Ozocardic A: a new alkylanacardic acid from Ozoroa pulcherrima

One new alkylanacardic acid, ozocardic A (1), along with the known and related metabolites 6-tridecyl anacardic acid (2) and β-sitosterol (3) was isolated from Ozoroa pulcherrima. The structure of the new compound was elucidated by detailed spectroscopic analysis such as ¹H, ¹³C NMR, COSY, HMQC, HMBC, and HREIMS. The structures of known compounds (6-tridecyl anacardic acid (2) and β-sitosterol (3)) were identified by the comparison of their spectral data with those published in the literature.     

INCREASED APOPTOSIS,CHANGES IN INTRACELLULAR Ca2+, AND FUNCTIONAL ALTERATIONS IN LYMPHOCYTES AND MACROPHAGES AFTER IN VITRO EXPOSURE TO STATIC MAGNETIC FIELD

Electromagnetic-related alteration of cellular functions is well documented for extremely low-frequency low-energy pulsing electromagnetic fields (ELF-EMF). In this study we examined the in vitro effects of static magnetic fields (SMF) on the cellular immune parameters of the C57Bl/ 6 murine macrophages, spleen lymphocytes, and thymic cells. The cells were exposed in vitro for 24 h at 37 C, 5% CO2, to 250-1500 G SMF. Exposure to the SMF resulted in the decreased phagocytic uptake of fluorescent latex microspheres, which was accompanied by an increased intracellular Ca2+ level in macrophages. Exposure to SMF decreased mitogenic responses in lymphocytes, as determined by incorporation of [3H]thymidine into the cells. This was associated with the increased Ca2+ influx in concanavalin A-stimulated lymphocytes. Furthermore, exposure to SMF produced markedly increased apoptosis of thymic cells, as determined by flow cytometry. Overall, in vitro exposure of immunocompetent cells to 250-1500 G SMF altered several functional parameters of C57Bl/6 murine macrophages, thymocytes, and spleen lymphocytes.     

Calcium,magnesium, sodium and potassium levels in foodstuffs from the second French Total Diet Study

Calcium (Ca), magnesium (Mg), sodium (Na) and potassium (K) contents in 1319 foodstuffs habitually consumed by the French population were determined for the second French Total Diet Study (TDS), using micro-sampling flame atomic absorption spectrometry after microwave-assisted digestion. Concentration and distribution of these minerals in food samples were reported and compared with results from the previous French TDS. For Ca, the results indicate that the food presenting the highest levels are dairy products (1597 mg kg^?1), tofu (802 mg kg^?1) and some fish and cereal products; for Mg, tofu (1340 mg kg^?1), “Sweeteners, honey and confectionery” (672 mg kg^?1) especially dark chocolate (2225 mg kg^?1) and certain grains such as nuts and oilseeds (1069 mg kg^?1) and some cereal products; for Na, processed meats such as delicatessen (12,422 mg kg^?1), “Salts, spices, soup and sauces” (21,028 mg kg^?1), some cheeses and cereal products; and for K, “Cereal and cereal products” (4378 mg kg^?1), “Meats and offal” (3993 mg kg^?1), “Nuts and oilseeds” (7355 mg kg^?1) and “Sweeteners, honey and confectionery” (3445 mg kg^?1) (especially chocolate).     

The Aging Males' Symptoms (AMS) scale: Update and compilation of international versions

Background

The interest of clinical research in aging males increased in recent years and thereby the interest to measure health-related quality of life (HRQoL) and symptoms of aging men. The Aging Males' Symptoms scale (AMS) became the most commonly used scale to measure HRQoL and symptoms in aging males in many countries worldwide. The aim of this paper is to review the current state of the instrument particularly concerning versions of the scale in different languages in the light of the quality of the translation process.

AMS versions available

Most of the translations were performed following international methodological recommendations for linguistic & cultural adaptation of HRQoL instruments. Mainly the English version was used as source language for the translation into Dutch, Spanish, Portuguese, Italian, Swedish, and Japanese (attached as additional PDF-files). Preliminary versions that were derived only from forward translations are of secondary quality and available in Finnish, Flemish, and Russian. It is recommended to complete the translation process for the latter languages before using them in international studies.

Translations in process

The AMS scale is in the process of consensus finding of two existing French versions, and the versions in the Korean, Thai, and Indonesian languages have not yet been completed in the translation process.

Conclusion

The AMS scale is obviously a valuable tool for assessing health related quality of life in aging men, because it is used worldwide. It is a standardized scale according to psychometric norms. Most of the currently available language versions were translated following international standards for linguistic and cultural translation of quality of life scales. Assistance is offered to help interested parties in the translation process.     

Targeting of HIV-p24 particle-based vaccine into differential skin layers induces distinct arms of the immune responses

Skin routes of immunization such as subcutaneous (SC), intradermal (ID) and transcutaneous (TC) administration are utilized for vaccination against various pathogens, without understanding their potential impact on the outcome of immune responses. We demonstrated that SC immunization induced HIV-1 p24 specific IgG in absence of antigen-specific CD8 T cells, whereas the ID route induced both cellular and humoral responses. Interestingly, TC application through empty hair follicular ducts, targeting epidermal Langerhans Cells (LCs), induced major CD8 effector cells, in the absence of IgG. However, high levels of mucosal IgA, were localized in the stratified epithelium of the vagina after TC prime. We propose that re-directing the immune responses by targeting differential skin immunization routes, offers enormous potential for innovative vaccination strategies, especially against HIV.     

Uterine scars and subsequent vaginal birth: follow-up of 73 parturients in the Central Maternity Hospital of Bangui (Central African Republic)

Uterine rupture is a threat during vaginal deliveries of women with uterine scars from previous caesarean deliveries or other surgery. Special prudence among this group has resulted in a rise of cesarean rates in developed countries but also in Africa. The lack of available data in this domain in our country led us to conduct this preliminary study, with the objectives of: determining the frequency of deliveries among these patients and of the complications associated with them; identifying some of the risk factors and assessing maternal and fetal prognosis. This should facilitate further studies to determine the management attitudes most appropriate to the realities of our health system. We conducted a cross-sectional study during the last six months of 1999 at the central maternity hospital in Bangui. We included in this study only women with previous caesarean scars giving birth again during the study period. We followed them from admission to the labour room until discharge, without intervening in their delivery. Structured questionnaires enabled us to collect data on clinical, social and demographic variables. We recorded 74 births, including one set of twins, among the 73 parturient subjects. Vaginal delivery occurred in 45 cases (60.8%), and caesarean in 29. Women with a single uterine scar gave birth by vaginal delivery significantly more often than they had caesareans. We recorded 7 cases of uterine rupture, most often associated with a birth interval less than 2 years. One uterine rupture led to the mother's death. Perinatal mortality was 10.8%: no newborn survived these uterine ruptures. Vaginal delivery remains possible for women with uterine scars when adequate monitoring of a trial of labor is available and on condition that the pelvis is normal and the birth interval exceeds two years.     

A novel mutation disrupting the cytoplasmic domain of CRB1 in a large consanguineous family of Palestinian origin affected with Leber congenital amaurosis

Leber congenital amaurosis (LCA) is a genetically heterogeneous autosomal recessive condition responsible for congenital blindness or greatly impaired vision since birth. Eight LCA loci have been mapped, but only six out of eight genes have been hitherto identified. A genome-wide screen for homozygosity was conducted in a large consanguineous family originating from Palestine, for which no mutation was found in any of the six known LCA genes and that excluded the LCA3 and LCA5 loci. Evidence for homozygosity, however, was found in all affected patients of the family on chromosome 1q31, a region in which the human homologue of the Drosophila melanogaster crumbs gene (CRB1) has been mapped. Consequently, we proposed a hypothesis that the disease-causing mutation in this family might lie in an unexplored region of this LCA gene. As a matter of fact, while no mutation was found in any of the 11 CRB1 exons originally reported, we identified a 10-bp (del 4121-4130) deletion segregating with the disease in a later reported 12th exon lying in the 3' end of the gene. Interestingly, this deletion disrupts an amino acid sequence that was shown to be crucial for the function of the protein in the Drosophila counterpart (CRB).     

Rebeccamycin derivatives as dual DNA-damaging agents and potent checkpoint kinase 1 inhibitors

Rebeccamycin is an indolocarbazole class inhibitor of topoisomerase I. In the course of structure-activity relationship studies on rebeccamycin derivatives, we have synthesized analogs with the sugar moiety attached to either one or both indole nitrogens. Some analogs, especially those with substitutions at the 6' position of the carbohydrate moiety, exhibit potent inhibitory activity toward checkpoint kinase 1 (Chk1), a kinase that has a major role in the G(2)/M checkpoint in response to DNA damage. Some of these compounds retained a genotoxic activity either through intercalation into the DNA and/or by topoisomerase I-mediated DNA cleavage. We explored the structure-activity relationship between these compounds and their multiple targets. These rebeccamycin derivatives represent a novel class of potential antitumor agents that have a dual effect and might selectively induce the death of cancer cells.     

Age-dependent variations of human and rat colon myofibroblasts in culture: Influence on their functional interactions with colon cancer cells

Epithelial-mesenchymal interactions play a pivotal role in colon cancer invasion and metastasis. We aimed at elucidating the impact of long-term cultivation on the phenotypic and functional characteristics of primary fibroblasts and their interaction with the human colon adenocarcinoma cell line LoVoC5. We used fibroblasts from human colon tumor tissue, normal human colon mucosa, rat normal colon and 2 rat colon-derived myofibroblast cell lines, MIC316 and MG. The following parameters were studied: cell shape and size, growth curve, intermediate filament expression and extracellular matrix synthesis. Coculture models with or without cell contacts were used to test the effects on LoVoC5 cell proliferation, spreading and adhesion. Irrespective of their origin, fibroblastic cells in primary cultures presented marked phenotypic and functional changes with time. Before passage 5, they presented as large, slow-growing cells expressing vimentin and alpha-smooth muscle actin; synthesizing laminin-1, fibronectin and collagens I and IV; and inducing LoVoC5 proliferation, spreading and adhesion. After passage 15, they presented as small, fast-growing cells inconstantly expressing alpha-smooth muscle actin and synthesizing mainly type I collagen. In coculture with or without cell contacts, they inhibited LoVoC5 proliferation and allowed only limited cell spreading and adhesion. Myofibroblastic cell lines presented as large, fast-growing cells expressing vimentin and alpha-smooth muscle actin and synthesizing mainly type I collagen. They had no significant effects on LoVoC5 proliferation, spreading and adhesion. Our results underline the importance of age-dependent variations in colon mesenchymal cells in culture and for the in vitro study of epithelial-mesenchymal interactions in colon cancer.     

Clinical pharmacokinetics of the antitumor drug navelbine (5'-noranhydrovinblastine)

Eleven patients with advanced cancer received navelbine (15 mg/m2) as a single i.v. bolus injection. At least 1 week later, the patients were given a 2-fold increased dose of navelbine (30 mg/m2) and, for seven of them, the 30-mg/m2 dose was repeated after a delay longer than a week. After each administration, plasma and urine were collected for 72 h and monitored for navelbine concentration by radioimmunoassay. The comparison of dose-normalized plasma level profiles showed significant time dependence (P less than 0.05) in four of the seven assessable patients. Some patients also exhibited significant (P less than 0.05) nonlinear (dose dependent) kinetic profiles. Only 3 of the 10 appreciable patients were characterized by both time independent and linear profiles. However, the plasma concentration decay curves presented a triphasic shape similar to that obtained with other antitumor Vinca alkaloids and the data were consistent with a three-compartment pharmacokinetic model. The dose and/or time dependence evidenced for most of the patients did not result in marked changes in pharmacokinetic parameters among courses. The pharmacokinetics of navelbine were characterized by a high plasma clearance (0.27 to 1.49 liter.h-1.kg-1), a large distribution volume (8.2 to 48.2 liter.kg-1), and a long terminal half-life (22.1 to 67.8 h). Urine excretion was low (less than 7.9%). Thus, navelbine pharmacokinetics resembles that of other antitumor Vinca alkaloids.