Importance of using complementary process analyzers for the process monitoring, analysis, and understanding of freeze drying.

The aim of the present paper is to demonstrate the importance of using complementary process analyzers (PAT tools) for the process monitoring, analysis, and understanding of freeze drying. A mannitol solution was used as a model system. Raman spectroscopic, near-infrared (NIR) spectroscopic, plasma emission spectroscopic, and wireless temperature measurements (TEMPRIS) were simultaneously performed in-line and real-time during each freeze-drying experiment. The combination of these four process analyzers to monitor a freeze-drying process is unique. The Raman and NIR data were analyzed using principal component analysis (PCA) and multivariate curve resolution (MCR), while the plasma emission spectroscopic and wireless temperature measurement data were analyzed using univariate data analysis. It was shown that the considered process analyzers do not only complement but also mutually confirm each other with respect to process step end points, physical phenomena occurring during freeze drying (process understanding), and product characterization (solid state). Furthermore and most important, the combined use of the process analyzers helped to identify flaws in previous studies in which these process analyzers were studied individually. Process analyzers might wrongly indicate that some process steps are fulfilled. Finally, combining the studied process analyzers also showed that more information per process analyzer can be obtained than previously described. A combination of Raman and plasma emission spectroscopy seems favorable for the monitoring of nearly all critical freeze-drying process aspects.

Decreased antibiotic susceptibility of Enterobacteriaceae causing community-acquired urinary tract infections in French Amazonia.

OBJECTIVES: Urinary tract infections (UTIs) have rarely been studied in the Amazon region. We aimed to describe the epidemiology of bacteria causing UTIs in French Guiana. PATIENTS AND METHODS: We performed a monocenter retrospective study of adults consulting at the emergency department of Cayenne Hospital in 2014 with a diagnosis of UTI. The bacterial species and resistance profile were described. RESULTS: Two-hundred-and-eighty-nine patients presenting with UTI were included: 82 (28.4%) presented with cystitis, 166 (57.4%) with pyelonephritis, and 41 (14.2%) with male UTI. E. coli was predominant (74.1%), and had decreased susceptibility to ampicillin, amoxicillin-clavulanic acid, fluoroquinolones, co-trimoxazole, and furans compared with data from metropolitan France. Extended-spectrum beta-lactamases (ESBL) was isolated in 3.1% of E. coli and 31.6% of K. pneumoniae. CONCLUSIONS: Antibiotic susceptibility in UTI is lower than reported in metropolitan France without evidence for an excessive consumption of antibiotics.

Enzymatically prepared n-alkyl esters of glucuronic acid: the effect of freeze-drying conditions and hydrophobic chain length on thermal behavior.

In this work, some of the physicochemical properties of enzymatically prepared n-alkyl esters of glucuronic acid are presented. Two questions are addressed. The first concerns the influence of post-purification freeze-drying conditions on octyl glucuronate thermotropic behavior. Depending on the amount of water added before freeze-drying, the alpha/beta anomeric ratio determined by (1)H NMR is affected and differences are observed in DSC thermograms probably due to polymorphism. The second question concerns the effect of hydrophobic chain length on the thermal behavior. An increase of both transition temperature and transition enthalpy is observed by increasing the number of carbon atoms in the alkyl chain (C8

Thyroid endocrine status of wild European eels (Anguilla anguilla) in the Loire (France). Relationships with organic contaminant body burdens.

In teleost fish, thyroid function is involved in various critical physiological processes. Given the complexity of the hypothalamo-pituitary-thyroid (HPT) axis, a large number of genes and proteins can be the potential target of endocrine-disrupting compounds (EDCs). The aim of this study was to evaluate, in yellow and silver European eels (Anguilla anguilla), potential effects of EDCs on thyroid status by analyzing the associations between EDC body burdens and thyroid hormones (THs). In yellow individuals, greater free T3/T4 ratios (FT3/FT4) and lower plasma FT4 levels were associated with greater concentrations of polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs), as highlighted by significant correlations with many congeners. Few positive relationships with alkylphenols were noticed. In contrast, silver eels usually exhibited less significant correlations between THs and contaminant loads. Expression of a series of genes involved in the HPT axis was also investigated in the silver individuals. Concerning mRNA expression in silver females, some main correlations were noticed: thyroid-stimulating hormone (TSHß) gene expression was significantly correlated to numerous PCBs, and hepatic mRNA levels of deiodinase 2 (Deio 2) were negatively correlated to 2-hydroxyfluorene (2-OHF) and 2-naphtol (2-OHNa). Thyroid receptor (TRα and TRß) mRNA levels exhibited weak negative correlations with some PBDEs in silver females and males. Hepatic vitellogenin (Vtg) mRNA levels were detected in all silver males but at lower levels than in silver females. In males, Vtg mRNA levels were positively associated to FT4/TT4. In silver females, strong positive correlations were found between congeners of PCBs, PBDEs and PFAS suggesting potential estrogenic effects. Overall, the observed results indicate that several organic contaminants, mainly dl-, ndl-PCBs and PBDEs, could be associated with changes in thyroid homeostasis in these fish, via direct or indirect interactions with peripheral deiodination, metabolism of T4 and mechanisms involved in TSHß, Deio 2 and Vtg gene transcription.

Pediatric bacterial meningitis in French Guiana.

OBJECTIVE: Controlling vaccine-preventable infectious diseases is a public health priority in French Guiana but there is currently no epidemiological data on pediatric bacterial meningitis in this overseas department. Our aim was to describe data related to pediatric bacterial meningitis in French Guiana and compare it with that of metropolitan France. METHODS: We conducted a multicenter retrospective study from 2000 to 2010 to describe the clinical picture, biological data, epidemiology, and outcome of pediatric bacterial meningitis case patients in French Guiana. RESULTS: The median age of bacterial meningitis patients was 6months [0-15] and the sex ratio 1.06. We observed a total of 60 bacterial meningitis case patients. Most presented with pneumococcal meningitis (24 patients; 40%); 11 with Haemophilus influenzae type b meningitis (23%), five with group B streptococcal meningitis (8.5%), and five others (8.5%) with staphylococcal meningitis (three patients presented with coagulase-negative staphylococci and two with Staphylococcus aureus). Only one patient presented with group B meningococcal meningitis, an 18-month-old infant. We recorded 14 deaths (overall case fatality: 23%); eight were due to Streptococcus pneumoniae (case fatality: 33%). The overall sequelae rate was 28%. It was 32% for patients presenting with pneumococcal meningitis. We observed that 38% of children who had never been vaccinated were infected by a vaccine-preventable bacterium. We observed many differences in the distribution of the bacteria and in the patients' prognosis when comparing the French Guiana data with that of metropolitan France. CONCLUSION: Improving vaccination coverage would decrease the incidence of H. influenzae meningitis.

Dexamethasone inhibits both growth hormone (GH)-induction of insulin-like growth factor-I (IGF-I) mRNA and GH receptor (GHR) mRNA levels in rat primary cultured hepatocytes.

Glucocorticoids are potent inhibitors of growth. In this work, we investigated whether glucocorticoids inhibit the stimulatory action of GH on IGF-I gene expression in rat hepatocytes. GH increased IGF-I mRNA levels 11-fold after 24 h, whereas high doses of DXM (10(-6)M) caused a slight (2.6-fold) increase of IGF-I mRNA levels. However, high doses of DXM (10(-6)M) inhibited the induction of IGF-I mRNA by GH. To assess the role of GHR in this inhibition, we investigated the regulation of GHR expression. High doses of DXM decreased GHR mRNA levels. This effect was already detectable 6 h after addition of 10(-6)M DXM and was dose-dependent, with a maximal inhibition observed at a concentration of 10(-6)M. In conclusion, our results show that high doses of DXM inhibits the GH-induced IGF-I gene expression and the GHR gene expression. The parallel decrease of GHR and GH-induced IGF-I mRNA suggests that the GH resistance caused by DXM is mediated by diminished GH receptor synthesis.

A one step process for grafting organic pendants on alumina via the reaction of alumina and phosphonate under microwave irradiation.

Phosphonate esters react with gamma-alumina under microwave (MW) irradiation; this reaction is a simple preparative method to graft organic pendant groups onto the surface of alumina; the efficiency of the grafting was readily checked by solid-state NMR techniques (31P and 27Al).

Delayed culture of Leishmania in skin biopsies.

Between January 1997 and October 1998, 16 skin biopsies collected from 13 patients with cutaneous leishmaniasis in French Guiana were inoculated in culture medium after travel for 3-17 days from the place of biopsy to the culture laboratory in France. Each biopsy fragment was introduced near the flame of a Bunsen burner into the transport medium (RPMI medium supplemented with 10% fetal calf serum) which was maintained at ambient temperature during postal delivery to France. In France the biopsies were ground in sterile saline before being inoculated into NNN culture tubes. The cultures were incubated at 25 degrees C and subcultured every week until the 5th week. The cultures were positive in 9 cases, remained negative in 4, and were contaminated in 3 cases. Positive results were obtained at all seasons and for 3 different Leishmania species. The study indicates that delayed culture can yield useful results from biopsies taken in field conditions.

Analysis of interleukin-6, interleukin-10 and leukemia inhibitory factor (LIF) production by peripheral blood cells from patients with systemic lupus erythematosus identifies LIF as a potential marker of disease activity.

The objective of this study was to determine the extent of interleukin (IL)-6, -10 and/or LIF involvement in systemic lupus erythematosus (SLE). Specific ELISA were used to measure cytokines in the supernatants of 48 hours cultures of whole blood stimulated or not by lipopolysaccharide and phytohemagglutinin, from controls (n = 10) or SLE patients divided according to the median of the SLE activity measurements (SLAM): < 9, group 1 (n = 11), and 9, group 2 (n = 10). Comparing median basal and stimulated cytokine concentrations from patients and controls, IL-6 was significantly higher in all SLE patients, IL-10 was significantly higher in both non- and stimulated situations only for SLE group 1 patients. With regard to LIF, it was significantly enhanced only in stimulated cultures of whole blood from group 2 patients as compared to control subjects. In conclusion, the production of cytokines involved in B-cell regulation and inflammation was altered in SLE, and LIF appears to be a potential marker of disease activity.

Association of Guillain-Barré syndrome and Henoch-Schönlein purpura: is immunoglobulin a responsible for the neurologic syndrome?

Guillain-Barré syndrome and Henoch-Schönlein purpura (HSP) appeared simultaneously in a 35-year-old woman. During the course of the Guillain-Barré syndrome, the presence of IgA aggregates and a decrease in complement components were noted in the cerebrospinal fluid. These abnormalities disappeared when the neurologic syndrome remitted. This suggests the responsibility of IgA immune complexes, characteristic of HSP, in the occurrence of the associated Guillain-Barré syndrome.

Binding of tobramycin to Escherichia coli ribosomes: characteristics and equilibrium of the reaction.

A sample of [3H] tobramycin (5,000 Ci/Mole) has been synthetized and incubated with the bacterial ribosome and its subunits. The results obtained show that this antibiotic has two types of binding sites. The primary one is probably responsible for the inhibition of protein synthesis whereas the secondary one is probably related to the misreading and reading through of the messenger RNA.

Hematological and serum chemistry profiles of free-ranging southern two-toed sloths in French Guiana.

Free-ranging southern two-toed sloths (Choloepus didactylus) were translocated during the flooding of a forest at a hydroelectric dam site in French Guiana. Over an 11 mo period blood samples were collected from 90 sloths (38 males, 52 females) in order to determine hematological and serum chemistry reference values. Mean values and range of values were calculated for 13 hematological and 21 serum chemistry parameters. Variations associated with sex, age and reproductive status were identified. Males had a significantly lower red blood cell count than females. Immature animals had more monocytes while adults had more neutrophils and higher mean corpuscular hemoglobin concentration. Aspartate aminotransferase and triglyceride values were higher in young than in adult sloths but uric acid was lower. Lactating females showed lower red blood cells count and iron levels than non-lactating females. These profiles will help to provide reliable baseline data for medical evaluation of sloths.

Intestinal parasitoses among Wayampi Indians from French Guiana.

Intestinal parasitism and its epidemiological characteristics were studied in an isolated Amerindian population from Upper Oyapock (French Guiana) that has retained its traditional social and cultural specificities. This population consisted of 138 Wayampi Indians, 68 adults and 70 children (below the age of 15 years), with a sex ratio (M/F) of 0.86, spread over the four villages of the community of Trois Sauts, corresponding to more than two thirds of the population recorded as inhabiting the sector in the last census (375 inhabitants). Fecal examination combined the direct examination of fresh feces with the quantitative techniques of Kato-Katz method, Baermann and MIF staining. Overall, 92% of the subjects were found to have intestinal parasites, 85% if only direct examination of fresh stools was taken into account. Fourteen species of human parasite were identified: seven protozoa and seven helminths. We observed in particular 1) a high frequency of hookworm infection due to Necator americanus. Over 50% of subjects were affected, with a range of 25% to 75% according to the village, but with only moderate parasite loads; 2) a high level of parasitism by E. histolytica/E. dispar (17%), Stongyloides stercoralis (16%) and Hymenolepis nana (18%); 3) a lower level of parasitism by Ascaris lumbricoides and very low levels (almost absent) of Trichiuris trichiura; 4) the absence of Schistosoma and fluke eggs. With the exception of H. nana, which was more frequent in children than in adults, there was no significant difference in the level of parasitism according to sex and age. Although the Wayampi of French Guiana are French citizens and consequently have quite high incomes and ready access to clinics and medicines, intestinal parasites are far from under control in this population. A lack of fecal hygiene and the habit of walking barefoot are widespread in the unchanging Amazonian environment and contribute to this phenomenon.

[Leishmania (Viannia) braziliensis Vianna, 1911 in French Guiana. Clinical, therapeutic and epidemiological considerations in the ninth human diagnosed case]. / Leishmania (Viannia) braziliensis Vianna, 1911 en Guyane française. Considérations cliniques, thérapeutiques et épidémiologiques à propos du neuvième cas humain diagnostiqué.

The authors report the ninth case of cutaneous Leishmaniasis without mucosal involvement due to Leishmania (Viannia) braziliensis (isoenzymatic profile related to zymodeme MON-44) diagnosed in a legionnaire who recently arrived in French Guiana. The skin lesion as a single ulcerated nodule of the dorsum of the left ringfinger was cured after two courses of four intramuscular injections of pentamidine isothionate (total posology of pentamidine-base: 16.6 mg/kg). The transmission occurred during nocturnal trekking in forest and swamps just behind the coastal belt at Degrad Saramaka (7 km South of Kourou). In French Guiana, the good level of medical care and the early treatment of the majority of the cases of Leishmaniasis may explain the rarity of mucosal lesions. Since the clinical aspect of the lesion is not sufficient to prejudge the identity of the causative species, it is necessary to perform cultivation of Leishmania for iso-enzymatic identification. The adaptation of pentamidine doses and long term follow up of patients infected by L. (V.) braziliensis could be defined more precisely.

[Impetigo in French Guyana. A clinical, bacteriological, toxicological and sensitivity to antibiotics study]. / L'impétigo en Guyane Française. Etudes clinique, bactériologique, toxinologique et de sensibilité aux antibiotiques.

OBJECTIVE: We evaluated pertinent features of impetigo in French Guyana due to the increasing number of therapeutic failures with macrolides and fusidic acid. PATIENTS AND METHODS: A prospective study study was conducted over a 14-month period in the dermatology unit of the Cayenne hospital. Two groups of patients were identified: group 1 included patients with impetigo and group 2 patients with infected skin reactions. Epidemiological, bacteriological, toxinological (exofoliatines, leukocidine) and antibiotic data were recorded. RESULTS: Forty-one patients with impetigo and 31 patients with infected skin reactions were included. Staphylococcus infection alone was identified in most patients (68 p. 100) in the impetigo group. Exfoliatine-producing strains were strongly associated with Staphylococcus-induced bullous and non-bullous impetigo (93 p. 100) compared with other origins (impetigo with streptococcal infection or infected skin reactions). Resistance to macrolides was high (erythromycin 41 p. 100, fusidic acid 42 p. 100) for all isolated strains of Staphylococcus aureus. CONCLUSION: A sub-group of patients with impetigo was identified. These patients had pure staphylococcal infections characterized by strong association with exfoliatine production. The rate of resistance to macrolides was particularly high in this sub-group. Resistance to fusidic acid was high for all Staphylococcus strains isolated.

[Staphylococcus aureus septicemia producing Panton-Valentine leukocidin. 3 cases]. / Septicémies a Staphylococcus aureus producteurs de leucocidine de Panton-Valentine.

BACKGROUND: A strong association has been observed between furuncles and Panton-Valentine leukocidin-producing Staphylococcus aureus. CASE REPORTS: Within one year, we cared for three men at the Cayenne hospital who had Staphylococcus aureus septicemia with severe pleuropulmonary involvement originating from furuncular lesions. The Staphylococcus aureus strains isolated from the skin lesions and from blood cultures produced Panton-Valentine leukocidin. CONCLUSION: These cases demonstrate the gravity of S. aureus septicemia in young patients with furunculosis. These cases are the first reported with severe S. aureus infections associated with Panton-Valentine leukocidin producing strains.

Hematology and serum biochemistry values of free-ranging red howler monkeys (Alouatta seniculus) from French Guiana.

One hundred twenty-two wild red howler monkeys (Alouatta seniculus) were translocated during flooding of the forest at a hydroelectric dam site in French Guiana. Blood samples from 103 animals were evaluated for 13 hematologic and/or 22 serum chemistry parameters. Significant age-specific variation was found for white blood cell (WBC), lymphocyte, and platelet counts and for alkaline phosphatase values. Adult males and females had significant differences in red blood cell count, packed cell volume, and hemoglobin, creatinine, cholesterol, and calcium values. In juveniles, amylase and cholesterol levels were significantly lower in males than in females. Significant differences associated with reproductive status were also observed; i.e., lower cholesterol level in pregnant females and higher packed cell volume in lactating females. Chronic stress due to habitat disappearance may have been responsible for significant differences between thin animals and those in good condition. Thin animals had lower WBC, eosinophil, basophil, and monocyte counts and higher platelet counts. Capture stress was probably responsible for high and variable levels of creatine kinase, aspartate aminotransferase, and lactate dehydrogenase.

Combined caffeine and bright light reduces dangerous driving in sleep-deprived healthy volunteers: a pilot cross-over randomised controlled trial.

AIM OF THE STUDY: To explore the effects of caffeine and bright light therapy on simulated nighttime driving in sleep-deprived healthy volunteers. PARTICIPANTS AND METHODS: Twelve male healthy volunteers aged 20 to 50 years participated in a randomized cross-over study of simulated nighttime driving at a sleep laboratory, followed by recovery sleep with polysomnography at home. The volunteers received variable combinations of caffeine 200mg (C+), caffeine placebo (C-), bright light 10,000 lux (L+), and bright light placebo<50 lux (L-), in four sessions (C+L+, C+L-, C-L+, C-L-), in random order with a wash-out period of 7 days. Treatments were given at 1 a.m. and testing was performed at 1:30 a.m., 3 a.m., 4 a.m., and 6 a.m. Lane drifting was the primary outcome measure. Other measures were reaction times, self-rated fatigue, sleepiness and recovery sleep. RESULTS: Without treatment, lane drifting increased throughout the night, and objective and subjective vigilance declined. Paired comparisons showed that lane drifting was significantly worse at 6 a.m. and at 4 a.m. than at 1:30 a.m. There was a global treatment effect on lane drifting. Lane drifting at 6 a.m. was significantly decreased with C+L+ compared to C-L-. CONCLUSIONS: Bright light therapy combined with caffeine administered at 1 a.m. decreased lane drifting by healthy volunteers during simulated nighttime driving.