Development of novel adenoviral vectors to overcome challenges observed with HAdV-5 based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult

Development of novel adenoviral vectors to overcome challenges observed with HAdV-5-based constructs

Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in pre-clinical models and clinical trials over the last two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread pre-existing immunity have been shown to significantly impede the effectiveness of HAdV-5 mediated gene transfer. It is therefore that the in depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes

The ratio of fecal coliform to fecal streptococci traditional ice cream marketed in Tabriz

Origin of contamination for traditional ice cream consist of using of using primarily contaminated or unpasteurized ingredients (i.e., milk or cream). Determination of coliform-Enterococcns ratio is among methods used for investigation of fecal coliform's origin. This study aims to enumerate fecal coliform and Enterococci as well as their ratio, in order to find out the origin of contamination in traditional ice cream. Consequently, 21 traditional ice cream samples were collected throughout Tabriz. Samples were prepared and then enumation of fecal coliforms and Enterococci were performed according to the Iranian standards (No. 356, 2946 and 2198 respectively). Mean level of contamination for fecal coliforms was 6.67 and for Enterococci was 307.1. on the other hand, the fecal coliforms-Enterococci ratio was determined as 0.0217. Regarding the normal mean ratio of coliforms and Enterococci in cow's intestine, therefore the origin of contamination for traditional ice creams were distinguished as cow's feces which could enter cow's milk direct and lor indirectly

STUDY OF RELATIONSHIP BETWEEN DEPTH OF PERIODONTAL POCKETS, ANAEROBIC BACTERIA AND INFLAMMATORY CELLS IN PERIODONTITIS

In this study 100 cases of advanced periodontitis were compared with a control group of 100 persons. The parameters were the depth of the periodontal pockets, radiographic images, presence of inflammatory cells and different types of anaerobic bacteria in the pockets. The depth of pocket was measured by a sterile probe and the presence of inflammatory cells was determined through sterile curettage. The smears were stained by Gimsa and Gram methods. For the purpose of microbiological studies, subgingival plaque samples were taken on paper points and were plated on brucella agar medium supplemented with rabbit blood, haemin and vitamin K1. The results indicated that with increasing depth of the pocket, the number of mixed anaerobic infections increases, and the presence of inflammatory cells especially polymorphonuclears is more prominent in comparison to the control group. As the pocket depth increases the conditions become more favourable for anaerobic bacteria and in consequence the incidence of isolation of these bacteria increases. On the other hand as the number of anaerobic bacteria and inflammatory cells and the secretion of destructive enzymes increases, the resultant injury to periodontal tissue increases