43 patients with seronegative, HLA-B27 negative juvenile arthritis, 7 patients with juvenile dermatomyositis (DM) and 16 children with systemic lupus erythematosus (SLE). We found that CD5+ B cell levels were high in juvenile arthritis (p less than 0.01), normal in juvenile DM and decreased in SLE (p less than 0.01) compared to 33 age matched controls. In juvenile arthritis, the increase of CD5+ B cells appeared to be independent of discuss activity and was present in all the onset types except in a subset of patient with late onset pauciarthritis.     

Increase of alpha 2-presynaptic adrenoceptor response after neuronal uptake inhibition in vivo

alpha 2-adrenoceptor antagonists, yohimbine or idazoxan (1 mg kg-1 i.p.), administered alone, did not change noradrenaline content in the central and peripheral tissues of the rat (hypothalamus, brain stem, frontal cortex and heart). The inhibition of neuronal uptake by desipramine (DMI) administered alone or prior to alpha 2-adrenoceptor antagonists did not affect the neurotransmitter content either. alpha-methyl-p-tyrosine (alpha-MT) 6 hr before sacrifice, induced a marked disappearance of the noradrenaline content, greater in central nervous tissues than in heart. When the catecholamine synthesis was inhibited by alpha-MT, neither alpha 2-adrenoceptor antagonists nor DMI at the dose used, significantly changed the disappearance rate of noradrenaline in any of the tissues studied. Under these experimental conditions, however, the combination of DMI plus alpha 2-adrenoceptor antagonists significantly decreased the neurotransmitter content in all tissues when the values were compared with the control or DMI-treated groups. The present results might suggest evidence in favour of a functional coupling between presynaptic alpha 2-autoreceptors and noradrenaline uptake mechanism.     

Multiple inhibitors of mitogen-induced proliferation of normal lymphocytes in juvenile chronic arthritis sera

We evaluated the effect of 47 serum samples obtained from 34 children with juvenile chronic arthritis (JCA) on mitogen-induced proliferation of normal peripheral blood lymphocytes (nPBL). We found that sera from patients with active disease, and particularly those with the systemic form, inhibited significantly PHA-induced proliferation of nPBL at all the PHA concentrations tested. This inhibitory activity was independent of the treatment and was correlated with the value of the erythrocyte sedimentation rate. Part of the JCA sera inhibitory effect could be reversed by the addition of exogenous interleukin 2 (IL-2), but not of interleukin 1 (IL-1) or interferon-gamma, moreover, JCA sera were able to partially inhibit the IL-2 dependent proliferation of CTLL. When we tested serum fractions obtained by Sephadex G-200 chromatography for their inhibitory activity, we observed that: a) two major peaks of inhibitory activity on PHA-induced proliferation were present: peak 1 with MW less than 600,000 and peak 2 with MW between 70,000 and 35,000; b) the inhibitory activity present in the high MW peak was in part IL-2 related; and c) both peaks contained elevated levels of acute phase proteins (APP) which are known to inhibit mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. We conclude that sera from patients with active systemic JCA contain inhibitory activity on mitogen-induced lymphocyte proliferation. This activity is due to the presence of multiple inhibitors, one of which appears to be IL-2 related; at least part of the inhibitory activity may be due to elevated serum levels of APP.