La sculpture et l'infrastructure du sporoderme de Ginkgo biloba comparées à celles des enveloppes polliniques des cyccadales

The Ginkgo biloba sporoderm, when examined with transmission and scanning electron microscopes, shows a sculpture and a texture which are very different from those observed in cycads.The ornamental units are “rugules” which are evenly disperesed over the pollen grain surface except on the germinal zones which is decorated with “verrucoïde” components mixed with a few ridges. (2) The exine is composed of a tripartite sexine, the middle zone of which is full of irregular pits, and of a thick and strongly lamellated nexine.     

5′-Monohydroxyphylloquinone from Anacystis and Euglena

The monohydroxy analogue of phylloquinone found in Anacystis nidulans and Euglena gracilis has been characterized as 5′-monohydroxyphylloquinone by MS analysis.     

La toxicité rénale du lithium: une réévaluation

Lithium salts are a well-established prophylactic treatment of relapses in bipolar disorder. Their most common renal side-effect is nephrogenic diabetes insipidus leading to polyuria. Only recently has their undesirable effect on renal function been recognized. This effect is due to the development of renal tubulo-interstitial lesions. The rate of progression is slow, with an annual loss of glomerular filtration estimated to be 2.2 ml/min. End-stage renal disease has been reported in some patients. In France, a recent survey showed that 0.2% of dialysed patients had lithium-induced renal disease. This complication occurs in a small percentage of lithium-treated patients, after 1 or 2 decades of treatment. However, its exact prevalence in the long-term is unknown. Lithium-treated patients should be regularly monitored. This monitoring should include annual measurements of serum creatinine and estimated creatinine clearance, as well as measurements of serum calcium (because hyperparathyroidism may develop). In early renal toxicity, discontinuation of lithium should be discussed with the patient by both the treating psychiatrist and the nephrologist.     

La biologie délocalisée, une activité transversale

A ce jour, aucun texte réglementaire ne permet d’obliger le biologiste à mettre en œuvre un système d’assurance qualité adapté à la gestion de la biologie délocalisée. La SFBC a réuni un groupe d’experts afin de formaliser des recommandations dès 1998 [1]. Actuellement, ce sujet est à l’ordre du jour des organismes internationaux, et il est vraisemblable qu’une normalisation interviendra dans le futur, à terme opposable aux biologistes en relation avec un établissement de soins pratiquant une délocalisation des analyses de biologie médicale: une annexe à la future norme ISO/CEN 15189 concernant les recommandations pour la biologie délocalisée est en cours de validation, faisant suite aux recommandations du groupe européen EC4 [2].     

Pour une histoire du désir

The striking feature of the history of sexual desire is the contrast between the omnipresence of sexual desire in human societies, regardless of the period considered, and the negative representation constantly and systematically given to this desire by philosophers and religious leaders. Sexual desire was automatically rejected by those who were disgusted by the animal side of man. The Stoics of the first century A.D., rapidly followed by theologians of the young Christian religion, were convinced that animals only act to satisfy their physical needs, but that moral man had to distinguish himself from the animals by refusing to act simply for pleasure. For Cicero and Seneca “seeking an act because of the pleasure it procures is an abuse”. They applied this principle to food as well as bodily care: unthinking animals live to eat, while moral humans eat to live; food and maintenance of the body ensure health but do not provide pleasure. Similarly, sexuality is only justified for reproductive purposes. However, as already observed by Saint Augustine, this is not the way in which human beings act, and this Church Father had to admit that he had never met a husband able to claim that he “only had sexual intercourse in the hope of fathering”. Other thinkers were more moderate and distinguished acceptable desire, kept under the control of reason and leading to positive action from degrading, irrational desire ending in passion (always considered to be unreasonable). Only the second form of desire must be avoided; the first leads to happiness and fulfilment and remains the force that usually drives human action. Christian thinkers of the Middle Ages, attentive to the real life of believers, finally accepted that the human characteristic of memory is one of the most beautiful gifts of God, allowing man to remember past pleasures and therefore to rightfully experience the desire to repeat these pleasures: coitus without a reproductive purpose therefore appears to be part of the divine plan. A theologian, in contrast with dominant religious opinion, even declared “if someone eats a pear or a beautiful fruit only for the pleasure, it is not a sin. The same applies when a man has intercourse with his wife only for the pleasure”. However, far from theoretical discussions, individuals declared their deep attachment to desire, during the Renaissance, at the court of the Sun King, in salons of the Enlightenment or even, in contrast with a widely held belief, in the new industrial world of the 19th century. Today, while religious authorities still generally have a Stoic view of pleasure and desire, modern thought has advanced in its understanding of the place of desire in human experience and recognizes it an essential driving role responsible for fulfilment and a powerful stimulus for all forms of creativity. The history of sexual desire therefore corresponds to the steps of enrichment of basic animal instinct by the human species and the individual and social forms of expression of this desire.     

Ammonites diartianus d'Orbigny, 1850,Vascoceratidae du cénomanien supérieur de saint-calais (Sarthe)

Ammonites diartianus d'Orbigny is a Vascocerasoof late Cenomanian (Sciponoceras gracile Zone) age, occuring in both Sarthe (France) and southern England. It is the earliest vascoceratid known from France, and its recognition is of great significance, lending support to recent suggestions that the classic Vascoceras gamai - mundaeChoffat group are of Upper Cenomanian age.     

La citréomontanine,nouvelle α-pyrone polyéthylénique isolée de Penicillium pedemontanum

Citreomontanin, a new polyene 2-pyrone was isolated from the mycelium of P. pedemontanum. Based upon spectral data, it was assigned the structure: (all-E)-4-methoxy-5-methyl-6-(7,9,11- trimethyl-1,3,5,7,9,11-tridecahexaenyl)-2 H-pyran-2-one.     

Protective effects of Ginkgo biloba extract (EGb761) and its constituents quercetin and ginkgolide B against β-amyloid peptide-induced toxicity in SH-SY5Y cells

Ginkgo biloba extract EGb761 has been shown to protect against β-amyloid peptide (Aβ)-induced neurotoxicity but the specific mechanisms remain unclear. In the present study, effects of EGb761 and two of its constituents, quercetin and ginkgolide B, on the cytotoxic action of Aβ (1-42) were tested with human neuroblastoma SH-SY5Y cells. We found that EGb761 was able to block Aβ (1-42)-induced cell apoptosis, reactive oxygen species (ROS) accumulation, mitochondrial dysfunction and activation of c-jun N-terminal kinase (JNK), extracellular signal-regulated kinase 1/2 (ERK1/2) and Akt signaling pathways. Both quercetin and ginkgolide B may be involved in the inhibitory effects of EGb761 on JNK, ERK1/2 and Akt signaling pathways. Ginkgolide B also helped to improve mitochondrial functions but quercetin failed to show this effect. Additional experiments suggest that, protective effects of EGb761 against Aβ toxicity may be associated with its antioxidant and platelet activating factor (PAF) antagonist activities. Quercetin but not ginkgolide B is one of the constituents responsible for the antioxidant action of EGb761. Both quercetin and ginkgolide B may be involved in the PAF antagonist activity of EGb761. Overall, actions of individual EGb761 components provide further insights into direct mechanisms underlying the neuroprotective effects of EGb761.     

Progress in antischistosomal N,N′-diaryl urea SAR

N,N′-Diaryl ureas have recently emerged as a new antischistosomal chemotype. We now describe physicochemical profiling, in vitro ADME, plasma exposure, and ex vivo and in vivo activities against Schistosoma mansoni for twenty new N,N′-diaryl ureas designed primarily to increase aqueous solubility, but also to maximize structural diversity. Replacement of one of the 4-fluoro-3-trifluoromethylphenyl substructures of lead N,N′-diaryl urea 1 with azaheterocycles and benzoic acids, benzamides, or benzonitriles decreased lipophilicity, and in most cases, increased aqueous solubility. There was no clear relationship between lipophilicity and metabolic stability, although all compounds with 3-trifluoromethyl-4-pyridyl substructures were metabolically stable. N,N′-diaryl ureas containing 4-fluoro-3-trifluoromethylphenyl, 3-trifluoromethyl-4-pyridyl, 2,2-difluorobenzodioxole, or 4-benzonitrile substructures had high activity against ex vivo S. mansoni and relatively low cytotoxicity. N,N-diaryl ureas with 3-trifluoromethyl-4-pyridyl and 2,2-difluorobenzodioxole substructures had the highest exposures whereas those with 4-fluoro-3-trifluoromethylphenyl substructures had the best in vivo antischistosomal activities. There was no direct correlation between compound exposure and in vivo activity.     

La pyrimidine (2-méthyl-4-amino-5-amino-méthylpyrimidine), facteur de croissance de microorganismes (Rhodotorula,Mucorinées,Dematium)

Sans résuméNous exprimons toute notre reconnaissance à la Direction des Etablissements Dr. A.Wander A. G. (Berne), pour son appui; nous sommes redevables au Dr. R. J.Williams (Corwallis, Oregon) d'un échantillon d'acide pantothénique, aux EtablissementsHoffmann. La Roche Bâle (Département scientifique, Dr. M.Guggenheim) des diverses pyrimidines utilisées, et au Prof.Hörlein, I. G. Farbenindustrie A. G. de l'aneurine synthétique employée. Nous les remercions très vivement.     

Hit discovery of Mycobacterium tuberculosis inosine 5′-monophosphate dehydrogenase,GuaB2, inhibitors

Tuberculosis remains a global concern. There is an urgent need of newer antitubercular drugs due to the development of resistant forms of Mycobacterium tuberculosis (Mtb). Inosine 5′-monophosphate dehydrogenase (IMPDH), guaB2, of Mtb, required for guanine nucleotide biosynthesis, is an attractive target for drug development. In this study, we screened a focused library of 73 drug-like molecules with desirable calculated/predicted physicochemical properties, for growth inhibitory activity against drug-sensitive MtbH37Rv. The eight hits and mycophenolic acid, a prototype IMPDH inhibitor, were further evaluated for activity on purified Mtb-GuaB2 enzyme, target selectivity using a conditional knockdown mutant of guaB2 in Mtb, followed by cross-resistance to IMPDH inhibitor-resistant SRMV2.6 strain of Mtb, and activity on human IMPDH2 isoform. One of the hits, 13, a 5-amidophthalide derivative, has shown growth inhibitory potential and target specificity against the Mtb-GuaB2 enzyme. The hit, 13, is a promising molecule with potential for further development as an antitubercular agent.     

Synthesis and hybridizing properties of isoDNAs including 3′-O,4′-C-ethyleneoxy-bridged 5-methyluridine derivatives

3′,4′-Ethyleneoxy-bridged 5-methyluridine derivatives with methyl groups in the bridge, (R)-Me-3′,4′-EoNA-T and (S)-Me-3′,4′-EoNA-T, were synthesized, and these two analogs and unsubstituted 3′,4′-EoNA-T were successfully incorporated into a 2′,5′-linked oligonucleotide (isoDNA). Their duplex-forming ability with complementary DNA and complementary RNA, and triplex-forming ability with double-stranded DNA, were evaluated by UV-melting experiments. The results indicated that isoDNAs, including these 3′,4′-EoNA analogs, could hybridize exclusively with complementary RNA. In particular, 3′,4′-EoNA-T and (R)-Me-3′,4′-EoNA-T modifications within isoDNA could stabilize the duplexes with complementary RNA compared with unmodified or 3′,4′-BNA-modified isoDNAs.