Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Toxicologic pathology”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Toxicological pathology of cockleburs (Xanthium spp.) for broiler chickens.

Spiking mortality syndrome (SMS) in chickens resembles cocklebur toxicity in cattle, sheep, pigs, and rats. In order to determine if cockleburs are toxic to broiler chicks, crushed burs were fed (25% wt:wt) to broilers for 21 days. Ingestion of cockleburs resulted in significant failure to properly gain body weight. Otherwise, chicks did not develop clinical signs of illness or gross or microscopic lesions. Although there were some significant differences in serum chemistry values among chick groups, there were no consistent patterns. Severe hypoglycemia is said to be a characteristic finding in chicks that die with SMS. Because glucose levels were not low in chicks that were fed cockleburs, we feel certain that cockleburs do not cause SMS.

Animal Feed↗
PubMed1999

Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profiles.

A study was undertaken to develop demographic, toxicologic, and pathological profiles of methamphetamine-related deaths. Anatomic and toxicologic findings in 413 deaths where methamphetamine was detected were compared with findings in a control group of 114 drug-free trauma victims. The number of cases per year did not change significantly over the course of the study. Mean age was 36.8 years, but 11% were over the age of 50. Decedents were overwhelmingly male (85.2%) and Caucasian (75%). Blood concentrations of methamphetamine and amphetamine were indistinguishable in cases where methamphetamine was related to the cause of death (MR) and cases where it was not (non-MR) (2.08 vs. 1.78 mg/L, p = 0.65, and 0.217 vs. 0.19 mg/L, p = 0.82). Coronary artery disease, ranging from minimal to severe multivessel, was identified in 79 of the 413 drug users, but in only six of the 114 drug-free controls (p = 0.0004), and MR decedents had enlarged hearts compared with controls. There were also ten cases of subarachnoid and intracranial hemorrhage in the MR group. Abnormalities of the liver (34%) and lungs (24.7%) were frequent. In 65% of these cases, death was due to accidental methamphetamine toxicity. In the remaining cases, methamphetamine was an incidental finding. We conclude that, in our jurisdiction, neither the rate of detection nor the number of methamphetamine deaths has increased significantly in the past 13 years. Decedents are almost all Caucasian males, and many were approaching middle-age. Methamphetamine use is strongly associated with coronary artery disease and with subarachnoid hemorrhage.

Accidents↗
PubMed2000

Polyamines in the lung: polyamine uptake and polyamine-linked pathological or toxicological conditions.

The natural polyamines putrescine, cadaverine, spermidine, and spermine are found in all cells. These (poly)cations exert interactions with anions, e.g., DNA and RNA. This feature represents their best-known direct physiological role in cellular functions: cell growth, division, and differentiation. The lung and, more specifically, alveolar epithelial cells appear to be endowed with a much higher polyamine uptake system than any other major organ. In the lung, the active accumulation of natural polyamines in the epithelium has been studied in various mammalian species including rat, hamster, rabbit, and human. The kinetic parameters (Michaelis-Menten constant and maximal uptake) of the uptake system are the same order of magnitude regardless of the polyamine or species studied and the in vitro system used. Also, other pulmonary cells accumulate polyamines but never to the same extent as the epithelium. Although different uptake systems exist for putrescine, spermidine, and spermine in the lung, neither the nature of the carrier protein nor the reason for its existence is known. Some pulmonary toxicological and/or pathological conditions have been related to polyamine metabolism and/or polyamine content in the lung. Polyamines possess an important intrinsic toxicity. From in vitro studies with nonpulmonary cells, it has been shown that spermidine and spermine can be metabolized to hydrogen peroxide, ammonium, and acrolein, which can all cause cellular toxicity. In hyperoxia or after ozone exposure, the increased polyamine synthesis and polyamine content of the rat lung is correlated with survival of the animals. Pulmonary hypertension induced by monocrotaline or hypoxia has also been linked to the increased polyamine metabolism and polyamine content of the lung. In a small number of studies, it has been shown that polyamines can contribute to the suppression of immunologic reactions in the lung.

Animals↗
PubMed2005

Confounders in interpreting pathology for safety and risk assessment.

The contribution of pathology to toxicity assessment is invaluable but often not clearly understood. Pathology endpoints are the central response around which human health risk assessment is frequently determined; therefore, it is important that the general toxicology community understand current concepts and nomenclature of toxicologic pathology. Toxicologic pathology encompasses the study of changes in tissue morphology that help define the risk of exposure to xenobiotics. Toxicologic pathology is a discipline that has changed and adapted over time including methods of analysis and nomenclature of lesions. As risk assessments are updated for chemicals in commerce, frequently the older literature must be reviewed and reevaluated. When interpreting pathology data from animal studies, it is important to consider the biological significance of a lesion as well as its relationship to the ultimate adverse health effect. Assessing the potential for a chemical to cause harm to humans must include the examination of the entire pathology database in context of the study design, the mode of action of the chemical of concern, and using the most current interpretation of a lesion to determine the significance for human health effects of a particular tissue response.

Animals↗
PubMed1983

Toxicological and pathological findings in fatalities involving pentazocine and tripelennamine.

Toxicological and pathological findings are described in fatalities involving pentazocine (Talwin) and tripelennamine (Pyribenzamine). Procedures using thin-layer chromatography, gas chromatography, ultraviolet spectrophotometry, and spectrophotofluorometry are described, as well as the quantitative analysis of biological specimens of drug abuse and homicide victims. Microscopic findings in lung specimens from drug abuse deaths are also described.

Chromatography, Gas↗
PubMed1985

The incident at Tuol Chrey: pathologic and toxicologic examinations of a casualty after chemical attack.

The results of the pathologic and toxicologic examinations of specimens from a casualty who died several weeks after a chemical attack in Kampuchea are discussed. While the effects of tricothecene mycotoxins have been described in domestic and experimental animals, there is a paucity of information about the pathologic effects of these toxins in humans. The possible effects of endemic diseases such as falciparum malaria, viral hepatitis, and nutritional deficiencies, as well as of the sudden, unexpected death syndrome among refugees from Southeast Asia, have been reviewed. If the results of the histologic examinations in this case are considered alone, it is not possible to establish a cause-effect relationship. However, the circumstances of injury, the relationship of pathologic findings to the studies of experimental animals, and the results of the toxicologic examinations of environmental and biologic specimens indicate that the combinations of tricothecene mycotoxins detected are not consistent with natural occurrence and provide evidence that the pathologic effects are related to a toxic agent.

Adult↗
PubMed2002

Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies.

The unprecedented advances in molecular biology during the last two decades have resulted in a dramatic increase in knowledge about gene structure and function, an immense database of genetic sequence information, and an impressive set of efficient new technologies for monitoring genetic sequences, genetic variation, and global functional gene expression. These advances have led to a new sub-discipline of toxicology: "toxicogenomics". We define toxicogenomics as "the study of the relationship between the structure and activity of the genome (the cellular complement of genes) and the adverse biological effects of exogenous agents". This broad definition encompasses most of the variations in the current usage of this term, and in its broadest sense includes studies of the cellular products controlled by the genome (messenger RNAs, proteins, metabolites, etc.). The new "global" methods of measuring families of cellular molecules, such as RNA, proteins, and intermediary metabolites have been termed "-omic" technologies, based on their ability to characterize all, or most, members of a family of molecules in a single analysis. With these new tools, we can now obtain complete assessments of the functional activity of biochemical pathways, and of the structural genetic (sequence) differences among individuals and species, that were previously unattainable. These powerful new methods of high-throughput and multi-endpoint analysis include gene expression arrays that will soon permit the simultaneous measurement of the expression of all human genes on a single "chip". Likewise, there are powerful new methods for protein analysis (proteomics: the study of the complement of proteins in the cell) and for analysis of cellular small molecules (metabonomics: the study of the cellular metabolites formed and degraded under genetic control). This will likely be extended in the near future to other important classes of biomolecules such as lipids, carbohydrates, etc. These assays provide a general capability for global assessment of many classes of cellular molecules, providing new approaches to assessing functional cellular alterations. These new methods have already facilitated significant advances in our understanding of the molecular responses to cell and tissue damage, and of perturbations in functional cellular systems. As a result of this rapidly changing scientific environment, regulatory and industrial toxicology practice is poised to undergo dramatic change during the next decade. These advances present exciting opportunities for improved methods of identifying and evaluating potential human and environmental toxicants, and of monitoring the effects of exposures to these toxicants. These advances also present distinct challenges. For example, the significance of specific changes and the performance characteristics of new methods must be fully understood to avoid misinterpretation of data that could lead to inappropriate conclusions about the toxicity of a chemical or a mechanism of action. We discuss the likely impact of these advances on the fields of general and genetic toxicology, and risk assessment. We anticipate that these new technologies will (1) lead to new families of biomarkers that permit characterization and efficient monitoring of cellular perturbations, (2) provide an increased understanding of the influence of genetic variation on toxicological outcomes, and (3) allow definition of environmental causes of genetic alterations and their relationship to human disease. The broad application of these new approaches will likely erase the current distinctions among the fields of toxicology, pathology, genetic toxicology, and molecular genetics. Instead, a new integrated approach will likely emerge that involves a comprehensive understanding of genetic control of cellular functions, and of cellular responses to alterations in normal molecular structure and function.

Animals↗
PubMedDate not supplied

The case for perfusion fixation of large tissue samples for ultrastructural pathology.

We present the case for the perfusion fixation of large, freshly isolated tissue samples of liver and lung from dog, rat, and mouse. Individual lobes of liver and lung were fixed by vascular perfusion using a technique that is simple and quick to perform and results in a reproducibly high standard of ultrastructural preservation compared to immersion fixation. A major advantage to the use of this technique lies in the ability to provide tissue samples for diagnostic ultrastructural pathology and toxicological pathology while avoiding the need for whole-organ or whole-body perfusion fixation. This advantage therefore permits the use of fresh tissue from the same organ for other investigative purposes (e.g., drug metabolism studies and pharmacokinetics), thereby allowing correlation of structure and function. The advantages of perfusion fixation compared to immersion fixation are discussed, and potential applications for tissue preparation of postmortem specimens and also for scanning electron microscopy are indicated.

Animals↗
PubMed1984

Quantitative histochemistry in pathology and toxicology. An evaluation of the original two-wave length method of Ornstein.

A quantitative histochemical procedure for use in general pathologic and toxicologic studies, based on the original two-wave length microdensitometric method of Ornstein, has been developed. Basic mathematical formulas and necessary parameters have been derived from Ornstein's calculations. A computer simulation of the behavior of these equations in analyzing a photometric field demonstrated the importance of careful choice of working wave lengths for both reference wave length (lambda ref) and correction wave length (lambda cor), the importance of minimizing "empty space" in the photometric field, and the importance of accuracy and stability of transmission readings. An easy procedure for choosing lambda ref and lambda cor is described. The effects of mounting media, varying chromophores analyzed, internal glare, and measuring diaphragms and monochromator in the photometric apparatus are assessed. This method is compared with a scanning technique, and the formulas employed are related to alternative calculations done by Patau. The application of this two-wave length method is well suited to accurately determine extinction values from tissues and cytologic specimens at varying powers of magnification utilizing a variety of histochemical chromophores, which makes the method ideally applicable to general purpose use in pathologic and toxicologic studies.

Computers↗
PubMedDate not supplied

Toxicoproteomics: proteomics applied to toxicology and pathology.

Global measurement of proteins and their many attributes in tissues and biofluids defines the field of proteomics. Toxicoproteomics, as part of the larger field of toxicogenomics. seeks to identify critical proteins and pathways in biological systems that are affected by and respond to adverse chemical and environmental exposures using global protein expression technologies. Toxicoproteomics integrates 3 disciplinary areas: traditional toxicology and pathology, differential protein and gene expression analysis, and systems biology. Key topics to be reviewed are the evolution of proteomics, proteomic technology platforms and their capabilities with exemplary studies from biology and medicine, a review of over 50 recent studies applying proteomic analysis to toxicological research, and the recent development of databases designed to integrate -Omics technologies with toxicology and pathology. Proteomics is examined for its potential in discovery of new biomarkers and toxicity signatures, in mapping serum,plasma. and other biofluid proteomes, and in parallel proteomic and transcriptomic studies. The new field of toxicoproteomics is uniquely positioned toward an expanded understanding of protein expression during toxicity and environmental disease for the advancement of public health.

Animals↗
PubMed2006

The transduction of rat submandibular glands by an adenoviral vector carrying the human growth hormone gene is associated with limited and reversible changes at the infusion site.

Adenoviral vectors have been shown to efficiently deliver exogenous genes to salivary glands and have therefore been investigated as tools for the treatment of human disease. The purpose of this study was to evaluate the response of F344 rats to intraductal infusion of the right submandibular salivary gland with an adenoviral vector encoding the gene for human growth hormone (AdCMVhGH). Co-administration of hydroxychloroquine (HCQ) was used to redirect the secretion of human growth hormone (hGH) from saliva into serum. This paper documents the findings of the pathology evaluation of this National Toxicology Program study. The right submandibular salivary gland (infusion site) was the primary target organ, with microscopic lesions characteristic of a mild to moderate insult observed at 3 days post infusion in vector exposed animals. These lesions were characterized by variable degrees of acute glandular inflammation, degeneration and necrosis, with more severe lesions in the higher dose groups. Rats at 28 days post infusion had milder inflammation, degeneration and necrosis compared to day 3 rats, with variable degrees of regeneration. In conclusion, the effects on the salivary glands are reversible as indicated by the milder inflammation and degeneration in the day 28 rats concomitant with mild to moderate regeneration. Therefore, the vector appears relatively innocuous with limited tissue toxicity. [The supplemental data referenced in this paper is not printed in this issue of Toxicologic Pathology. It is available as a downloadable file in the online edition of Toxicologic Pathology, 34(4). In order to access the full article online, you must have either an individual subscription or a member subscription accessed through www.toxpath.org.].

Adenoviridae↗