Interaction of vinblastine analogues with tubulin

Summary Studies of the interaction between vinblastine-like alkaloids and their receptor, i.e. tubulin, are reported. They shed some light on the structure-activity relationships in this medicinally important series: the configurations at C₁₄ and C₁₆ as well as the presence of the methoxycarbonyl group on C₁₆ seem to play an essential role in the determination of biological activity.This work was supported by CNRS (A.T.P. No 3232).We thank Dr D. Pantaloni for interesting discussions, Drs N. and Y. Langlois for discussions and for supplying synthetic material, and Eli Lilly Laboratories for gifts of vinblastine, vincristine and leurosidine.     

早期母子隔离应激对大鼠学习记忆能力的影响

目的探讨早期母子隔离应激对幼鼠学习记忆能力的影响。方法30只SD新生大鼠用于实验，实验随机分成3组，正常对照纽、母子隔离15分钟纽、母子隔离3小时纽。在生后40天，三组大鼠进行Morris水迷宫及记录海马脑片长时程增强电位（LTP）实验。结果Morris水迷宫测试，与正常组比较母子隔离3h组大鼠寻找平台需要的潜伏期延长（P〈0．05），而母子隔离15分钟组大鼠寻找平台需要的潜伏期与正常组比较则无明显变化（P〉0．05）；海马脑片长时程增强电位提示：正常对照组条件刺激（CS）前后fEPSP斜率变化率为：64．7±22．9％；母子隔离3h组为：35．3±14．2％，低于正常组（P〈0．01）；母子隔离15min组为：66．3±29．7％，与正常组比较无显著性意义（P〉0．05）。结论幼鼠生后早期过度的应激导致大鼠的学习记忆能力减弱。     

Karyotype of South American pampas ofPseudalopex gymnocercus (Carnivora,Canidae)

Summary The karyotype of the pampas fox has 2n=74 and a NF=76. Except forChrysocyon brachyurus, 2n=74 is a common diploid number for the South American Canidae. This number is higher than in theVulpes group and lower than in the group of the typicalCanis. No marker chromosomes are present in the South American Canidae.     

Spatial learning impairments in PLB1Triple knock-in Alzheimer mice are task-specific and age-dependent

We recently generated an advanced mouse model of Alzheimer’s disease (AD) by targeted knock-in of single-copy mutated human amyloid precursor-protein (APP) and tau genes, crossed with a non-symptomatic presenilin (PS1A246E) over-expressing mouse line. These PLB1_Triple mice presented with age-dependent and AD-relevant phenotypes. Homozygous PLB1_Triple mice aged 4–12 months were assessed here in a battery of spatial learning tasks: Exp.1 radial-arm water maze (spatial reference and working memory) Exp.2 open-field water maze (spatial reference memory); Exp.3 home cage observation system with spatial learning (IntelliCage); Exp.4 spontaneous object recognition (SOR; novel object and spatial object shift). A separate test with high-expression transgenic APP mice matching the design of experiment 1 was also performed. Spatial deficits in PLB1_Triple mice were confirmed at 12, but not 4 months in both water maze tasks. PSAPP mice, by contrast, presented with severe yet non-progressive spatial learning deficits already at 4 months. During tests of spatial learning in SOR and IntelliCage, PLB1_Triple mice neither acquired the location of the water-rewarded corner, nor recognize novel or spatially shifted objects at 4 months, indicating these protocols to be more sensitive than the water maze. Collectively and in line with AD symptomatology, PLB1_Triple mice present with a graded and progressive age-dependent loss of spatial memory that can be revealed by the use of a battery of tasks. With the emergence of subtle deficits progressively increasing in severity, PLB1_Triple mice may offer a more patho-physiologically relevant model of dementia than aggressive expression models.     

Eubotriol and eubol,new diterpenes fromSideritis euboea

Summary 2 new diterpenes Eubotriol (ent-kaur-16-ene-7, 15, 18triol) (I), and eubol (ent-kaur-16-ene-7-acetoxy-15, 18 diol) (II) have been isolated from Sideritis euboea Helder.This work was supported by National Research Council (C.N.R.), Roma.     

Antagonism of V2-receptor effect of antidiuretic hormone by atrial natriuretic peptide in man

Summary Human -atrial natriuretic peptide (h-ANP) makes the urine of dehydrated volunteers hypotonic to plasma despite high circulating concentrations of antidiuretic hormone. Urinary dilution with h-ANP also occurs in subjects receiving indomethacin. Therefore, h-ANP antagonises effects of antidiuretic hormone on distal tubular V₂-receptors in man, probably without involving prostaglandins.     

Entrainment of human circadian rhythms by artificial bright light cycles

Summary Artificial bright light cycles (LD 816) of about 5000 lux during the light period were applied to two subjects in a temporal isolation unit, who had shown free-running circadian rhythms in sleep-wakefulness and rectal temperature. The circadian rhythms were successfully entrained by the artificial light cycle, but the phase relation of the rhythms to the light cycle was substantially different between the two subjects. The result indicated that the artificial bright lights are able to reset human circadian rhythms.     

Thyroid function parameters during a selenium repletion/depletion study in phenylketonuric subjects

Phenylketonuric (PKU) subjects have a limited supply of selenium (Se) in their phenylalanine-restricted diet. A Se repletion (1 g Se/kg/day)/depletion study was conducted in PKU children to determine the effect of Se on thyroid function parameters.The initial plasma Se concentration (mean±SD: 0.26±0.12 mol/L, p<0.00003, n=10) and glutathione peroxidase (GSH-Px) activity (140±58 U/L, p<0.00003, n=10) were significantly lower compared to agematched controls. After 14 weeks of supplementation, the plasma Se concentration (mean ±SD: 0.74±0.20 mol/L) normalized (normal range: 0.57–1.15 mol/L, mean ±SD: 0.76±0.13 mol/L, n=32) and remained stable thereafter during repletion. Plasma GSH-Px activity reached normal values after 18 weeks of supplementation (312±57 U/L; normal range: 238–492 U/L, mean ±SD: 345±54 U/L, n=32) and increased significantly for up to eight weeks thereafter (332±52 U/L). Individual and mean thyroid parameters were initially normal in all cases. The mean concentrations of plasma thyroxine (T₄: p<0.025), free T₄ (FT₄: p<0.01) and reverse triiodothyronine (rT₃: p<0.005) decreased to 75% of their initial value within three weeks of Se supplementation and remained stable thereafter, within a normal physiological range during selenium supplementation. They increased back to their initial values three weeks (T₄: p<0.05, FT₄: p<0.05) and six weeks (rT₃: p<0.025) respectively, after the end of the supplementation. In conclusion, Se supplementation modifies thyroid function parameters in Se-deficient PKU subjects most likely by an increase in activity of type I 5-deiodinase (5-DIase I).Preliminary results of this study were presented as posters on the 4th International Congress on Trace Elements in Medicine and Biology, Chamonix, France (1993) and the 4th Joint Meeting of the Lawson Wilkens Pediatric Endocrine Society and the European Society for Paediatric Endocrinology, San Francisco, California, Ped Res (1993) 33: S93 (abstract 537). Support in part by Research Grants of Nutricia BV, (The Netherlands).     

Inhibition and stimulation by 5-bromodeoxyuridine of erythropoiesis by chick blood island cells

Summary Erythropoiesis in liquid cultures of cell populations resolved from chick blastodiscs at the primitive streak and head-fold stages was totally inhibited by 5–8 g/ml of 5-bromodeoxyuridine. However, concentrations of 0.2 /ml of the nucleoside enhanced the number of erythroid cells formed.This work was supported by grants from the Medical Research Council and National Research Council of Canada. We thank MissesK. Beall andN. N. McGrath for technical assistance. S. D. W. is an Associate of the Medical Research Council.     

急性一氧化碳中毒迟发性脑病大鼠模型的建立

目的探讨建立适合实验研究需要的急性一氧化碳中毒迟发性脑病大鼠模型。方法64只雄性sD大鼠，随机分成空气对照组（AC组）和模型组（CO组），每纽32只。采用静态吸入式染毒，选取染毒后3、7、14、28d为时相点，应用Morris水迷宫实验检测平均潜伏期等学习记忆能力，Tunel法检测海马回神经元凋亡。结果CO组大鼠较AC组平均潜伏期延长（F=35．93，P〈0．01），海马回神经元凋亡指数增高（P〈0．01）。结论本实验成功建立了可行性较高的急性一氧化碳中毒迟发性脑病大鼠模型，为进一步研究其发病机制和防治方法提供比较好的基础。     

HAb18G/CD147-mediated calcium mobilization and hepatoma metastasis require both C-terminal and N-terminal domains

HAb18G/CD147 is a heavily glycosylated protein containing two immunoglobulin superfamily domains. Our previous studies have indicated that overexpression of HAb18G/CD147 enhances metastatic potentials in human hepatoma cells by disrupting the regulation of store-operated Ca²⁺ entry by nitric oxide (NO)/cGMP. In the present study, we investigated the structure-function of HAb18G/CD147 by transfecting truncated HAb18G/CD147 fragments into human 7721 hepatoma cells. The inhibitory effect of HAb18G/CD147 on 8-bromo-cGMP-regulated thapsigargin-induced Ca²⁺ entry was reversed by the expression of either C or N terminus truncated HAb18G/CD147 in T7721C and T7721N cells, respectively. The potential effect of HAb18G/CD147 on metastatic potentials, both adhesion and invasion capacities, of hepatoma cells was abolished in T7721C cells, but not affected in T7721N cells. Release and activation of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, were found to be enhanced by the expression of HAb18G/CD147, and this effect was abolished by both truncations. Thapsigargin significantly enhanced release and activation of MMPs (MMP-2 and MMP-9) in non-transfected 7721 cells, and this effect was negatively regulated by SNAP. However, no effects of thapsigargin or SNAP were observed in T7721 cells, and expression of HAb18G/CD147 enhanced secretion and activation of MMPs at a stable and high level. Taken together, these results suggest that both ectodomain and intracellular domains of HAb18G/CD147 are required to mediate the effect of HAb18G/CD147 on the secretion and activation of MMPs and metastasis-related processes in human hepatoma cells by disrupting the regulation of NO/cGMP-sensitive intracellular Ca²⁺ mobilization although each domain may play different roles.Received 1 April 2004; received after revision 15 June 2004; accepted 22 June 2004     

Un nouveau système polymorphe robertsonien chez une nouvelle espèce de «Leggada» (Mus goundae Petter)

Summary A sample of 6 Leggada from N'Délé (Central African Republic) morphologically different from all these studied up to now, constitue a new species, which will be described by Dr F.Petter asMus goundae Petter. The caryological analysis reveals a new robertsonian polymorphical system. The diploïd numbers are 2N=16, 17, 18 or 19, whereas theN.F. is constant and equal to 30. The 3 first pairs of autosomes, constituted by SM or MC elements are identical in the 4 types, as well as pairs V (MC) and VI (AC) morphologically constant by all individuals. The robertsonian mechanisms, from which polymorphism originates, take place at pairs IV, VII and VIII. The fourth pair, while heterozygote by 2N=19, assembling one MC and two AC elements, is homozygote and MC by 2N=18, 17 and 16; pairs VII and VIII are both constituted by two AC in the cases of 19 and 18 chromosomes; to form caryotypes with 17 and 16 chromosomes these 2 pairs will fusion: by 2N=17 the mutation is heterozygote (1 MC and 2 AC) and it becomes homozygote by 2N=16 giving birth to 2 MC. The sexual chromosomes are from TR Type (X MC andY SM).From these observations arises the problem of low chromosome numbers (16–20) which shall be discussed in a further publication.     

Dyslexia and specifically distorted drawings of the face—a new subgroup with prosopagnosia-like signs

Summary Identification of a subgroup (38%) of dyslexics (new syndrome?). These, against controls (5.5%), drew neolithic face configurations analogous to those visually experienced in prosop-agnosia. Essential symptoms of this subgroup are seen as result of specific early ways of processing visual data: lexical shapes (letters, words) and facial features, as if these were concrete entities, not abstract component parts. Thus, with letters, taken as entities, d=q, d=b, N=Z.This study was made possible by a visiting professorship at the University of Heidelberg, Department of Neurology. Thanks are due to its Director, Professor Dr.Heinz Gänshirt, as well as to DirectorSchmitt of the Heidelberger Schulamt and to Psychologist GretRuder-Trümpy for facilitating the collection of the drawings.     

Amylase secretion from rat parotid glands as dependent on co-operation between sympathetic and parasympathetic nerves

Summary A slow, long-lasting degeneration secretion from the parotid gland was brought about in anaesthetized rats by section of the auriculo-temporal nerve 16–19 h in advance. This parasympathetic background activity greatly increased the secretion of amylase elicited by sympathetic nerve stimulation.Supported by grants from the Swedish Medical Research Council (project nr 00539) to N.E. and from the Medical Faculty, University of Lund, to P.G.     

Synthese von 22,26-Imino-cholestan-Derivaten

Summary 3, 16-diacetoxy-5-pregnane-20-one and the analogue pregn-5-ene derivative have been converted into (22R, 25R)-22, 26-imino-5-cholestane-3, 16-diol. The configuration at C-22 and C-25 was determined by transformation into the known (22R, 25R)-5-solanidane-3-one. Application of the Ruschig method led to (25R)-22,26-imino-5-cholest-22(N)-ene-3, 16-diol.

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Solanum-Alkaloide. XVI. Mitteilung. — XV. Mitteilung:K. Schreiber undH. Ripperger, Tetrahedron Letters Nr.27, 9 (1960).     

Suppressed collagenolytic activity in polymorphonuclear leucocytes from diabetic humans

Summary Extracts of polymorphonuclear leucocytes (PMNL) from diabetic human exhibited less collagenolytic activity than extracts from normoglycemic control subjects. Partially purified control extracts produced ^A and ^B collagen breakdown products of the type generated by mammalian collagenase; the diabetic preparation produced decreased amounts of the same products. The diabetic PMNLs may synthesize abnormally low levels of collagenase or contain inactive forms of this enzyme.Supported by a grant (No. DE-03987) from the National Institute of Dental Research (N.I.H.), USA. This study forms part of the Ph.D. thesis of G.A. Nicoll.Acknowledgments. The authors wish to thank Ms Salema Karim and Mr F.R. Singh for excellent technical assistance.     

饮用咖啡与胰腺癌患病的Meta分析

目的 综合评价饮用咖啡因素与胰腺癌发生的相关性,进一步探讨胰腺癌的危险因素.方法 检索1970.01.01/2010.10.01国内外公开发表的有关人群饮用咖啡和胰腺癌发生的病例对照研究,制定纳入标准,采用Rev Man4.2软件对研究资料进行Meta分析,定量综合评价饮用咖啡与胰腺癌的关系.结果 共有15组病例-对照研究符合入选标准,累积胰腺癌病例共3 335例和正常对照者共15 064例.Meta分析显示,合并OR=1.08(95％ CI:0.88～1.31),(P=0.48),差异无统计学意义；男性组结果显示,OR和95％ CI为1.14(0.95-1.37),差距不具有统计学意义(P=0.15),女性组结果显示OR和95％CI为1.18(0.98-1.43),(P=0.09),由于P＜0.1,故属于边缘性显著差异.结论 女性胰腺癌患者中有饮用咖啡习惯与无饮用咖啡习惯的人相比,饮用咖啡的习惯可能会增加胰腺癌的发病风险.     

C-18 hydroxy steroids from the Mediterranean gorgonianLeptogorgia sarmentosa

Summary Five new polyoxygenated steroids, 24-methylcholesta-1,4,22E-trien-16, 18,20-triol-3-one (1), cholest-1,4,22E-trien-16, 18,20-triol-3-one (2), 24-methylcholesta-4,22E-dien-16, 18, 20-triol-3-one (3), cholesta-4,22E-dien-16, 18,20-triol-3-one (4) and 27-nor-24-methylcholesta-4,22E-dien-16,18,20-triol-3-one (5), have been found in a marine organism, the gorgonianLeptogorgia sarmentosa.This work has been done with the financial support of Progetto Finalizzato der la Chimica Fine e Secondaria, C.N.R., Roma. The authors are grateful to Zoological Station of Naples for collecting the gorgonian. Thanks are also due to Mr A. Crispino and Mr G. Scognamiglio for their technical assistance.     

Axillary 5α-androst-16-en-3-one in men and women: Relationships with olfactory acuity to odorous 16-androstenes

Summary Axillary 5-androst-16-en-3-one (5-androstenone) levels were found to be significantly higher in men than in women but do not vary between left and right axillae, are not related to age, handedness or degree of hirsutism (in women) nor to anosmia to this steroid. In men (but not in women), levels are related linearly to axillary cholesterol concentrations but not to squalene. Olfactory thresholds for 5-androstenone varied widely, the lowest recorded being 0.2 ppb, but there was no difference in thresholds between men and women. Women (70%) found the smell repellant but anosmia did not differ greatly between men and women (9–20%). Anosmia to the smell of 5-androst-16-en-3-ol was most marked in women (90%) rather than in men (45%). Axillary 5-androstenone values were generally consistent with the musky or strong smells of male axillary extracts, compared with the sweet smell of those from female subjects.Supported by the Herbert Dunhill Trust.