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ABSTRACTBackgroundDiabetes mellitus (DM) is a common comorbidity among people with tuberculosis (TB). Despite the availability of guidelines on how to integrate dual TB/DM in Tanzania, the practice of integration at various healthcare levels is unclear.ObjectiveTo explore the participants’ experiences and perceptions on the pathway towards clinical management of dual TB/DM.MethodThe research was carried out in Dar es Salaam, Iringa, and Kilimanjaro regions between January and February 2020. A qualitative, in-depth interview approach was used to collect participants’ experiences and perspectives on the acquisition of dual TB/DM services at various levels of healthcare facilities. The information gathered were coded and classified thematically.ResultsThe participants’ perception of TB services within the healthcare facilities was positive due to the support they received from the healthcare providers. On the other hand, participants reported difficulty receiving management in various health facilities for each condition in terms of access to dual TB/DM care and access to DM medication. This was viewed as a significant challenge for the participants with dual TB/DM.ConclusionsThe current disjunction and disruption in healthcare for people with dual TB/DM makes it difficult to access services at various levels of health facilities. For optimal clinical management for people with dual TB/DM, patient-centered strategies and integrated approaches are urgently needed.

L’observance aux corticoïdes inhalés (CI) demeure un enjeu de la prise en charge de l’asthme, même chez les patients recevant régulièrement une ordonnance de leur médecin. La fréquence des interruptions spontanées des CI par les patients et celle des changements de dose ont été étudiées.

To assess the current Tanzania health facilities readiness in integrating clinical management of dual Tuberculosis (TB) and Diabetes Mellitus (DM) by using the Service Availability and Readiness Assessment (SARA) manual of the World Health Organization prior to implementing an integrated service model.

A lack of the complete pig proteomehas left a gap in our knowledge of the pig genome and has restricted the feasibility of using pigs as a biomedical model. In this study, we developed a tissue-based proteome map using 34 major normal pig tissues. A total of 5841 unknown proteinisoforms were identified and systematically characterized, including 2225 novel protein isoforms, 669 protein isoforms from 460 genes symbolized beginning with LOC, and 2947 protein isoforms without clear NCBI annotation in the current pig reference genome. These newly identified protein isoforms were functionally annotated through profiling the pig transcriptome with high-throughput RNA sequencing of the same pig tissues, further improving the genome annotation of the corresponding protein-coding genes. Combining the well-annotated genes that have parallel expression patternand subcellular witness, we predicted the tissue-related subcellularlocationsand potential functions for these unknown proteins. Finally, we mined 3081 orthologous genes for 52.7% of unknown protein isoforms across multiple species, referring to 68 KEGG pathways as well as 23 disease signaling pathways. These findings provide valuable insights and a rich resource for enhancing studies of pig genomics and biology, as well as biomedical model application to human medicine.

Décrire les caractéristiques et la prise en charge de patients migraineux suivis médicalement en officines.

Objective: To estimate the economic impact of community pharmacists' interventions following the detection of problems related to nonsteroidal antiinflammatory drugs (NSAIDs), whether in a prescription or self-medication format. The evaluation focused on the gastroduodenal adverse events that could be avoided and the subsequent savings of healthcare resources spent on treating these adverse effects.Methods: A previous study conducted during a 12-week period in 924 French community pharmacies provided the number of interventions for drug-related problems concerning NSAIDs. A simulation model was constructed to compare 2 strategies: a systematic pharmacist's intervention and the absence of intervention. The base-case patient was assumed to have been taking an NSAID for 3 months. The model's inputs were extracted from medical literature and from an institutional medical database.Results: In this study, 608 interventions were the results of NSAID-related problems. All of these interventions reduced the risk of gastrointestinal adverse events and avoided a total cost of €37 300.Conclusions: This model indicates that the dispensing of NSAIDs by pharmacists and related pharmaceutical care activities have a positive impact by reducing the number of gastrointestinal complications. The model quantifies the costs thus avoided. It also underlines the necessity of effective collaboration between the prescriber and the pharmacist if optimal patient management is to be achieved.

Conjugated linoleic acid (CLA), and especially rumenic acid, are isomers of linoleic acid which have a great potential in human nutrition for their beneficial properties. The most important sources of natural CLA are milk and dairy products such as cheese. This study was delineated to assess the effects of sampling according to the cheese wheel, the seasonal and regional influence on CLA content in French Emmental cheese and, finally, the effects of culinary preparation of three different dishes (gratin, b?chamel sauce and cheese fondue) and processed cheese. The rumenic acid content of Emmental cheese varied between 0.6% and 1.5% of total fatty acids according to the season and region of production, and appeared homogeneous through the cheese wheel. The culinary utilization and processing did not change the rumenic acid content of Emmental cheese.Teneur en acide linol?ique conjugu? (CLA) dans l?Emmental fran?ais : effet de la saison, de la zone de production, de la fabrication et du mode de pr?paration culinaire. Les isom?res conjugu?s de l?acide linol?ique (CLA) et, en particulier, l?acide rum?nique (C18:2 9 cis 11 trans) poss?dent des effets b?n?fiques d?un grand int?r?t en nutrition humaine. Le lait et les produits laitiers, tels que les fromages, sont d?importantes sources naturelles d?acide rum?nique. Ce travail avait pour but d?en ?tablir la r?partition au sein de la meule de fromage, d??tudier l?influence de la saison et de l?origine r?gionale sur la teneur en CLA de l?Emmental fran?ais et enfin, de mesurer les effets de son utilisation, soit en cuisine dans la pr?paration de sauce b?chamel, de gratin et de fondue, soit dans la fabrication de fromage fondu. La teneur de l?Emmental fran?ais en acide rum?nique varie de 0,6 % ? 1,5 % de la teneur totale en acide gras selon la saison et la r?gion de production, elle est homog?ne au sein de la meule de fromage. Aucune modification significative de la teneur en CLA n?est observ?e lors de l?utilisation de l?Emmental, aussi bien pour les trois pr?parations culinaires que pour la fabrication de fromage fondu.

To assess the relationship between conditions of milk production and cheese contents of components of nutritional interest, it is necessary to know to what extent the compositional variability of cheese depends on that of milk. The respective effects of milk composition and the cheese-making process on cheese compositional variability in components of nutritional interest were therefore studied under real conditions of cheese production considering four different cheese-making technologies. The nutritional characteristics of the original milk were subject to high variations partly due to animal species (cow vs. goat). Apart from the aspects related to the dry matter content of cheese, the cheese compositional variability in fatty acids, b?carotene, xanthophylls and vitamin E depended mainly on the composition of the original milk. For vitamin A, it was partially influenced by both the original milk composition and the cheese-making process. Regarding folates and minerals, as well as total antioxidant capacity, the cheese composition varied mainly with the cheese-making process. In addition, the cheese-making technology had a significant effect on the cheese composition in minerals and folates, but did not influence the other components affected by the cheese-making process. Consequently, the cheese contents of fat-soluble compounds depend directly on the conditions of milk production. On the contrary, the composition of cheese in water-soluble compounds varies independently of the conditions of milk production. The total antioxidant capacity of pressed cheeses, unlike the original milk, was positively correlated with some fat-soluble antioxidants. It could therefore be influenced by the conditions of milk production.Effets respectifs de la composition du lait et de la transformation fromag?re sur la variabilit? de composition du fromage en compos?s d?int?r?t nutritionnel. De fa?on ? ?tudier la relation entre les conditions de production du lait et les teneurs en compos?s d?int?r?t nutritionnel dans le fromage, il est n?cessaire de savoir dans quelle mesure la variabilit? de composition du fromage d?pend de celle du lait d?origine. Les effets respectifs de la composition du lait et de la transformation fromag?re sur la variabilit? de composition du fromage en compos?s d?int?r?t nutritionnel ont donc ?t? ?tudi?s en conditions r?elles de production du fromage et en consid?rant quatre technologies fromag?res diff?rentes. Les caract?ristiques nutritionnelles du lait ? l?origine du fromage sont soumises ? de grandes variations en partie dues ? l?esp?ce animale (vache vs. ch?vre). Mis ? part les aspects li?s ? la teneur en mati?re s?che du fromage, la variabilit? de composition du fromage en acides gras, en b?carot?ne, en xanthophylles et en vitamine E d?pend principalement de la composition du lait d?origine, alors que pour la vitamine A celle-ci est influenc?e ? la fois par la composition du lait d?origine et par la transformation fromag?re. Par contre, la composition en folates et en min?raux du fromage, ainsi que son potentiel antioxydant total, varient principalement avec la transformation fromag?re. Par ailleurs, le type de technologie fromag?re exerce un effet important sur la composition du fromage en min?raux et en folates, mais n?a aucun effet sur les autres compos?s influenc?s par la transformation fromag?re. En cons?quence, la teneur du fromage en compos?s liposolubles, contrairement aux compos?s hydrosolubles, d?pend directement des conditions de production du lait. Le potentiel antioxydant total des fromages ? p?te press?e, ? la diff?rence de leur lait d?origine, est positivement corr?l? avec certains compos?s antioxydants liposolubles. Il pourrait par cons?quent ?tre influenc? par les conditions de production du lait.

In a study of the evolution of conjugated linoleic acid (CLA) during cheese production, the influence of Emmental cheese processing on the CLA content and the CLA isomer composition was evaluated. The use of raw and thermised milk, changes of processing temperature and the effect of propionic acid bacteria (PAB) were investigated. The content of CLA in raw milk was 8·6±1·9 mg/g fat and in the ripened cheese at 70 d was 8·6±1·6 mg/g fat, under normal processing conditions. No changes in the CLA content and CLA isomer composition were observed during Emmental cheese manufacturing process. Changes in cooking and moulding temperatures did not influence the CLA content. CLA content of cheese made from microfiltered milk with two different Propionibacterium freudenreichii strains was very close to cheeses made without PAB. CLA levels seem to be stable in this type of dairy product under the conditions examined.

Selective serotonin reuptake inhibitors (SSRIs) are the treatment of choice for clinical depression and a range of anxiety-related disorders. They are well tolerated over extended periods with more than 50 million people worldwide benefiting from their use. Here we show that 3 structurally distinct SSRIs—fluoxetine, paroxetine, and citalopram—act directly on Burkitt lymphoma (BL) cells to trigger rapid and extensive programmed cell death. SSRIs unexpectedly stimulated calcium flux, tyrosine phosphorylation, and down-regulation of the c-myc and nm23 genes in Burkitt lymphoma cells remaining faithful to the biopsy phenotype. Resultant SSRI-induced apoptosis was preceded by caspase activation, poly(ADP-ribose) polymerase-1 (PARP-1) cleavage, DNA fragmentation, a loss of mitochondrial membrane potential, and the externalization of phosphatidylserine, and reversed by the overexpression of bcl-2. Normal peripheral blood mononuclear cells and tonsil B cells, whether resting or stimulated into cycle, were largely resistant to SSRI-induced death as were 5 non-BL lymphoid cell lines tested. We discuss these findings within the context of whether the SSRI class of antidepressants could find future application as potential therapeutics for the highly aggressive and—because of its association with AIDS—increasingly more common Burkitt lymphoma.

OBJECTIVE: To estimate the economic impact of community pharmacists' interventions following the detection of problems related to nonsteroidal antiinflammatory drugs (NSAIDs), whether in a prescription or self-medication format. The evaluation focused on the gastroduodenal adverse events that could be avoided and the subsequent savings of healthcare resources spent on treating these adverse effects.METHODS: A previous study conducted during a 12-week period in 924 French community pharmacies provided the number of interventions for drug-related problems concerning NSAIDs. A simulation model was constructed to compare 2 strategies: a systematic pharmacist's intervention and the absence of intervention. The base-case patient was assumed to have been taking an NSAID for 3 months. The model's inputs were extracted from medical literature and from an institutional medical database.RESULTS: In this study, 608 interventions were the results of NSAID-related problems. All of these interventions reduced the risk of gastrointestinal adverse events and avoided a total cost of 37 300.CONCLUSIONS: This model indicates that the dispensing of NSAIDs by pharmacists and related pharmaceutical care activities have a positive impact by reducing the number of gastrointestinal complications. The model quantifies the costs thus avoided. It also underlines the necessity of effective collaboration between the prescriber and the pharmacist if optimal patient management is to be achieved.

Population size is governed through cells reacting to a variety of intrinsic and extrinsic cues. Tumors, while liberated from many of the homeostatic constraints placed on physiologic counterparts, can nonetheless remain subject to both social and environmental control. Burkitt lymphoma cells faithful to the biopsy phenotype were used to model the reliance of the colony, if any, on an inbuilt population sensor. Below a normally suicidal threshold number of cells, low picomolar quantities of exogenous CD40 ligand (CD40L/CD154) were found to sustain the clone without the discernible shift in phenotype that accompanies high CD40L encounter. Although CD154 was undetectable in populous cultures, message was induced as numbers became limiting. Correspondingly, attempts to neutralize endogenous CD40L activity failed to perturb cells at optimal densities but resulted in their marked decline as the critical threshold was approached. These data reveal an auto-inducible survival mechanism seemingly regulated through the monitoring of population size, a process somewhat akin to that of “quorum sensing” among gram-negative bacteria in which diffusible molecules provide a means of communication to coordinate gene expression with population density. This process could be activated as cells discern depletions in their community or when deprived of signals otherwise furnished within an appropriate environmental niche.

Serotonin (5-HT), a well-known neurotransmitter of the central nervous system, has been implicated in diverse aspects of immune regulation. Here we show that 5-HT can efficiently drive programmed cell death in established Burkitt lymphoma (BL) lines that remain faithful to the original biopsy phenotype (group 1). Group 1 BL cells cultured in the presence of 5-HT exhibited marked suppression of DNA synthesis that was accompanied by extensive apoptosis—serotonin-driven apoptosis was complete within 24 hours, was preceded by early caspase activation, and was accompanied by a decline in mitochondrial membrane potential. BL cells that had drifted to a lymphoblastic group 3 phenotype were relatively resistant to these actions of serotonin, and the forced ectopic expression of either bcl-2 orbcl-xL provided substantial protection from 5-HT–induced apoptosis. 5-HT receptor antagonists (SDZ205-557, granisetron, methysergide) failed to inhibit serotonin-induced apoptosis, whereas the selective serotonin reuptake inhibitors (SSRI)—fluoxetine (Prozac), paroxetine (Paxil), and citalopram (Celexa)—substantially blocked the monoamine actions. Western blot analysis showed that BL cells expressed protein for the 5-HT transporter, and transport assays confirmed active uptake of serotonin by the cells. Unlike what was suggested for neuronal cells, there was no evidence that intracellular oxidative metabolites were responsible for the 5-HT–induced programmed death of BL cells. These data indicate that serotonin drives apoptosis in biopsylike BL cells after its entry through an active transport mechanism, and they suggest a novel therapeutic modality for Burkitt lymphoma.

Streptococcus thermophilus is a lactic acid bacterium widely used for manufacturing milk products. The protein composition of three strains of S. thermophilus grown in either M17 medium or milk was investigated. These conditions were chosen on the basis of the observed technological differences between these strains. Protein extracts prepared from cells harvested at the same pH (5.2 ? 0.1), were analyzed by two-dimensional gel electrophoresis. Gel comparison revealed qualitative and quantitative differences between the two growth media and between the strains. Some proteins with quantitative variation were partially identified. The most significant medium-related differences concerned the number of spots detected and the heat shock protein (GroEL, HSP70) levels which were higher in milk than in M17. On the contrary, the levels of enzymes (proton translocating ATPase, pyruvate kinase, tributyrin esterase, phospho-glycerate kinase, glyceraldehyde-3-phosphate dehydrogenase, fructose diphosphate aldolase, superoxide dismutase) and of a putative penicillin binding protein were lower in milk than in M17. Strain-related differences were accentuated in milk for heat shock proteins, tributryrine esterase and dinitrogenase reductase. ?tude comparative de la composition prot?ique de trois souches de Streptococcus thermophilus cultiv?es dans le milieu M17 ou dans le lait. S. thermophilus est une bact?rie lactique tr?s utilis?e pour la fabrication de produits laitiers. La composition prot?ique de trois souches de S. thermophilus cultiv?es dans le milieu M17 ou dans le lait a ?t? ?tudi?e. Ces conditions ont ?t? choisies sur la base des diff?rences technologiques observ?es entre les souches. Les extraits prot?iques pr?par?s ? partir des cellules r?colt?es au m?me pH (5,2 ? 0,1), ont ?t? analys?s par ?lectrophor?se bidimensionnelle. La comparaison des gels a r?v?l? des diff?rences qualitatives et quantitatives entre les deux milieux et entre les souches. Certaines prot?ines pr?sentant une variation quantitative ont ?t? partiellement identifi?es. Les diff?rences les plus significatives en fonction du milieu de croissance concernent le nombre de taches d?tect?es et la quantit? de prot?ines de choc thermique (GroEL, HSP70) qui sont plus ?lev?s dans le lait que dans le M17. Les quantit?s d'enzymes (ATPase translocatrice de proton, pyruvate kinase, tributyrine est?rase, phospho-glyc?rate kinase, glycerald?hyde-3-phosphate deshydrog?nase, fructose diphosphate aldolase, superoxyde dismutase) et d'une prot?ine putative de liaison de la penicilline sont, au contraire, plus faibles dans le lait que dans le M17. Les diff?rences entre les souches sont accentu?es dans le lait pour les prot?ines de choc thermique, la tributryrine est?rase et la dinitrog?nase r?ductase.

Compared to many cheeses, lipolysis of Emmental is generally low. It concerns about 1-2% of cheese fat and the amount of free fatty acids (FFAs) varies from 2 to 7 g.kg-1of ripened cheese. In this work, we studied the extent of lipolysis due to propionic acid bacteria (PAB). The release of FFAs during the ripening of Emmental cheeses made from microfiltered milk, with or without propionic acid bacteria (PAB) was followed. The usual cooking step in the cheese process (up to 50 ?C and 30 min) inactivated the lipoprotein lipase (EC 3.1.1.34) and the main factor in the lipolysis of Emmental cheese was shown to be the lipolytic activity of PAB. This activity was strain-dependent and not related to the production of propionic acid in cheese. The most abundant FFAs were palmitic acid, oleic acid, myristic acid and stearic acid as in milk fat and it was concluded that lipolytic activity of PAB is non-specific. Lastly, an interaction still not elucidated was evidenced between certain PAB strains and thermophilic lactobacilli strains regarding lipolysis extent in Emmental cheese. Contribution des bact?ries propioniques ? la lipolyse de l'emmental. La lipolyse est comme la prot?olyse et la glycolyse un ph?nom?ne majeur de l'affinage des fromages. Comparativement ? de nombreux autres fromages, la lipolyse de l'emmental est g?n?ralement limit?e. Elle porte sur environ 1 ? 2% de la mati?re grasse du fromage et la teneur en acides gras libres (AGL) varie de 2 ? 7 g.kg-1dans le fromage affin?. Dans plusieurs exp?rimentations en fromagerie pilote, nous avons ?tudi? l'intensit? de la lipolyse g?n?r?e par les bact?ries propioniques. La lib?ration des AGL au cours de l'affinage d'emmentals fabriqu?s ? partir de lait microfiltr? ensemenc? ou non en bact?ries propioniques, d?montre que la cuisson habituelle du caill? en cuve (au moins 50 ?C pendant 30 min) inactive la lipoprot?ine lipase (EC 3.1.1.34) et que l'activit? lipolytique des bact?ries propioniques est majoritairement responsable de la lipolyse de l'emmental. Cette activit? est souche d?pendante et n'est pas corr?l?e avec l'intensit? de la fermentation propionique. Des lactobacilles thermophiles homofermentaires interagissent avec les bact?ries propioniques sur la lipolyse de l'emmental, par un m?canisme non ?lucid?. Les acides palmitique, ol?ique, myristique et st?arique sont les AGL les plus abondants au m?me titre que dans le lait. L'activit? lipolytique des bact?ries propioniques ne semble donc pas sp?cifique.

The relationships between the texture and composition of Abondance cheese (Haute-Savoie, France) and the milk used for its production, were investigated under real conditions of cheese production. Ten different types of pasture, exploited by three producers, were involved. Milk characteristics, linked to the type of pasture, affected cheese texture, as did the cheesemaking process. Cheeses from milk produced on mountain pastures (M, n = 5, 1 500-1 850 m) exhibited different rheological properties from those produced with milk from valley pastures (V, n = 5, 850-1 100 m): they were less elastic and less deformable. Rheological characteristics were mainly linked to the proportion of 18 atoms of carbon unsaturated fatty acids, which was higher in M milks, and to the proteolysis of cheese. Plasmin activity, which was higher in M milks, could enhance primary proteolysis in the corresponding cheeses. Differences in sensory texture, which were greater between M cheeses than between V cheeses, were attributed to variations in moisture and salt content. These differences could be linked to the cheesemaking process and also to the characteristics of milks, such as their pH-value and acidifying ability. Relations entre la texture de fromages d'Abondance, leur composition, et celle des laits produits par des vaches p?turant diff?rents types de pelouse. Les relations entre la texture du fromage d'Abondance (Haute-Savoie, France), sa composition et celle du lait utilis? pour sa fabrication ont ?t? ?tudi?es dans des conditions r?elles de production du fromage. Dix p?turages diff?rents, exploit?s par 3 producteurs, ont ?t? ?tudi?s. Les caract?ristiques du lait, li?es aux types de p?turage ont jou? un r?le dans l'?laboration de la texture, de m?me que les param?tres de fabrication. Les fromages fabriqu?s ? partir de laits produits sur des p?turages de montagne (M, n = 5, 1 500-1 850 m) ?taient moins ?lastiques et moins d?formables que les fromages issus de laits produits sur des p?turages de vall?e (V, n = 5, 850-1 100 m). Ces caract?ristiques rh?ologiques ?taient li?es principalement ? la teneur en acides gras insatur?s ? 18 atomes de carbone des laits, plus ?lev?e dans les laits M, et ? la prot?olyse des fromages. La plasmine, plus active dans les laits M, contribuerait ? une prot?olyse primaire plus importante dans ces fromages. Les fromages M pr?sentaient une plus grande diversit? de texture que les fromages V, en partie associ?e ? des diff?rences de teneurs en eau et en sel. Ces diff?rences seraient li?es ? la technologie mise en oeuvre et ? certaines caract?ristiques du lait comme son pH et son aptitude ? s'acidifier.

Raw cow milk microflora: diversity and influence of conditions of production. The microbial composition of 158 raw cow milk samples taken from 27 farms located in the French Alps area was determined. Microbial analyses included the total mesophilic aerobic bacteria count as well as numeration of some useful cheesemaking microorganisms (lactic acid bacteria, halophilic bacteria, propionic acid bacteria...), spoilage bacteria (Pseudomonas, enterobacteriaceae, Clostridium spp.) and some of the pathogenic bacteria (coagulase positive staphylococci, Escherichia coli). Milk samples were of good overall microbial quality (mean value less than 10 000 cfu.mL-1) and had different contents of useful cheesemaking microorganisms or spoilage bacteria. Five different groups of milks were then separated according to their total count and to their relative contents in useful cheesemaking and spoilage microorganisms. When incubated at 37 ?C for 24 h without any starters addition, milks of the different groups did not have the same ability to produce acid and to coagulate. At the farm level, milk suppliers practices were studied. Farmers differed by their way of washing the milking equipment and by their pre-milking and post-milking udder preparation. Combination of these practices influenced the microbial load and composition of the milk produced. La composition microbiologique de 158 ?chantillons de laits crus de vache pr?lev?s ? la fin de la traite chez 27 producteurs des d?partements de Savoie et Haute-Savoie a ?t? ?tudi?e. Seize groupes microbiens ont ?t? choisis parmi les groupes d'int?r?t technologique (flore acidifiante m?sophile, flore halotol?rante, bact?ries propioniques...), les groupes d'alt?ration (Pseudomonas, ent?robact?ries, Clostridium spp.) ou certains groupes potentiellement pathog?nes (staphylocoques ? coagulase positive, Escherichia coli). Si en moyenne les laits analys?s renferment tr?s peu de germes (moyenne inf?rieure ? 10 000 ufc.mL-1), il est possible de distinguer 5 classes de laits qui diff?rent par leur teneur en flore m?sophile a?robie revivifiable (de 1 200 ? 15 000 ufc.mL-1en moyenne) et par leur proportion en flore d'int?r?t technologique et en flore d'alt?ration. Les laits des diff?rentes classes ne poss?dent pas les m?mes capacit?s intrins?ques ? l'acidification spontan?e et ? la coagulation. De m?me, l'aspect des coagulums obtenus varie. Une enqu?te r?alis?e chez tous les producteurs lors du pr?l?vement des laits montre que leurs pratiques diff?rent pour le lavage du mat?riel de traite et les soins apport?s aux mamelles avant et apr?s la traite. Ces pratiques et leur combinaison influencent le niveau des populations microbiennes et la proportion entre les flores d'int?r?t technologique et les flores d'alt?ration.

Qualitative aspect of proteolytic activity of thermophilic lactobacilli using in Swiss cheeses. The average peptidic pattern was established from 253 French Emmental cheeses sampled in 50 factories. It contained 53 peptidic peaks, 4 of which were the most important in quantity. Two Lactobacillus helveticus strains and five Lactobacillus delbrueckii ssp. lactis strains were tested in Emmental experimental cheesemaking in association with three different propionic strains (21 cheeses). The Propionibacterium freudenreichii strains did not affect the peptidic pattern of ripened Emmental cheese. On the other hand, 13 peptidic peaks were significantly influenced by the thermophilic lactobacilli strain. The two species of thermophilic lactobacilli were discriminated by three peptidic peaks. Seven peptidic peaks were correlated with the ammonia amount in ripened Emmental cheese. No significant correlation was found between peptidic peaks and SN/TN and NPN/TN. At the same time, the peptidic pattern produced by the seven lactobacilli strains were studied in laboratory. The most specific peptidic peak of the French Emmental cheese were not found by using the Hammarsten casein as substrate. Another substrate, similar to hard cooked cheeses, lyophilized and sterilized by ionisation was tested. This substrate was obtained with microfiltered milk and Streptococcus thermophilus strains only. This substrate digested by thermophilic lactobacilli allowed to find the specific peptidic peaks of the French Emmental cheese. For example, the 14th peak obtained in laboratory was significantly different according to lactobacilli species, as it was observed in the Emmental cheese experiments. This peak distinguished the strains inside the Lb. delbrueckii ssp. lactis too. Le profil peptidique moyen de l'Emmental fran?ais est ?tabli ? partir de 253 profils recueillis dans 50 fromageries. Il comprend 53 pics dont 4 majeurs d'un point de vue quantitatif. Deux souches de Lactobacillus helveticus et 5 souches de Lactobacillus delbrueckii ssp. lactis ont ?t? test?es en fabrication exp?rimentale d'emmental avec 3 souches de bact?ries propioniques diff?rentes (21 fromages). La souche de Propionibacterium freudenreichii n'influence pas le profil peptidique de l'emmental affin?. En revanche, 13 pics du profil peptidique sont significativement influenc?s par la souche de lactobacilles thermophiles ensemenc?e. Trois pics discriminent l'esp?ce. Sept pics sont corr?l?s avec le taux d'ammoniaque des emmentals affin?s ; aucune corr?lation significative n'est mise en ?vidence entre les pics des profils peptidiques et NS/NT ou NPN/NT. Le profil peptidique produit par les 7 souches de lactobacilles utilis?es en fabrication est ?galement ?tudi? au laboratoire. Les pics majeurs caract?risant l'emmental ne sont pas retrouv?s en utilisant la cas?ine Hammarsten comme substrat. Un substrat fromage lyophilis? et st?rilis? par ionisation a ?t? r?alis? ? partir de mini fromages de fabrication type p?te cuite, ?labor?s avec du lait microfiltr? et ajout de Streptococcus thermophilus. Avec un tel substrat hydrolys? par les lactobacilles thermophiles, nous retrouvons les pics majeurs du profil peptidique de l'emmental. Le pic 14 obtenu au laboratoire est significativement diff?rent selon l'esp?ce Lb. helveticus ou Lb. delbrueckii ssp. lactis, comme nous l'avons observ? en fabrication exp?rimentale d'emmental. Il discrimine ?galement la souche au sein de l'esp?ce Lb. delbrueckii ssp. lactis.

Qualitative aspect of proteolytic activity of thermophilic lactobacilli using in Swiss cheeses. The average peptidic pattern was established from 253 French Emmental cheeses sampled in 50 factories. It contained 53 peptidic peaks, 4 of which were the most important in quantity. Two Lactobacillus helveticus strains and five Lactobacillus delbrueckii ssp. lactis strains were tested in Emmental experimental cheesemaking in association with three different propionic strains (21 cheeses). The Propionibacterium freudenreichii strains did not affect the peptidic pattern of ripened Emmental cheese. On the other hand, 13 peptidic peaks were significantly influenced by the thermophilic lactobacilli strain. The two species of thermophilic lactobacilli were discriminated by three peptidic peaks. Seven peptidic peaks were correlated with the ammonia amount in ripened Emmental cheese. No significant correlation was found between peptidic peaks and SN/TN and NPN/TN. At the same time, the peptidic pattern produced by the seven lactobacilli strains were studied in laboratory. The most specific peptidic peak of the French Emmental cheese were not found by using the Hammarsten casein as substrate. Another substrate, similar to hard cooked cheeses, lyophilized and sterilized by ionisation was tested. This substrate was obtained with microfiltered milk and Streptococcus thermophilus strains only. This substrate digested by thermophilic lactobacilli allowed to find the specific peptidic peaks of the French Emmental cheese. For example, the 14th peak obtained in laboratory was significantly different according to lactobacilli species, as it was observed in the Emmental cheese experiments. This peak distinguished the strains inside the Lb. delbrueckii ssp. lactis too.

The major protein zero (MPZ) is involved in peripheral myelin folding. Using nested reverse transcription‐PCR, we amplified several fragments of MPZmRNAs in white blood cells and in peripheral nerve tissue. Cloning of PCR products revealed the existence of three alternative splicing patterns: one resulted in the complete loss of exon 3 and two others induced partial skipping of the exon 3 sequence. All three alternative splicing mechanisms produced a frame‐shift and created an identical premature stop codon in exon 4. We conclude that the existence of these MPZRNA transcript variants may be the result of deliberate splicing decisions and may have functional implications in the cell.

Human recombinant [ 125]TNF-α was incubated with non-adherent human neutrophils, cells adherent to fibronectin-coated plastic, or adherent cells scraped into suspension (post-adherent). Binding of TNF to all cells increased with doses of added TNF but adherent cells little TNF, Binding of TNF by post-adherent cells was greater than when adherent, but still significantly less than of non-adhered neutrophils, suggesting that TNF receptors were relocated on the adherent surface of neutrophils. Scatchard analysis showed that adherent cells expressed significantly fewer TNF receptors, but of higher affinity, then non-adherent cells. The results suggest that altered expression of TNF receptors might contribute to the differential effects of TNF on adherent and non-adherent neutrophils.

Success in making a cheese acceptable in both flavour and texture depends partly on curd properties which determine the retention of fat and moisture and, thus, cheese yield and composition (Green & Grandison, 1993). When considering farmhouse and/or Appelation d'Origine Contrôlée cheese where milk treatments are not allowed, curd properties depend only on milk composition and clotting characteristics, which are subject to wide fluctuations over the year owing to the cow's stage of lactation and nutritional factors (O'Keeffe, 1984; Macheboeuf et al. 1993). These variations often result in seasonal differences in the chemical or sensory properties of the cheese (Kefford et al. 1995) which are sometimes difficult to understand (Grandison et al. 1985). Only a few studies have assessed the cheesemaking quality of milk by actually making ripened cheese; most studies report milk coagulation properties and curd firmness. The object of this work was to study the influence of the chemical composition and clotting characteristics of the milk on the chemical and sensory properties of ripened cheeses when milk characteristics vary widely.

Since there was no study available on the comparative anatomical neurochemistry of the noradrenaline (NA) and adrenaline (A) containing neurons of the lower brain stem, we studied the distribution of the activities of the three major catecholamines (CA)-synthesizing enzymes in coronal sections of the rat medulla oblongata dissected into microcubes. In the dorso-medial region, there was a 1500 μm rostro-caudal difference in the localization of the peak of PNMT activity compared with the peaks of TH and DBH activities. This result led to a new microdissection technique allowing the preferential microdissection of the C2 A neurons versus the A2 NA neurons.The response of these two populations of CA neurons was then studied after a sustained decrease in blood pressure induced in young SHR by a 14 days dihydralazine treatment. The C2 adrenergic region exhibited an overall increase in TH, DBH and PNMT activity (+69%, +45% and +33%; p < 0.01 respectively) while the A2 noradrenergic region was unaffected. Thus, the NA and A neurons of the rat dorso-medial lower brain stem do not seem to exhibit the same biochemical response after a prolonged hypotension.This preliminary result favors the hypothesis of a different functional role for the neighboring A2 and C 2 neurons in central control of blood pressure.

The activities of the catecholamine synthesizing enzymes have been determined in discrete brain areas and in peripheral tissues of rats, at different times after clipping the left renal artery (two-kidney Goldblatt hypertension, 2KGH) and in sham operated animals. Three days after clipping the only enzymatic change was a slight decrease in plasma dopamine-β-hydroxylase (DBH) activity. Ten days after clipping no change in enzymatic activity was found at the central level. However, the DBH and the phenylethanolamine-N-methyltransferase (PNMT) activities were increased in the adrenal medulla (49.0, P<0.001 and 36.6, P<0.001, respectively) and DBH activity was also increased in the superior cervical ganglia ( 22.8, P<0.01). These data suggest that sympathetic hyperactivity is present in 2KGH rats when hypertension is established. In addition, as this type of hypertension does not alter the PNMT activity in brainstem areas, it seems that the alterations in PNMT activity reported for genetically hypertensive rats are unlikely to be secondary to the elevated blood pressure.

1. Neutrophils from patients with chronic obstructive bronchitis and emphysema or age-matched control subjects were cultured on a substrate of 125I-fibronectin. The neutrophils from patients with lung disease digested significantly more fibronectin and released more elastase into the culture supernatant than did cells from control subjects. Preincubation of neutrophils from emphysematous patients with plasma from control subjects significantly inhibited fibronectin digestion by the patients' neutrophils by, on average, 10%. Preincubation of control subjects' neutrophils with plasma from emphysematous patients had no effect on fibronectin digestion. 2. Tumour necrosis factor increased fibronectin digestion in a dose-dependent manner when the cytokine was added to the adherent cells but not when preincubated with the polymorphonuclear leucocytes in suspension. Bacterial endotoxin in concentrations above 6 μg/ml significantly increased fibronectin digestion by neutrophils, but leukotriene B4, interferon-μ and interleukin-1α had no significant effects. 3. Dexamethasone inhibited fibronectin digestion by neutrophils in a dose-dependent manner, from 11% at 10−10 mol/l to 68% at 10−3 mol/l.

Acute chest syndrome (ACS) is a life-threatening complication of sickle cell disease (SCD) with blood transfusion an integral part in its management. Red cell exchange (RCE) transfusion is usually regarded as preferable to top-up transfusion, because it reduces the proportion of Hemoglobin (Hb) S while at the same time avoiding circulatory overload. Despite its obvious benefits, RCE is underutilized, particularly in low-resource settings which may be due to scarcity of blood products and of expertise in carrying out exchange transfusion. We report on a young woman with SCD with severe ACS who responded promptly and dramatically to a RCE of only 0.95 L (instead of the recommended 1.4 L) and had in the end an HbS level of 48% (instead of the recommended level below 30%). Limited RCE resulted in significant clinical improvement. We suggest that limited RCE may be of benefit than no RCE in SCD patients with ACS, particularly in settings where RCE is not available.