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Attempts on Parasite Studies
Published in Yamuna Deepani Siriwardana, Leishmaniasis in Sri Lanka, 2023
Controversial evidence has been produced regarding MLEE, and this biochemical technique has been continuously challenged in the recent past by true genetic-based methods. Isoenzyme characterization is a technique introduced in the 1970s (Chance et al., 1974). MLEE examines the enzyme profile of the organism under study and enzyme mobility patterns in an electrically charged field. Organisms within the genus Leishmania are subdivided into species and strains by examining the mobility patterns of a group of iso-enzymes. Parasites are assigned to the main operational taxonomic unit (OTU) known as zymodemes based on the mobility patterns of iso-enzymes. MLEE does not always reflect the true genetic basis of the organism under study (Massamba et al., 1998; Moreno et al., 1986; Cupolillo et al., 1995; Alam et al., 2009; Kuhls et al., 2008). Genetic variation is already known to exist within the Leishmania parasites that belong to the same zymodeme (Reale et al., 2010). Genetic studies on zymodeme MON-37 of L. donovani have not really reflected the genetic or geographical basis of the said classification (Alam et al., 2009).
Evaluation of the Dermal Irritancy of Chemicals
Published in David W. Hobson, Dermal and Ocular Toxicology, 2020
Over 700 enzymes have been isolated, each capable of catalyzing a specific organic or inorganic reaction. Some enzymes are found only in specific organs, while others are found in most every cell of the body. Enzymes may also be quite specific to certain compartments or organelles within the cells, such as cytosol, lysosomes, peroxisomes, membrane border, nucleus or nucleolus, endoplasmic reticulum, Golgi bodies, or mitochondria. Enzymes common to many or most organs of an individual animal may exist in different forms, which demonstrate dissimilar patterns on electrophoresis. Different forms of the same enzyme are called isozymes, or, more preferably, isoenzymes. Levels of enzymes in body fluids usually have a “normal” range which often varies with species, age, sex, etc., and may vary from one individual animal to another. Using blood, one or more baseline levels may be obtained prior to any procedure. Increased levels of enzymes may be due to leakage from injured or dying cells, or due to increased synthesis as a result of damage or tissue insult or an increase in the number or activity of cells producing the enzyme.
The Cardiovascular System and its Disorders
Published in Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss, Understanding Medical Terms, 2020
Walter F. Stanaszek, Mary J. Stanaszek, Robert J. Holt, Steven Strauss
Laboratory tests utilized to evaluate myocardial damage, such as from a myocardial infarction, include determination of serum creatine phosphokinase (CPK) and lactic dehydrogenase (LDH), both of which are released when muscle is damaged. CPK levels rise within 3-4 hours of an MI, but other muscle damage (such as an IM injection) will also elevate levels of the enzyme: isoenzyme studies can help distinguish the origin of elevated CPK. LDH also rises in response to numerous events, but electrophoresis can separate the isoenzymes to differentiate between myocarditis and congestive heart failure, for example.
Aldehyde oxidase mediated drug metabolism: an underpredicted obstacle in drug discovery and development
Published in Drug Metabolism Reviews, 2022
Siva Nageswara Rao Gajula, Tanaaz Navin Nathani, Rashmi Madhukar Patil, Sasikala Talari, Rajesh Sonti
The first and foremost factor for the underprediction is the species difference. There are vast differences in AO isozyme’s expression ranging from the absence of expression in dogs, cats, and pigs; to one active isozyme in humans and chimpanzees; four isozymes in rats, mice, and rabbits (Beedham et al. 1987; Sahi et al. 2008). Reports have shown that no single species can reliably predict AO-metabolism for all AO-substrates. Hence, a preclinical animal model to human extrapolation is inaccurate (Garattini and Terao 2012). Also, there are significant differences in activity between various species in mice and rats. When 12 different strains of rats were tested for AO activity, the highest activity was found in Sea:SD rats, whereas the lowest activity was found in WKA/Sea rats (Sugihara et al. 1995). Dalvie et al. performed both in vivo and in vitro zoniporide metabolism studies. In vivo study showed that zoniporide metabolized to 2-oxozoniporide by AO, which was observed in humans and rats but completely absent in dogs (Dalvie et al. 2010). In vitro study conducted on the S9 fraction across species and strain showed a great difference in the formation of 2-oxozoniporide (Dalvie et al. 2013).
Evaluation of the effect of Bovis Calculus Artifactus on eight rat liver cytochrome P450 isozymes using LC-MS/MS and cocktail approach
Published in Xenobiotica, 2021
Yun-Jing Zhang, Wen-Li Zhou, Fei Yu, Qian Wang, Can Peng, Jia-Yi Kan
However, there are differences between species in the homotype composition, expression and catalytic activity of drug metabolic enzymes and the use of human liver microsomes would have made more sense to predict clinical drug–drug interactions (DDIs). Also, even when the amino acid sequences are highly identical between the isozymes, this does not automatically mean similar catalytic specificity. Therefore cautions should be applied when extrapolating the results to humans (Martignoni et al. 2006) and the use of human liver microsomes would have made more sense to predict human DDIs. And in vitro studies cannot simulate the real physiological environment. Cautions should be applied when extrapolating the results to humans. A more comprehensive investigation should therefore be performed in the future by using human liver microsomes and in vivo studies.
Targeting citrullination in autoimmunity: insights learned from preclinical mouse models
Published in Expert Opinion on Therapeutic Targets, 2021
Ylke Bruggeman, Fernanda M.C. Sodré, Mijke Buitinga, Chantal Mathieu, Lut Overbergh, Maria J.L. Kracht
Aberrant citrullination and PAD activity are a common denominator in many autoimmune diseases, like RA, SLE, IBD, MS and T1D. Pan-PAD inhibitors have been successfully used in multiple in vivo mouse models of autoimmunity, reducing disease severity and, in some cases, preventing disease onset. In general, PAD inhibition was associated with a reduction in tissue inflammation, citrullination, and autoantibody titers. Of note, the efficacy of the compounds was variable in different disease models and strains. Although immune modulatory and tissue-specific regulatory roles of PADs have been demonstrated, the exact underlying mechanisms and contribution of the different isozymes are still poorly understood and likely differ per pathology. Understanding the exact role of the different PAD isozymes in disease will aid in clinical translation.