Guinea pig models for translation of the developmental origins of health and disease hypothesis into the clinic

Over 30 years ago Professor David Barker first proposed the theory that events in early life could explain an individual\u27s risk of non-communicable disease in later life: the developmental origins of health and disease (DOHaD) hypothesis. During the 1990s the validity of the DOHaD hypothesis was extensively tested in a number of human populations and the mechanisms underpinning it characterised in a range of experimental animal models. Over the past decade, researchers have sought to use this mechanistic understanding of DOHaD to develop therapeutic interventions during pregnancy and early life to improve adult health. A variety of animal models have been used to develop and evaluate interventions, each with strengths and limitations. It is becoming apparent that effective translational research requires that the animal paradigm selected mirrors the tempo of human fetal growth and development as closely as possible so that the effect of a perinatal insult and/or therapeutic intervention can be fully assessed. The guinea pig is one such animal model that over the past two decades has demonstrated itself to be a very useful platform for these important reproductive studies. This review highlights similarities in the in utero development between humans and guinea pigs, the strengths and limitations of the guinea pig as an experimental model of DOHaD and the guinea pig\u27s potential to enhance clinical therapeutic innovation to improve human health. (Figure presented.)

Estrogenic effect of Erythrina variegata L. in prepubertal female rats

Alcoholic extract of Erythrina variegata L. leaves was evaluated by uterotrophic assay in 17 day old prepubertal female rats and was chromatographically processed for compound isolation. The animals divided into 3 (n=6) groups were treated for 7 days as follows: Control group (Grp I) –vehicle, 0.5% Na CMC, 5 mL/kg bw p.o, E. variegata alcohol extract group (Grp II) – 250 mg/kg bw/day in vehicle p.o., Ethinyl estradiol group (Grp III) - 30μg/kg bw/day in vehicle, p.o. 24 h post last exposure to extract. Animals were sacrificed and the uterus and ovaries examined for classical morphological and histomorphometric changes induced by estrogen stimulation. Extract treatment increased the absolute and normalized uterine weight, uterine diameter, endometrial thickness, luminal epithelial cell height, diameter of ovary and the number of primary and secondary ovarian follicles relative to vehicle control. Presence of ciliated epithelial cells in the oviduct and signs of vascularization in the cortex of ovarian sections in this group similar to EEG is indicative of estrogenic activity of the tested extract. This is consequent to the antioxidant activity of β-sitosterol, daucosterol and oleanolic isolated from the extract. This study supports the earlier reported hypolipidaemic and anti-atherosclerotic activities, lending scientific validity to anti-obesity claims in traditional medicine

Estrogenic effect of <i style="mso-bidi-font-style: normal">Erythrina variegata</i> L. in prepubertal female rats

223-227Alcoholic extract of <i style="mso-bidi-font-style: normal">Erythrina variegata L. leaves was evaluated by uterotrophic assay in 17 day old prepubertal female rats and was chromatographically processed for compound isolation. The animals divided into 3 (n=6) groups were treated for 7 days as follows: Control group (Grp I) –vehicle, 0.5% Na CMC, 5 mL/kg bw p.o, E. variegata alcohol extract group (Grp II) – 250 mg/kg bw/day in vehicle p.o., Ethinyl estradiol group (Grp III) - 30μg/kg bw/day in vehicle, p.o. 24 h post last exposure to extract. Animals were sacrificed and the uterus and ovaries examined for classical morphological and histomorphometric changes induced by estrogen stimulation. Extract treatment increased the absolute and normalized uterine weight, uterine diameter, endometrial thickness, luminal epithelial cell height, diameter of ovary and the number of primary and secondary ovarian follicles relative to vehicle control. Presence of ciliated epithelial cells in the oviduct and signs of vascularization in the cortex of ovarian sections in this group similar to EEG is indicative of estrogenic activity of the tested extract. This is consequent to the antioxidant activity of β-sitosterol, daucosterol and oleanolic isolated from the extract. This study supports the earlier reported hypolipidaemic and anti-atherosclerotic activities, lending scientific validity to anti-obesity claims in traditional medicine

An Approach for Intrusion Detection Using Novel Gaussian Based Kernel Function

Software Security and Intrusion Detection need to be dealt at three levels Network, Host level and Application level. In this paper the major objective is to design and analyze the suitability of Gaussian similarity measure for intrusion detection. The objective is to use this as a distance measure to find the distance between any two data samples of training set such as DARPA Data Set, KDD Data Set. This major objective is to use this measure as a distance metric when applying k-means algorithm. The novelty of this approach is making use of the proposed distance function as part of k-means algorithm so as to obtain disjoint clusters. This is followed by a case study, which demonstrates the process of Intrusion Detection. The proposed similarity has fixed upper and lower bounds

MD-1, a poly herbal formulation indicated in diabetes mellitus ameliorates glucose uptake and inhibits adipogenesis – an in vitro study

Abstract Background Type 2 Diabetes (T2D) is a polygenic disease requiring a multipronged therapeutic approach. In the current scenario, the use of polyherbals is increasing among the diabetics. MD-1, a poly herbal formulation is constituted as a mixture of six popular anti diabetic herbs, used in the management of Diabetes mellitus (DM). The physicochemical, biochemical and in vitro efficacy studies have been carried out to ascertain the possible mechanisms underlying the anti-diabetic action of MD-1. Methods MD-1 was evaluated for residual toxins as per Ayurvedic Pharmacoepia of India (API) procedures. The hydro alcoholic extract of the formulation (HAEF) was evaluated for anti oxidant activity against 2, 2-diphenyl-1-picrylhydrazil (DPPH) and nitric oxide radicals in vitro. The effect of HAEF on carbohydrate digestive enzymes α-glucosidase and α-amylase was studied using biochemical assays. HAEF was studied for its glucose lowering potential in L6 myotubes and 3T3L1 preadipocytes, using 2-deoxy-D-[1-3H] glucose (2-DG) uptake assay. Effect of MD-1 on adipogenesis was evaluated in 3T3L1 adipocytes using oil O red staining. The effect of HAEF on mRNA expression of peroxisome proliferator activated receptor gamma (PPARγ) and glucose transporter 4 (GLUT4) in 3T3L1 adiocytes was investigated by reverse transcriptase polymerase chain reaction (RT-PCR). Statistical analysis was performed by student t-test, ANOVA. Results Residual toxins present within the API limits and HAEF demonstrated strong antioxidant potential and significantly inhibited the α-glucosidase (IC50 63.6 ± 0.46 μg/mL) and α-amylase (IC50 242.81 ± 1.26 μg/mL) activity. HAEF significantly (p < 0.05) enhanced the insulin stimulated glucose uptake in both the cell lines studied. Unlike standard pioglitazone (PGZ), HAEF modulated the mRNA expression of PPARγ and GLUT4 (p < 0.0001) in 3T3L1 adipocytes, without inducing adipogenesis. Conclusion Physicochemical parameters established in the study may serve as reference standards in regular quality control. Absence of residual toxins underpins the safety. The enhanced glucose uptake and favorable modulation of insulin sensitivity through a plausible weak PPARγ agonism is similar to the distinct PPARγ activation pattern of several reported natural compound agonists. The differential binding modes of such dynamic combinatorial ligands within the formulation unlike synthetic ligands like thiozolidinediones (TZD) can be linked to the safe mitigation of diabetic complications by MD-1