Postnatal Organ Development as a Complicating Factor in Juvenile Toxicity Studies in Rats

2016 ◽  
Vol 45 (1) ◽  
pp. 248-252 ◽  
Author(s):  
Catherine A. Picut ◽  
George A. Parker
Keyword(s):  
Organ Development ◽  
Normal Organ ◽  
Toxicity Studies ◽  
Histopathological Evaluation ◽  
The Brain ◽  
Precocious Development

Toxicologic pathologists must evaluate tissues of immature animals from a number of types of nonclinical toxicity studies. The pathologist who is familiar with normal postnatal organ development is in a better position to appropriately detect and differentiate between abnormal, delayed, or precocious development. Vacuolation and apoptosis in multiple tissue types are normal components of development that could influence the interpretation of some tissues. Unique postnatal features such as the germal matrix in the brain, gonocytes in the testes, and saccules in the lung may complicate the histopathological evaluation. With the knowledge of normal organ development and critical windows therein, it is possible to design targeted studies to identify xenobiotic toxicity.

scholarly journals Alternative splicing during mammalian organ development

2021 ◽  
Author(s):  
Pavel V. Mazin ◽  
Philipp Khaitovich ◽  
Margarida Cardoso-Moreira ◽  
Henrik Kaessmann
Keyword(s):  
Gene Expression ◽  
Alternative Splicing ◽  
Regulatory Networks ◽  
Organ Development ◽  
Functional Diversification ◽  
Mammalian Genomes ◽  
Species Comparisons ◽  
Time Specific ◽  
The Brain ◽  
Gene Expression Levels

AbstractAlternative splicing (AS) is pervasive in mammalian genomes, yet cross-species comparisons have been largely restricted to adult tissues and the functionality of most AS events remains unclear. We assessed AS patterns across pre- and postnatal development of seven organs in six mammals and a bird. Our analyses revealed that developmentally dynamic AS events, which are especially prevalent in the brain, are substantially more conserved than nondynamic ones. Cassette exons with increasing inclusion frequencies during development show the strongest signals of conserved and regulated AS. Newly emerged cassette exons are typically incorporated late in testis development, but those retained during evolution are predominantly brain specific. Our work suggests that an intricate interplay of programs controlling gene expression levels and AS is fundamental to organ development, especially for the brain and heart. In these regulatory networks, AS affords substantial functional diversification of genes through the generation of tissue- and time-specific isoforms from broadly expressed genes.

scholarly journals Acute Toxicity of Leaf Extracts of Enydra fluctuans Lour in Zebrafish (Danio rerio Hamilton)

Scientifica ◽  
2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jobi Xavier ◽  
Kshetrimayum Kripasana
Keyword(s):  
Acute Toxicity ◽  
Basal Membrane ◽  
Brain Parenchyma ◽  
Herbaceous Plant ◽  
Histopathological Changes ◽  
Oral Toxicity ◽  
Leaf Extracts ◽  
Toxicity Studies ◽  
The Brain ◽  
Oral Acute Toxicity

The present study was focused on the concentration-dependent changes in oral acute toxicity of leaf extracts of E. fluctuans in zebrafish. The study was also aimed at the details of histopathological changes in the gill, liver, brain, and intestine of zebrafish exposed to the leaf extracts of the plant E. fluctuans. Enydra fluctuans Lour is an edible semiaquatic herbaceous plant used widely for the alleviation of the different diseases. Since there were no toxicity studies conducted on this plant, the present study was an attempt to look into the elements of toxicity of the plants. Two types of experiments are conducted in the present study. First, the acute oral toxicity study was conducted as per the OECD guidelines 203. Second, histopathological changes were observed in the fishes exposed to the lethal concentrations of plant extract. The oral acute toxicity studies conducted on Zebrafish have revealed that the leave extracts of E. fluctuans were toxic to the tested fish at the concentration of 200 mg/kg body weight. The histopathological studies conducted on the intestine of treated fishes showed that treatment has induced rupturing of the villi structure and fusion of villi the membrane and detachment of the villi structure from the basal membrane of the intestine. The histology of the liver also showed severe vacuolization in the cells while it is not affected in control. The studies on gills showed the detachment of the basal epithelial membrane in the gills compared to control which might have led to death of the fish. The histopathological observations of brain tissues treated with test samples also revealed the marked impingement in the brain parenchyma while the control is normal without impingement of the brain.

scholarly journals Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Caroline E. Rasmussen ◽  
Jette Nowak ◽  
Julie M. Larsen ◽  
Emma Moore ◽  
David Bell ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Coagulation Factor ◽  
Limit Of Quantification ◽  
Toxicity Studies ◽  
Clinical Observations ◽  
Brain Exposure ◽  
Human Proteins ◽  
The Brain

Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals.

Primary meningeal osteosarcoma of the brain during childhood

2008 ◽  
Vol 1 (4) ◽  
pp. 325-329 ◽  
Author(s):  
Adnan Dagcinar ◽  
Fatih Bayrakli ◽  
Ozlem Yapicier ◽  
Memet Ozek
Keyword(s):  
Pediatric Patients ◽  
Complete Resection ◽  
Rare Tumors ◽  
Initial Surgery ◽  
Histopathological Evaluation ◽  
Fast Progression ◽  
History Of ◽  
Clonic Seizures ◽  
The Brain ◽  
Tumor Enlargement

✓ Primary meningeal osteosarcomas are rare tumors, with only 19 reported cases in the literature; only 4 of these, including the present case, are in pediatric patients. In this report, the authors present the case of an 8-year-old boy with a history of generalized tonic–clonic seizures who was found to harbor a meningeal osteosarcoma within the sylvian fissure. Initial working diagnoses included meningioma and glioma. After tumor enlargement and progressive symptoms, the patient underwent a large frontotemporal craniotomy and complete resection of the lesion, which recurred 6 and 12 months after the initial surgery and was surgically treated after each recurrence. The rarity of primary meningeal osteosarcomas can make their diagnosis difficult, and histopathological evaluation is mandatory for diagnosis. Because of their fast progression, they must be treated aggressively by means of surgery, chemotherapy, and radiotherapy.

scholarly journals A Comparison of the Neuroprotective and Reactivating Efficacy of a Novel Bispyridinium Oxime K870 with Commonly Used Pralidoxime and the Oxime HI-6 in Tabun-Poisoned Rats

2021 ◽  
Vol 64 (3) ◽  
pp. 145-152
Author(s):  
Jiří Kassa ◽  
Jana Hatlapatková ◽  
Jana Žďárová Karasová ◽  
Vendula Hepnarová ◽  
Filip Caisberger ◽  
...  
Keyword(s):  
Brain Damage ◽  
Acetylcholinesterase Activity ◽  
Sublethal Dose ◽  
Neuroprotective Effects ◽  
Hi 6 ◽  
Histopathological Evaluation ◽  
Acute Neurotoxicity ◽  
Neuroprotective Efficacy ◽  
The Brain

Aim: The comparison of neuroprotective and central reactivating effects of the oxime K870 in combination with atropine with the efficacy of standard antidotal treatment in tabun-poisoned rats. Methods: The neuroprotective effects of antidotal treatment were determined in rats poisoned with tabun at a sublethal dose using a functional observational battery 2 h and 24 h after tabun administration, the tabun-induced brain damage was investigated by the histopathological evaluation and central reactivating effects of oximes was evaluated by the determination of acetylcholinesterase activity in the brain using a standard spectrophotometric method. Results: The central reactivating efficacy of a newly developed oxime K870 roughly corresponds to the central reactivating efficacy of pralidoxime while the ability of the oxime HI-6 to reactivate tabun-inhibited acetylcholinesterase in the brain was negligible. The ability of the oxime K870 to decrease tabun-induced acute neurotoxicity was slightly higher than that of pralidoxime and similar to the oxime HI-6. These results roughly correspond to the histopathological evaluation of tabun-induced brain damage. Conclusion: The newly synthesized oxime K870 is not a suitable replacement for commonly used oximes in the antidotal treatment of acute tabun poisonings because its neuroprotective efficacy is only slightly higher or similar compared to studied currently used oximes.

Investigation of normal organ development with fetal MRI

2007 ◽  
Vol 17 (10) ◽  
pp. 2458-2471 ◽  
Author(s):  
Daniela Prayer ◽  
Peter C. Brugger
Keyword(s):  
Fetal Mri ◽  
Organ Development ◽  
Normal Organ

Surviving, Remembering, Adversity

2017 ◽  
Author(s):  
Jay Schulkin
Keyword(s):  
Learning And Memory ◽  
Memory Consolidation ◽  
Aging Process ◽  
Life Cycles ◽  
Developmental Changes ◽  
Organ Development ◽  
Organ Systems ◽  
The Brain ◽  
Role Of Information

Chapter 7 speaks about how, while CRF is intimately involved in organ development, it is also linked to devolution of function and conditions of danger. CRF expression itself reveals developmental changes particularly in the brain. CRF is linked to diverse forms of learning and timing of events. But CRF may either enhance or degrade learning and memory. CRF tends to enhance salience and visibility, therefore learning and memory consolidation may be enhanced. However, excessive CRF expression begins to compromise these essential capabilities and promotes neural atrophy deterioration. The role of information molecules is to promote survival systems across life cycles. On the adaptive side, CRF promotes change and attention to change; on the nonadaptive side, CRF promotes decreased tissue capability and the acceleration of an aging process in end organ systems, as this chapter will discuss.

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