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Organic farming has become more prevalent in recent years as consumer demand for organic food and fiber has rapidly grown. Until recently, organic fertilizers and soil amendments have largely been based on the practices of returning crop residues, manures and related agricultural wastes back to crop production areas. One rapidly growing segment in commercial organic fertilizer development is the use of spent microbial biomass (SMB) from industrial fermentation processes. While SMB is widely accepted in many organic farming systems (OFS), little is known concerning the effectiveness, environmental impact, and influence on prokaryotic communities in soils receiving this treatment. In this study, a comparative analysis of bacterial communities associated with OFS and conventional farming systems was performed over a growing season for a field containing yellow dent corn (Zea mays). A statistically significant increase in microbial population α-diversity, along with a strong recruitment of Proteobacteria and Actinobacteria populations, was observed in soils treated with SMB when compared to areas in the field that utilized conventional farmer practices. These phyla are members of the copiotrophic subgroup, and considered a signature for the use of traditional organic fertilizers. These results provide valuable new information that SMB functions similarly to traditional organic fertilizers in promoting a high level of functional prokaryotic diversity and plant growth-promoting bacteria, but in contrast do not contribute directly to viable microorganisms in the soil due to the sterilization of SMB prior to land application.

We present an experimental study of the Rydberg 1 S 0 - and 1 P 1 - series of ytterbium for principal quantum numbers in the range of n = 70–90. The study is performed using trap loss spectroscopy in a magneto-optical trap operating on the 6 1 S 0 → 6 1 P 1 transition at 399 nm. Compared to the commonly used Rydberg spectroscopy method using field-ionization and ion detection, trap loss spectroscopy is significantly simpler and requires a less sophisticated experimental setup. Using this method we determine relative values of the scalar and tensor electric polarizabilities of both, 6 s n s 1 S 0 - and 6 s n p 1 P 1 - Rydberg states.

White biotechnology has made a positive impact on the chemical industry by providing safer, more efficient chemical manufacturing processes that have reduced the use of toxic chemicals, harsh reaction conditions, and expensive metal catalysts, which has improved alignment with the principles of Green Chemistry. The genetically-modified (GM) biocatalysts that are utilized in these processes are typically separated from high-value products and then recycled, or eliminated. Elimination routes include disposal in sanitary landfills, incineration, use as a fuel, animal feed, or reuse as an agricultural soil amendment or other value-added products. Elimination routes that have the potential to impact the food chain or environment have been more heavily scrutinized for the fate and persistence of biological products. In this study, we developed and optimized a method for monitoring the degradation of strain-specific DNA markers from a genetically-modified organism (GMO) used for the commercial production of 1,3-propanediol. Laboratory and field tests showed that a marker for heterologous DNA in the GM organism was no longer detectable by end-point polymerase chain reaction (PCR) after 14 days. The half-life of heterologous DNA was increased by 17% (from 42.4 to 49.7 h) after sterilization of the soil from a field plot, which indicated that abiotic factors were important in degradation of DNA under field conditions. There was no evidence for horizontal transfer of DNA target sequences from the GMO to viable organisms present in the soil.

Background:Protease-activated receptor-2 (PAR2) is a member of a family of G-protein-coupled receptors involved in multiple physiological mechanisms. Compelling evidences have unravelled the key roles of PAR2 in the pathology of both rheumatoid arthritis (RA) and osteoarthritis (OA)1. Indeed, in vitro, in vivo and ex vivo experiments showed that this receptor promotes inflammation, cartilage erosion (and subsequent bone degradation), and pain. However, the signalling pathways involved in these functions are not well understood2. This is of importance as some pathways can promote the pathogenesis3while others prevent it4. We developed a new series of small molecules as novel biased PAR2 inhibitors to treat rheumatic diseases.Objectives:To evaluate the efficacy and mechanism of action of new biased PAR2 inhibitors on cartilage erosion and inflammation.Methods:The potency of compounds to inhibit human PAR2 signalling was evaluated in vitro by FLIPR calcium assay in HEK293 cells. The same assay was used to determine their selectivity over human PAR1 and PAR4 as well as murine versions of PAR2. The effect of several PAR2 inhibitors on 9 signalling pathways (Gi2, GoB, Gz, Gq, G13, G14, G15, B arrestin 2, EPAC) was evaluated by the BRET-based bioSens-All™ technology. In vitro anti-hypertrophic effect was determined by measuring the mRNA level of type II collagen, aggrecan and MMP13 in rat chondrocytes after IL1β stimulation. In vitro anti-inflammatory effect was determined by measuring the secretion of IL6, IL8, IL1β, TNFα and IFNγ by human monocytes. In vivo, the pharmacodynamic of our small molecules was assessed after intravenous and oral administration. Therapeutic efficacy of a compound was then evaluated in a collagen-induced arthritis model in DBA1/J mice. In this model, measures of the arthritis index score, body weight, plasma level of TNFα, IL6, IL8 and IL1β and histological evaluation of cartilage erosion were performed.Results:Our new series of small molecules are potent PAR2 inhibitors (IC50Conclusion:Our results show the potency of biased PAR2 inhibitors to reduce both the inflammation and cartilage erosion in rheumatoid arthritis. They confirm the huge potential of PAR2 as a therapeutic target and unravel the relevance of biased antagonism of this receptor to treat rheumatic diseases.References:[1]McCulloch et al., Frontiers in Endocrinology, 2018;2Hollenberg et al., British Journal of Pharmacology, 2014;3Sharma et al., Genes and Immunity, 2015;4Rayees et al., Cell Reports, 2019Disclosure of Interests:Thibaut Brugat Employee of: Domain Therapeutics, Baptiste Rugeri Employee of: Domain Therapeutics, Gaël Hommet Employee of: Domain Therapeutics, Alexia Dumont Employee of: Domain Therapeutics, Luc Baron Employee of: Domain Therapeutics, Célia Halter Employee of: Domain Therapeutics, Meriem Sémache Employee of: Domain Therapeutics, Arturo Mancini Employee of: Domain Therapeutics, Camille Amalric Employee of: Domain Therapeutics, Marie Giambelluco Employee of: Domain Therapeutics, Nathalie Lenne Employee of: Domain Therapeutics, Marjorie Sidhoum Employee of: Domain Therapeutics, Christel Franchet Employee of: Domain Therapeutics, Stanislas Mayer Employee of: Domain Therapeutics, Xavier Leroy Employee of: Domain Therapeutics, Stephan Schann Employee of: Domain Therapeutics

Bacterial–bacteriophage interactions are a well-studied and ecologically-important aspect of microbiology. Many commercial fermentation processes are susceptible to bacteriophage infections due to the use of high-density, clonal cell populations. Lytic infections of bacterial cells in these fermentations are especially problematic due to their negative impacts on product quality, asset utilization, and fouling of downstream equipment. Here, we report the isolation and characterization of a novel lytic bacteriophage, referred to as bacteriophage DTL that is capable of rapid lytic infections of an Escherichia coli K12 strain used for commercial production of 1,3-propanediol (PDO). The bacteriophage genome was sequenced and annotated, which identified 67 potential open-reading frames (ORF). The tail fiber ORF, the largest in the genome, was most closely related to bacteriophage RTP, a T1-like bacteriophage reported from a commercial E. coli fermentation process in Germany. To eliminate virulence, both a fully functional Streptococcus thermophilus CRISPR3 plasmid and a customized S. thermophilus CRISPR3 plasmid with disabled spacer acquisition elements and seven spacers targeting the bacteriophage DTL genome were constructed. Both plasmids were separately integrated into a PDO production strain, which was subsequently infected with bacteriophage DTL. The native S. thermophilus CRISPR3 operon was shown to decrease phage susceptibility by approximately 96%, while the customized CRISPR3 operon provided complete resistance to bacteriophage DTL. The results indicate that the heterologous bacteriophage-resistance system described herein is useful in eliminating lytic infections of bacteriophage DTL, which was prevalent in environment surrounding the manufacturing facility. Electronic supplementary material The online version of this article (10.1007/s10295-018-2015-7) contains supplementary material, which is available to authorized users.

The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores.

Summary Switchgrass (Panicum virgatum L.) is a C4 perennial grass and has been identified as a potential bioenergy crop for cellulosic ethanol because of its rapid growth rate, nutrient use efficiency and widespread distribution throughout North America. The improvement of bioenergy feedstocks is needed to make cellulosic ethanol economically feasible, and genetic engineering of switchgrass is a promising approach towards this goal. A crucial component of creating transgenic switchgrass is having the capability of transforming the explants with DNA sequences of interest using vector constructs. However, there are limited options with the monocot plant vectors currently available. With this in mind, a versatile set of Gateway- compatible destination vectors (termed pANIC) was constructed to be used in monocot plants for transgenic crop improvement. The pANIC vectors can be used for transgene overexpres- sion or RNAi-mediated gene suppression. The pANIC vector set includes vectors that can be utilized for particle bombardment or Agrobacterium-mediated transformation. All the vectors contain (i) a Gateway cassette for overexpression or silencing of the target sequence, (ii) a plant selection cassette and (iii) a visual reporter cassette. The pANIC vector set was function- ally validated in switchgrass and rice and allows for high-throughput screening of sequences of interest in other monocot species as well.

Le Glucagon-like peptide-1 (GLP-1) presente, outre ses effets sur le metabolisme glucidique, de nombreux effets pleiotropes, dont certains tres prometteurs au niveau du systeme cardiovasculaire. Les donnees experimentales avec le GLP-1 et les etudes cliniques preliminaires menees avec les agonistes du recepteur au GLP-1 temoignent d’une reduction de la pression arterielle systolique et des parametres lipidiques, de l’amelioration de la fonction endotheliale et de certains marqueurs de risque cardiovasculaire, tels que le Brain natriuretic peptide (BNP), la high sensitivity C-Reactive Protein (hsCRP) et le Plasminogen activating inhibitor 1 (PAI-1). Il existe egalement, dans les modeles animaux comme chez l’homme, des arguments en faveur d’un effet protecteur en situation d’ischemie myocardique et d’une amelioration de la fonction cardiaque en cas de cardiopathie sous-jacente. Ainsi, les agonistes du recepteur au GLP-1 constituent une option therapeutique prometteuse pour la prise en charge des patients diabetiques de type 2, qui presentent, par definition, un haut risque cardiovasculaire.

La mesure continue du glucose est devenue un element essentiel de la prise en charge du patient diabetique. L’autosurveillance glycemique, meme intensifiee, n’apporte qu’une information parcellaire et transversale sur le niveau d’equilibre glycemique du patient. Les outils de mesure continue du glucose ont ete perfectionnes, autant sur le plan pratique que sur leur precision de mesure. Apres avoir ete utilises essentiellement en milieu hospitalier, les capteurs de glucose sont maintenant souvent proposes aux patients pour un usage en ambulatoire. De nombreuses situations cliniques constituent ainsi des indications d’enregistrement continu du glucose, afin de diagnostiquer les raisons d’un equilibre glycemique insuffisant. Si l’objectif est d’ameliorer l’equilibre metabolique, le capteur de glucose doit etre porte plusieurs semaines, voire plusieurs mois. Le patient doit accepter de porter regulierement le capteur, et beneficier d’une education therapeutique pour esperer ameliorer son equilibre glycemique. Au-dela de la seule mesure continue du glucose, le capteur, lorsqu’il est couple a une pompe a insuline, represente une evolution majeure dans la prise en charge therapeutique du patient diabetique.

L’objectif de cette etude est de comparer les proprietes pharmacodynamiques des deux modalites d’administration de l’insuline basale au cours d’une epreuve de jeune total de 36 heures pratiquee par 24 diabetiques de type 1 lors de leur formation a l’insulinotherapie fonctionnelle. Au cours de l’etude, seule l’insuline basale a ete delivree et la dose a ete determinee individuellement par la formule d’Howorka. Quinze patients etaient traites par une injection quotidienne d’un analogue lent (groupe Glargine) et neuf par perfusion continue a debit unique par pompe d’un analogue rapide (groupe Pompe). En cas d’hyper- ou d’hypoglycemie, une correction insulinique ou une collation glucidique ont ete respectivement delivrees afin de maintenir une glycemie normale (0,6-1,2 g/l). L’analyse des courbes de mesure en continu du glucose interstitiel (Glucoday ® ) a permis de determiner les parametres de variabilite glycemique asymptomatique suivants : ecart type de la moyenne des concentrations de glucose interstitiel, index MAGE ( Mean Amplitude Glycemic Excursions ) et MODD ( Mean Of Daily blood glucose Differences ). Les resultats montrent que la moyenne et l’ecart-type de la moyenne des concentrations de glucose interstitiel, les index MAGE et MODD ne different pas significativement entre les deux groupes. Le nombre de collations glucidiques administrees est identique dans les deux groupes, mais le nombre de corrections insuliniques administrees est plus eleve dans le groupe pompe. En conclusion, le controle glycemique au cours d’un jeune total de 36 heures est au moins aussi satisfaisant avec une injection quotidienne d’un analogue lent de l’insuline (glargine) qu’avec la perfusion continue a debit unique par pompe d’un analogue rapide de l’insuline (lispro ou asparte).

Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.

These data demonstrate occurrence of natural infection of SVNaV in soybean under greenhouse conditions during winter in the absence of field-grown soybeans or any infected host plant within the greenhouse. The observations point to the likelihood that overwintering viruliferous adult thrips may have the potential to serve as a local source of SVNaV; however, the epidemiological significance needs to be determined. Accepted for publication 5 October 2015. Published 14 October 2015.

Diabetes & Metabolism - In Press.Proof corrected by the author Available online since jeudi 31 octobre 2013

The alleles RHCE*ceBI (RHCE*ce 48C, 712G, 818T, 1132G) and RHCE*ceSM (RHCE*ce 48C, 712G, 818T) encode the low-prevalence Rh antigen STEM. These alleles frequently travel in cis with RHD*DOL. To estimate the frequency of these alleles, we tested a total of more than 700 samples in two populations. Blood samples were obtained from patients with sickle cell disease and from blood donors of African descent. DNA extractions and analyses were performed by standard methods. In the United States, none of 70 patient samples had the RHCE*818 nucleotide change. Two of 220 donors (frequency of 0.009) were heterozygous for RHCE*818C/T (RHCE*ceBI). One of these samples had RHD/RHD*DOL and the other had RHD/RHD*DOL-2. In these 290 samples, no other RHD*DOL alleles were found. In Brazil, 1 of 244 patients with sickle cell disease (frequency of 0.004) and 1 of 171 donors (frequency of 0.006) were heterozygous for RHCE*818C/T (RHCE*ceBI). Testing of more than 500 additional samples from people of African descent, selected because they had a diverse range of common and variant RHCE alleles, did not reveal a sample with RHD*DOL or RHD/RHD*DOL-2 in the absence of RHCE*ce(818T). Although the numbers are small, our study shows that in the United States, the frequency of RHCE*818T is 0.007 (2 in 290 samples) and in Brazil it is 0.004 (2 in 515 samples). The four RHCE*818T alleles were RHCE*ceBI.

Switchgrass (Panicum virgatum L.) is a C4 perennial grass and has been identified as a potential bioenergy crop for cellulosic ethanol because of its rapid growth rate, nutrient use efficiency and widespread distribution throughout North America. The improvement of bioenergy feedstocks is needed to make cellulosic ethanol economically feasible, and genetic engineering of switchgrass is a promising approach towards this goal. A crucial component of creating transgenic switchgrass is having the capability of transforming the explants with DNA sequences of interest using vector constructs. However, there are limited options with the monocot plant vectors currently available. With this in mind, a versatile set of Gateway-compatible destination vectors (termed pANIC) was constructed to be used in monocot plants for transgenic crop improvement. The pANIC vectors can be used for transgene overexpression or RNAi-mediated gene suppression. The pANIC vector set includes vectors that can be utilized for particle bombardment or Agrobacterium-mediated transformation. All the vectors contain (i) a Gateway cassette for overexpression or silencing of the target sequence, (ii) a plant selection cassette and (iii) a visual reporter cassette. The pANIC vector set was functionally validated in switchgrass and rice and allows for high-throughput screening of sequences of interest in other monocot species as well.

Thr Rh blood group system is highly complex both in the number of discreet antigens and in the existence of partial antigens, especially D and e. Recently, several partial c antigens have been reported. Here we report findings on an African American man with sickle cell disease whose RBCs typed C+c+ and whose plasma contained anti-c. Hemagglutination tests, DNA extraction, PCR-RFLP, reticulocyte RNA isolation, RT-PCR cDNA analyses, cloning, and sequencing were performed by standard procedures. RBCs from the patient typed C+c+ but his plasma contained alloanti-c. DNA analyses showed the presence of RHCE*Ce in trans to RHCE*ceAR with RHD*D and RHD*Weak D type 4.2.2. The amino acid changes on RhceAR are such that C+c+ patient made alloanti-c. This case shows that RhceAR carries a partial c antigen and illustrates the value of DNA testing as an adjunct to hemagglutination to aid in antibody identification in unusual cases.

Heavy alcohol consumption may accelerate the progression of hepatitis C-related liver disease and/or limit efforts at antiviral treatment in opioid-dependent patients receiving heroin-assisted treatment (HAT). Our study aims to assess alcohol intake among HAT patients by self-reports compared to direct ethanol metabolites.Fifty-four patients in HAT were recruited from the centre for HAT at the University of Basel, Switzerland. The patients completed the Alcohol Use Disorder Identification Test (AUDIT), a self-report questionnaire on past-week ethanol intake and provided samples for the determination of ethyl glucuronide (UEtG) and ethyl sulphate (UEtS) in urine and of ethyl glucuronide (HEtG) in hair.Eighteen patients scored above the AUDIT cut-off levels. Twenty-six patients tested positive for UEtG and 29 for UEtS. HEtG identified ethanol intake of more than 20 g/d in 20 additional cases that did not appear in the AUDIT. Using the total score of the AUDIT, HEtG detected 14 additional cases of relevant alcohol intake.The findings of this study, which is the first assessing alcohol intake in HAT patients using direct ethanol metabolites and self reports, suggest the complementary use of both. Improved detection of hazardous or harmful alcohol consumption in the context of HCV and heroin dependence will allow for earlier intervention in this population. This ultimately will contribute to an improvement in quality of life of patients in HAT. Furthermore, a significant reduction of costs can be achieved through a reduction of complications caused by alcohol intake.

Aim Ethyl glucuronide (EtG) is used commonly as a marker for the detection of non-compliance of patients in alcohol withdrawal therapy in psychiatric hospitals in Europe and in work-place monitoring programmes in the United States. With the increased use of this new marker, questions related to an unintentional uptake of ethanol resulting in detectable EtG concentrations have been discussed. The aim of this study was to determine the concentration ranges of EtG and ethyl sulphate (EtS) after the consumption of very small amounts of ethanol (1 and 3 g), which are more likely to be incidental than intended. Methods Drinking experiments with ethanol amounts of 1 and 3 g, respectively, were performed on a total of 31 volunteers. EtG and EtS analysis in urine was performed by electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), and creatinine concentration was determined using the Jaffe reaction. Furthermore, data obtained from this experimentation were then compared to data from literature. Results and conclusions The maximum concentration of EtG normalized to creatinine after the uptake of 1 g and 3 g of ethanol was found to be 0.32 mg/l and 1.53 mg/l, respectively, and 0.15 mg/l and 1.17 mg/l for EtS; these peak concentrations are considered to be positive by many laboratories testing urine for ethanol conjugates in work-place testing progammes.

An electrospray ionization tandem mass spectrometry (ESI-MS/MS) library which contains over 5,600 spectra of 1,253 compounds relevant in clinical and forensic toxicology has been developed using a hybrid tandem mass spectrometer with a linear ion trap. Pure compound solutions—in some cases solutions made of tablets—were prepared and 1 to 2,000 ng of each compound were injected into the system using standard reversed-phase analytical columns with gradient elution. To obtain maximum mass spectral information enhanced product ion spectra were acquired with positive and/or negative ionization at low, medium, and high collision energies and additionally applying collision energy spread. In this mode, all product ions generated by the different collision energies are trapped in the linear ion trap prior to their detection. The applicability of the library for other types of hybrid tandem mass spectrometers with a linear ion trap of the same manufacturer as well as a standard triple-quadrupole tandem mass spectrometer has been investigated with a selection of compounds. The spectra of the developed library can be used to create methods for target analysis, either screening methods or quantitative procedures by generating transitions for multiple reaction monitoring. For those procedures, suitable transitions and convenient collision energies are selected from the library. It also has been utilized to identify compounds with a multi target screening approach for clinical and forensic toxicology with a standardized and automated system. The novel aspects compared to our former library produced with a standard triple-quadrupole mass spectrometer are the enlargement of the ESI-MS/MS library and the additional acquisition of spectra with collision energy spread.

For 12 volunteers of a drinking experiment the concentration-time-courses of ethyl sulfate (EtS) and ethanol were simulated and fitted to the experimental data. The concentration-time-courses were described with the same mathematical model as previously used for ethyl glucuronide (EtG). The kinetic model based on the following assumptions and simplifications: a velocity constant k(form) for the first order formation of ethyl sulfate from ethanol and an exponential elimination constant k(el). The mean values (and standard deviations) obtained for k(form) and k(el) were 0.00052 h(-1) (0.00014) and 0.561 h(-1) (0.131), respectively. Using the ranges of these parameters it is possible to calculate minimum and maximum serum concentrations of EtS based on stated ethanol doses and drinking times. The comparison of calculated and measured concentrations can prove the plausibility of alleged ethanol consumption and add evidence to the retrospective calculation of ethanol concentrations based on EtG concentrations.

Ethyl sulfate (EtS) is a non-oxidative metabolite of ethanol, used for forensic purposes as an ethanol consumption marker in addition to the ethanol metabolite ethyl glucuronide (EtG) which after certain scientific publications is prone to biological degradation. As ethanol is widely consumed in many western cultures, knowledge about the stability of ethyl sulfate against biodegradation is of importance for forensic investigations-where EtS until now was thought to be stable against bacterial degradation. Using standardized test methods from the panel of OECD tests, the stability of EtS against bacterial degradation was assessed in this study. These experiments showed that EtS was stable in the closed bottle test (CBT) (OECD 301 D), but not in the manometric respiratory test (MRT) (OECD 301 F) with higher bacterial density. With respect to forensic investigations the assumption of EtS stability could be disproved and the possibility of bacterial degradation of EtS should be taken into account when alcohol uptake some hours prior to death needs to be ruled out by determination of alcohol consumption markers in putrefied corpses, where ethanol concentration could have been generated post-mortem by fermentation processes. (C) 2009 Elsevier Ireland Ltd, All rights reserved Ethyl sulfate (EtS) is a non-oxidative metabolite of ethanol, used for forensic purposes as an ethanol consumption marker in addition to the ethanol metabolite ethyl glucuronide (EtG) which after certain scientific publications is prone to biological degradation. As ethanol is widely consumed in many western cultures, knowledge about the stability of ethyl sulfate against biodegradation is of importance for forensic investigations-where EtS until now was thought to be stable against bacterial degradation. Using standardized test methods from the panel of OECD tests, the stability of EtS against bacterial degradation was assessed in this study. These experiments showed that EtS was stable in the closed bottle test (CBT) (OECD 301 D), but not in the manometric respiratory test (MRT) (OECD 301 F) with higher bacterial density. With respect to forensic investigations the assumption of EtS stability could be disproved and the possibility of bacterial degradation of EtS should be taken into account when alcohol uptake some hours prior to death needs to be ruled out by determination of alcohol consumption markers in putrefied corpses, where ethanol concentration could have been generated post-mortem by fermentation processes. (C) 2009 Elsevier Ireland Ltd, All rights reserved

Background Ethyl glucuronide (EtG) and ethyl sulphate (EtS) are specific and sensitive markers of ethanol consumption well established in monitoring withdrawal treatment in patients with chronic alcoholism. Recently, bacterial decomposition as well as in vitro and post-mortem formation of EtG was reported. The aim of this study was to investigate the influence of different preservatives on the stability of EtG and EtS concentrations in urine samples. Methods Urine samples were doped with glucuronidase-positive Escherichia coli after sterile filtration. The preservatives used were thymol, chlorhexidine, boric acid and the combination of chlorhexidine, ethylparabene and sodium propionate. Different aliquots of urine samples were stored refrigerated (4–8 °C), at room temperature (18 ± 1 °C) and in an incubator (36 ± 1 °C) for a period of 9 days with daily sampling. EtG and EtS analyses were performed by LC–ESI-MS/MS. The number of bacteria was detected by counting the colony forming units on Columbia blood agar plates. Results and conclusions Chlorhexidine on its own as well as in the aforementioned combination, and boric acid proved useful preservatives, while EtG degraded in samples doped with thymol. Addition of these preservatives did not interfere with the LC–MS/MS analysis.

BACKGROUND: Heavy alcohol consumption may accelerate the progression of hepatitis C (HCV)-related liver disease and/or limit efforts at antiviral treatment. As most of the patients in methadone maintenance treatment (MMT) suffer from hepatitis C infection, this study was conducted to identify the alcohol intake among these patients at a Swiss Psychiatric University Clinic by self-reports and direct ethanol metabolites as biomarkers of ethanol consumption. PATIENTS AND METHODS: A convenience sample of 40 MMT patients (15 women, 25 men; median age 39 years) of the total 124 patients was asked and consented to participate in this study. This sample was not different in age, gender distribution, and rate of hepatitis C infection from the total sample. The Alcohol Use Disorders Identification Test (AUDIT) and self-reported ethanol intake during the previous 7 days were assessed. In addition, ethyl glucuronide (EtG) in urine, and fatty acid ethyl esters (FAEEs) and EtG in hair were determined using LC-MS/MS and gas chromatograph/mass spectrometer. The limit of quantitation for UEtG, HEtG, and FAEEs were 0.1 mg/l, 2.3 pg/mg, and 0.1 ng/mg, respectively. RESULTS: Fourteen participants reported abstinence from alcohol for the previous 7 days. AUDIT scores were > or =8 in 15 male and >5 in 5 female participants. Direct ethanol metabolites were as follows (median, min, max, standard deviation): UEtG (19 positives; 9.91, 1.38 to 251, 62.39 mg/l); the values of HEtG were 17.65, 0 to 513, 105.62 pg/mg [in 2 cases no material, 8 abstinent (up to 7 pg/mg), 15 social drinkers (up to 50 g per day), and 15 excessive users (>50/60 g/d)]. For the 13 cases, where enough material for additional determination of HFAEEs was available, the values were 0.32, 0 to 1.32, 0.44 ng/mg. Among the 30 HEtG-positive participants, 20 had not reported the corresponding ethanol intake using question 1 (frequency) and 2 (quantity) of the AUDIT. Of the 14 participants reporting no alcohol intake during the previous 7 days, 4 were UEtG-positive. HEtG and AUDIT correlated significantly (r = 0.622, p < 0.0001), but this was not the case for UEtG and self-reported ethanol intake during the previous 7 days. CONCLUSION: (1) HEtG identified 20 cases of daily ethanol intake of more than 20 g, that would have been missed by the sole use of question 1 (frequency) and 2 (quantity) of the AUDIT. (2) Using the total score of the AUDIT, HEtG confirmed 10 more cases positive for alcohol intake. (3) Episodic heavy drinking is with 22.5% more frequent than in general population, and (4) of the 14 participants who reported no alcohol intake during the previous 7 days, 4 were UEtG positive. Improved detection of alcohol consumption, which is hazardous or harmful in the context of HCV and opiate dependence, would allow for earlier intervention in this population which is at particular risk of liver disease and fatal respiratory-depressed overdose. The combined use of self-reports and direct ethanol metabolites seems promising.

Recent studies show that ethyl glucuronide (EtG) can be decomposed by bacteria; whilst so far no degradation of ethyl sulphate (EtS) has been observed. In the present study, in vitro experiments with bacterial colonies were performed. Bacteria (Escherichia coli, Klebsiella pneumoniae, Clostridium sordellii) were isolated from autopsy material (liver, heart blood, urine, ascites, pericardial fluid, pleural fluid) tested for beta-glucuronidase activity, and three bacterial strains were added to nutrient-deficient medium containing EtG and/or EtS and incubated at 36 +/- 1 degrees C. Samples were taken after various intervals up to 11 days, and EtG and EtS were determined by electrospray ionisation tandem mass spectrometry (LC-ESI-MS/MS). EtG was degraded by E. coli and C. sordellii--complete degradation occurred in the range of 3-4 days--and these bacteria exhibited beta-glucuronidase activity. EtS was not affected within 11 days of incubation.

This study was conducted to identify the alcohol consumption among hepatitis C-positive people receiving opioid maintenance therapy using self-report and biomarkers. A total of 49 people (28 male, 21 female) were hepatitis C virus (HCV) positive and were included. The alcohol use disorder identification test (AUDIT) and self-reported ethanol intake in the last 28 days were assessed. In addition to gamma-glutamyl-transferase (GGT) and mean corpuscular volume (MCV), ethyl glucuronide (EtG) and ethyl sulphate (EtS) were determined in serum and urine (UEtG, UEtS, SEtG) using liquid chromatography/tandem mass-spectroscopy (LC/MS-MS) with deuterated internal standards. Abstinence from alcohol was reported for the last 28 days by 13 participants and for the last 7 days by 22. AUDIT was8 in 27 cases. The maximum values were 34.8 mg/l for UEtG, 5.3 mg/l for UEtS and 0.15 for SEtG. Among the 19 UEtG positives, 8 had not reported any ethanol intake in the 7 days prior to the study. Six participants reported intake of up to 320 g of ethanol in the last 7 days, but were negative for SEtG, UEtG and UEtS. Self-reported ethanol intake in the last 28 days correlated with AUDIT score (r = 0.733, P0.001), with the direct ethanol metabolites and MCV. In this population, abstinence and episodic heavy drinking are more common than in the general population. Episodic heavy drinking is a significant cause of acute risk in this population. Results from biomarker testing could indicate cases of under- as well as over-reporting of alcohol consumption. Further research on the diagnostic accuracy of direct ethanol metabolites, including the use of phosphatidylethanol (PEth), in this setting is needed.

Diamond-Like Nanocomposite (DLN, Dylyn®) coatings are amorphous, hard and wear resistant coatings, deposited using a plasma-assisted CVD process. These coatings consist of two interpenetrating networks, one being a diamond-like carbon (a-C:H) network and the other a glass-like a-Si:O network. This specific structure leads to lower internal stress, better adhesion and higher temperature stability as compared to diamond-like carbon. The structure and bonding type were investigated using grazing-incidence X-ray diffraction (GIXRD) and X-ray photoelectron spectroscopy (XPS), respectively. The coefficient of friction of Diamond-Like Nanocomposites, as measured in a standard ball-on-disk tribometer using a steel counterbody, is typically 0.04 to 0.08 in air of 50% relative humidity (RH). Even in humid air of 90% RH and under water, the coefficient of friction stays below 0.1. The wear factor of Diamond-Like Nanocomposite coatings was determined using profilometric measurements of the wear track after a ball-on-disk test and is typically 2 x 10 -7 mm 3 /N m. Under water, an extremely low wear factor, below 5 x 10 -8 mm 3 /N m, was measured. This low-friction and low-wear behaviour of Diamond-Like Nanocomposite coatings, also in humid environments, enables industrial applications of these coatings as hard, self-lubricating coatings on sliding parts in the automotive, chemical, pharmaceutical or biomedical industry.

The direct ethanol metabolites, ethyl glucuronide (EtG) and ethyl sulfate (EtS), are of increasing importance for clinical and forensic applications, but there are only few studies on the kinetics of EtG in serum and none on EtS. In this study, 13 volunteers (social drinkers) drank ethanol in the form of white wine to reach a blood alcohol concentration of 0.51 +/- 0.17 g/kg, and blood and urine samples were analyzed for EtG and EtS simultaneously by chromatography-tandem mass spectrometry (LC-MS/MS). Mean peak serum EtG and EtS concentrations were 2.9 +/- 1.3 and 2.8 +/- 1.6 micromol/l, respectively, and were reached between 4.0 +/- 0.9 h after the start of drinking (3.0 +/- 0.5 h for EtS). The mean time differences between reaching maximum blood ethanol levels and serum metabolite levels were 2.3 +/- 0.9 h for EtG and 1.2 +/- 0.5 h for EtS. In the last blood samples collected (10-11 h after the start of drinking), 11 (of 13) volunteers were still positive for EtG in serum, whereas only 2 were positive for EtS. In the serum of one female person, no EtS was detectable at any time; however, it was excreted in the urine in (low) concentrations. Ethanol was detectable in the serum for up to 8.6 h after the start of drinking, whereas EtG and EtS were detectable up to more than 5.8 h (EtG) and 4.0 h (EtS), respectively. Mean peak urinary concentrations were 401 +/- 232 micromol/l for EtG and 266 +/- 153 micromol/l for EtS, and mean peak levels were reached 6.2 +/- 0.9 h (EtG) and 5.3 +/- 1.2 h (EtS) after the start of drinking. Maximum concentrations of EtG and EtS in serum showed a wide interindividual variation and could not be correlated to the maximum blood ethanol concentrations. Correlations (p0.001, Kendall's Tau b) were found when comparing pairs of parameters, but mostly involved areas under the curve (AUC) of metabolites or of ethanol; one correlation linked the peak concentrations of EtG and EtS in urine.

A 37-year-old female subject had been convicted of driving under the influence of alcohol, and 19 months later, claimed abstinence after supervised disulfiram treatment. Our aim was to elucidate the value of direct ethanol metabolites as measures of abstinence. Ethyl glucuronide (EtG) and fatty acid ethyl esters (FAEE) in hair, phosphatidylethanol in whole blood and EtG and ethyl sulphate in urine were measured. The results were compared with self-report of alcohol consumption and traditional blood biomarkers for chronically elevated alcohol consumption as carbohydrate deficient transferrin (CDT), gamma glutamyl transpeptidase, mean corpuscular erythrocyte volume, aspartate aminotransferase and alanine aminotransferase. EtG was found in distal parts of hair only, whereas the proximal parts were negative. Furthermore, FAEE concentrations were found in the typical distribution over the hair length and showed values typical for either moderate social drinking or abstinence. CDT was above cut-off in 9 out of 16 analyses with a decreasing tendency and the lowest values in the last 2 months before the end of sampling. The data suggest that in addition to traditional markers, a combination of direct ethanol metabolites can be useful in the expert assessment of judging driving ability. A careful individual interpretation of the results for the different markers, however, is an absolute necessity.

Parkinson's disease (PD) is one of the most common neurological disorders in humans with an overall prevalence of 1:1000 with the incidence increasing to as high as 3.4% among people aged 75 years.1,2 The clinical phenotype includes resting tremor, muscular rigidity, bradykinesia, and postural instability. The signs and symptoms of the disease are the consequence of a striatal deficiency of dopamine resulting from neuronal death in the substantia nigra. It is characterised by the presence of the Lewy body, an intracytoplasmic inclusion body found in many brain regions which is not entirely specific to, but is a highly sensitive marker for, Parkinson's disease. The pathogenesis of idiopathic Parkinson's disease is unknown. For the overwhelming majority of PD patients, the disease has previously been thought to occur sporadically. However, there is increasing evidence of a genetic contribution to the disorder.1,3 Recently, two studies have investigated familial aggregation of PD using large, population based, case-control studies. Elbaz et al 4 reported an odds ratio of 3.2 for the presence of PD in first degree relatives (parents and sibs) of 175 cases as compared to 481 controls. Analyses stratified by age showed this aggregation to be stronger for younger PD patients. Familial aggregation of PD in Iceland was studied using a cohort of 772 cases, with 560 having onset of disease at >50 years of age.5 In this study, the odds ratio for PD was 6.7 for sibs and 3.2 for offspring of affected subjects. These studies are consistent with others reporting the risk to be anywhere from two to 14 times higher for first degree relatives as compared to the risk in members of unaffected families.6–9 Genetic linkage analyses in families with either autosomal dominant forms of PD or with an autosomal recessive, juvenile form …

The alleles RHCE*ceBI (RHCE*ce 48C, 712G, 818T, 1132G) and RHCE*ceSM (RHCE*ce 48C, 712G, 818T) encode the low-prevalence Rh antigen STEM. These alleles frequently travel in cis with RHD*DOL. To estimate the frequency of these alleles, we tested a total of more than 700 samples in two populations. Blood samples were obtained from patients with sickle cell disease and from blood donors of African descent. DNA extractions and analyses were performed by standard methods. In the United States, none of 70 patient samples had the RHCE*818 nucleotide change. Two of 220 donors (frequency of 0.009) were heterozygous for RHCE*818C/T (RHCE*ceBI). One of these samples had RHD/RHD*DOL and the other had RHD/RHD*DOL-2. In these 290 samples, no other RHD*DOL alleles were found. In Brazil, 1 of 244 patients with sickle cell disease (frequency of 0.004) and 1 of 171 donors (frequency of 0.006) were heterozygous for RHCE*818C/T (RHCE*ceBI). Testing of more than 500 additional samples from people of African descent, selected because they had a diverse range of common and variant RHCE alleles, did not reveal a sample with RHD*DOL or RHD/RHD*DOL-2 in the absence of RHCE*ce(818T). Although the numbers are small, our study shows that in the United States, the frequency of RHCE*818T is 0.007 (2 in 290 samples) and in Brazil it is 0.004 (2 in 515 samples). The four RHCE*818T alleles were RHCE*ceBI. Immunohematology 2011;27:66–67.

Introduction L’essai randomise LEAD 6 realise sur une periode de 26 semaines a montre chez des patients initialement mal controles par MET ± SU, que le liraglutide (LIRA), analogue du GLP1 administre en une prise quotidienne, etait plus efficace que l’exenatide (EXE) administre en deux prises, dans l’amelioration de l’HbA1c, la sensibilite a l’insuline et la fonction βcellulaire, avec moins d’hypoglycemies. L’extension de cette etude a compare les effets du relais EXE a LIRA (EXE→LIRA) en comparaison aux patients continuant le LIRA (LIRA→LIRA). Patients et Methodes Au total, 389 patients ayant complete l’etude LEAD 6 ont ete inclus dans la phase d’extension non randomisee de 14 semaines. Les patients ont beneficie du LIRA 1,8 mg 1x/jour (apres deux periodes de 1 semaine a 0,6 mg puis 1,2 mg/jour) en remplacement d’EXE 10 μg 2x/jour, ou ont poursuivi le traitement initial par LIRA 1,8 mg. Resultats Le relais EXE→LIRA ameliore l’equilibre glycemique a 26 semaines : l’HbA1c diminue de 0,32 % (p Conclusion Le relais EXE→LIRA apporte des benefices additionnels sur le controle glycemique, la fonction βcellulaire, ainsi que sur le poids et la pression arterielle. Le maintien du traitement par LIRA permet un controle glycemique durable, une perte de poids et une reduction de la pression arterielle, associes a une incidence reduite d’hypoglycemies et de nausees.

Objectif evaluation de l'efficacite et de la tolerance de l'exenatide en pratique clinique courante apres un an de traitemen.t Patients et methodes etude observationnelle retrospective monocentrique portant sur 142 patients diabetiques de type 2 suivis un an apres l'initiation d'exenatide (51, 4% hommes, âge moyen 57,5±8, 7 ans, duree du diabete 11,3±6,77 ans, poids 101, 1±17,8kg, IMC 36,3±6, 7, HbA1c 8, 6±1, 2%). Tous les patients ont ete traites par exenatide en association a la metformine et a un sulfamide hypoglycemiant, avec arret des thiazolidinesdiones ou de l'insuline, si besoin. L'exenatide a ete administre a la dose de 5μg × 2/j pendant un mois, puis de 10μg × 2/j. Resultats L'exenatide a ete arrete chez 67 patients avant un an et poursuivi chez 75 patients.L'exenatide a ete interrompu essentiellement pour desequilibre glycemique ou pour effets secondaires, surtout digestifs, chez 78,4%, respectivement 16, 9% des patients ayant arrete le traitement. L'HbA1c a diminue de 0, 8 3% (de 8, 28 a 7, 45%, p La reduction de l'HbA1c est la plus marquee pour les patients du 3 e quartile de perte de poids (− 1,07%, − 3,98 kg) et comparable pour le 1er (− 0,87%, − 12,8 kg) et le 2 e quartile (− 0,91%, −7, 23kg).La majorite des patients (77, 33%) ameliorent l'HbA1c et obtiennent une perte ponderale a un an. Conclusion En pratique clinique l'exenatide est efficace sur le controle glycemique et la perte ponderale. Le taux initial d'HbA1c et le traitement initial par metformine-sulfamide semblent etre des facteurs predictifs de bonne reponse. Un suivi rapproche est indispensable afin d'identifier precocement les mauvais repondeurs.

Endocrine crises can occur in diabetes mellitus, in pituitary failure when there is a lack of ACTH, TSH or ADH secretion, in severe hyper- or hypothyroidism (thyroid storm and myxedema coma), severe hyper- or hypoparathyroidism (parathyroid crisis and tetany), in adrenal failure and in patients with pheochromocytoma or carcinoid tumors. Cushing's syndrome can be associated with psychotic crises. This review describes the most important clinical features and the basic diagnostic and therapeutic aspects of the non diabetic endocrine crises.

Introduction L’insulinotherapie fonctionnelle permet d’adapter le traitement au mode de vie des patients qui peuvent varier la quantite de glucides des repas. Le but de cette etude est d’apprecier les modifications de l’alimentation induites par cette « liberte alimentaire », et les repercussions sur le poids et l’HbA1c. Patients et Methodes Une enquete alimentaire (a partir d’un journal de 7 jours) a ete realisee avant l’education a l’insulinotherapie fonctionnelle (M0) et a ete renouvelee 6 mois plus tard chez 56 patients diabetiques. Nous avons etudie les modifications des apports alimentaires et analyse l’evolution du poids, de l’HbA1c, des doses basales d’insuline a 6 mois (M6) et a 12 mois (M12). Resultats L’apport calorique total est plus faible a M6 (2 169 vs 2 077 Kcal/j, NS ) et le pourcentage de lipides et de glucides est legerement superieur (respectivement 37,9 et 44,3 % vs 38,2 et 44,4 %, NS ). La consommation de sucres simples augmente a M6 (54 g vs 61 g/j, p = 0,013 ), cette augmentation est egalement significative chez les patients traites par pompe ( p ) et chez les patients dont le diabete evolue depuis moins de 20 ans ( p ). Le poids chute de 0,16 kg a M6 ( NS ) avec un amaigrissement de 1,88 kg au cours des 6 mois suivants ( p = 0,04 ). L’HbA1c diminue discretement a M6 (7,73 ± 0,73 vs 7,65 ± 0,91 %, NS) avec une baisse plus marquee a M12 (7,42 ± 0,73 %, p Discussion Cette etude concerne uniquement des patients motives pour remplir 2 journaux alimentaires. Conclusion L’insulinotherapie fonctionnelle offre une plus grande liberte alimentaire et les patients diabetiques majorent significativement leur consommation de sucres simples avec une reduction non significative de l’apport calorique global. Le poids diminue discretement a 6 mois avec un amaigrissement significatif a 1 an. La baisse de l’HbA1c, discrete a 6 mois, est significative a 1 an, avec des hypoglycemies significativement moins nombreuses.

Objectif Evaluer l’efficacite et la tolerance de l’exenatide et rechercher des criteres predictifs de repondeurs a ce traitement. Patients et Methodes Etude clinique prospective portant sur 85 DT2 (35 F, 50 H, âge = 58 ± 8 ans, duree diabete = 11,2 ± 7,6 ans, poids = 101,4 ± 20,3 kg, IMC = 36,6 ± 7,3 kg/m 2 , tour de taille = 118,2 ± 12,6 cm, HbA1c = 8,5 ± 1,1 %). Tous ont beneficie, apres arret eventuel de TZD ou Insuline, de l’instauration d’exenatide 5 μg X 2/j pendant 1 mois puis 10 μg X 2/j, en association avec Met et Su. Une reevaluation clinique et biologique a ete effectuee a 4 mois. Resultats L’exenatide a ete interrompu chez 11 patients (12,9 %) pour intolerance digestive et chez 4 (4,7 %) pour desequilibre glycemique majeur. L’analyse a donc porte sur 70 patients suivis durant 4 mois : l’HbA1c a diminue de 0,44 % (de 8,55 a 8,11 %, p = 0,003), le poids de 4,4 kg (de 101,4 a 97,0 kg, p 2 (de 36,6 a 35 kg/m 2 , p La reduction d’HbA1c est comparable (−0,43 % vs −0,35 % p = 0,88) entre le tertile des patients ayant perdu le plus de poids (−8 kg en moyenne) et celui des patients ayant perdu le moins de poids (−0,8 kg en moyenne). Ci-dessous l’evolution de l’HbA1c et du poids en fonction des tertiles des criteres predictifs testes: Tertile inferieur Tertile intermediaire Tertile superieur HbA1c initiale [6,6–7,9[ :+0,27 % /−3,35 kg [7,9–9,0[ : −0,23 % /-5,15 kg [9,0–11,9[ : −1,42 % /−4,36 kg Age [32–55[ : −0,49 % /−3,53 kg [55–61[ : −0,40 % /−5,66 kg [61–77[ : −0,44 % /−3,50 kg Duree diabete [2–8[ : −0,67 % /−2,78 kg [8–10[ : −0,60 % /−5,25 kg [10–40[ : −0,10 % /−4,89 kg IMC initial [24,8–32,9[ : −0,59 % /−3,71 kg [32,9–38,5[ : −0,24 % /−4,56 kg [38,5–62,2[ : −0,50 % /−4,65 kg Conclusion L’exenatide est efficace mais l’interruption pour intolerance digestive est frequente. La reduction d’HbA1c n’est pas correlee a l’importance de la perte de poids. Les meilleurs resultats sont obtenus en « add on » de Met + Su chez des patients dont le diabete evolue depuis moins de 10 ans.

Introduction L'objectif principal de l'insulinotherapie fonctionnelle (ITF) est d'offrir au patient une plus grande flexibilite dans la gestion de son traitement. Le but de l'etude est d'evaluer l'impact clinique et metabolique d'une annee d'ITF. Materiels et methodes L'etude prospective a porte sur 35 diabetiques de type 1 formes a l'ITF lors d'une hospitalisation de 5 jours (17 F et 18 H, 26 sous multi injections et 9 sous pompe, âge = 42,4±12 ans, poids=71,6±12kg, HbA1c=7,73±0,99 %, duree diabete = 19,1±11 ans). Une evaluation clinique et biologique a ete effectuee initialement puis apres 6 et 12 mois d'ITF. Les resultats a 1 an ont ete analyses en sous-groupes (type de traitement, HbA1c initiale et duree du diabete). Resultats L'HbA1c a diminue de 0,22 % (de 7,73 a 7,51 %, p = 0,1) avec une meilleure reponse dans les sous-groupes « multi injections » (− 0,28 % vs −0,05 %, p = 0,09), « duree diabete > 20 ans » (− 0,36 % vs −0,06 %, p = 0,07) et « HbA1c initiale ≥ 8 % » (− 0,34 % vs − 0,1 %, p = 0,08). Les hypoglycemies vs 5,71/mois, p = 0,03). Cette reduction est plus marquee dans les sous-groupes « pompe », « duree diabete > 20 ans » et « HbA1c initiale p La dose d'insuline basale a diminue (de 0,31 a 0,27 UI/kg/j, p = 0,0003). Les doses d'insuline totale et prandiale n'ont pas ete modifiees significativement. Le poids a augmente de 1,7kg (de 71,6 a 73,3kg, p = 0,33). L'apport calorique total est reste stable (de 2 140 a 2 104 Kcal/j) mais la repartition des apports s'est modifiee avec une majoration des apports en lipides (de 36,5 a 38,5 %, p = 0,045) et en glucides simples (de 55,3 a 64,4g/j, p = 0,024). Conclusion L'ITF permet donc une reduction de l'HbA1c et de la frequence des hypoglycemies. La reevaluation des besoins en insuline a permis de detecter un surdosage en insuline basale. Le gain de liberte alimentaire n'a pas eu de retentissement sur l'apport calorique total mais l'augmentation de la part des produits gras et des glucides simples explique la prise de poids.

Introduction L'objectif de ce travail est de comparer les proprietes pharmacocinetiques des 2 modalites d'administration de l'insuline basale au cours d'une epreuve de jeune total de 36 heures pratiquee par 24 patients diabetiques de type 1 lors de leur formation a l'insulinotherapie fonctionnelle. Materiels et methodes Seule l'insuline basale a ete delivree lors du jeune et la dose a ete determinee pour chaque patient par la formule d'Howorka. 15 patients (8 H 7 F, âge=39,6±12,5 ans, poids=76,4±13 KG, HbA1c=7,67±1 %, duree diabete=20,5±9,8 ans) etaient traites par une injection d'analogue lent (glargine : 0,28±0,08 UI/Kg/J) (groupe glargine) et 9 patients (5 H 4 F, âge=43,3±12,3 ans, poids=70±13kg, HbA1c=7,93±0,9 %, duree diabete=21,77±7,7 ans) etaient traites par perfusion continue a debit unique d'un d'analogue rapide (Lispro ou Aspart : 0,29±0,07 UI/Kg/J) par pompe (groupe pompe). L'analyse des courbes de mesure en continu du glucose interstitiel (Glucoday ® ) enregistrees lors du jeune nous a permis de determiner les parametres de variabilite glycemique asymptomatique que sont l'ecart type de la moyenne du glucose interstitiel, les index MAGE (Mean Amplitude Glycaemic Excursions) et MODD (Mean Of Daily blood glucose Differences). Resultats La moyenne et l'ecart type de la moyenne de glucose interstitiel (pompe=0,99±0,09g/L vs glargine=0,99±0,15 g/L, p =NS), l'index MAGE (pompe=0,78±0,38g/L vs glargine=0,75±0,31g/L, p =NS) et l'index MODD (pompe=0,44±0,22g/L vs glargine=0,37±0,26g/L, p =NS) ne different pas significativement entre les 2 groupes. Conclusion Les criteres de variabilite glycemique analyses dans ce travail plaident en faveur d'un controle glycemique a jeun au moins aussi satisfaisant avec une injection sous cutanee quotidienne d'un analogue lent de l'insuline (Glargine) qu'avec la perfusion sous-cutanee continue a debit unique d'un analogue rapide de l'insuline (Lispro ou Aspart) par pompe.

Introduction L'objectif de ce travail est d'evaluer l'effet moyen des corrections insuliniques et des collations glucidiques a l'aide d'une mesure continue du glucose au cours d'un jeune total chez des patients diabetiques de type 1. Materiels et methodes Notre etude clinique a porte sur 24 diabetiques de type 1 (13 hommes et 11 femmes, 15 traites par multi-injections et 9 par pompe externe, 42.1±11,8 ans, duree diabete=22,6±9,5 ans, IMC=25,3±3,1kg/m 2 , HbA1c=7,93±0,88 %) ayant beneficie d'une mesure en continu du glucose interstitiel (Glucoday ® ) au cours d'une epreuve de jeune total d'une duree de 36 heures pratiquee a l'occasion de leur formation a l'insulinotherapie fonctionnelle. La dose d'insuline basale (glargine ou debit basal par pompe SC) delivree au cours du jeune a ete determinee par la formule d'Howorka. En cas de glycemie > 1,2g/L ou Resultats L'effet hypoglycemiant moyen d'une correction insulinique d'une unite d'analogue rapide debute apres environ 20 minutes, puis croit jusqu'a la 3 e heure pour atteindre alors environ − 0,3g/L. L'effet hyperglycemiant moyen d'une collation de 10 grammes de glucides simples debute apres environ 15 minutes puis croit rapidement pour atteindre environ + 0,3g/L a 1h 30 avant de s'attenuer progressivement pour atteindre + 0,2g/L apres 3 heures. Conclusion Ces resultats permettent de valider la conduite a tenir pour restaurer une glycemie normale en cas d'hyperglycemie (1 UI d'analogue rapide diminue la glycemie de 0,3g/L en 3 heures) ou d'hypoglycemie (10g de glucides simples remontent la glycemie de 0,3g/L en 1h 30).

Atmospheric carbon dioxide data obtained at Barrow, Alaska for the May–September period of 1978 were studied to understand the causes of the day-to-day and within-day variations. Sixteen instances of 24-h change in average CO 2 concentration of from 15 to 50% of the annual range (approx. 14 ppm) were identified. Within-day variations of up to 50% of the annual range were noted. The variations were found to be related to local and synoptic scale meteorology interacting with local and regional sources and sinks of CO 2 . The results are consistent with an overall source of CO 2 in the tundra of the Alaskan North Slope and a significant sink for CO 2 in the ice-free areas of the seas bordering Alaska. The analysis provides an interpretation of the Barrow CO 2 record which can be used in the selection of representative data for studying large scale trends.

Two waterspouts were observed aloft from a private aircraft recently near Lower Matecumbe Key, Florida. Color slides and zoom movies of both waterspout vortices on the sea surface and aloft were obtained. A detailed description of the equipment used and a discussion of the synoptic pattern of that day are presented. The data show some interesting details regarding the dynamics of the observed waterspout circulations. Both waterspouts traversed a similar path. A subsequent ground survey of the paths taken over the Key, together with damage reports and eyewitness accounts, indicate that the second waterspout was much more intense than the first. The authors plan to make detailed calculations, using the zoom movies, of a radial profile of the tangential and vertical wind speeds about the second waterspout vortex. Rates of forward motion and funnel diameter at various levels below the cloud base will also be obtained. An additional, more quantitative report of this interesting encounter will be forth...

D-C motors are used almost universally on rubber calenders to obtain a wide speed range, good speed regulation, maximum braking under emergency conditions, suitable matching of speeds of the auxiliaries with the calender, and on the modern drives, electrical tension regulation of the fabric. The majority of the calenders in operation are driven by adjustable speed d-c motors with conventional armature resistor starting and with rheostat control of the motor field for speed regulation. The more modern installations are equipped with adjustable voltage systems to obtain greater flexibility of operation, better synchronization with auxiliary machines, more suitable power for the constant torque requirements of calender loads, and improved electrical braking under emergency conditions.

Winter variability over periods of 1 to 5 days in surface CO2 concentration at Barrow, Alaska was studied by examining the relation between CO2 concentration and air mass. The largest positive anomalies of CO2 concentration occurred with relatively deep surface-based Arctic air masses. The long residence time in the Arctic of these air masses is qualitatively compatible with both a natural CO2 source, such as the Arctic Ocean, and transport of anthropogenic CO2 from mid-latitudes in a manner similar to that proposed for the Arctic haze. Trajectories suggest that the anthropogenic CO2 source region of eastern Asia does not contribute significantly to the positive anomalies. The largest negative CO2 anomalies were associated with the influx of air from the North Pacific or North Atlantic regions above a shallow surface-based Arctic layer. The moisture sounding data suggest mixing or diffusion of this air aloft to the surface through the inversion layer.

Variability in atmospheric CO/sub 2/ concentration over periods of 1-5 days at Cape Mutatula, American Samoa, was studied. The variability was found to be the result of the alternating influences of three air mass source regions. Partitioning of Samoa CO/sub 2/ data according to these air mass source regions revealed annual cycles in the partitioned data sets corresponding to those of the tropical South Pacific. The midlatitude southern hemisphere, and the tropical North Pacific regions.