Vivo Clinical Applications

Daly, P.F. Cohen, J.S. (1989). Magnetic resonance spectroscopy of tumors and potential in vivo clinical applications A review. Cancer Res. 49,770-779. 

In vivo analytical devices ideally should be capable of monitoring several different physiological parameters simultaneously without interfering with an ongoing medical procedure, such as surgery. The devices should be biocompatible, simple to implement and operate, and highly reliable and safe. Fiber-optic chemical sensors can meet most of these requirements since the optical fibers are small (few hundred micrometers in diameter), flexible, nontoxic, and chemically inert. Optical fibers have already proven to be valuable for in vivo clinical applications such as endoscopic procedures and laser power transmission for surgical applications. 

Center for Healthcare Technologies at Lawrence Livermore National Laboratory in Livermore, potentially capable to measure pH at or near the stroke site29. The probe is the distal end of a 125 pm fibre tapered up to a diameter of 50 pm. A fluorescent pH-indicator, seminaphthorhodamine-1-carboxylate, is embedded inside a silica sol-gel matrix which is fixed to the fibre tip. Excitation of the dye takes place at 533 nm and the emission in correspondence of the acid (580 nm) and basic (640 nm) bands are separately detected. The use of this ratiometric technique obviates worrying about source fluctuations, which have the same effects on the two detected signals. The pH sensor developed was first characterised in the laboratory, where it showed fast response time (of the order of tens of seconds) and an accuracy of 0.05 pH units, well below the limit of detection necessary for this clinical application (0.1 pH units). The pH sensor was also tested in vivo on rats, by placing the pH sensor in the brain of a Spraque-Dawley rat at a depth of approximately 5 mm30. 

The potential of the chemically modified nucleic acid molecules has been proven by in vitro studies however, the in vivo therapeutic applicability of these molecules seems to be unsatisfactory because of their possible toxic effects (largely unknown) and adverse bioavailability. In this view, both antisense and transfection technologies require reliable and efficient systems for their delivery into target cells. On the basis of this consideration, the development of an efficient nucleic acid delivery system represents one of the key steps for these therapeutic agents, which are necessary for a practical clinical utilization of natural or unnatural oligonucleotides. 

In contrast to other analytical methods, ion-selective electrodes respond to an ion activity, not concentration, which makes them especially attractive for clinical applications as health disorders are usually correlated to ion activity. While most ISEs are used in vitro, the possibility to perform measurements in vivo and continuously with implanted sensors could arm a physician with a valuable diagnostic tool. In-vivo detection is still a challenge, as sensors must meet two strict requirements first, minimally perturb the in-vivo environment, which could be problematic due to injuries and inflammation often created by an implanted sensor and also due to leaching of sensing materials second, the sensor must not be susceptible to this environment, and effects of protein adsorption, cell adhesion, and extraction of lipophilic species on a sensor response must be diminished [13], Nevertheless, direct electrolyte measurements in situ in rabbit muscles and in a porcine beating heart were successfully performed with microfabricated sensor arrays [18],... 

The use of triphenylethylene SERMs as Pgp inhibitors for clinical application has been hampered by unacceptable toxicity at doses required to achieve adequate cellular concentration, which is likely due to the involvement of proteins with the ability to bind these compounds. For instance, toremifene is able to reverse MDR and to sensitize human renal cancer cells to vinblastine in vitro. However, in vivo toremifene is tightly bound to serum proteins, in particular a 1-acid glycoprotein (AAG), which may limit its tissue availability (Braybrooke et al. 2000). In agreement with this, Chatterjee and Harris (1990) have shown that tamoxifen and 4-OH-tamoxifen were similarly potent in reversing MDR in Chinese hamster ovary (CHO) cells with acquired resistance to adriamycin. However, the addition of AAG (0.5 to 2 mg/ml, the range found in vivo) to cell cultures decreased the effect of tamoxifen on reversing MDR, and at the highest AAG concentration there was a complete reversal of the effects of... 

A variety of cell culture systems for the modelling of the tracheo-bronchial epithelium are available. These include primary cultures and cell lines of human and animal origins, plus airway cells with characteristics of lung disease such as CF. The advantages and limitations of using a simple culture system compared to one that recreates to a greater extent the epithelial structure and function in vitro should be considered according to the pre-clinical application required. However, this choice is complicated by the lack of comparative data, both between the different cell systems and for in vitro-in vivo correlation, upon which to base such decisions. 

Another potential clinical application of potent, peripherally acting DA agonists is the lowering of intraocular pressure in, for example, glaucoma [18]. There is in vivo and in vitro evidence that dopamine receptors might modulate the intraocular pressure. The influence of both agonists and antagonists for D1 and D2 receptors has been studied. Some human data are also available [19]. 

Proton NMR spectroscopy ( H MRS) has shown to offer excellent possibilities for evaluation of biochemistry in vivo. Due to its non-invasive character it is of increasing interest not only for the study of human brain diseases, which describe the majority of clinical applications, but also for metabolic characterization of organs outside the brain, as prostate, liver, heart or skeletal muscle. Studies on skeletal muscle have been of increasing interest during the last years, since it was shown that MRS enables the differentiation between two muscular lipid compartments the bulk fat components along the fasciae and muscular boundaries, which are called extramyocellular lipids (EMCL), and the metabolically highly active intramyocellular lipids (IMCL). The latter are stored in spherical droplets in the cytoplasm of muscle... 

In the 1980s several advances were made, which suggested that the ability of HSC to proliferate without loss of self-renewal might be harnessed ex vivo. Expansion of immature hematopoietic and progenitor cells, sufficient for clinical application, now seemed within reach. 

Most of the drug delivery systems that have been studied for clinical application are capable of rate- and/or time-controlled drug release. The therapeutic advantages in these approaches lie in the in vivo predictability of release rate, minimized peak plasma levels, predictable and extended duration of action and reduced inconvenience of frequent re-dosing and hence, improved patient compliance [1]. 

The precise role of neurosteroids in cognition as well as neurological and psychiatric disorders is currently under investigation. Although data from human studies are sparse, results obtained from in vitro and in vivo experiments show promising leads for future clinical applications of neurosteroids. 

Two clinical applications have validated the field of gene therapy. The first involves ex vivo transfer of a gene that encodes for... 

The initial inflammatory reactions associated with chitosan application to hard and soft tissues need to be controlled before it can be considered for clinical application as scaffold. Further, as it takes too long for biodegradation of implanted chitosan in vivo, generally chitosan is concluded to be not suitable for the scaffold for degenerative medicine in especially dental pulp tissue surrounding hard tissue. 

The Raman effect has also been broadly applied to online and bench-top quantitative applications, such as determination of pharmaceutical materials and process monitoring [4-6], in vivo clinical measurements [7], biological materials [8, 9], to name only a few. Because the absolute Raman response is difficult to measure accurately (sample presentation and delivered laser power can vary), these measurements are almost always calculated as a percentage with respect to the response from an internal standard. This standard is typically part of the sample matrix in a drug product, the standard may be an excipient in a biological sample, it is commonly water. 

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