Use Of Experimental Models Research Articles

Use of artificial sphincter to bowel segment using rectus muscle interposition

The use of artificial urinary sphincter around the urethra or bladder neck for the management of urinary incontinence secondary to intrinsic urethral sphincter deficiency is now well accepted. However, its use around the bowel to serve as a sphincter in urinary pouches is still anecdotal. Its use in experimental models has been met with failure because of ischemic bowel necrosis at the cuff site. To obviate these difficulties, a new technique was devised using a flap of rectus muscle that acted as a cushion between the cuff and the bowel wall. Results in five dogs showed that bowel wall ischemia is avoided with cuff pressure of 51–60 cm applied constantly for four weeks while providing pressure to leak around the closed cuff with a pressure of 62–75 cm water. Further study is needed to confirm the long-term effect of this technique on the bowel wall and the ability of the sphincter to maintain continence.

Update on genetic and molecular investigations of diseases with general impairment of peroxisomal functions

A group of genetically determined peroxisomal diseases is characterized by both multiple enzymatic deficiencies and abnormal structural features of the organelle. The primary cause of the phenotypes is likely to involve peroxisome assembly impairment. Complementation analyses performed on fibroblasts of patients revealed tge existence of at least eight groups that do not reflect the clinical classifications. Recently, the use of experimental models led to the identification of a gene encoding for a peroxisomal membrane protein (PAF-1) in which a mutation was associated with the altered phenotype in a complementation group of the Zellweger syndrome (paradigm of these diseases). Also revealed in Zellweger probands are mutations of a gene encoding another peroxisomal protein (PMP70).

In vitro metabolism and peripheral dopaminergic activity of sim 2055, an epinine prodrug

Omics has broadened our view of transcriptional and gene regulatory networks of multifactorial diseases, such as metabolism associated liver disease and its advanced stages including hepatocellular carcinoma. Identifying liver disease biomarkers and potential treatment targets makes use of experimental models, e.g. genetically engineered mice, which show molecular features of human pathologies but are experimentally tractable. We compared gene expression profiling data from human to our studies on transgenic mice with hepatocyte deletion of Cyp51 from cholesterol synthesis with the aim of identifying the human liver disease state best matched by the Cyp51 knockout model. Gene Expression Omnibus was used to identify relevant human datasets. We identified enriched and deregulated genes, pathways and transcription factors of mouse and human disease samples. Analysis showed a closer match of the Cyp51 knockout to the female patient samples. Importantly, CYP51 was depleted in both mouse and female human data. Among the enriched genes were the oxysterol-binding protein-related protein 3 (OSBPL3), which was enriched in all datasets, and the collagen gene COL1A2, which was enriched in both the mouse and one human dataset. KEGG and Reactome analyses revealed the most enriched pathway to be ECM-receptor interaction. Numerous transcription factors were differentially expressed in mice of both sexes and in the human female dataset, while depleted HNF4α and RXRα:PPARα-isoform1 were a hallmark in all cases. Our analysis exposed novel potential biomarkers, which may provide new avenues towards more personalized approaches and different targets in females and males. The analysis was only possible because of availability of open data resources and tools and broadly consistent annotation.

Cerebral ischemia revisited: new insights as revealed using in vitro brain slice preparations.

The elucidation of the pathophysiological mechanisms of cerebral ischemia/hypoxia dictates the use of experimental models which mimic this disabling brain condition. In vivo experimental models have been available for many decades and are responsible for the bulk of, though incomplete, knowledge we have about these mechanisms. Since study in isolation of each postulated mechanism is impossible in vivo, the need for an in vitro experimental model has intensified in recent years. Consequently, rat and guinea pig hippocampal slice preparations have emerged as the models of choice. This review attempts to highlight some of the results obtained using brain slices in the study of cerebral ischemia/hypoxia and compare them to those obtained in vivo. Both the biochemical and the physiological correlates of energy metabolism, ion homeostasis, neurotransmission and neuromodulation of this brain condition are reviewed. The agreements, and especially the disagreements, between the in vivo and in vitro findings are emphasized. Details are given of the possible roles of both lactic acid, Ca2+ and excitotoxins in the neuronal damage inflicted by cerebral ischemia/hypoxia. Recent attempts to protect brain slices against experimental cerebral ischemic/hypoxic damage are also reviewed here briefly.

Use of experimental models to study the development of renal function.

By use of animal experiments it has been demonstrated that renal cells are immature at birth. Membrane transport is quantitatively and qualitatively different. The control of fluid and electrolyte balance is therefore different in infancy. The increased filtered load at birth as well as hormones will induce tubule maturation. The use of animal experiments will in the future give an insight into how external factors influence growth and maturation.

O4E1048) - Analysis of the role of bradykinin in inflammation by the use of experimental models of inflammation of air pouch type.

O4E1048) - Analysis of the role of bradykinin in inflammation by the use of experimental models of inflammation of air pouch type.

The use of experimental models to study the biting habits of Australian snakes in both “defensive” and “hunting” bites

The use of experimental models to study the biting habits of Australian snakes in both “defensive” and “hunting” bites

Finite strain and progressive deformation in models of diapiric structures

The distribution of strain within and around gravitationally produced diapiric structures was studied through the use of experimental models which were deformed in a large-capacity centrifuge. A new method of model construction was developed which is equivalent to building the model of initially square 1-mm elements. After deformation the elements assume shapes which approximate parallelograms and their finite strains can easily be calculated. If several initially identical models are deformed to different extents, the finite strain states of an element in each of the models define points on the deformation path of that element. The deformation path can be used to make estimates of the nature of the internal fabric which would be expected in the equivalent element of the natural structure. This method was applied to the study of the finite strain in diapiric ridges. The models demonstrate that the highest strain is always in the region above the diapir. Within the diapir initial vertical stretching is followed by vertical flattening. Large portions of the structure can be seen to suffer what would in natural examples be called polyphase deformation, even though all of the deformation was due to a single buoyant overturn of unstable density stratification. The strain patterns within the models support the contention that in salt diapirs the buoyant salt has a lower viscosity than the overlying sediments, but that in mantled gneiss domes the reverse is true.

Use of solute diuresis in the prevention of acute renal failure

Reconsideration of the initial descriptions of “lower nephron nephrosis” coupled with an examination of laboratory models leads to a reintroduction of tubular obstruction by casts and cell debris as a likely definitive etiologic mechanism. The use of experimental models confirms that the clinical course and pathologic anatomy may be recreated with laboratory situations in which various proteins are precipitated in the renal tubule. Whether induced by water-loading or by solute diuresis, urine production prevents or ameliorates the renal lesion, presumably by the creation of more rapid tubular flow and more dilute tubular urine. The properties of mannitol, the most simple, reliable, and effective compound to produce osmotic diuresis, are described. In light of the foregoing information it seems reasonable to expect that the kidney which is making urine in adequate quantities may well be protected against the “acute tubular necrosis” type of insult. A plan is hereby presented for the administration of mannitol in both emergency and elective situations with a view toward the elimination of this unfortunate renal complication.