Interleukin-32 promotes detachment and activation of human Langerhans cells in a human skin explant model.

BACKGROUND: Cross-talk between skin keratinocytes (KCs) and Langerhans cells (LCs) plays a fundamental role in the body's first line of immunological defences. However, the mechanism behind the interaction between these two major epidermal cells is unknown. Interleukin (IL)-32 is produced in inflammatory skin disorders. We questioned the role of IL-32 in the epidermis. OBJECTIVES: We aimed to determine the role of IL-32 produced by KCs on surrounding LCs. METHODS: We used an ex vivo human explant model from healthy donors and investigated the role of IL-32 on LC activation using imaging, flow cytometry, reverse transcriptase quantitative polymerase chain reaction and small interfering (si)RNA treatment. RESULTS: Modified vaccinia virus ankara (MVA) infection induced KC death alongside the early production of the proinflammatory cytokine IL-32. We demonstrated that IL-32 produced by MVA-infected KCs induced modest but significant morphological changes in LCs and downregulation of adhesion molecules, such as epithelial cell adhesion molecule and very late antigen-4, and CXCL10 production. The treatment of KCs with IL-32-specific siRNA, and anti-IL-32 blocking antibody significantly inhibited LC activation, demonstrating the role of IL-32 in LC activation. We also found that some Toll-like receptor ligands induced a very high level of IL-32 production by KCs, which initiated LC activation. CONCLUSIONS: We propose, for the first time, that IL-32 is a molecular link between KCs and LCs in healthy skin, provoking LC migration from the epidermis to the dermis prior to their migration to the draining lymph nodes.

Artificial streams in the assessment of environmental hazard of chemicals.

Artificial streams are dynamic mesocosms, simulating aquatic systems and rivers. They are useful to study ecotoxicity of chemicals and their effects on flora and fauna colonizing the streams or introduced into the channels. These artificial rivers can also be used to study the influence of ecological and hydrodynamic parameters, such as the kind of substrate of river and flow rate. Responses of the bivalve Unio tumidus to substrate type (silt, sand, and pebbles) and water flow rate (high and low) were investigated after 15 and 35 days in the channels, in order to optimize the experimental conditions for ecotoxicity study with methyl methacrylate (MMA). The toxicological effects of different concentrations of MMA on bivalves and on communities of invertebrates and diatoms were determined after several weeks of exposure at a high flow rate. Biomarkers responses measured in the digestive gland and the gills of U. tumidus were the activities of detoxification systems as early indicators of toxicity and lipid peroxidation as a marker of cytotoxicity. Effects of MMA resulted in a decrease in antioxidant activities. Disturbances in bivalves appeared at lower concentrations than in communities. This indicates sensitivity of the biomarkers studied, which are predictive indicators of ecotoxicity.

[Management of other ectopic pregnancies (cornual, interstitial, angular, ovarian)]. / Prise en charge des autres ectopies annexielles (cornuale, interstitielle, angulaire, ovarienne).

OBJECTIVES: To provide recommendations for management of interstitial and ovarian pregnancies. MATERIALS AND METHODS: A Medline search was conducted and discussed by a study group of experts. RESULTS: Ovarian and interstitial pregnancies are rare forms of ectopic pregnancy. Diagnostic criteria and methods are described on the basis of a review of the literature. Surgery is the usual management of interstitial pregnancy. Conservative treatment has replaced hysterectomy. Laparoscopy is an attractive way to manage interstitial pregnancies but laparotomy may still be used. Cornual resection is required. Medical treatment with methotrexate is another alternative. Local MTX seems to be more efficient than systemic administration. Management of interstitial pregnancy under laparoscopic control is an attractive way if feasible. Strong recommendations cannot be established due to the small number of reported cases reports. The pre therapeutic score cannot be used as doses are still not clear for interstitial pregnancies. For ovarian pregnancy, management is often surgical. Laparoscopy is more and more used for small gestational sacs. Methotrexate has also been used for ovarian pregnancies. Laparoscopic treatment associated with systemic MTX seems to be the more efficient way. CONCLUSION: Because of limited data it is very hard to establish recommendations from low power studies (NP 5).

Patient-controlled epidural analgesia during labor: the effects of the increase in bolus and lockout interval.

UNLABELLED: Most studies use a bolus size of <6 mL of 0.125% bu- pivacaine for patient-controlled epidural analgesia (PCEA) during labor. In this double-blinded, randomized study, we compared the efficacy of a larger bolus injected via a PCEA pump to a conventional PCEA setting. By using a combination of 0.125% bupivacaine with 1:800,000 epinephrine and 0.625 microg/mL sufentanil, the first PCEA setting was typical (4 mL/8 min), whereas the other combined a 12-mL bolus dose and a 25-min lockout interval, i.e., similar maximal hourly dose. Rescue analgesia was provided with 6 mL of 0.25% bupivacaine. Patient satisfaction and pain were scored on verbal and visual analog scales. Data were analyzed from 103 parturients in the 12-mL/25-min group and 100 in the 4-mL/8-min group. In the 12-mL/25-min group, the median pain score on a 0- to 10-cm visual analog scale was lower at 6-cm cervical dilation (1 [range = 0-8] vs 3 [0-8]) and at delivery (1 [0-10] vs 2 [0-10]). Satisfaction was also better (70% vs 38% "excellent" opinions, at 6-cm cervical dilation). Use of the pump (ratio of successful and total demands) was high and similar in both groups. Rescue analgesia was comparable. Doses of analgesics were greater in the 12-mL/25-min group (hourly bupivacaine dose = 13.9 +/- 5.3 [mean+/- SD] vs 9.4 +/- 4.1 mg). No differences were noted between groups for the severity of hypotension, ephedrine requirement, outcome of the delivery, and Apgar scores. IMPLICATIONS: A patient-controlled epidural analgesia setting that allows a parturient to receive an increased analgesic dose improves satisfaction with patient-controlled epidural analgesia during labor.

"Cyclamen Red" colors based on a macrocyclic anthocyanin in carnation flowers.

The "cyclamen" red (or pink) colors in carnation flowers-cultivars Red Rox and eight others-are based on the presence of a new macrocyclic anthocyanin, pelargonidin 3,5-di-O-beta-glucoside(6' ', 6' "-malyl diester) identified by spectroscopic methods. The instability of the bridging malyl group with sugars in acidic medium readily causes the formation of the opened ring form, 3-O-(6' '-O-malylglucoside)-5-O-glucoside. The issue of cyclamen colors based in carnations on this original acylated pelargonidin derivative simulating those based on simpler cyanidin glycosides in Rosa cultivars is discussed using CIELAB colorimetric coordinates.

Induction of labor with mifepristone (RU 486) in intrauterine fetal death.

In a double-blind controlled multicentric study involving 94 patients with an intrauterine fetal death, we investigated the efficacy and tolerance of mifepristone (RU 486), a steroid compound that antagonizes progesterone action at the receptor level. Success of treatment was defined as the occurrence of fetal expulsion within 72 hours after the first drug intake. Mifepristone treatment (600 mg per day for 2 days) was considered to be effective in 29 of 46 patients (63%). There were only eight successes in 48 patients (17.4%) in the placebo group (p = 0.001, chi 2 test). Tolerance was good in the mifepristone group. In the placebo group, disseminated intravascular coagulation occurred in one woman for whom the investigator waited several weeks for spontaneous expulsion. This large double-blind controlled study provides evidence that mifepristone is of interest in the management of intrauterine fetal death. It could provide a pharmacologic alternative to the use of prostaglandins in this indication.

[Antithrombin III deficiency and pregnancy. Apropos of a case]. / Déficit en antithrombine III et grossesse. A propos d'un cas.

Congenital deficiency of antithrombin III is a disease inherited as an autosomal dominant which predisposes to thromboembolism. Pregnancy and the postpartum period constitute a major additional risk factor for thromboembolism in deficient women. However, pregnancy may be envisaged without risk since there has been an improvement in knowledge concerning the physiology of the AT III molecule, its exact role in coagulation, the application of accurate laboratory tests which measure the deficiency, and especially the programming of pregnancy under cover of preventive treatment consisting of the perfusion of AT III concentrate in association with heparin. The treatment is restricting and costly but is, nevertheless, the only one to recreate conditions that are similar to physiological conditions, and its effect is therefore more certain.

Renal, pancreatic and hepatic dysplasia sequence.

A renal, pancreatic and hepatic dysplasia sequence (RPHD sequence) was found in a male premature baby who died a few minutes after birth. Autopsy documented multicystic dysplastic kidneys, a dysplastic pancreas with dilated ducts, cysts, fibrosis and inflammatory infiltrates, prominent portal tracts containing dilated bile ducts and hypoplastic lungs. Other organs were normal. This triad constitutes a "dysplastic sequence" and was first reported by Ivemark et al. as "familial dysplasia of kidneys, liver and pancreas". Since then, this combination of abnormalities has been named "polycystic dysplasia" and "renal-hepatic-pancreatic dysplasia", but mostly "Ivemark syndrome", at the risk of being confused with asplenia-cardiac anomaly syndrome, which was reviewed by Ivemark et al. and also bears Ivemark's name.

[Anorexia nervosa and pregnancy]. / Anorexie mentale et grossesse.

We report the case of a pregnancy associated with severe anorexia nervosa. The patient weighed 33 kg for 1 m 51 at conception. The pregnancy was obtained during a spontaneous cycle. Despite nutritional and psychological case, the patient continued to lose weight and weighed only 28 kgs at 33 weeks of amenorrhea, when she gave birth to a hypotrophic child of 1130 gr after artificial starting. The case provides discussion of the relation ship between anorexia nervosa and pregnancy.

[Uterine rupture after tubal reimplantation]. / Rupture utérine après réimplantation tubaire.

The authors report a case of rupture of the right cornu of the uterus in the ninth month of pregnancy in a woman who had had her right tube implanted into her uterus. This complication is considered, in the discussion, to be rare. It is very difficult to prevent it happening during pregnancy. It would seem that a prophylactic caesarean operation should be carried out if the insertion of the placenta is in the area of the implantation.

[Cancer of the ovary and pregnancy. Apropos of 4 cases]. / Cancer de l'ovaire et grossesse. A propos de 4 cas.

The value and the limitations of echo scans and extemporaneous examination in four cases are reported. Any adnexial organic tumour should be treated in the knowledge that it could be a cancer of the ovary. This is the only possible approach for avoiding contamination during surgery insufficient exoresis and the necessity of further intervention.

Comparative study of methods chosen by the Association Française de Normalisation (AFNOR) for evaluating sensitizing potential in the albino guinea-pig.

An evaluation was made of the different protocols recommended by the Association Française de Normalisation (AFNOR) for assessing the sensitizing potential of chemicals in the guinea-pig. The methods studied were those of Magnusson & Kligman (J. invest. Derm. 1969, 52, 268), Maguire (J. Soc. cosmet. Chem. 1973, 24, 151), Maurer et al. (Agents & Actions 1975, 5, 174), Klecak et al. (J. Soc. cosmet. Chem. 1977, 28, 53), Dossou & Sicard (1984, to be published) and a hitherto unpublished method of Guillot, Gonnet, Clément & Brulos. Results obtained by each method were compared in tests on the allergenic reference substances dihydrocoumarin, p-phenylenediamine, formalin, penicillin G and benzocaine (ethoform) and on propylene glycol (negative control). The results showed that the number of animals sensitized often varies with the choice of experimental protocol, that inclusion of tests on a control substance is essential, and that while quantitative differences were found, the methods were qualitatively similar in their capacity to identify allergens in the guinea-pig.

Anti-irritant potential of cosmetic raw materials and formulations.

Synopsis The investigation studied the anti-irritant potential of several substances commonly employed in cosmetic formulations as basic components of the emulsion or as active ingredients, and evaluated the effect of the emulsifier. Five different emulsions were made irritating by addition of croton oil, in sufficient quantity to provoke a clearly adverse reaction in the rabbit, i.e. primary cutaneous irritation index (PII) close to 2. The PII was determined according to the official French methods by applying to symmetrical areas of the back, the irritant base as control and the same base containing the test substance. Fifty-five ingredients were evaluated: gelling agents, plant extracts, molecules defined as healing, anti-inflammatory substances or anaesthesic compounds, etc. The test substances were added to the emulsion at concentrations close to the ones generally found in cosmetics. The qualitative and the quantitative composition of the oil phase was similar for each emulsion. Several gelling agents, thickeners and polymers which notably reduce skin contact with an irritant, gave good results. Some of the usual healing, anti-inflammatory, local anaesthesic compounds gave the expected results. Some ingredients, though well known, were ineffective. The type of emulsifier, by modifying cutaneous penetration and bio-availability of the active ingredients, may play an important role.

Evaluation of the cutaneous-irritation potential of 56 compounds.

The primary cutaneous irritation of 56 chemicals was tested in the rabbit using three different procedures. The three protocols selected for the tests were the method published by the French authorities for the testing of cosmetics and toiletries (Journal Officiel 21 April 1973, p. 3862; ibid 5 June 1973, p. 3953) and the methods proposed for the testing of chemicals by the Association Française de Normalisation (AFNOR) and, in 1979, by the Organisation for Economic Co-operation and Development. The results of the three sets of tests were compared and the effects of differences in procedure and numbers of animals were studied, together with the possible relation between irritancy and the pH of the test material. It was concluded that the AFNOR protocol best met the requirements for such tests and that gloves should be worn for the handling of all substances classified as moderately or severely irritant on that scale.