Étude de la cytotoxicitéin vitro de dérivés du carbazole III. 3-Amino et 3-nitro-1,4-diméthyl-9H-carbazoles diversement substitués en position 6

La synthèse d'une série de 3-nitro et 3-amino-1,4-diméthyl-9H-carbazoles diversement substitués en positions 6 et 8 est décrite. Leur activité cytotoxique, évaluée in vitro au moyen de la culture clonogénique de la leucémie L1210, dépend fortement de la nature et de la position des substituants. Le plus cytotoxique d'entre eux, le dérivé 3-amino 6-hydroxy, présente une cytotoxicité comparable à celle de l'acétate de N2-méthyl-9-hydroxy ellipticinium (NMHE). Ces résultats et ceux présentés dans les deux publications précédentes, permettent une discussion détaillée des relations structure-activité dans la série du 9H-carbazole et du 1,4-diméthyl 9H-carbazole et suggèrent, pour les dérivés du 3-amino 1,4-diméthyl 9H-carbazole, un mécanisme d'action proche de celui des dérivés de l'ellipticine.     

Maladies alcooliques du foie et dénutrition

The aim of this study is to try to answer to four questions from a literature review.

1) What is the prevalence of malnutrition in alcoholic patients with and without liver disease?

2) Is nutritional status independently correlated with survival in patients with alcoholic cirrhosis?

3) Is nutritional supplementation useful in patients with severe liver disease?

4) What energy substrate and nitrogen sources should be used for intravenous nutrition in patients with cirrhosis?

The answers to these questions are:

1) The prevalence of malnutrition in alcoholic patients depends on definition of the studied population. The objective assessment of nutritional status by quantitative clinical and biological parameters is difficult.

2) It has not been demonstrated that nutritional status has an independent prognostic value in patients with alcoholic cirrhosis.

3) The effectiveness of supplementary parenteral nutrition on survival and nutritional status of patients with severe alcoholic liver disease has not been proved.

4) Neither fat emulsions nor conventional amino acids solutions are contraindicated in patients with cirrhosis when parenteral nutrition is necessary.

Synthèse par SRN et évaluation de l'activité amoebicide de nouveaux dérivés quinoléiniques

Des dérivés quinoléiniques porteurs de chaînes carbonées, soufrées ou phosphorées, ainsi que des furoquinoléines sont obtenus à partir du Clioquinol (Vioforme) par des réactions de substitution nucléophile radicalaires en chaîne (S_RN¹) inédites dans cette famille d'hétérocycles. Une évaluation de leur activité in vitro est effectuée sur des cultures d'Entamoeba histolytica et de Trichomonas vaginalis.     

Quelques dérivés de l'amino-11 vinburnine à propriétés protectrices cérébrales

Quelques dérivés de l'amino-11 vinburnine (amides, aminoamides, urée, carbamates) sont préparés. Leurs propriétés protectrices contre l'œdème cérébral provoqué chez le rat par le triéthylétain sont évaluées.     

Indane-1,3-diones IX, synthèse et activité anti-inflammatoire de 2-polyaza-arylindane-1,3-diones et de leurs dérivés N- ou O-substitués

Les auteurs étudient les voies d'accès à des 2-polyaza-arylindane-1,3-diones et à leurs dérivés diversement substitués sur l'hétérocycle et l'homocycle ainsi que la pharmacomodulation de leur activité anti-inflammatoire. Ces β dicétoénamines fournissent en milieu alcalin des anions multidents conduisant en présence d'agents électrophiles à une C, N ou O-substitution; la mise en œuvre de la réaction de Mitsunobu a abouti à une N-(ω-amino-)-alkylation régiospécifique ou régiosélective. Parmi les diverses modifications structurales, la N-éthylation de la molécule de base, éventuellement couplée avec une méthoxylation en 5 sur l'homocycle s'est avérée efficace pour l'émergence d'une activité anti-inflammatoire en séries pyridazinyle, pyrimidinyle et tétrazolyle. Parmi les 3 molécules les plus actives 31, 43 et 50, la seconde a fait l'object d'une étude plus approfondie.     

Définition et évolution du statut nutritionnel au cours d'une greffe osseuse allogénique (15 malades): Rôle de la nutrition parentérale et de l'apport azoté

Our work concerned 15 patients (9 males, 6 females) with a mean age of 29.5 years, having a hematologic malignant disease and undergoing allogenic bone marrow transplantation.We studied :

1. The metabolic disorders induced by the conditioning regimen (chemotherapy and total body irradiation) pregraft accompanying cytolysis (day −7, −5, −2).

2. The corrective effect of a total parenteral nutrition introduced 2 days before the transplantation and pursued during 30 days post-graft (day −2 to day 30).

3. The interest of a high calorie intake (BEE × 2) and, after randomisation, of a variable nitrogen intake (24% of the total calorie intake for group A [8 patients] and 14% for group B [7 patients]). The patient characteristics of these two groups were closely comparable. Urinary parameters were studied daily (3-methylhistidine, cratinine, nitrogen) and blood parameters weekly (transferrin, pre-albumin, albumin, retinol binding protein).

We observed globally :

-- An excellent result of the nutritional support without significant weight loss;

-- protein catabolism stopped with a recovery of synthesis of RBP after day 7 and pre-albumin from day 7;

-- a decrease in muscle catabolism.

The randomized study showed :

-- a significant difference in nitrogen excretion between group A and group B;

-- earlier and better protein synthesis recovery in group A, particularly with regard to RBP and pre-albumin.

In conclusion, we recommend for the patients undergoing bone marrow transplantation :

-- nutritional support should be introduced before the conditioning regimen;

-- a high calorie intake (BEE × 2) with a nitrogen intake between 14% and 24% of the total calorie intake;

-- cyclic parenteral nutrition should be pursued during the second and third month post-graft.

Pharmacomodulation d'adrénolytiques aα en série benzopyrannique

Un même substituant aminométhylé a été fixé sur quatre hétérocycles oxygénés de la famille du benzopyranne. Deux voies de synthèse ont été utilisées pour chacun de ces composés. Vingt dérivés intermédiaires et quatre dérivés amino-méthylés sont décrits et leur structure établie par les procédés spectroscopiques. L'étude pharmacologique a mis en évidence l'intérêt de ces composés sur les récepteurs α-adrénergiques tant en ce qui concerne l'activité que la sélectivité.     

Stress oxydant et maladies neurodégénérativesOxydative stress in neurodegenerative diseases

Oxidative stress is involved in cellular death pathways of neurodegenerative diseases. Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis are the most frequent of these affections. In each case, there are evidences of an altered oxidative status. Oxidative stress play a role in all the pathophysiological hypothesis of Alzheimer’s disease, and several anti-oxidant compounds are efficient. In amyotrophic lateral sclerosis patients, only an association of vitamin E with riluzole, a glutamate inhibitor, has shown to have a favourable effect. The pathogenesis of Parkinson's disease implies oxidative stress in the dopaminergic neuronal death of the substantia nigra. The arguments include alterations of brain iron content, impaired mitochondrial function, alterations of protective systems. The neurotoxin 1–méthyl–4–phényl–1,2,3,6–tetrahydropyridine is a Parkinson model caused by an inhibition of the complex I of the mitochondrial respiratory chain. DATATOP study, using selegiline, an inhibitor of mono-amine oxidase with anti-oxidant properties, showed a modest neuroprotective effect of this compound but a lack of effect of vitamin E.     

Medicine, landscapes, symbols: “The country Doctor” by Honoré de Balzac

This paper considers examples from research that has interpreted literary works including representations of topographical landscapes, in order to examine the geographical and social perspectives of the author, and of the society in which the author was living and working. We focus especially on the use of representations of therapeutic landscapes in literature to convey the author's perceptions of the aspects of social and physical environments that contribute to human well-being. The novel entitled The country Doctor (Le Médecin de campagne) by Honoré de Balzac, first published in 1833, is the particular focus of this paper and we consider this book in the context of the historical period when it was written and other novels of the period which also portray doctors and medicine in varying ways. We present an interpretation of Balzac's novel which focuses on four themes arising from the discussion in the introduction of this paper: the symbolic use of ideas of ‘therapeutic landscapes’ to represent the ‘heroic’ role of the doctor; the link between landscapes and ideas of medicine and health, corresponding to the Hippocratic heritage; the representation, through images of salubrious landscapes, of planning and economic development and the role of the leader; the significance of the contrast between the ‘therapeutic’ rural world and the unhealthy urban settings found in Paris. We conclude that The country Doctor is interesting because of the ways that it reflects the three aspects of landscape (physical, social and symbolic) that Gesler (1998. In: Kearns, R., Gesler W. (Eds.), Putting Health into Place: Landscape, Identity and Well-Being. Syracuse University Press, Syracuse, NY, pp. 17–35 (Chapter 2)) has identified as central ‘therapeutic’ qualities. Not only does the book reflect a conceptual model of what a therapeutic landscape might be, but it also uses this landscape symbolically as an allegory for spiritual progress and redemption, and for medical and social advance. The novel represents a period of transition from traditional social values and prescientific medical theory towards modernization of society associated with the growing domination of medical science, which continued into the 20th century.     

Nutrition, démences vasculaires et maladie d’Alzheimer

Approximately 770,000 persons in France suffer from dementia. Alzheimer’s disease is the most frequent cause of dementia, followed by the vascular and mixed forms of dementia. In mixed dementia, the vascular lesions contribute to the severity of the cognitive impairment linked to neurodegenerative lesions. In fact, although the prevalence of cerebrovascular disease and Alzheimer’s disease are both high, some data suggest that their association is not fortuitous. Some vascular risk factors, that also represent risk factors for the development of dementia, are liable to be modified, and especially by nutrition. The question is to what extent nutritional factors may de implicated in the risk of developing dementia, and thus to estimate the possibility of modulating this risk by environmental measures. Cognitively impaired patients lose weight and present many nutritional deficiencies, but transversal studies do not allow to establish a causal link between nutrition and the risk of developing dementia. Longitudinal and cohort studies show an association between diabetes, hyperhomocysteinemia, hypercholesterolemia, low intake in n-3 fatty acids and oxidative stress and the risk of dementia. These nutritional factors contribute to the process of atherosclerosis, but also seem implicated in the physiopathology of neurodegenerative lesions by complex mechanisms. On the whole, few interventional studies have been conducted. Only these studies will help propose specific nutritional recommendations for the prevention of the risk of dementia, and/or to develop a new therapeutic approach. Meanwhile, the priority seems to prevent vascular risk factors, in accordance with the objectives of the Programme National Nutrition et Santé.     

Manifestations digestives et nutritionnelles des déficits immunitaires congénitaux et acquis chez l'enfant

The gastrointestinal and nutritional impact of congenital immunodeficiencies is varied and non-specific (serious refractory diarrhea, exsudative enteropathy, enterocolitis and chronic infections by Cryptosporidium, Giardia, rotavirus, Candida, etc.). Ulcerative colitis and autoimmune diseases are less frequent. Available therapeutic tools (immunoglobulins, implantable venous accesses and BMT) are reasonably effective. AIDS in children can be either rapidly or slowly progressive, and is usually due to maternofetal transmission. Gastrointestinal lesions are non-specific (candidiasis, chronic malabsorptive diarrhea, hepatitis, cryptosporidiosis, CMV, giardiasis, herpes) and cause overall malnutrition. Early nutritional support is indicated, but the modalities and results remain to be determined.     

Comparing the spatial genetic structures of the Flavescence dorée phytoplasma and its leafhopper vector Scaphoideus titanus

The Nearctic leafhopper Scaphoideus titanus Ball is the vector of “Flavescence dorée” phytoplasma (FDp) in European vineyards. We studied the genetic diversity and structure of S. titanus populations in France and of the FDp they carried. A total of 621 S. titanus individuals, sampled in 24 FDp-infected and uninfected vineyards, were genotyped using seven polymorphic microsatellite loci. The mean observed heterozygosity in S. titanus populations was between 0.364 and 0.548. There was evidence of only a low level of population genetic differentiation (mean F_ST = 0.027) suggesting that there is long-distance gene flow between S. titanus populations. This may be a consequence of the high migration capacity of the vector associated with large effective population size and, at least in part, of passive dispersion over long distances by the transport of grapevine-planting material carrying eggs. For each insect, FDp was detected and typed by nested-PCR followed by RFLP and sequencing of a 674 bp fragment of the FDp map gene. Twelve of the 24 populations were found to be infected by FDp, with the percentage of infected individuals varying from 3% to 29%. FDp isolates were classified into two FDp genetic clusters (FD1 and FD2), which differed by 12–13 SNPs. FD1 genotypes were detected in the insect populations at two sites and the FD2 genotypes in the other ten populations. Both FD1 and FD2 genotypes were found to be transmitted by the insect. No significant relationship was found between the genetic structure of these French S. titanus populations and the distribution of the various FDp strain types they carried. Nevertheless, overall genetic differentiation between FDp-infected and healthy S. titanus “subsamples” was found to be significantly higher than zero. These results suggest that FDp-infected S. titanus individuals are more philopatric (disperse less) than healthy S. titanus.     

IGF-I : métabolisme et action physiologique

Insulin-like growth factor-I (IGF-I) was discovered on the basis of its ability to stimulate cartilage sulfation and to substitute for GH as determined using in vivo and in vitro systems. Now, IGF-I is considered as mediating the large majority of the effects of GH by both endocrine and autocrine/paracrine mechanisms. IGF-I can be produced by a wide variety of cell types but hepatic production is responsible for % 50 of circulating IGF-I. The IFG-I gene expression is controleed mainly by GH; but other hormones such as estradiol, andogrens and cortisol are involved in its modulation as well as nutritional status. IGF-I, a 70 amino acid polypeptide sharing % 40 of homology with proinsulin, is present in the circulation and throughout the extracellular space almost entirely (% 95 of circulating IGF-I) bound to members of a family of high affinity insulin-like growth factor binding proteins (IGFBSs), six of which have been cloned and sequenced. IGFBPs have been proposed to play several major functions that are essential to co-ordinate and regulate bioavailability and biological activities of IGF-I. Most of the cellular effects of IGF-I are mediated by binding to the IGF-I receptor whose structure is very close to that of insulin receptor. The effects of IGF-I in vitro are either acute anabolic effects on protein and carbohydrate metabolism or longer term mitogenic effects. IGF-I stimulates DNA synthesis, cell replication and cell proliferation ; it is also a potent inducer of several specific cell differenciation and has been described as an inhibitor of apoptosis. In vivo, mitogenic effect of IGF-I results in its role in postnatal growth and most of the promoting activity of GH are mediated by IGF-I. Metabolic effects of IGF-I are similar to that of insulin but the presence of IGFBPs, which prolong IGF actions, buffers the acute hypoglycaemic effects of IGF-I.     

Fatty Acids Profile and Cholesterol Contents of Three Brazilian Brycon Freshwater Fishes

This study was carried out to determine the cholesterol and fatty acids in muscle tissue (filet) of three in natura species of Brazilian fishes Brycon cephalus (matrinxã), B. microlepis (piraputanga) and B. orbignyanus (piracanjuba). The non-native fishes were collected in farms (cultured in pond and cages) near Maringá. The native species were collected in Cuiabá–Manso rivers (B. microlepis), and Paraná river (B. orbignyanus) that belong to the Platina hydrographic basin. Differences were observed (P<0.05) for moisture (70.48–74.06%), ashes (1.05–1.32) and crude protein (18.84–20.03%). The total lipids and cholesterol contents were found in the range of 2.49–7.94% and 40.99–52.79 mg/100 g, respectively. The native species presented the smallest values when compared to the non-native. All species presented oleic acid, C18:1 n -9, as predominant, (38.34–48.77%), followed by palmitic acid, C16:0, (21.90–26.57%) and stearic acid, C18:0, (8.32–15.66%). The largest amount of total n -3 polyunsaturated fatty acids was observed in the wild B. microlepis (3.61%) and B. orbignyanus (3.06%).