Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver

Thiazolidinediones are a class of Peroxisome Proliferator Activated Receptor γ (PPARγ) agonists that reduce insulin resistance in type 2 diabetic patients. Although no detectable hepatic toxicity has been evidenced in animal studies during preclinical trials, these molecules have nevertheless induced hepatic adverse effects in some treated patients. The mechanism(s) of hepatotoxicity remains equivocal. Several studies have been conducted using PCR analysis and microarray technology to identify possible target genes and here we review the data obtained from various in vivo and in vitro experimental models. Although PPARγ is expressed at a much lower level in liver than in adipose tissue, PPARγ agonists exert various PPARγ-dependent effects in liver in addition to PPARγ-independent effects. Differences in effects are dependent on the choice of agonist and experimental conditions in rodent animal studies and in rodent and human liver cell cultures. These effects are much more pronounced in obese and diabetic liver. Moreover, our own recent studies have shown major interindividual variability in the response of primary human hepatocyte populations to troglitazone treatment, supporting the occurrence of hepatotoxicity in only some individuals

Growth of Lactobacillus reuteri NCIMB 30242 during yogurt fermentation and bile salt hydrolysis activity in the product

International audienceAbstractThe synthesis of bile salt hydrolase has been linked to the health benefit of Lactobacillus reuteri toward lowering blood cholesterol. The aim of this study was to examine the growth and bile salt hydrolysis activity (BSHA) of L. reuteri NCIMB 30242 during milk fermentation with a yogurt starter. There was little growth of L. reuteri during a 4-h co-fermentation with a yogurt culture, and an inoculation of 4.5 × 107 CFU.mL−1 was needed to obtain the 108 CFU.mL−1 target in the product. Enrichment of milk with sugars, minerals, or peptone-based ingredients did not improve growth of L. reuteri. Viable counts of L. reuteri above 1.5 × 108 CFU.mL−1 generated texture defects. Free and microencapsulated (ME) cultures were tested for BSHA in the yogurt drinks. L. reuteri cells which grew during the 4-h lactic fermentation had 40% less BSHA than L. reuteri added directly via the commercial culture. The BSHA of free cells was apparently three times higher than in the ME culture. This study adds data showing that the yogurt production process could affect the functionality of probiotic bacteria

A novel therapeutic strategy for pancreatic neoplasia using a novel RNAi platform targeting PDX-1

Bi-functional shRNA (bi-shRNA), a novel RNA interference (RNAi) effector platform targeting PDX-1 utilizing a systemic DOTAP-Cholesterol delivery vehicle, was studied in three mouse models of progressive pancreatic neoplasia. Species-specific bi-functional PDX-1 shRNA (bi-shRNAPDX-1) lipoplexes inhibited insulin expression and secretion while also substantially inhibiting proliferation of mouse and human cell lines via disruption of cell cycle proteins in vitro. Three cycles of either bi-shRNA<sup>mousePDX-1</sup> or shRNA<sup>mousePDX-1</sup> lipoplexes administered intravenously prevented death from hyperinsulinemia and hypoglycemia in a lethal insulinoma mouse model. Three cycles of shRNA<sup>mousePDX-1</sup> lipoplexes reversed hyperinsulinemia and hypoglycemia in an immune-competent mouse model of pancreatic neoplasia. Moreover, three cycles of the bi-shRNA<sup>humanPDX-1</sup> lipoplexes resulted in near complete ablation of tumor volume and considerably improved survival in a human PANC-1 implanted SCID-mouse model. Human pancreatic neoplasia specimens also stained strongly for PDX-1 expression. Together, these data support the clinical development of a novel therapeutic strategy using systemic bi-shRNA<sup>PDX-1</sup> lipoplexes against pancreatic neoplasia

Florida Public Health Association 2009 Survey of Academic Public Health Programs in Florida

Preparing the public health workforce is essential to the protection ofthe health and wellbeing ofthe state and the nation. Yet, a workforce shortage is looming. It is anticipated that by 2020, the nation will be facing a shortfall ofmore than a quarter of a million public health workers. To address this impeding shortage, the Association ofSchools ofPublic Health (ASPH) has stressed the need to build public health education capacity, with emphasis on competencies and curriculum in emerging diseases, with joint degrees, and with diverse approaches to education, including certificates and distance learning. To assess Florida’s available public health professional preparation programs in meeting workforce needs, the Academic Committee ofthe Florida Public Health Association (FPHA) undertook a survey of the nine public and private universities offering the MPH degree in the state

Fermentation technologies for the production of exopolysaccharide-synthesizing Lactobacillus rhamnosus concentrated cultures

The exopolysaccharide (EPS)-producing cultures such as Lactobacillus rhamnosus RW-9595M present a challenge for the culture producers because the high viscosity of the fermented growth medium makes it difficult to recover the cells by centrifugation or filtration. This study examined four approaches to reduce viscosity of the medium while producing high cell densities: incubation temperature, extended incubation in the stationary growth phase, production in alginate gel beads and fed-batch fermentation technology. Automated spectrophotometry (AS) was used to study the effects of temperature, pH and lactate level on growth of the strain. In AS assays, there was no significant difference in final maximal biomass production at temperatures ranging between 34\ub0C to 44\ub0C, but lower yields were noted at 46\ub0C. A pH below 6.0 and a lactate concentration higher than 4% almost completely prevented growth. Under batch fermentation conditions, the viscosity of the medium obtained at 37\ub0C was two fold higher than for 44\ub0C. For cultures produced at 37\ub0C, centrifugation at 10000 g during 5 min did not allow complete recovery of cells, in contrast to cultures grown at 44\ub0C. An extended period of incubation (5 hrs) in the stationary growth phase did not reduce the final viscosity of the growth medium. For similar biomass levels, the glucose-based fed-batch fermentation allowed a 40% reduction in viscosity of the fermented medium in comparison to traditional batch cultures. High-density cell populations (3 x 1010 CFU/g) were obtained when L. rhamnosus RW-9595M was grown in alginate beads. However, overall biomass yields in the immobilized cell bioreactor were half of those obtained in free-cell fermentations. Therefore three methods of producing concentrated EPS-producing cultures are proposed

Swine Influenza Virus Antibodies in Humans, Western Europe, 2009

Serologic studies for swine influenza viruses (SIVs) in humans with occupational exposure to swine have been reported from the Americas but not from Europe. We compared levels of neutralizing antibodies against 3 influenza viruses—pandemic (H1N1) 2009, an avian-like enzootic subtype H1N1 SIV, and a 2007–08 seasonal subtype H1N1—in 211 persons with swine contact and 224 matched controls in Luxembourg. Persons whose profession involved contact with swine had more neutralizing antibodies against SIV and pandemic (H1N1) 2009 virus than did the controls. Controls also had antibodies against these viruses although exposure to them was unlikely. Antibodies against SIV and pandemic (H1N1) 2009 virus correlated with each other but not with seasonal subtype H1N1 virus. Sequential exposure to variants of seasonal influenza (H1N1) viruses may have increased chances for serologic cross-reactivity with antigenically distinct viruses. Further studies are needed to determine the extent to which serologic responses correlate with infection

RNA viruses in hymenopteran pollinators : evidence of inter-taxa virus transmission via pollen and potential impact on non-Apis hymenopteran species

Although overall pollinator populations have declined over the last couple of decades, the honey bee (Apis mellifera) malady, colony collapse disorder (CCD), has caused major concern in the agricultural community. Among honey bee pathogens, RNA viruses are emerging as a serious threat and are suspected as major contributors to CCD. Recent detection of these viral species in bumble bees suggests a possible wider environmental spread of these viruses with potential broader impact. It is therefore vital to study the ecology and epidemiology of these viruses in the hymenopteran pollinator community as a whole. We studied the viral distribution in honey bees, in their pollen loads, and in other non-Apis hymenopteran pollinators collected from flowering plants in Pennsylvania, New York, and Illinois in the United States. Viruses in the samples were detected using reverse transcriptase-PCR and confirmed by sequencing. For the first time, we report the molecular detection of picorna-like RNA viruses (deformed wing virus, sacbrood virus and black queen cell virus) in pollen pellets collected directly from forager bees. Pollen pellets from several uninfected forager bees were detected with virus, indicating that pollen itself may harbor viruses. The viruses in the pollen and honey stored in the hive were demonstrated to be infective, with the queen becoming infected and laying infected eggs after these virus-contaminated foods were given to virus-free colonies. These viruses were detected in eleven other non-Apis hymenopteran species, ranging from many solitary bees to bumble bees and wasps. This finding further expands the viral host range and implies a possible deeper impact on the health of our ecosystem. Phylogenetic analyses support that these viruses are disseminating freely among the pollinators via the flower pollen itself. Notably, in cases where honey bee apiaries affected by CCD harbored honey bees with Israeli Acute Paralysis virus (IAPV), nearby non-Apis hymenopteran pollinators also had IAPV, while those near apiaries without IAPV did not. In containment greenhouse experiments, IAPV moved from infected honey bees to bumble bees and from infected bumble bees to honey bees within a week, demonstrating that the viruses could be transmitted from one species to another. This study adds to our present understanding of virus epidemiology and may help explain bee disease patterns and pollinator population decline in general