Human Applications

The intracellular localization of stress proteins is problematic for the evaluation of the response in humans. Because the cells for the assay of stress proteins are not readily available through noninvasive procedures, the application of this response to human monitoring is limited. Recently, however, enhanced synthesis of stress proteins was demonstrated in primary cultures of human lymphocytes exposed to several metals (Yamada and Koizumi 1993). The specificity of the response was dependent on the metal to which the cultures were exposed. For example, cadmium and zinc induced both hsp70 and MT, while cobalt and triphenyltin induced only hsp70. Conversely, copper, mercury, nickel, and silver all induced synthesis of MT, but not of hsp70. Enhanced synthesis of stress proteins has also been demonstrated in vivo in lymphocytes and spleen cells excised from mice exposed to hyperthermia (Rodenhiser et al. 1985). 

Al-Aoukaty A, Appanna VD, Falter H (1992) Gallium toxicity and adaptation on Pseudomonas fluorescens. FEMS Microbiol Lett 71 265-272 

Amaral MD, Galego L, Rodrigues-Pousada C (1988) Stress response of Tetrahymena pyriformis to arsenite and heat shock differences and similarities. Eur J Biochem 171 463-470 

Ananthan J, Goldberg AL, Voellmy R (1986) Abnormal proteins serve as eukaryotic stress signals and trigger the activation of heat shock genes. Science 232 522-524 

Aoki Y, Lipsky MM, Fowler BA (1990) Alterations in protein synthesis in primary cultures of rat kidney proximal tubule epithelial cells by exposure to gallium, indium, and arsenite. Toxicol Appl Pharmacol 106 462-468 

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PET imaging using 8F-fluoromisonidazole (FMISO) and 18F-fluoroazomycinarabinofuranoside (FAZA) is well established for human application, allowing the measurement of hypoxia status. Their limitations include poor availability of the radiolabeled product and short lifetime of the 18F PET isotope (half life ca. 110 min). 

Dosage The test material should be one (concentration, vehicle, etc.) that is intended for human application. 

Dosage The test material should be one (concentration, vehicle, etc.) that is intended for human application. There will also be a sham-negative control (catheter in place but nothing administered), a vehicle control, and a positive control (generally 2% nonoxynol-9). 

Chloramphenicol [20 CAP D-(—)-ft reo-l-(p-nitrophenyl)-2-(dichloroacetamido)-l,3-propanediol] is an important antibiotic due to its broad activity against a number of clinically relevant microbial pathogens and its ability to penetrate easily the blood-brain barrier. Besides human application, CAP became widely and routinely used in veterinary practice and is used in Europe in most animal productions including fish128. 

The widespread occurrence of cyclic peptides and depsipeptides in natura makes the research on the development of rapid and efficient approaches for their generation mandatory. The rational design of synthetic cycfic peptide analogs, focused on biological activities that imitate natural structural motifs (turns, hefices, etc.), can help to increase their native properties and to adapted them for human applications, for example, in medicine [12-14]. 

In human applications, bis(pyridine-2-thiol-l-oxidato)zinc chelate has bacteriocidal and fungicidal properties comparable with selenium sulphide but is less toxic to mammals, making it suitable for controlling dandruff and seborrhoeic dermatitis138. ... 

As mentioned before, another relevant key development for the progress of animal cell culture technology was the WI-38 human diploid cell line obtained by Hayflick and Moorhead in 1961, since previously the options were the use of primary cultures or of heteroploid cell lines (derived from tumors or from cells that acquired tumor-like characteristics in culture). Because of that, heteroploid cells were not acceptable for the production of compounds for human applications, and therefore primary cultures from other species were employed (such as primary monkey kidney cells). 

Textbooks and educational courses may provide the principles of leadership, but it is human application and successes that identify the leader. Leaders are people who need to take responsibility for running an organization, at the same time as accommodating factors beyond their control. 

Bartsch, H, Hemminki, K., and O Neill, I. K., eds (1988), Methods for delecting DNA damaging agents in humans. Applications in cancer epidemiology and prevention. Interna-Uonal Agency for Research on Cancer, Lyon. 

Although stem cell-based strategies have generated some encouraging results, much work is needed to achieve a better understanding of the transplantation efficacy, long-term survival, and functional integration before any future human applications will be feasible. 

Nanoparticles were first developed in the mid-seventies by Birrenbach and Speiser. Later on, their application for the design of drug delivery systems was made available by the use of biodegradable polymers that were considered to be highly suitable for human applications. At that time, the research on colloidal carriers was mainly focusing on liposomes, but no one was able to produce stable lipid vesicles suitable for clinical applications. In some cases, nanoparticles have been shown to be more active than liposomes due to their better stability.This is the reason why in the last decades many drugs (e.g., antibiotics, antiviral and antiparasitic drugs, cytostatics, protein and peptides) were associated to nanoparticles. 

Aminopyridine is used broadly as an avicide. It is classified as a restricted use pesticide by the US Environmental Protection Agency. The compound is also being developed for clinical human application in the treatment of certain nerve conduction disorders, and it is used in experimental laboratory settings as an in vitro antagonist of voltage sensitive K" " channels. 

Moreover, both liposomes and clodronate have already been introduced in the clinic and it may be anticipated that their combination in the transient suppression of macrophage activity for human application would be easier to achieve than for any of the other candidate effector molecules which are known until now (5, 6). 

Together, these changes have expanded the spectrum of research opportunities for clinical pharmaceutical scientists and have fostered the continued evolution of the definition. The term translational research has evolved to define scientific endeavors that provide a critical link between research theory and human application. The result is that today, there is variety in the types of clinical pharmaceutical scientists to be found, which is in fulfillment of the Millis Commission imperative. 

Fig. 1 This figure represents the continuum of research endeavors within the pharmaceutical sciences. The shaded areas represent the research areas encompassed by the definition of a CPS. The arrows indicate the potential movement from one sphere of research to another. The overlap with genetics, discovery, drug delivery, and animal mechanistic studies represent areas of translational research that provide the critical link between research theory and human application. Abbreviation PK/PD, pharmacokinetics/pharmacodynamics.

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