Experimental model

Age matched adult females seem to be relatively protected against ischemia and reperfusion injury compared to males. TNF-alpha, IL-beta and IL-6 and activation of p38 MAPK are all decreased in hearts from female rats subjected to ischemia and reperfusion.222 Furthermore, intracellular sodium after ischemia and reperfusion is higher in hearts from male than female rats.223 

Different experimental techniques have been also used to investigate ischemia-reperfusion injury. Table 2. Experimental models of isolated hearts cannot consider the contribution of blood components or neurohormonal changes as this occurs in in vivo studies. However, these studies are able to dissect potential underlying mechanisms of the ischemic injury. The mode of perfusion (working heart vs Langendorff mode or constant flow vs constant pressure), the use of pacing, the composition of the perfusate and the end-points chosen to assess myocardial injury (arrhythmias, functional recovery 

In vivo model of coronary occlusion Anesthesia, intubation, thoracotomy. Induction of ischemia by coronary artery occlusion using a suture no-flow regional ischemia. Reperfusion is possible. ECG recording and study of arrhythmias. Measurement of infarct size by TTC staining. Assessment of contractile function by ultrasonography. 

Isolated working heart preparation Perfusion of the heart ex vivo through the left atrium and ejection via the aorta resembling physiological conditions. Measurement of cardiac output. Preload and afterload can be adjusted. Other characteristics similar to Langendorff preparation. 

With transgenic and transfection approaches, intraspecies differences should be taken in account. For example, infarct size following 30 min of ischemia and 24 h of reperfusion is highly strain-dependent in rats.226 Furthermore, overexpression of a certain protein with transfection might cause loss of its selectivity.227 

Before starting any experiment, as much background information as is available on the problem should be analysed to establish general understanding of the relationships that may or may not exist. On the basis of this, a clear aim for the experiment should be set by determining what exactly is to be found. 

The experiment is essentially a series of tests, with a product or a process where controllable changes are made to the independent variables and the effect of these on the dependent variable is measured. It is thus assumed that the dependent variable, y, is an (unknown) function of the independent 

The term independent highhghts the fact that it should be possible to change only one of the variables without changing all others. 

There are two basic forms of the experimental studies, as follows  

Descriptive studies concerned with the characterization of average properties and variation of properties of products and processes. They serve to establish reference points for other types of investigations, and help to avoid obvious mistakes. They may also be focused on the investigation of the opinions of general public and specialists in the relevant area on the quality of products and services, and on specific social, political, and economic problems. 

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Tailoring polymeric systems to suit an experimental model. 

Fish have many advantages as experimental models in the study of endocrine disruption, and although they do have some significant differences in their endocrine system to that of mammals, the underlying basis is very similar. Chemicals which are shown to be either actual or potential endocrine disrupters... 

These FI ratios allow the following relationships to he made between the performance characteristics found for a small-scale experimental model and a full-scale prototype ... 

Bradykinin stimulates natriuresis and, through stimulation of prostaglandin synthesis, inhibits the actions of antidiuretic hormone (ADH), thereby inhibiting water retention. Bradykinin further improves insulin sensitivity and cellular glucose utilization of skeletal muscle cells in experimental models. This, however, appears not to be relevant in the clinical context. 

This design was closely followed in the experimental model and in the later instruments. The experimental model (October, 1940) had as test body a dumbbell of two thin-walled glass spheres 4 mm. in diameter sealed to a glass rod 6 mm. long. A silica fiber 8 fi in diameter was stretched between the prongs of a silica fork, and the glass dumbbell was cemented with shellac to the middle of the fiber, perpendicular to it. A plane glass mirror 2 mm. square was also cemented near the middle of the fiber. The suspension was balanced... 

Desi I, Nagymajtenyi L, Papp A, et al. 1998. Experimental model studies of pesticide exposure. Neurotoxicology 19 611-616. 

Kaiser, W.M., Schroppel-Meier, G. Wirth, E. (1986). Enzyme activities in an artificial stroma medium An experimental model for studying effects of dehydration on photosynthesis. Planta, 167, 292-9. 

In parallel with the identification of distinct transporters for GABA there has been continued interest in the development of selective blockers of these transporters and the therapeutic potential that could result from prolonging the action of synaptically released GABA. It has been known for a long time that certain pro-drugs of nipecotic add (e.g. nipecotic acid ethyl ester) are able to cross the blood-brain barrier and are effective anticonvulsants in experimental models of epilepsy. More recently, several different systemically active lipophillic compounds have been described that act selectively on GAT-1, GAT-2 or GAT-3 (Fig. 11.4). Of these, tiagabine (gabitiil), a derivative of nipecotic acid that acts preferentially on GAT -1, has proved clinically useful in cases of refractory epilepsy. 

Since PD is caused by a relatively specific degeneration of the DA nigrostriatal tract and as there are specific toxins, for DA neurons, i.e. 6-OHDA and MPTP, it should be possible to produce appropriate experimental models. Certainly both toxins cause rotational behaviour in rats (Fig. 7.7) but no rodent shows a syndrome suggestive of PD. Tremor and akinesia can be seen, however, in primates after such toxins and these are being more widely used in experimental studies of PD and drug evaluation. Reserpine causes a depletion of all brain monoamines and produces motor defects in rats, which, even if not PD-like, do respond to DA manipulation. 

There are few experimental models. Even if appropriate lesions could be produced it will always be difficult to tell if an animal is experiencing hallucinations. Neuroleptics... 

There are two main approaches to research into anxiety. The first is to establish experimental models of anxiety in animals and humans in order to discover its neurobiological basis. The second is to investigate the actions of anti-anxiety drugs in the brain in the hope that this will give some clues to the cause(s) of anxiety. This chapter will discuss evidence from both these lines of research. 

The simplest experimental model of carcinogenesis is the three-stage model (Pitot and Dragan, 1994) consisting of ... 

A similar experimental model (P-carotene, toluene, 60°C, oxygen, 120 min) was later tested by Handetman et al. Using HPLC and mass analysis, the authors could... 

In the second oxidation method, a metalloporphyrin was used to catalyze the carotenoid oxidation by molecular oxygen. Our focus was on the experimental modeling of the eccentric cleavage of carotenoids. We used ruthenium porphyrins as models of cytochrome P450 enzymes for the oxidation studies on lycopene and P-carotene. Ruthenium tetraphenylporphyrin catalyzed lycopene oxidation by molecular oxygen, producing (Z)-isomers, epoxides, apo-lycopenals, and apo-lycopenones. 

Regarding the prevalence of pectinolytic enzymes in the soft rot symptoms, it is noteworthy that the experimental model developed on African violets stresses the dynamic aspect of the disease and illustrates a number of points which have long been questioned. 

Very early during research into the anodic oxidation of methanol in the 1960s, it was repeatedly attempted to build experimental models of methanol-oxygen or methanol-air fuel cells. Most of these studies were conducted in snlfnric acid solntions... 

Ornskov, E.,. Gottfries, M. Erickson, S. Folestad. Experimental modelling of drug membrane permeability by capillary electrophoresis using liposomes, micelles and microemulsions./. Pharm. Pharmacol. 2005, 57, 435 2. 

The most extensive evidence that supports a role for free radicals in pathological conditions of the brain is provided by studies on experimental models of cerebral ischaemia/reperfusion. Although a burst of free-radical production occurs during the reperfusion phase after temporary cerebral ischaemia, the contribution of this radical burst to brain cell death can not be directly quantified. Perhaps the best way to quantify the contribution of free radicals to brain damage after ischaemia/ reperfusion is to assess damage after treatment with free-radical scavengers or antioxidants. Numerous studies have been reported where free-radical scavengers/ antioxidants have been used to try to ameliorate brain... 

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