Experimental and toxicologic pathology : official journal of the Gesellschaft für Toxikologische Pathologie
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Exp. Toxicol. Pathol. · Jan 2011
ReviewInternational recommendations for training future toxicologic pathologists participating in regulatory-type, nonclinical toxicity studies.
The International Federation of Societies of Toxicologic Pathologists (IFSTP) proposes a common global framework for training future toxicologic pathologists who will support regulatory-type - nonclinical toxicology studies. Trainees optimally should undertake a scientific curriculum of at least 5 years at an accredited institution leading to a clinical degree (veterinary medicine or medicine). Trainees should then obtain 4 or more years of intensive pathology practice during a residency and/or on-the-job "apprenticeship," at least 2 years of which must be focused on regulatory-type toxicologic pathology topics. ⋯ A nonclinical pathway (e.g., a graduate degree in medical biology or pathology) may be possible if medically trained pathologists are scarce, but this option is not optimal. Regular, lifelong continuing education (peer review of nonclinical studies, professional meetings, reading, short courses) will be necessary to maintain and enhance one's understanding of current toxicologic pathology knowledge, skills, and tools. This framework should provide a rigorous yet flexible way to reliably train future toxicologic pathologists to generate, interpret, integrate, and communicate data in regulatory-type, nonclinical toxicology studies.
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Exp. Toxicol. Pathol. · Nov 2006
ReviewCarboxyhemoglobin and thiocyanate as biomarkers of exposure to carbon monoxide and hydrogen cyanide in tobacco smoke.
The determination of biomarkers in human body fluids is a useful tool, which allows the quantitative assessment of the exposure to chemicals or complex mixtures of chemicals and of early biological effects as a result of the exposure. Biomarkers require validation before their successful application in human studies. This review describes some general purposes of human biomonitoring and biomarkers including the requirements for validation. ⋯ Both biomarkers are significantly correlated with the daily cigarette consumption. Smoking machine-derived yields of the precursors carbon monoxide and hydrogen cyanide were not correlated with COHb/COex and SCN, respectively. It is concluded that, while COHb/COex is a useful biomarker for assessing the smoke inhalation, preferably in controlled studies, the application of SCN in body fluids as a biomarker for smoking is limited, mainly due to the abundance of other sources for SCN.
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Exp. Toxicol. Pathol. · Jul 2005
ReviewBiomonitoring of inhaled complex mixtures--ambient air, diesel exhaust and cigarette smoke.
Human biomonitoring comprises the determination of biomarkers in body-fluids, cells and tissues. Biomarkers are generally assigned to one of three classes, namely, biomarkers of exposure, effect or susceptibility. Since biomarkers represent steps in an exposure-disease continuum, their application in epidemiological studies ('molecular epidemiology') shows promise. ⋯ Finally, suitable study designs for evaluating PREPs are discussed. It is concluded that suitable biomarkers for assessing the exposure to complex mixtures such as ambient air, diesel exhaust and tobacco smoke as well as for evaluating the exposure-reducing properties of PREPs are already available. Future efforts should focus on the development and validation of biomarkers of effect.
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Traumatic brain injury (TBI) is the leading cause of death in childhood; however only very few studies focusing on the specific pathophysiology and treatment have been published to date. Head trauma is more likely in young children than in adults given the same deceleration of the body due to their large and heavy heads and weak cervical ligaments and muscles. Resulting brain injury is more severe due to their thin, pliable skulls and the yet unfused sutures. ⋯ For several other therapeutical means, e.g. hypothermia or specific surgical interventions, clinical evidence to date is insufficient to allow recommendation as rescue treatment for children at risk of severe neurological sequelae following TBI. This review discusses the clinical implication of pathophysiologic mechanisms of TBI in the developing brain according to the recent literature and current guidelines. It follows the clinical approach to a head injured child, that can be divided into three phases, i.e. initial assessment and stabilization, followed by first tier, and if necessary second tier therapeutic interventions to assure adequate oxygenation and perfusion of the brain.
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Exp. Toxicol. Pathol. · Oct 2004
ReviewTraumatic injury in the developing brain--effects of hypothermia.
Little is known about the underlying mechanisms of head trauma in the developing brains, despite considerable social and economic impact following such injuries. Age has been shown to substantially influence morbidity and mortality. Children younger than 4 years of age had worse cognitive, motor, and brain atrophy outcomes than children 6 years of age and older. ⋯ As an alternative/ adjunct to pharmacological approaches, hypothermia has been shown to be cerebroprotective in traumatized adult brains. Although a large number of animal studies have shown protective effects of hypothermia in a variety of damaging mechanisms after TBI, little data exist for young, developing brains. The injury mechanisms of TBI in the immature, effects of hypothermia following resuscitation on adult and immature traumatized brains, and some possible mechanisms of action of hypothermia in the immature traumatized brain are discussed in this review.