Neurologic Disorders in Immunocompetent Patients with Autochthonous Acute Hepatitis E.

Neurologic disorders, mainly Guillain-Barré syndrome and Parsonage­Turner syndrome (PTS), have been described in patients with hepatitis E virus (HEV) infection in industrialized and developing countries. We report a wider range of neurologic disorders in nonimmunocompromised patients with acute HEV infection. Data from 15 French immunocompetent patients with acute HEV infection and neurologic disorders were retrospectively recorded from January 2006 through June 2013. The disorders could be divided into 4 main entities: mononeuritis multiplex, PTS, meningoradiculitis, and acute demyelinating neuropathy. HEV infection was treated with ribavirin in 3 patients (for PTS or mononeuritis multiplex). One patient was treated with corticosteroids (for mononeuropathy multiplex), and 5 others received intravenous immunoglobulin (for PTS, meningoradiculitis, Guillain-Barré syndrome, or Miller Fisher syndrome). We conclude that pleiotropic neurologic disorders are seen in HEV-infected immunocompetent patients. Patients with acute neurologic manifestations and aminotransferase abnormalities should be screened for HEV infection.

On the cation dependence of interlamellar and interparticular water and swelling in smectite clays.

The osmotic character of long-range interlamellar swelling in smectite clays is widely accepted and has been evidenced in the interlayer space by X-ray diffraction. Such a behavior in mesopores was not experimentally confirmed until the determination of the mesopore size distribution in Na-montmorillonite prepared from MX80 bentonite using thermoporometry experiments. This is confirmed here for other montmorillonite samples where the interlayer cations are alkaline and Ca(2+) cations. The nature of the interlayer cation is found as strongly influencing the behavior of the size and the swelling of mesopores. These results are supported by the BJH (Barrett, Joyner and Halenda) pore radius values issued from the nitrogen adsorption-desorption isotherms at the dry state. Thermoporometry results as a function of relative humidity ranging from 11% to 97% have shown an evolution of the mesopore sizes for a purified Na-montmorillonite. New thermoporometry data are presented in this article and confirm that the interparticle spaces in K-, Cs-, or Ca-montmorillonites are not strongly modified for all the range of relative humidity: the swelling is not observed or is strongly limited. It appears in contrast that only Li- and Na-montmorillonites undergo a mesopore swelling, distinct from the interlayer swelling. More generally, our results confirm the possibility to use thermoporometry or differential scanning calorimetry to study the structure and the evolution of swelling materials in wetting conditions such as natural clays or biological cells. In this paper, we describe the different key steps of the hydration of swelling clays such as montmorillonites saturated with alkaline cations. Using thermoporometry results combined with X-ray diffraction data, we distinguish the evolution of the porosity at the two different scales and propose a sequence of hydration dependent on the interlayer cation. From this study, it is shown that the interlayer spaces are not completely filled when the mesopores start to fill up. This implies that the swelling observed in the mesopores for Li and Na samples is due to an osmotic swelling. For the other samples, it is difficult to conclude definitively. Furthermore, we determine the different proportion of water (interlayer water and mesopore water) present in our samples by the original combination of (1) X-ray diffraction data, (2) the pore size distribution obtained by thermoporometry, and (3) recent adsorption isotherm results. It is found that the interlayer space is never completely filled by water at the studied relative humidity values for all samples except for the Cs sample.

Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene.

The neuronal promoter of human aromatic l-amino acid decarboxylase gene has been analysed to elucidate the mechanisms of neuron type-specific expression. The (-560/+92) promoter segment was sufficient to direct luciferase expression at a higher level in SK-N-BE neuroblastoma cells, than in CHP126 neuroepithelia, HepG2 hepatoma or SK-Hep1 epithelioma cells. Deletions experiments showed that this segment contained a neuronal-specific (element T1) and a SK-N-BE-specific (element N1) cis-activating sequences. Element T1 (-72/-36) bound Sp1 and NF-Y proteins, and unidentified neuronal-specific factors. Element N1 (-102/-72) bound cell-specific factors, identified as HNF-3, N-Oct-3/Brn-2 and N-Oct-2. HNF-3 proteins recognized the sequence TCAGTAAATA that matches the consensus motif. Oct-1, N-Oct-2 and N-Oct-3 bound the AAATAATGC sequence that overlaps the HNF-3 binding site. In addition, we show that the HNF-3 binding sites from aldolase C and HNF-3beta gene promoters also bind N-Oct-2 and N-Oct-3 proteins. These data suggest a functional interplay of winged helix/forkhead and POU-domain transcription factors on a variety of neuronal gene promoters.

Multiple promoters of human choline acetyltransferase and aromatic L-amino acid decarboxylase genes.

The promoter regions of human choline acetyltransferase (ChAT) and aromatic L-amino acid decarboxylase (AADC) genes have been analyzed by transient transfection assays. AADC gene is transcribed from two alternative noncoding first exons, 1N and 1NN, expressed in pheochomocytoma and hepatoma cells, respectively. 5' flanking sequences of exon 1 N (from 9000 to 147 bp) display promoter activity in SK-N-BE neuroblastoma cells, but not in MC-I-XC cholinergic neuroepithelioma cells, and in AADC-rich non-neuronal cells. On the contrary, 5' flanking sequences of exon 1 NN (from 1117 to 119 bp) display high promoter activity in human hepatoma cells HepG2, but not in SK-N-BE cells, suggesting high degrees of specificity of promoters N and NN for AADC-expressing neuronal and non-neuronal cells, respectively. Preliminary evidence suggests that leukemia inhibitory factor suppresses the activity of the neuronal promoter in cultured sympathetic neurons. Two alternative first exons, R and M, have been localized in human ChAT gene, and the corresponding promoters characterized in cholinergic PC12 and NG-108-15 cells, and in non-cholinergic neuro2A cells. Several positively or negatively acting cis elements have been localized in the two promoters, as well as a cAMP-inducible, enhancer-like element in the second intron. Among the various cell lines studied, there was no correlation between promoter activities and the expression of the endogenous ChAT gene, suggesting that the fine-tuning of ChAT gene expression is controlled by silencer elements which remain to be localized.

Reliability of glucose measurement by glucose test strips in tropical conditions.

The reliability of glucose test strips and reflectance meters after storage in tropical conditions was assessed. In a first experiment, sealed bottles containing glucose test strips were stored for 1 month in closed sterilising ovens at 40 degrees C, one in dry (0% humidity) and the other in wet (75% humidity) conditions. Results were compared to measurements obtained with glucose test strips stored under standard Western conditions, in non-diabetic and diabetic patients, using the same standard reflectance meter. A second experiment was performed similarly, comparing the values obtained with reflectance meters stored in different conditions, using standard glucose test strips. Reproducibility was assessed on the basis of duplicate measurements for each condition of storage. We observed that temperature and humidity did not significantly affect the glucose test strips (1st experiment), while a slight underestimation of capillary blood glucose was found using reflectance meters stored at 50 degrees C, irrespective of the humidity (2nd experiment). All the correlation coefficients between duplicates were greater than 0.975 irrespective of the conditions of storage for glucose test strips and reflectance meters. Therefore, glucose test strips and reflectance meters appear fairly reliable at the grass-root level in the tropics, if used carefully.

Clinical classification of diabetes in tropical west Africa.

The objective of this work was to classify and describe the different types of diabetic patients detected in West Africa. In four health centres (three in Ivory Coast, one in Niger) 310 new cases were detected and followed up over 1 year. Classification was based on age at diagnosis, BMI, ketonuria, basal and stimulated C-peptide levels at inclusion, and response to antidiabetic therapy. In this population, males were predominant (sex ratio = 2.40), and random blood glucose levels very high at screening (mean +/- SE, 18.6 +/- 0.4 mmol/l). Only one case of fibrocalculous pancreatic diabetes and one possible case of diabetes mellitus related to malnutrition were detected. IDDM was diagnosed in 11.3% of the patients, half of them above 35 years. Leanness was observed in 59% of the patients with NIDDM. A dramatic decrease of fasting blood glucose was observed in all groups after 2 months of treatment, especially in NIDDM. As IDDM and non-obese NIDDM presented great similarities before treatment, even for C-peptide levels, a point score system is proposed to classify these two groups at baseline. In conclusion, it is confirmed that the form of diabetes previously defined as related to malnutrition is a very rare entity in black African populations. In contrast, African diabetes is characterised by the high proportion of NIDDM patients with low BMI, and reduced beta-cell function, rarely associated to ketonuria. This form of diabetes seems to be adequately controlled with oral hypoglycaemic drugs and/or diet in the year following diagnosis.

[Survey of nutritional pathology in Mauritania]. / Aperçu de la pathologie nutritionnelle en Mauritanie.

A display of the different nutritional problems in Mauritania, such as they could be studied under the working medical conditions in this country. This study shows the coexistence, into a low life level country, of nutritional deficiency diseases, and obesity induced diseases, especially frequent among the mature women. This reality emphasizes the complexity of the mechanisms responsible for the nutritional diseases, and advocates for a global action to improve the nutritional status of a population. This supposes to integrate all the known data, including social and cultural knowledges.

[Tropical diabetes mellitus, a new nutritional indicator?]. / Le diabète sucré tropical, un nouvel indicateur nutritionnel?

Studies on diabetes mellitus in tropical zones indicate that its traditional link with overnutrition depends not only on the economic level, but also on some ethnic, social and cultural factors. At present, we insist on the unexpected relationship between diabetes mellitus and undernutrition either in some major infantile forms (described in India and Nigeria) with calcareous pancreatitis, or some less severe forms observed in Africa. This tropical diabetes mellitus occurs in some patients with normal weight or inferior to normal; it is not very ketogenic, responding to glucagon stimulation, and seems more frequent in the chronic malnutrition areas. So, it is tempting to utilize diabetes mellitus as an indicator of nutritional disorder or of dietary toxic factors. However, we ought to consider it within a multifactor surroundings associating genetic determinism and the other factors of tropical aggressiveness.

[Risk of AIDS for the occasional traveler in Africa]. / Le risque du S.I.D.A. pour le voyageur occasionnel en Afrique.

The authors first point out the importance of A.I.D.S. in Africa; then they appreciate the risk of contamination for occasional traveller in Africa. They recall some epidemic features of tropical A.I.D.S., its originality suggesting some risk factors different from the ones faced in temperate countries. Importance of risk of heterosexual transmission is emphasized, as well as possible parenteral contamination in connection with the frequent use of disposable needles and syringes again utilized without preliminary sterilization. Taking into consideration all these possibilities, the authors expose some prophylactic advises intended for people travelling briefly in endemic zones.

[The nutritional immunodeficiency syndrome]. / Le syndrome d'immunodéficit nutritionnel.

There is a strong relationship between nutritional status and resistance to infection. This relationship must receive attention more especially as human being is young. Newborns and infants have some immunological immaturity in regard to systemic immunity as well as local (particularly intestinal), immune defense. Malnutrition is an aggravating factor vis a vis such an immunodeficiency. It modifies the regulating activities of the different lymphocyte populations, of the macrophages, of the complementary system. These disorders are bound to energy, proteins, vitamins and mineral deficiencies. But many metabolic phenomenons have still to be explored, as well as the effect of such a dysimmunity on immunization. Bowel epithelial cells, cross-roads between immunity and nutrition, seem to be the point we ought to select in order to dislocate the infection--malnutrition couple.

[Human malaria: dysglobulinemia-hypocholesterolemia syndrome]. / Paludisme. Le syndrome dysglobulinémie--hypocholestérolémie.

Comparative study of protein and lipid parameters within a homogenous sample of 144 non-immune subjects having stayed for four months in Central Africa, suggests a dysglobulinemia more significant in the infected group. This dysglobulinemia affects in particular the IgM which are negatively correlated with cholesterol, positively with apoproteins A2 and H.D.L. Such a peculiar profiling involving immunoglobulins, apoproteins and cholesterol is rapidly regressive after stopping exposure to parasitic risk. It appears as an adaptation syndrome--or resistance--to tropical environment.

[Imported malaria at hospitals in Bordeaux (France) in 1987 and 1988. Report of 185 cases]. / Le paludisme d'importation dans les hôpitaux de Bordeaux en 1987-1988. Etude de 185 cas.

100 cases of imported malaria were registered in Hospitals of Bordeaux in 1987 and 85 in 1988. Origin of infestation is Africa in 88 p.c. of the cases mainly from Central Africa (50 p.c.) in 1987 and western Africa (67 p.c.) in 1988. The most frequent species was Plasmodium falciparum 73 p.c. in 1987 and 82 p.c. in 1988. Admitted cases in Bordeaux were mainly French (81 p.c.) with a significant male prevailing and young adults. Mean age was 29 for Europeans and 19 for the others mainly Africans. Infestation risk is in close correlation with the duration of stay in endémic zones. It is maximum for stays between 2 and 11 months. Delay for first symptoms to appear following return from an endemic zone depends of species concerned during the first month, 83 p.c. of malaria fever at Plasmodium falciparum during the second quarter, 50 p.c. of fever at Plasmodium vivax, and after one year or more 40 p.c. at Plasmodium ovale. Only 1/4 of the cases were diagnosed during the first 48 hours. Delay in diagnosing may be prolonged and is in relationship with Plasmodium falciparum chemoresistance and self-medication. 21 strains of Plasmodium falciparum were chloroquinoresistant in vitro: 1 from French Guyana, 9 from Western Africa, and 11 from Central Africa. The strain from Guyana was also less sensible to quinine with a IC 50 = 480 nmol/l.

Performance and limits of the mixed-phase assay for chloramphenicol acetyltransferase at low [3H]acetyl-CoA concentration.

We have explored the possibility of increasing the sensitivity of the mixed-phase assay for chloramphenicol acetyltransferase (CAT) by using a low concentration (3.75 microM) of isotopically undiluted [3H]acetyl-CoA (200 mCi/mmol). Using extracts of PC12 cells transiently transfected with a plasmid CMV-CAT, we found that the assay was linear with time for about 8 h, unless 25% of the substrate was exhausted. Under the conditions of the assay, the tritiated substrate was relatively stable, as 75% was still available for the reaction after a 20-h incubation at 37 degrees C under the toluene phase in the absence of cell extract. CAT activity could be reliably measured with 4-8 ng protein of cell extract, corresponding to 50-100 transfected cells. We determined the range of linearity of the initial rate with the volume of cell extract and showed that, above a certain value, the rate becomes limited by the diffusion of 3H-acetylated chloramphenicol in the organic phase. The sensitivity of the new assay compared favorably with that of the previously described CAT assays and approached that of the luciferase assay.