PSAH Article Highlights
Poscente MD, Wang G, Filip D, Ninova P, Yadid-Pecht O, Andrews CN, Mintchev
MP. Real-time gastric motility monitoring using transcutaneous intraluminal
impedance measurements (TIIM). Physiol Meas. 2014 Feb;35(2):217-29.
Real-time gastric motility monitoring using transcutaneous intraluminal
impedance measurements (TIIM).
Aligned with efforts to develop mechanisms for characterizing gastric contractility, Poscente et al. (2014) report on two novel methods for evaluating gastric contractility. One method utlizes a transoral catheter that was modified to emit the signal inside the stomach. The second method involves a gastric retentive pill was designed to emit the signal. Both implementations were applied in vivo on two mongrel dogs. Gastric motility indices were calculated for each minute, with transluminal impedance measurements and the measurements from the force transducers were statistically evaluated. This paper reports the results of this study.
Zane P, Guo Z, Macgerorge D, Vicat P, Ollier C. Use of the pentagastrin dog
model to explore the food effects on formulations in early drug development. Eur
J Pharm Sci. 2013 Oct 1.
Use of the pentagastrin dog model to explore the food effects on formulations in early drug development.
The pentagastrin dog model is often used in early human drug development. In this article, the pentagastrin-induced Beagle dog model was validated internally to show that in the colony the dogs were generally responsive to known doses of pentagastrin that produces effects similar to gastrin in the stomach, i.e., increasing gastric acid production and lowering gastric pH. Zane et al., (2013) note that during their initial validation of this model, the results for 4 compounds were provided in the dog and a clear relationship between the effect of food in the dog and the effect of food in humans was observed.
Biodistribution and Pharmacokinetics of Dapivirine-Loaded Nanoparticles after Vaginal Delivery in Mice
PURPOSE: To assess the potential of polymeric nanoparticles (NPs) to affect the genital distribution and local and systemic pharmacokinetics (PK) of the anti-HIV microbicide drug candidate dapivirine after vaginal delivery.
METHODS: Dapivirine-loaded, poly(ethylene oxide)-coated poly(epsilon-caprolactone) (PEO-PCL) NPs were prepared by a nanoprecipitation method. Genital distribution of NPs and their ability to modify the PK of dapivirine up to 24 h was assessed after vaginal instillation in a female mouse model. Also, the safety of NPs upon daily administration for 14 days was assessed by histological analysis and chemokine/cytokine content in vaginal lavages.
Towards the characterization of an in vitro triple co-culture intestine cell model for permeability studies.
Caco-2 based cell models have been the gold standard in vitro method to study intestinal drug permeability, despite the absence of many important features with major influence in the drug absorption mechanism. In the present work, a triple co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic in a closely way the human intestinal epithelium, presenting the main components in the process of drug absorption, namely the absorptive cells that resemble enterocytes, mucus producers cells and cells able to induce M-cell phenotype on Caco-2 cells. All the three cell lines maintained their function when cultured together with each other being, thus, an asset to new orally administrated drugs development. The seeding ratio of 90:10 between Caco-2 and HT29-MTX showed to be the best to achieve physiological proportions after cells maturation and differentiation in culture. The formation of M-cells phenotype from enterocytes was identified for the first time in a co-culture system comprising Caco-2 and HT29-MTX cells through immunocytochemical techniques. Thus, the triple co-culture model presented in the herein work is a good and reliable alternative to the in vitro methods already existents for the study of drugs permeability.
The Comparative Oncology Trials Consortium (COTC), in collaboration with the Translational Genomics Research Institute (TGen), has just completed a proof-of-concept study confirming the feasibility of using dogs to support the treatment of cancer research in humans. TO that end, they determined te feacilitiy of collecting tissues from canine tumors, conducting prospective molecular profiling, and generating a personalized medicine report within one week. The one-week turnaround time for sample analysis is significant because it fits "a relevant clinical window for future comparative oncology trials to model human PMed advancements," said William Hendricks, Ph.D., a TGen staff scientist and an author of the study. “Future comparative oncology studies, optimizing the delivery of personalized medicine strategies, may aid cancer drug development.
Shared health challenges: developing cancer treatments for dogs and people: the importance of the dog as a model for this naturally occurring disease
Background: Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual
heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting.
- Fetal microchimerism (FMC) is a fascinating finding both in humans and preclinical species (e.g., dogs and mice). It would appear that during pregnancies, there is a bidirectional exchange of fetal-maternal DNA and this fetal can DNA persist in maternal tissues. FMC has been associated with a range of physiological effects, including autoimmune diseases, tissue, repair, immunosurveillance, and possibly even protection against Alzheimer's Disease. Furthermore, depending upon the site (tissue) from which the fetal DNA originates, the presence of FMC may either protect against or promote the development of various types of human cancers.
Fugazzola L, Cirello V, Beck-Peccoz P. Fetal microchimerism as an explanation of disease. Nat Rev Endocrinol. 2011 Feb;7(2):89-97.
Chan WF, Gurnot C, Montine TJ, Sonnen JA, Guthrie KA, Nelson JL. Male microchimerism in the human female brain. PLoS One. 2012;7(9):e45592.
Chan WF, Nelson JL. Microchimerism in the human brain: more questions than answers. Chimerism. 2013 Jan-Mar;4(1):32-3
The recent report of fetal microchimerism (FMC) in dogs (Golden Retrievers), along with the human-canine similarity in diseases processes, may support the use of the dog as a model of FMC-associated human disease processes.
Axiak-Bechtel SM, Kumar SR, Hansen SA, Bryan JN. Y-chromosome DNA Is Present in the Blood of Female Dogs Suggesting the Presence of Fetal Microchimerism. PLoS One. 2013 Jul 8;8(7):e68114.
This manuscript provides a compilation of mammalian animal models for metabolic, neuromuscular and ophthalmological orphan-designated conditions based on information gathered by the European Medicines Agency’s Committee for Orphan Medicinal and a literature review. The predictive value of the models and their advantages and limitations is discussed.
Animal models for metabolic, neuromuscular and ophthalmological rare diseases
Small RNAs appear to regulate gene expression at translational and transcriptional level and has been implicated in human diseases associated with deregulated miRNA expression such as Alzheimer's disease, cardiovascular diseases, and various cancer types. While small RNAs are considered to hold promise as therapeutic interventions, the current challenge is the transfer of in vitro settings to an in vivo model. Classical animal models rely on the laboratory kept animals under artificial conditions and often missing an intact immune system. Model organisms with spontaneously occurring tumors as e.g., dogs provide the possibility to evaluate therapeutic agents under the surveillance of an in intact immune system and thereby providing an authentic tumor reacting scenario. Considering the genomic similarity between canines and humans, this review discusses the role of miRNAs in human and canine cancer development and highlights the potential and advantages of the model organism dog for tumor research.
Comparison of non-coding RNAs in human and canine cancer