[Epidemiology and burden of rotavirus diarrhea in day care centers in Lyon, France]. / Epidémiologie et impact de la gastroentérite aiguë à rotavirus dans les crèches municipales de la ville de Lyon - saison 2004-2005.

Rotavirus is the main cause of severe, dehydrating diarrhoea in infants and young children. In industrialized countries, pediatric rotavirus gastroenteritis (PRGE) is responsible for high morbidity, particularly among children under 3 years of age attending day care centers (DCCs). The objectives of this study were to estimate the incidence, management and cost of PRGE in DCCs. We also described the nature of group A rotavirus genotypes. This study also compared the performance of different diagnostic techniques. The study was conducted from November 2004 to May 2005. Children aged less than 36 months, attending a participating DCC at least 4 times a week were included in the study. For any episode of acute gastroenteritis (AGE), defined as the occurrence of 3 or more watery or looser than normal stools and/or forceful vomiting within a 24 h period, a fecal specimen was tested by Elisa test IDEIA Rotavirus (Dako) and the immunochromatographic test VIKIA Rota-Adeno (BioMérieux). Sequencing by RT-PCR was performed to identify the rotavirus genotype. Among the 41 DCCs contacted, 18 (43.9%) agreed to participate. Out of 966 children, 547 attended a participating DCC at least 4 times a week and met the inclusion criteria. A total of 302 were included in the study. The clinical diagnosis of AGE was confirmed and validated, by the Elisa test, in 63 fecal specimens, of which 29 (46%) were positive for rotavirus antigen, with a predominance of P[8]G9 (86%). Our results showed good sensitivity and specificity for the VIKIA and Elisa methods when compared to RT-PCR. Among the PRGE cases, 36% were male and the median age was 12.2 months. The first rotavirus case was observed in December 2004 with a peak in January 2005. The incidence of PRGE cases was 2.2 [1.4-3.0] per 100 child-months in children aged less than 36 months of age, increasing to 3.4 per 100 child-months among children aged less than 24 months. Vomiting (P<0.0005) and behavior modification (P<0.001) were significantly more frequent for PRGE cases. A total of 85.7% PRGE cases sought medical attention. In 58.3% of these cases, at least one parent had to miss work for a mean duration of 2.1 days. The total cost of rotavirus cases seeking medical attention (with or without prescribed medication, days off work for parents or additional diaper consumption) was estimated at 275.54 euros/case. The PRGE incidence rate is similar to that estimated in European studies conducted in DDC. These findings confirm that rotavirus transmission occurs not only in DCCs but within the family. This is the first study to give an estimate of the incidence and the cost of rotavirus infection in DCCs in France.

Synthesis and cytotoxicity on sensitive and doxorubicin-resistant cell lines of new pyrrolo[2,1-c][1,4]benzodiazepines related to anthramycin.

A new 7,8-methylenedioxy analogue (4) of (+)-porothramycin B (2) and its water-soluble sodium bisulfite derivative (15) have been synthesized in high yields and have been shown to exhibit high cytotoxic activities against several tumor cell lines. The new pyrrolo[2,1-c][1,4]benzodiazepine 4 was as effective against the resistant cell lines as against the doxorubicin-sensitive cell lines tested.

Cytotoxic activities of novel hexahydroindolizino[8,7-b]indole derivatives prepared by 1,3-dipolar cycloaddition reactions of 3,4-dihydro-beta-carboline ylides.

A series of 1-cyano and 2-cyanohexahydroindolizino[8,7-b]indole derivatives was prepared by 1,3-dipolar cycloaddition of acrylonitrile with ylides derived from 3,4-dihydro-beta-carboline and its 6-methoxy, 6-benzyloxy, 9-methyl and 9-benzyl analogues. The products, together with their reduced 1- or 2-aminomethyl derivatives, were evaluated for cytotoxic activity in L1210 cancer cells. Compounds derived from 6-benzyloxy or 9-benzyl-3,4-dihydro-beta-carboline were found to be the most active, with IC(50)'s in the 2-50 microM range. Of these, two compounds, the 1- and 2-cyano 8-benzyloxyindolizino[8,7-b]indole derivatives 20a and 20c, respectively, were found by cytometric flux analysis to stop cancer cell growth at the G(2)M and 8N (>G(2)M) stage of the cell cycle. These two compounds also showed no loss of cytotoxic activity in K562R cancer cells resistant to doxorubicin.

New synthesis of benzo-delta-carbolines, cryptolepines, and their salts: in vitro cytotoxic, antiplasmodial, and antitrypanosomal activities of delta-carbolines, benzo-delta-carbolines, and cryptolepines.

The paper describes, in its first part, a new synthesis of benzo-delta-carbolines, cryptolepines, and their salts. The strategy is based on the association between halogen-dance and hetero-ring cross-coupling. It is fully convergent and regioselective with interesting overall yields from 27% to 70%. A halogen-dance mechanism in quinoline series is also proposed. The formal synthesis of potential antimalarial compounds and the first total synthesis of 11-isopropylcryptolepine are also described. In the second part, cytotoxic activity against mammalian cells and activities against Plasmodium falciparum and Trypanosoma cruzi of benzo-delta-carbolines and delta-carbolines were evaluated in vitro to study the structure-activity relationships. For benzo-delta-carbolines, methylation at N-5 increases the cytotoxic and antiparasitic activities. A further alkylation on C-11 generally increases the cytotoxic activity but not the antiparasitic activity, cryptolepine and 11-methylcryptolepine being the most active on both parasites. Taking advantage of the fluorescence of the indoloquinoline chromophore, cryptolepine was localized by fluorescence microscopy in parasite DNA-containing structures suggesting that these compounds act through interaction with parasite DNA as proposed for cryptolepine on melanoma cells. For delta-carbolines, methylation at N-1 is essential for the antimalarial activity. 1-Methyl-delta-carboline specifically accumulates in the intracellular parasite. It has weak cytotoxic activity and can be considered as a potential antimalarial compound.

Synthesis and cytotoxicity of gossypol related compounds.

Gossypol, gossypolone, reduced gossypol and new Schiff's bases of racemic gossypol and gossypolone were extracted or synthesized. Their cytotoxic activities on KB human cancer cells were determined. Gossypolone and the ethylamine derivative of gossypolone were the most active compounds (IC(50) in the micromolar range in both cases). The cytotoxicity of gossypol and gossypolone was increased when the tests were performed in the absence of serum and decreased when catalase as well as mannitol were added to the culture medium.

Cytotoxic 3,4-secoapotirucallanes from Aaglaia argentea bark.

Nine 3,4-secoapotirucallanes, argentinic acids A-I, were isolated from the bark of Aglaia argentea and transformed to their methyl esters 1-9. The structures were determined by spectral and chemical means. Compounds 1-8 showed moderate cytotoxic activity against KB cells (IC50 1.0-3.5 microg/mL).

Neurohormonal stimulation of histamine release from neuroendocrine cells of the human adenomatous prostate.

BACKGROUND: Neuroendocrine cells (NE) constitute a population of highly specialized cells in prostatic glands; histamine has never been described in these cells. This article shows the presence and the regulation of release of histamine in NE. METHODS: In 21 prostatic adenomas, NE were identified by specific antisera against neuroendocrine markers (chromogranin-A, synaptophysin), histamine, and histidine decarboxylase (HDC); a rate HDC-cDNA probe was used to detect this enzyme by in situ hybridization. RESULTS: Immunoreactive cells for chromogranin-A, histamine, and HDC were found among luminal epithelial glandular cells. Similar cells were also labeled with the HDC-cDNA probe. Glandular cells, isolated from prostatic adenomas, were shown to contain histamine (7-40 pmol/mg cellular protein). L(-) norepinephrine causes a time-dependent (t1/2 = 22 min) histamine release; the alpha 1-receptor antagonists WB-4101 and YM-617 specifically inhibited this release, in agreement with a mediation by alpha 1-adrenoreceptor subtype. CONCLUSIONS: There is some evidence for the presence in prostatic adenomas of histamine-forming cells of neuroendocrine type; histamine release from these cells is under the control of alpha 1-adrenoreceptor subtype.