Variations in zearalenone activation in avian food species.

Zearalenone (ZEA), a widely distributed oestrogenic fusariotoxin, constitutes a potential risk for human and animal health. ZEA is metabolised to the main metabolites identified in vitro and in vivo: alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). The efficiency to produce alpha-reduced metabolites appears of particular interest in risk assessment as alpha-reduced metabolites constitute activated forms whereas beta-reduced metabolites are less oestrogenic than ZEA. In this study ZEA activation was compared in avian food species. ZEA and its reduced metabolites were quantified in subcellular fractions of six avian species and rat livers. The alpha-ZOL/beta-ZOL ratio in rats was 19. The various avian food species cannot be considered to be equivalent in terms of ZEA reduction (P<0.001). Quails represented high "beta reducers", with alpha-ZOL/beta-ZOL ratio less than two. Weak "beta reducers" included on one part ducks and chickens showing alpha-ZOL/beta-ZOL ratio greater than 3 and up to 5.6 and on a second part geese, showing a lower production of alpha-ZOL than other poultry. Comparisons of enzyme kinetics in ducks and in quails show that these variations can be explained by the action of various isoforms of dehydrogenases. These results are relevant to food safety, in the context of frequently inevitable contamination of animal feed.     

Clinical mitochondrial dysfunction in uninfected children born to HIV-infected mothers following perinatal exposure to nucleoside analogues

Clinical and biological observations of mitochondrial dysfunction in children exposed to zidovudine (azidothymidine, AZT) during the perinatal period rapidly followed similar observations in animal experiments. To date, two different disorders have been identified. The first, asymptomatic hyperlactatemia, is observed during treatment in one third of exposed newborns, and is reversible with treatment cessation. In rare cases, it is associated with symptomatic acidosis. Regression may be slow, taking up to several months after the end of the treatment. The long-term clinical consequences of this biochemical disturbance are unknown. The second disorder involves severe neurological symptoms, which become clinically detectable during the first 2 years of life. These symptoms are associated with a series of biochemical and ultrastructural changes consistent with persistent mitochondrial dysfunction. This latter phenomenon is rare, and affects only 0.3-0.5% of exposed children in the French pediatric cohort, in which observations continue. Despite initial controversy, several similar observations in other cohorts have since confirmed its occurrence. The pathophysiology of these two mitochondrial dysfunctions may differ. Continued efforts to identify and understand clinical mitochondrial toxicities are essential, given the intensification and diversification of perinatal prophylaxis strategies, and the number of pregnant women potentially involved.     

Identification of a hemagglutinin-specific idiotype associated with reovirus recognition shared by lymphoid and neural cells

A xenogeneic antiserum raised to antireovirus immunoglobulin was used to define an idiotypic determinant present on antibodies to reovirus type 3 hemagglutinin. The same idiotype was identified on nonimmune lymphoid cells and on neuronal cells that specifically bind the hemagglutinin of type 3 reovirus. This idiotypic determinant, called Id3, is shared by (a) a monoclonal antibody to the neutralization site of hemagglutinin from type 3 reovirus; (b) BALB/c serum antibodies to the hemagglutinin of reovirus type 3; (c) R1.1, a murine thymoma cell line that binds reovirus type 3; (d) primary cultures of murine neuronal cells. The presence of an idiotype shared by antihemagglutinin antibodies and by structures on nonlymphoid cells suggests a general relationship between disparate receptors that recognize a common determinant. Furthermore, this suggests a novel approach for the study of viral receptor interactions and for analysis of mechanisms of autoimmune responses.     

Low-energy He/Ne laser in the prevention of radiation-induced mucositis

 Use of the low-energy helium-neon laser (LEL) appears to be a simple atraumatic technique for the prevention and treatment of mucositis of various origins. Preliminary findings, and significant results obtained for chemotherapy-induced mucositis in a previous phase III study, prompted a randomized multicenter double-blind trial to evaluate LEL in the prevention of acute radiation-induced stomatitis. Irradiation by LEL corresponds to local application of a high-photon-density monochromatic light source. Activation of epithelial healing for LEL-treated surfaces, the most commonly recognized effect, has been confirmed by numerous in vitro studies. The mechanism of action at a molecular and enzymatic level is presently being studied. From September 1994 to March 1998, 30 patients were randomized. Technical specification: 60 mW (25 mW at Reims, 1 patient), He-Ne, wavelength 632.8 nm. The trial was open to patients with carcinoma of the oropharynx, hypopharynx and oral cavity, treated by radiotherapy alone (65 Gy at a rate of 2 Gy/fraction, 5 fractions per week) without prior surgery or concomitant chemotherapy. The malignant tumor had to be located outside the tested laser application areas (9 points): posterior third of the internal surfaces of the cheeks, soft palate and anterior tonsillar pillars. Patients were randomized to LEL or placebo light treatment, starting on the first day of radiotherapy and before each session. The treatment time (t) for each application point was given by the equation : t (s)=energy (J/cm²)×surface (cm²)/Power (W). Objective assessment of the degree of mucositis was recorded weekly by a physician blinded to the type of treatment, using the WHO scale for grading of mucositis and a segmented visual analogue scale for pain evaluation. Protocol feasibility and compliance were excellent. Grade 3 mucositis occured with a frequency of 35.2% without LEL and of 7.6% with LEL (P<0.01). The frequency of "severe pain" (grade 3) was 23.8% without LEL, falling to 1.9% with LEL (P<0.05). Pain relief was significantly reduced throughout the treatment period (weeks 2–7). LEL therapy is capable of reducing the severity and duration of oral mucositis associated with radiation therapy. In addition, there is a tremendous potential for using LEL in combined treatment protocols utilizing concomitant chemotherapy and radiotherapy. Published online: 28 May 1999     

Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans

PURPOSE OF REVIEW: Herpes simplex encephalitis is a rare complication of herpes simplex virus 1 infection that strikes otherwise healthy individuals. Its pathogenesis has long remained elusive. We highlight the investigations dealing with the genetic basis of herpes simplex encephalitis in mice and humans. RECENT FINDINGS: Mouse models have revealed the impact of various host genes on protective immunity to herpes simplex encephalitis through strain-dependent variability (forward genetics) and via targeted knockouts (reverse genetics). These studies established in particular the crucial role of IFNalpha/beta in immunity to herpes simplex virus 1, paving the way towards the elucidation of the genetic cause of human herpes simplex encephalitis. Two children with rare, specific STAT1 or NEMO mutations displayed a broad impairment of IFNalpha/beta and IFNlambda-mediated immunity and predisposition to several infectious diseases including herpes simplex encephalitis. In contrast, children with UNC93B1 and TLR3 mutations displayed a selective impairment of dsRNA-induced IFNalpha/beta and IFNlambda production and predisposition to isolated herpes simplex encephalitis. SUMMARY: Herpes simplex encephalitis results from a series of monogenic primary immunodeficiencies that impair the TLR3 and UNC-93B-dependent production of IFNalpha/beta and IFNlambda in the central nervous system, at least in a fraction of children. This is not only crucial for the understanding of immunity to herpes simplex virus 1, but also for the diagnosis and treatment of herpes simplex encephalitis.     

Ethical issues and dentists' practices with children with intellectual disability: A qualitative inquiry into a local French health network

Background

The provision of dental care for children with intellectual disability raises many ethical questions.

Declining rates of gonorrhoea and syphilis in Strasbourg, France: a 20-year study.

OBJECTIVE--To report the epidemiology of gonorrhoea and syphilis during the years 1973-1992 in the Strasbourg STD clinic and to discuss the data in the light of changes in STD rates in western countries. DESIGN--Retrospective analysis of gonorrhoea and syphilis cases recorded annually, total number of consultations, HIV serology, STD among prostitutes. SETTING--Strasbourg, Bas-Rhin, FRANCE. SUBJECTS--Patients attending the public STD clinic in Strasbourg. RESULTS--From 1973 to 1992 79,786 consultations were recorded. Since 1984, a regular fall has been noted, from more than 4500 consultations a year in the 1970s, to 1519 consultations in 1992. A major decline in gonorrhoea was observed, especially since 1984. There were 457 new cases in 1973 (15.3% of all patients) whereas only seven new cases in 1992 (0.8% of all patients). Syphilis has been declining regularly since 1979, with a reinforcement in this decline since 1984: 168 cases were recorded in 1972 (6.4% of all patients), and only two cases in 1992 (0.2% of all patients). Positive HIV tests were found in 14% and 12% of patients in 1985-86, and the positivity rate has regularly decreased to reach 0.6% in 1992. Prostitutes represented 9.2% of all patients in 1980, and only 0.8% of patients in 1992. Since 1987, syphilis and gonorrhoea have been rarely recorded among prostitutes. CONCLUSIONS--A dramatic decline in both gonorrhoea and syphilis has been observed in Strasbourg, especially since 1984, with a parallel diminution in the STD clinic frequentation. A comparable trend in gonorrhoea rates was noted in many western countries, but syphilis rates are more heterogeneous among geographic areas. Changes in sexual behaviour due to the AIDS epidemic are probably responsible in part for this decline, but nevertheless the rarity of gonorrhoea and syphilis in Strasbourg in 1992 is not clearly explained.