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Mechanism of action of a nitroimidazole-thiadiazole ..
The concepts of target organ and critical effect have been developed to aid in the interpretation of toxicological data. Depending upon dose, duration and route of exposure, as well as host factors such as age, many toxic agents can induce a number of effects within organs and organisms. An important role of toxicology is to identify the important effect or sets of effects in order to prevent irreversible or debilitating disease. One important part of this task is the identification of the organ first or most affected by a toxic agent; this organ is defined as the target organ. Within the target organ, it is important to identify the important event or events that signals intoxication, or damage, in order to ascertain that the organ has been affected beyond the range of normal variation. This is known as the critical effect; it may represent the first event in a progression of pathophysiological stages (such as the excretion of small-molecular-weight proteins as a critical effect in nephrotoxicity), or it may represent the first and potentially irreversible effect in a disease process (such as formation of a DNA adduct in carcinogenesis). These concepts are important in occupational health because they define the types of toxicity and clinical disease associated with specific exposures, and in most cases reduction of exposure has as a goal the prevention of critical effects in target organs, rather than every effect in every or any organ.
The intent of this article is to give a perspective on several known mechanisms of toxicity and the need for future study. It is important to understand that mechanistic knowledge is not absolutely necessary to protect human or environmental health. This knowledge will enhance the professionals ability to better predict and manage toxicity. The actual techniques used in elucidating any particular mechanism depend upon the collective knowledge of the scientists and the thinking of those who make decisions regarding human health.
Synthesis and evaluation of new thiadiazole derivatives …
The synthesis of BDZ-g (GYKI 47409) was previouslydescribed,, and BDZ-h (GYKI47654) was synthesized analogously (see the ). GYKI 52466, BDZ-d (also knownas talampanel), and BDZ-f used in this study (theirchemical names are listed in the legend of Figure ) were previously reported.,,,, 2,5-Dimethyl-1,3,4-thiadiazole was purchased from Sigma-Aldrich(St. Louis, MO). All other chemicals used in making buffers were fromcommercial sources.
It is also necessary to mention the enterohepatic circulation. Polar toxicants and/or metabolites (glucuronides and other conjugates) are excreted with the bile into the duodenum. Here the enzymes of the microflora perform hydrolysis and liberated products can be reabsorbed and transported by the portal vein into the liver. This mechanism is very dangerous in the case of hepatotoxic substances, enabling their temporary accumulation in the liver.
Synthesis and evaluation of new thiadiazole derivatives as ..
Gadad AK, Palkar MB, Anand K, Noolvi MN, Boreddy TS, Wagwade J. Synthesis and biological evaluation of 2-trifluoromethyl/ sulfonamido-5,6-diaryl substituted imidazo(2,1-b)-1,3,4-thiadiazoles: A novel class of cyclooxygenase-2 inhibitors. Bioorg & Med Chem. 2008, 16:276-283
Gupta A, Mishra P, Kashaw SK, Kashaw V, Stables JP. Synthesis of 3-aryl amino/amino-4-aryl-5-imino-D2-1,2,4-thiadiazoline and evaluated for anticonvulsant activity. Eur J Med Chem. 2008, 43:749-754
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1 Synthesis of 1,2,3-thiadiazoles
The section then provides two general overviews on toxicology at the mechanistic level. Mechanistically, modern toxicologists consider that all toxic effects manifest their first actions at the cellular level; thus, cellular responses represent the earliest indications of the bodys encounters with a toxic agent. It is further assumed that these responses represent a spectrum of events, from injury through death. Cell injury refers to specific processes utilized by cells, the smallest unit of biological organization within organs, to respond to challenge. These responses involve changes in the function of processes within the cell, including the membrane and its ability to take up, release or exclude substances; the directed synthesis of proteins from amino acids; and the turnover of cell components. These responses may be common to all injured cells, or they may be specific to certain types of cells within certain organ systems. Cell death is the destruction of cells within an organ system, as a consequence of irreversible or uncompensated cell injury. Toxic agents may cause cell death acutely because of certain actions such as poisoning oxygen transfer, or cell death may be the consequence of chronic intoxication. Cell death can be followed by replacement in some but not all organ systems, but in some conditions cell proliferation induced by cell death may be considered a toxic response. Even in the absence of cell death, repeated cell injury may induce stress within organs that compromises their function and affects their progeny.
This paper shows that megazol inhibits protein synthesis of T
The chapter is then divided into more specific topics, which are grouped into the following categories: mechanism, test methods, regulation and risk assessment. The mechanism articles mostly focus on target systems rather than organs. This reflects the practice of modern toxicology and medicine, which studies organ systems rather than isolated organs. Thus, for example, the discussion of genetic toxicology is not focused upon the toxic effects of agents within a specific organ but rather on genetic material as a target for toxic action. Likewise, the article on immunotoxicology discusses the various organs and cells of the immune system as targets for toxic agents. The methods articles are designed to be highly operational; they describe current methods in use in many countries for hazard identification, that is, the development of information related to biological properties of agents.
Mechanism of action of a nitroimidazole ..
The chapter continues with five articles on the application of toxicology in regulation and policy-making, from hazard identification to risk assessment. The current practice in several countries, as well as IARC, is presented. These articles should enable the reader to understand how information derived from toxicology tests is integrated with basic and mechanistic inferences to derive quantitative information used in setting exposure levels and other approaches to controlling hazards in the workplace and general environment.
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