Sample records for rats morphological characterization
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The rat whole embryo culture assay using the Dysmorphology Score system.
Zhang, Cindy; Panzica-Kelly, Julie; Augustine-Rauch, Karen
2013-01-01
The rat whole embryo culture (WEC) system has been used extensively for characterizing teratogenic properties of test chemicals. In this chapter, we describe the methodology for culturing rat embryos as well as a new morphological score system, the Dysmorphology Score (DMS) system for assessing morphology of mid gestation (gestational day 11) rat embryos. In contrast to the developmental stage focused scoring associated with the Brown and Fabro score system, this new score system assesses the respective degree of severity of dysmorphology, which delineates normal from abnormal morphology of specific embryonic structures and organ systems. This score system generates an approach that allows rapid identification and quantification of adverse developmental findings, making it conducive for characterization of compounds for teratogenic properties and screening activities.
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Hoffman, Ewelina; Patel, Aateka; Ball, Doug; Klapwijk, Jan; Millar, Val; Kumar, Abhinav; Martin, Abigail; Mahendran, Rhamiya; Dailey, Lea Ann; Forbes, Ben; Hutter, Victoria
2017-12-01
Progress to the clinic may be delayed or prevented when vacuolated or "foamy" alveolar macrophages are observed during non-clinical inhalation toxicology assessment. The first step in developing methods to study this response in vitro is to characterize macrophage cell lines and their response to drug exposures. Human (U937) and rat (NR8383) cell lines and primary rat alveolar macrophages obtained by bronchoalveolar lavage were characterized using high content fluorescence imaging analysis quantification of cell viability, morphometry, and phospholipid and neutral lipid accumulation. Cell health, morphology and lipid content were comparable (p < 0.05) for both cell lines and the primary macrophages in terms of vacuole number, size and lipid content. Responses to amiodarone, a known inducer of phospholipidosis, required analysis of shifts in cell population profiles (the proportion of cells with elevated vacuolation or lipid content) rather than average population data which was insensitive to the changes observed. A high content image analysis assay was developed and used to provide detailed morphological characterization of rat and human alveolar-like macrophages and their response to a phospholipidosis-inducing agent. This provides a basis for development of assays to predict or understand macrophage vacuolation following inhaled drug exposure.
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NASA Astrophysics Data System (ADS)
Coccini, T.; Roda, E.; Barni, S.; Manzo, L.
2013-04-01
Renal morphological parameters were determined in rats intratracheally instilled with model cadmium-containing silica nanoparticles (Cd-SiNPs, 1mg/rat), also exploring whether their potential modifications would be associated with toxicogenomic changes. Cd-SiNP effects, evaluated 7 and 30 days post-exposure, were assessed by (i) histopathology (Haematoxylin/Eosin Staining), (ii) characterization of apoptotic features by TUNEL staining. Data were compared with those obtained by CdCl2 (400μg/rat), SiNPs (600μg/rat), 0.1 ml saline. Area-specific cell apoptosis was observed in all treatment groups: cortex and inner medulla were the most affected regions. Apoptotic changes were apparent at 7 days post-exposure in both areas, and were still observable in inner medulla 30 days after treatment. Increase in apoptotic frequency was more pronounced in Cd-SiNP-treated animals compared to either CdCl2 or SiNPs. Histological findings showed comparable alterations in the renal glomerular (cortex) architecture occurring in all treatment groups at both time-points considered. The glomeruli appeared often collapsed, showing condensed, packed mesangial and endothelial cells. Oedematous haemorrhagic glomeruli were also observed in Cd-SiNPs-treated animals. Bare SiNPs caused morphological and apoptotic changes without modifying the renal gene expression profile. These findings support the concept that multiple assays and an integrated testing strategy should be recommended to characterize toxicological responses to nanoparticles in mammalian systems.
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Sokolis, Dimitrios P; Dimitriou, Constantinos A; Lelovas, Pavlos; Kostomitsopoulos, Nikolaos G; Dontas, Ismene A
2017-01-01
Arterial function is regulated by estrogen, but no consistent pattern of arterial mechanical remodeling in response to depleted estrogen levels is available. To examine long-term effects of ovariectomy (OVX) on the mechanical properties, morphology, and histological structure of the carotid artery in middle-aged rats and a potentially protective effect of Sideritis euboea extract (SID), commonly consumed as "mountain tea". 10-month-old female Wistar rats were allocated into control (sham-operated), OVX, OVX+SID, and OVX+MALT (maltodextrin; excipient used for dilution of SID) groups. They were sacrificed after 6 months and their carotid arteries were submitted to inflation/extension tests and to dimensional and histological evaluation. Remodeling in OVX rats was characterized by a decreased in situ axial extension ratio, along with increased opening angle, thickness, and area of the vessel wall and of its medial layer, but unchanged lumen diameter. Compositional changes involved increased elastin/collagen densities. Characterization by the "four-fiber" microstructure-motivated model revealed similar in situ biaxial response of carotid arteries in OVX and control rats. Carotid artery remodeling in OVX rats was largely consistent with hypertensive remodeling, despite the minor arterial pressure changes found, and was not altered by administration of SID, despite previous evidence of its osteo-protective effect.
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Reproductive alterations in hyperinsulinemic but normoandrogenic MSG obese female rats.
Gaspar, Renato Simões; Benevides, Renata Ohana Alves; Fontelles, João Lucas de Lima; Vale, Caroline Castro; França, Lucas Martins; Barros, Paulo de Tarso Silva; Paes, Antonio Marcus de Andrade
2016-05-01
Obesity and metabolic syndrome are the common causes of reproductive and fertility disorders in women. In particular, polycystic ovary syndrome, which is clinically characterized by hyperandrogenism, oligo/anovulation, and polycystic ovarian morphology, has been increasingly associated with metabolic disorders. However, given the broad interplay between metabolic and reproductive functions, this remains a field of intense research. In this study, we investigated the effect of monosodium l-glutamate (MSG)-induced obesity on reproductive biology of female rats. Newborn female rats were subcutaneously injected with MSG (4g/kg/day) or equiosmolar saline (CTR) each 2 days up to postnatal day (pnd) 10. On pnd 60, estrous cycle was evaluated using vaginal smears twice a day for 15 days, which showed MSG rats to be oligocyclic. Thereafter, animals were killed on estrous phase for blood and tissue collection. MSG rats had increased body mass, accumulation of retroperitoneal and visceral fat pads, and visceral adipocyte hypertrophy compared with CTR rats. MSG rats were also dyslipidemic and hyperinsulinemic but were normoglycemic and normoandrogenic. Ovarian morphology analysis showed that MSG rats had a two-fold decrease in oocyte count but a six-fold increase on ovarian follicular cysts, along with a higher number of total primordial and atretic follicles. Moreover, MSG rats had a four-fold increase in anti-Müllerian hormone immunohistochemical staining on antral follicles. Taken together, data presented here characterize MSG obesity as a unique model to study the metabolic pathways underlying reproductive disorders in the absence of overactivated hypothalamic-pituitary-gonadal axis. © 2016 Society for Endocrinology.
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Hepatic damage in newborns from female rats exposed to the pesticide derivative ethylenethiourea.
Lemos, Patrícia Veruska Ribeiro Barbosa; Martins, José Luiz; Lemos, Sidney Pereira Pinto; Santos, Fernando Leandro dos; Silva, Sílvio Romero Gonçalves e
2012-12-01
To evaluate hepatic morphological-histological abnormalities in newborns from female rats exposed to ethylenethiourea. A randomized study was conducted on fifty-five newborn Wistar rats were studied: 34 in the experimental group, whose mothers had been exposed to 1% ethylenethiourea; and 21 in the control group, whose mothers had received 0.9% physiological solution. The solution was administered via gavage on the 11(th) day of gestation. Cesarean section was performed on the 20(th) day of gestation. The newborns' livers were examined and any morphological-histological abnormalities were registered. The presence of megakaryocytes was quantified in 50 microscope fields, as the total number of these cells per mm(2). The entire experimental group presented abnormalities of embryonic formation, with musculoskeletal anomalies, digestive system anomalies, hepatic congestion and friability, hydrops and delayed intrauterine growth. The histopathological analysis showed that morphological-histological hepatic destructuring had occurred in all entire experimental with removal of the hepatic trabeculae and severe hepatic megakaryocytosis. The mean megakaryocyte density ranged from 107.9 to 114.2 per mm(2), and it was eight times greater than in the control group, thus characterizing a situation of extramedullary hematopoiesis. The fetal exposure to ethylenethiourea caused hepatic damage characterized by severe extramedullary hematopoiesis.
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Rajeev, S.; Sutton, D. A.; Wickes, B. L.; Miller, D. L.; Giri, D.; Van Meter, M.; Thompson, E. H.; Rinaldi, M. G.; Romanelli, A. M.; Cano, J. F.; Guarro, J.
2009-01-01
Isolation and characterization of the new species Chrysosporium ophiodiicola from a mycotic granuloma of a black rat snake (Elaphe obsoleta obsoleta) are reported. Analysis of the sequences of different fragments of the ribosomal genes demonstrated that this species belongs to the Onygenales and that this species is genetically different from other morphologically similar species of Chrysosporium. This new species is unique in having both narrow and cylindrical-to-slightly clavate conidia and a strong, pungent odor. PMID:19109465
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Yi, Yuxin; Wu, Shixing; Ye, Maosheng; Zeng, Yi; Zhang, Ping; Xie, Yiqun
2014-04-01
To determine the effect of polygona-polysaccharose (PP) on learning and memory ability in rats with Alzheimer's disease (AD). Forty five Sprague-Dawley rats were assigned into 3 groups. Rats in the sham-operated group were injected with normal saline. Rats in the Aβ group were injected with Aβ1-42. Rats in the PP group were injected with 16% PP solution for 45 days consecutively. The Morris water maze was used to investigate the ability of learning and memory in the rats. The effect of Aβ and PP on the hippocampus cells was observed by HE and Congo red staining of methanol. Rats in the sham-operated group had no obvious morphological change; and morphology of rats in the PP group was basicaly normal. The layer of pyramidal cells in the Aβ group was decreased. The cells appeared sparse and irregular and became smaller. Karyopyknosis and vacuolar degeneration cells were also found. More positive staining materials aggradated in the Aβ group compared with the PP group by Congo red staining (P<0.05). Aβ infusion into the hippocampus results in the impairment of the neuronal degeneration in the rats, which shows similar characterizations of AD. PP can reduce the deposition of Aβ in the hippocampus.
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Barbosa, Everton Horiquini; Soares, Roberto Oliveira; Braga, Natália Nassif; Almeida, Sebastião de Sousa; Lachat, João-José
2016-06-01
This study aimed to compare the effects of environmental enrichment in nourished (on a diet containing 16% protein) and malnourished (on a diet containing 6% protein) rats during the critical period of brain development, specifically focusing on the optic nerve. By means of morphologic and morphometric assessment of the optic nerve, we analyzed the changes caused by diet and stimulation (environmental enrichment) on postnatal day 35, a time point ideal for such morphological analysis since developmental processes are considered complete at this age. Malnourished animals presented low body and brain weights and high body-to-brain weight ratio compared to well-nourished rats. Furthermore, malnourished animals showed morphological changes in the optic nerve such as edema and vacuolization characterized by increased interstitial space. The malnourished-stimulated group presented lesions characteristic of early protein malnutrition but were milder than lesions exhibited by malnourished-non-stimulated group. The morphometric analysis revealed no difference in glial cell density between groups, but there was significantly higher blood vessel density in the stimulated rats, independent of their nutritional condition. Our data indicate that protein malnutrition imposed during the critical period of brain development alters the cytoarchitecture of the optic nerve. In addition, we affirm that a 1-hour exposure to an enriched environment everyday was sufficient for tissue preservation in rats maintained on a low-protein diet. This protective effect might be related to angiogenesis, as confirmed by the increased vascular density observed in morphometric analyses.
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The sensitivity of male rat reproductive organs to monosodium glutamate.
Iamsaard, Sitthichai; Sukhorum, Wannisa; Samrid, Rarinthorn; Yimdee, Jindaporn; Kanla, Pipatphong; Chaisiwamongkol, Kowit; Hipkaeo, Wiphawi; Fongmoon, Duriya; Kondo, Hisatake
2014-01-01
This study aimed to investigate the sensitivity of the testis, epididymis, seminal vesicle, and sperm acrosome reaction (AR) to monosodium L- glutamate (MSG) in rats. Rats were divided into four groups and fed with non-acidic MSG at 0.25, 3 or 6 g/kg body weight for 30 days or without MSG. The morphological changes in the reproductive organs were studied. The plasma testosterone level, epididymal sperm concentration, and sperm AR status were assayed. Compared to the control, no significant changes were discerned in the morphology and weight of the testes, or the histological structures of epididymis, vas deferens and seminal vesicle. In contrast, significant decreases were detected in the weight of the epididymis, testosterone levels, and sperm concentration of rats treated with 6 g/kg body weight of MSG. The weight loss was evident in the seminal vesicle in MSG-administered rats. Moreover, rats treated with MSG 3 and 6 g/kg exhibited partial testicular damage, characterized by sloughing of spermatogenic cells into the seminiferous tubular lumen, and their plasma testosterone levels were significantly decreased. In the 6 g/kg MSG group, the sperm concentration was significantly decreased compared with the control or two lower dose MSG groups. In AR assays, there was no statistically significant difference between MSG-rats and normal rats. Testicular morphological changes, testosterone level, and sperm concentration were sensitive to high doses of MSG while the rate of AR was not affected. Therefore, the consumption of high dose MSG must be avoided because it may cause partial infertility in male. Copyright © 2014 by Academy of Sciences and Arts of Bosnia and Herzegovina.
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Characterization of dynamic physiology of the bladder by optical coherence tomography
NASA Astrophysics Data System (ADS)
Yuan, Zhijia; Keng, Kerri; Pan, Rubin; Ren, Hugang; Du, Congwu; Kim, Jason; Pan, Yingtian
2012-03-01
Because of its high spatial resolution and noninvasive imaging capabilities, optical coherence tomography has been used to characterize the morphological details of various biological tissues including urinary bladder and to diagnose their alternations (e.g., cancers). In addition to static morphology, the dynamic features of tissue morphology can provide important information that can be used to diagnose the physiological and functional characteristics of biological tissues. Here, we present the imaging studies based on optical coherence tomography to characterize motion related physiology and functions of rat bladder detrusor muscles and compared the results with traditional biomechanical measurements. Our results suggest that optical coherence tomography is capable of providing quantitative evaluation of contractile functions of intact bladder (without removing bladder epithelium and connective tissue), which is potentially of more clinical relevance for future clinical diagnosis - if incorporated with cystoscopic optical coherence tomography.
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Impaired renal function and development in Belgrade rats
Veuthey, Tania; Hoffmann, Dana; Vaidya, Vishal S.
2013-01-01
Belgrade rats carry a disabling mutation in the iron transporter divalent metal transporter 1 (DMT1). Although DMT1 plays a major role in intestinal iron absorption, the transporter is also highly expressed in the kidney, where its function remains unknown. The goal of this study was to characterize renal physiology of Belgrade rats. Male Belgrade rats died prematurely with ∼50% survival at 20 wk of age. Necropsy results indicated marked glomerular nephritis and chronic end-stage renal disease. By 15 wk of age, Belgrade rats displayed altered renal morphology associated with sclerosis and fibrosis. Creatinine clearance was significantly lower compared with heterozygote littermates. Urinary biomarkers of kidney injury, including albumin, fibrinogen, and kidney injury molecule-1, were significantly elevated. Pilot morphological studies suggest that nephrogenesis is delayed in Belgrade rat pups due to their low iron status and fetal growth restriction. Such defects in renal development most likely underlie the compromised renal metabolism observed in adult b/b rats. Belgrade rat kidney nonheme iron levels were not different from controls but urinary iron and transferrin levels were higher. These results further implicate an important role for the transporter in kidney function not only in iron reabsorption but also in glomerular filtration of the serum protein. PMID:24226520
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Gopal, Venkatesh; Solomon, Joseph H.; Hartmann, Mitra J. Z.
2011-01-01
In all sensory modalities, the data acquired by the nervous system is shaped by the biomechanics, material properties, and the morphology of the peripheral sensory organs. The rat vibrissal (whisker) system is one of the premier models in neuroscience to study the relationship between physical embodiment of the sensor array and the neural circuits underlying perception. To date, however, the three-dimensional morphology of the vibrissal array has not been characterized. Quantifying array morphology is important because it directly constrains the mechanosensory inputs that will be generated during behavior. These inputs in turn shape all subsequent neural processing in the vibrissal-trigeminal system, from the trigeminal ganglion to primary somatosensory (“barrel”) cortex. Here we develop a set of equations for the morphology of the vibrissal array that accurately describes the location of every point on every whisker to within ±5% of the whisker length. Given only a whisker's identity (row and column location within the array), the equations establish the whisker's two-dimensional (2D) shape as well as three-dimensional (3D) position and orientation. The equations were developed via parameterization of 2D and 3D scans of six rat vibrissal arrays, and the parameters were specifically chosen to be consistent with those commonly measured in behavioral studies. The final morphological model was used to simulate the contact patterns that would be generated as a rat uses its whiskers to tactually explore objects with varying curvatures. The simulations demonstrate that altering the morphology of the array changes the relationship between the sensory signals acquired and the curvature of the object. The morphology of the vibrissal array thus directly constrains the nature of the neural computations that can be associated with extraction of a particular object feature. These results illustrate the key role that the physical embodiment of the sensor array plays in the sensing process. PMID:21490724
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Modeling Alzheimer’s disease in transgenic rats
2013-01-01
Alzheimer’s disease (AD) is the most common form of dementia. At the diagnostic stage, the AD brain is characterized by the accumulation of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss. Despite the large variety of therapeutic approaches, this condition remains incurable, since at the time of clinical diagnosis, the brain has already suffered irreversible and extensive damage. In recent years, it has become evident that AD starts decades prior to its clinical presentation. In this regard, transgenic animal models can shed much light on the mechanisms underlying this “pre-clinical” stage, enabling the identification and validation of new therapeutic targets. This paper summarizes the formidable efforts to create models mimicking the various aspects of AD pathology in the rat. Transgenic rat models offer distinctive advantages over mice. Rats are physiologically, genetically and morphologically closer to humans. More importantly, the rat has a well-characterized, rich behavioral display. Consequently, rat models of AD should allow a more sophisticated and accurate assessment of the impact of pathology and novel therapeutics on cognitive outcomes. PMID:24161192
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NASA Astrophysics Data System (ADS)
Bizheva, Kostadinka; Tan, Bingyao; Fisher, Carl J.; Mason, Erik; Lilge, Lothar D.
2017-02-01
Brain tumors are characterized with morphological changes at cellular level such as enlarged, non-spherical nuclei, microcalcifications, cysts, etc., and are highly vascularized. In this study, two research-grade optical coherence tomography (OCT) systems operating at 800 nm and 1060 nm with axial resolution of 0.95 µm and 3.5 µm in biological tissue respectively, were used to image in vivo and ex vivo the structure of brain tumours in rats. Female Fischer 344 rats were used for this study, which has received ethics clearance by the Animal Research Ethics Committees of the University of Waterloo and the University Health Network, Toronto. Brain tumours were induced by injection of rat brain cancer cell line (RG2 glioma) through a small craniotomy. Presence of brain tumours was verified by MRI imaging on day 7 post tumour cells injection. The in vivo OCT imaging session was conducted on day 14 of the study with the 1060 nm OCT system and both morphological OCT, Doppler OCT and OMAG images were acquired from the brain tumour and the surrounding healthy brain tissue. After completion of the imaging procedure, the brains were harvested, fixed in formalin and reimaged after 2 weeks with the 800 nm OCT system. The in vivo and ex vivo OCT morphological images were correlated with H and E histology. Results from this study demonstrate that UHR-OCT can distinguish between healthy and cancerous brain tissue based on differences in structural and vascular pattern.
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Qin, Shuang-Li; Deng, Jie; Lou, Di-Dong; Yu, Wen-Feng; Pei, Jinjing; Guan, Zhi-Zhong
2015-01-01
This study was designed to characterize changes in the expression of mitofusin-1 (Mfn1) and fission-1 (Fis1), as well as in mitochondrial morphology in the kidney of rats subjected to chronic fluorosis and to elucidate whether any mitochondrial injury observed is associated with increased oxidative stress. Sixty Sprague-Dawley (SD) rats were divided randomly into 3 groups of 20 each, i.e., the untreated control group (natural drinking water containing <0.5mg fluoride/L), the low-fluoride group (drinking water supplemented with 10mg fluoride/L, prepared with NaF) and the high-fluoride group (50mg fluoride/L), and treated for 6 months. Thereafter, renal expression of Mfn1 and Fis1 at both the protein and mRNA levels was determined by immunohistochemistry and real-time PCR, respectively. In addition, the malondiadehyde (MDA) was quantitated by the thiobarbituric acid procedure and the total antioxidative capability (T-AOC) by a colorimetric method. The morphology of renal mitochondria was observed under the transmission electron microscope. In the renal tissues of rats with chronic fluorosis, expression of both Mfn1 protein and mRNA was clearly reduced, whereas that of Fis1 was elevated. The level of MDA was increased and the T-AOC lowered. Swollen or fragmented mitochondria in renal cells were observed under the electronic microscope. These findings indicate that chronic fluorosis can lead to the abnormal mitochondrial dynamics and changed morphology in the rat kidney, which in mechanism might be induced by a high level of oxidative stress in the disease. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Rong, Shengzhong; Gao, Yanhui; Yang, Yanmei; Shao, Hanwen; Okekunle, Akinkunmi Paul; Lv, Chunpeng; Du, Yang; Sun, Hongna; Jiang, Yuting; Darko, Gottfried M; Sun, Dianjun
2018-05-03
Epidemiological studies indicated that chronic exposure to high water iodine is associated with primary hypothyroidism (PH) and subclinical hypothyroidism (SCH). However, the mechanism is not well understood. In this study, we explored whether chronic exposure to high water iodine from potassium iodate (KIO 3 ) can induce hypothyroidism in addition to determining if nitric oxide (NO) is involved in the pathogenesis. 96 female Wistar rats were divided into six groups: control, I 1000μg/L , I 3000μg/L , I 6000μg/L , N-nitro-L-arginine methylester (L-NAME) and L-NAME+I 6000μg/L . After 3 months, urine iodine concentration, thyroid hormone, NO and nitric oxide synthase (NOS) serum levels were determined. Additionally, thyroid expression of inducible nitric oxide synthase (iNOS) was also investigated. Thyroid morphology was observed under light microscopy and transmission electron microscope. SCH as indicated by elevated serum thyrotropin (TSH) was induced among rats exposed to 3000 μg/L I - , while rats treated with 6000 μg/L I - presented PH characterized by elevated TSH and lowered total thyroxine in serum. Moreover, serum NO, NOS and iNOS expression in the thyroid were significantly increased in I 3000μg/L and I 6000μg/L groups. Changes in thyroid function and morphology in the L-NAME+I 6000μg/L group were extenuated compared to I 6000μg/L group. These findings suggested that chronic exposure to high water iodine from KIO 3 likely induces hypothyroidism with significant morphology changes in female Wistar rats and NO appears to be involved in the pathogenesis. Copyright © 2018 Elsevier Ltd. All rights reserved.
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Masuyama, Taku; Miyajima, Katsuhiro; Ohshima, Hayato; Osawa, Masaru; Yokoi, Norihide; Oikawa, Toshihiro; Taniguchi, Kazuyuki
2005-12-01
A rat mutant, whitish chalk-like teeth (wct), with white, chalk-like abnormal incisors, was discovered and morphologically and genetically characterized. The mutant rats showed tooth enamel defects that were similar to those of human amelogenesis imperfecta. The wct mutation was found to disturb the morphological transition of ameloblasts from secretory to maturation stages and to induce cyst formation. This mutation also disturbs the transfer of iron into the enamel, resulting in the whitish chalk-like incisors. A genetic linkage study indicated that the wct locus maps to a specific interval of rat chromosome 14 between D14Got13 and D14Wox2. Interestingly, the human chromosomal region orthologous to wct, a 5.5-Mb interval in human chromosome 4q21, is a critical region for the locus of human amelogenesis imperfecta AIH2. These results strongly suggest that this wct mutant is a useful model for the identification of genes responsible for amelogenesis imperfecta and molecular mechanisms of tooth development.
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A pancreatic venular defect in the BB/Wor rat.
Majno, G.; Joris, I.; Handler, E. S.; Desemone, J.; Mordes, J. P.; Rossini, A. A.
1987-01-01
BB rats develop spontaneous autoimmune diabetes mellitus characterized morphologically by insulitis, an inflammatory lymphocytic infiltration of the islets of Langerhans. To investigate the role of the vascular endothelium of the pancreas in this destructive process, the authors injected diabetes-prone (DP) and diabetes-resistant (DR) BB/Wor rats as well as other nondiabetic strains of rats with Monastral blue B, a colloidal pigment that identifies leaky microvasculature. They found evidence of a venular defect limited to the pancreas that is specific to the BB rat. Light- and electron-microscopic evidence suggests that this defect is due to a population of trapped (marginating) intravascular monocytes, which may be activated by the colloidal pigment and release vasoactive mediators. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3618725
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NASA Astrophysics Data System (ADS)
Manikandan, Ramar; Manikandan, Beulaja; Raman, Thiagarajan; Arunagirinathan, Koodalingam; Prabhu, Narayanan Marimuthu; Jothi Basu, Muthuramalingam; Perumal, Muthulakshmi; Palanisamy, Subramanian; Munusamy, Arumugam
2015-03-01
The present study was aimed at biosynthesis of silver nanoparticles (AgNPs) using ethanolic extract of rose (Rosa indica) petals and testing their potential antibacterial activity using selective human pathogenic microbes, anticancer activity using human colon adenocarcinoma cancer cell line HCT 15 as well as anti-inflammatory activity using rat peritoneal macrophages in vitro. The biologically synthesized AgNPs were also characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The characterized AgNPs showed an effective antibacterial activity against Gram negative (Escherichia coli, Klebsiella pneumoniae) than Gram positive (Streptococcus mutans, Enterococcus faecalis) bacteria. MTT assay, analysis of nuclear morphology, mRNA expression of Bcl-2, Bax and protein expression of caspase 3 as well as 9, indicated potential anticancer activity. In addition, green synthesized AgNPs also attenuated cytotoxicity, nuclear morphology and free radical generation (O2- and NO) by rat peritoneal macrophages in vitro. The results of our study show the potential green synthesis of silver nanoparticles in mitigating their toxicity while retaining their antibacterial activities.
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Functional restoration of cirrhotic liver after partial hepatectomy in the rat.
Hashimoto, Masaji; Watanabe, Goro
2005-01-01
Although cirrhosis is the terminal stage of various liver diseases, thanks to recent advances one might eliminate some causes of liver damage. Liver has a potent regeneration capacity. It is important to evaluate the regenerating cirrhotic liver after partial hepatectomy, morphologically and functionally, in the long term. We evaluated the functional capacity of the rat liver rendered cirrhotic by orally administered thioacetamide, and examined the correlation between morphological and functional restoration after 2/3 hepatectomy in comparison with hepatectomized normal rats and sham-operated cirrhotic rats. Morphological restoration was evaluated by remnant liver weight, proliferating cell nuclear antigen labeling index, and fibrosis ratio. Functional restoration was evaluated by the indocyanine green disappearance rate and aminopyrine clearance. Cirrhotic rats were functionally deteriorated in comparison with the normal rats. Morphological restoration in cirrhotic rats was delayed in comparison with normal rats. Functional restoration after 2/3 hepatectomy was advanced in comparison with morphological restoration. In comparison with sham-operated cirrhotic rats, functional restoration of the cirrhotic liver was accelerated by partial hepatectomy. In cirrhotic rats, functional restoration of the liver after 2/3 hepatectomy was advanced in comparison with morphological restoration. Partial hepatectomy seemed to promote functional restoration of the cirrhotic liver.
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Rösch, Sarah; Aretzweiler, Christoph; Müller, Frank; Walter, Peter
2017-02-01
To characterize the course of retinal degeneration in the pink-eyed RCS rat in vivo and in vitro. Retinal function of RCS rats at the age of 2 to 100 weeks was determined in vivo using full-field electroretinography (ERG). Retinal morphology was evaluated in vivo using spectral domain Optical Coherence Tomography (sd-OCT) and Fluorescence angiography (FA) as well as postmortem using immunohistochemistry (IH). As a control, retinal function and morphology of non-dystrophic Wistar rats were analyzed. RCS rats showed an extinction of the ERG beginning with the age of 4 weeks. In the OCT, the outer part of the retina (OPR) could be clearly distinguished from the inner part of the retina (IPR) until the age of 8 weeks. However, at this age, it was impossible to determine from OCT images whether the OPR was formed by the outer nuclear layer (ONL) or by cellular debris built in the course of retinal degeneration. In contrast, immunohistochemistry always enabled to differentiate between ONL and debris (RCS 4 weeks of age: OPR mainly formed by ONL; RCS 8 weeks of age: OPR consisted mainly of cell debris, only 1-2 cell rows of photoreceptor somata were left). In general, data obtained in vivo were confirmed by data obtained post mortem. Apart from the problem to differentiate between debris and ONL at the age of 8 weeks in the RCS rat, ERG and OCT are useful methods to evaluate retinal function and structure in vivo and to complement immunohistochemical analysis of the degeneration process.
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Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Potu, Bhagath Kumar; Nayak, Satheesha; Bhat, P Gopalakrishna; Mailankot, Maneesh
2010-05-01
The interaction of mobile phone radio-frequency electromagnetic radiation (RF-EMR) with the brain is a serious concern of our society. We evaluated the effect of RF-EMR from mobile phones on passive avoidance behaviour and hippocampal morphology in rats. Healthy male albino Wistar rats were exposed to RF-EMR by giving 50 missed calls (within 1 hour) per day for 4 weeks, keeping a GSM (0.9 GHz/1.8 GHz) mobile phone in vibratory mode (no ring tone) in the cage. After the experimental period, passive avoidance behaviour and hippocampal morphology were studied. Passive avoidance behaviour was significantly affected in mobile phone RF-EMR-exposed rats demonstrated as shorter entrance latency to the dark compartment when compared to the control rats. Marked morphological changes were also observed in the CA(3) region of the hippocampus of the mobile phone-exposed rats in comparison to the control rats. Mobile phone RF-EMR exposure significantly altered the passive avoidance behaviour and hippocampal morphology in rats.
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Neuroendocrine mechanisms of development of experimental hyperandrogen-induced anovulation.
Reznikov, A G; Sinitsyn, P V; Tarasenko, L V; Polyakova, L I
2003-10-01
An experimental model of hyperandrogen-induced anovulatory infertility (s.c. implantation of Silastic capsules containing testosterone into adult female rats) was used to study morphological, hormonal, and biochemical measures characterizing the state of the hypothalamo-hypophyseal-ovarian system. Impairments in functional androgen metabolism in the hypothalamus were seen, with decreases in the Luliberin sensitivity of the hypophysis, changes in the structure of estral cycles, and morphological changes in the ovaries; these findings are evidence for neuroendocrine disturbances in the control of ovulation. Flutamide, an experimental antiandrogen, led to partial normalization of the hormonal, biochemical, and morphological characteristics, as well as to recovery of fertility in females with anovulatory infertility.
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NASA Technical Reports Server (NTRS)
Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily
1996-01-01
Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.
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Kelchner, J; McIntosh, J R; Boedecker, E; Guggenheim, S; McIntosh, R M
1976-09-15
Serial administration of mercuric chloride to rats was followed by development of antibodies to tubular basement membrane and renal tubular epithelial antigen (RTE) and glomerulonephritis characterized by granular deposits of hosts IgG, C3 and RTE along the glomerular capillary walls. The glomerular fixed antibody was directed against RTE. These studies suggest that tubular injury by mercury may lead to release of RTE and autosensitization and subsequent antibody production to this antigen result in formation of and glomerular deposition of circulating immunopathogenic complexes (RTE-anti-RTE) and glomerular morphologic alterations.
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Wu, Chuyan; Lin, Feng; Qiu, Shuwei; Jiang, Zhongli
2014-01-01
To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention.
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Manikandan, Ramar; Manikandan, Beulaja; Raman, Thiagarajan; Arunagirinathan, Koodalingam; Prabhu, Narayanan Marimuthu; Jothi Basu, Muthuramalingam; Perumal, Muthulakshmi; Palanisamy, Subramanian; Munusamy, Arumugam
2015-03-05
The present study was aimed at biosynthesis of silver nanoparticles (AgNPs) using ethanolic extract of rose (Rosa indica) petals and testing their potential antibacterial activity using selective human pathogenic microbes, anticancer activity using human colon adenocarcinoma cancer cell line HCT 15 as well as anti-inflammatory activity using rat peritoneal macrophages in vitro. The biologically synthesized AgNPs were also characterized by UV-visible spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), energy-dispersive X-ray spectroscopy (EDX) and X-ray diffraction (XRD). The characterized AgNPs showed an effective antibacterial activity against Gram negative (Escherichia coli, Klebsiella pneumoniae) than Gram positive (Streptococcus mutans, Enterococcus faecalis) bacteria. MTT assay, analysis of nuclear morphology, mRNA expression of Bcl-2, Bax and protein expression of caspase 3 as well as 9, indicated potential anticancer activity. In addition, green synthesized AgNPs also attenuated cytotoxicity, nuclear morphology and free radical generation (O2(-) and NO) by rat peritoneal macrophages in vitro. The results of our study show the potential green synthesis of silver nanoparticles in mitigating their toxicity while retaining their antibacterial activities. Copyright © 2014 Elsevier B.V. All rights reserved.
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Delghingaro-Augusto, Viviane; Madad, Leili; Chandra, Arin; Simeonovic, Charmaine J; Dahlstrom, Jane E; Nolan, Christopher J
2014-05-01
Prenatal and postnatal factors such as intrauterine growth restriction (IUGR) and high-fat (HF) diet contribute to type 2 diabetes. Our aim was to determine whether IUGR and HF diets interact in type 2 diabetes pathogenesis, with particular attention focused on pancreatic islet morphology including assessment for inflammation. A surgical model of IUGR (bilateral uterine artery ligation) in Sprague-Dawley rats with sham controls was used. Pups were fed either HF or chow diets after weaning. Serial measures of body weight and glucose tolerance were performed. At 25 weeks of age, rat pancreases were harvested for histologic assessment. The birth weight of IUGR pups was 13% lower than that of sham pups. HF diet caused excess weight gain, dyslipidemia, hyperinsulinemia, and mild glucose intolerance, however, this was not aggravated further by IUGR. Markedly abnormal islet morphology was evident in 0 of 6 sham-chow, 5 of 8 sham-HF, 4 of 8 IUGR-chow, and 8 of 9 IUGR-HF rats (chi-square, P = 0.007). Abnormal islets were characterized by larger size, irregular shape, inflammation with CD68-positive cells, marked fibrosis, and hemosiderosis. β-Cell mass was not altered by IUGR. In conclusion, HF and IUGR independently contribute to islet injury characterized by inflammation, hemosiderosis, and fibrosis. This suggests that both HF and IUGR can induce islet injury via converging pathways. The potential pathogenic or permissive role of iron in this process of islet inflammation warrants further investigation. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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Histological assessment of ovaries and uterus of rats subjected to nandrolone decanoate treatment.
Gerez, Juliana Rubira; Frei, Fernando; Camargo, Isabel Cristina Cherici
2005-07-01
This study aimed to analyze the effects of nandrolone decanoate on the ovaries and uterus of adult females rats. This drug was administered intraperitoneally, at one, two and three doses of 3 mg nandrolone decanoate/kg of body weight, respectively, in the first, second and third week of treatment. The females of the control group received a physiological solution. The rats treated with nandrolone decanoate showed estral acyclicity and there was destruction of follicular units and an absence of corpus luteum in the ovaries. In the uterus, the drug promoted morphological alterations, characterized by vacuolated epithelium and endometrial stroma fibrosis. Ovary, uterus and pituitary weights were not affected by the steroid treatment. Nandrolone decanoate affects the sexual cycle and promotes histological alterations in the ovaries and uterus of adult female rats.
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Ofusori, David A; Komolafe, Omobola A; Adewole, Olarinde S; Arayombo, Babatunde E; Margolis, Denise; Naicker, Thajasvarie
2016-01-01
To investigate the histological and immunohistochemical effects of aqueous leaf extract of Xylo- pia aethiopica on the pancreas in streptozotocin-induced diabetic rats, 30 adult Wistar rats were divided into three groups (n=10). Group A was the control (administered with equivalent vol- ume of citrate buffer), group B animals were made diabetic by a single intraperitoneal injection of streptozotocin dissolved in citrate buffer (65 mg/kg), group C animals were made diabetic as above and treated with 200mg/kg body weight of aqueous leave extract of Xylopia aethiop- ica for 25 days. Upon animal sacrifice, the pancreas were excised, fixed in 10% formol saline and processed for light microscopy and immunohistochemistry.. The results revealed destruc- tion of the islet cells in the untreated diabetic group as compared with the controls. The extract treated group was characterized by recovery/regenerative processes indicated by improvement in islet morphology. In untreated diabetic rats immunoreactive P-cells were sparse, at variance from the controls. The group treated with aqueous leaf extract of Xylopia aethiopica revealed more intense staining for insulin and significant (p<0.05) increase in the percentage of immuno- labelled surface area when compared with the untreated diabetic group, suggesting the ability of P-cells to secrete insulin in the extract treated rats. We conclude that the aqueous leaf extract of Xylopia aethiopica improves recovery process of P-cells in streptozotocin-induced diabetic rats and might become useful in the management of diabetes related complications.
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MAG-EPA reduces severity of DSS-induced colitis in rats.
Morin, Caroline; Blier, Pierre U; Fortin, Samuel
2016-05-15
Ulcerative colitis (UC) is a chronic disease characterized by diffuse inflammation of the intestinal mucosa of the large bowel. Omega-3 (ω3) fatty acid supplementation has been associated with a decreased production of inflammatory cytokines involved in UC pathogenesis. The aim of this study was to determine the preventive and therapeutic potential of eicosapentaenoic acid monoglyceride (MAG-EPA) in an in vivo rats model of UC induced by dextran sulfate sodium (DSS). DSS rats were untreated or treated per os with MAG-EPA. Morphological, histological, and biochemical analyses were performed following MAG-EPA administrations. Morphological and histological analyses revealed that MAG-EPA pretreatment (12 days pre-DSS) and treatment (6 days post-DSS) exhibited strong activity in reducing severity of disease in DSS rats. Following MAG-EPA administrations, tissue levels of the proinflammatory cytokines TNF-α, IL-1β, and IL-6 were markedly lower compared with rats treated only with DSS. MAG-EPA per os administration decrease neutrophil infiltration in colon tissues, as depicted by myelohyperoxidase activity. Results also revealed a reduced activation of NF-κB pathways correlated with a decreased expression of COX-2 in colon homogenates derived from MAG-EPA-pretreated and treated rats. Tension measurements performed on colon tissues revealed that contractile responses to methacholine and relaxing effect induced by sodium nitroprusside were largely increased following MAG-EPA treatment. The combined treatment of MAG-EPA and vitamin E displayed an antagonistic effect on anti-inflammatory properties of MAG-EPA in DSS rats. Copyright © 2016 the American Physiological Society.
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Inherited tertiary hypothyroidism in Sprague-Dawley rats.
Stoica, George; Lungu, Gina; Xie, Xueyi; Abbott, Louise C; Stoica, Heidi M; Jaques, John T
2007-05-07
Thyroid hormones (THs) are important in the development and maturation of the central nervous system (CNS). The significant actions of THs during CNS development occur at the time when TH levels are lower than those in the mother and the hypothalamic-thyroid (HPT) axis is not fully functional. In the developing rat nervous system, primarily the cerebellum, the first three postnatal weeks represent a period of significant sensitivity to thyroid hormones. This study presents a spontaneous, inherited recessive hypothyroidism in Sprague-Dawley rats with devastating functional consequences to the development of the CNS. The clinical signs develop around 14 day's postnatal (dpn) and are characterized by ataxia, spasticity, weight loss and hypercholesterolemia. The afflicted rats died at 30 days due to severe neurological deficits. The deterioration affects the entire CNS and is characterized by progressive neuronal morphological and biochemical changes, demyelination and astrogliosis. The cerebellum, brain stem, neocortex, hippocampus and adrenal gland medulla appear to be most affected. Thyroid Stimulating Hormone (TSH), T3 and T4 levels were significantly lower in hypothyroid rats than control. Immunohistochemistry and RT-PCR demonstrated a reduction of Thyrotropin Releasing Hormone (TRH) in the hypothalamus of hypothyroid rats. The weight of both thyroid and pituitary glands were significantly less in hypothyroid rats than the corresponding normal littermate controls. Transmission electron microscopy demonstrates consistent postsynaptic dendritic, synaptic and spine alterative changes in the brain of hypothyroid rats. These data suggest that we discovered a tertiary form of inherited hypothyroidism involving the hypothalamus.
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Analysis of gene expression in single live neurons.
Eberwine, J; Yeh, H; Miyashiro, K; Cao, Y; Nair, S; Finnell, R; Zettel, M; Coleman, P
1992-01-01
We present here a method for broadly characterizing single cells at the molecular level beyond the more common morphological and transmitter/receptor classifications. The RNA from defined single cells is amplified by microinjecting primer, nucleotides, and enzyme into acutely dissociated cells from a defined region of rat brain. Further processing yields amplified antisense RNA. A second round of amplification results in greater than 10(6)-fold amplification of the original starting material, which is adequate for analysis--e.g., use as a probe, making of cDNA libraries, etc. We demonstrate this method by constructing expression profiles of single live cells from rat hippocampus. This profiling suggests that cells that appear to be morphologically similar may show marked differences in patterns of expression. In addition, we characterize several mRNAs from a single cell, some of which were previously undescribed, perhaps due to "rarity" when averaged over many cell types. Electrophysiological analysis coupled with molecular biology within the same cell will facilitate a better understanding of how changes at the molecular level are manifested in functional properties. This approach should be applicable to a wide variety of studies, including development, mutant models, aging, and neurodegenerative disease. Images PMID:1557406
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Gevaert, Thomas; Hutchings, Graham; Everaerts, Wouter; Prenen, Hans; Roskams, Tania; Nilius, Bernd; De Ridder, Dirk
2014-04-01
The KIT receptor is considered as a reliable marker for a subpopulation of interstitial cells (IC), and by persistent neonatal inhibition of KIT we have investigated the role of this receptor in the development of IC-networks in bladder and we have observed the functional consequences of this inhibition. Newborn rat pups were treated daily with the KIT inhibitor imatinib mesylate (IM). After 7 days animals were sacrificed and bladder samples were dissected for morphological and functional studies. Morphological research consisted of immunohistochemistry with IC specific antigens (KIT and vimentin) and electron microscopy. The functional studies were based on isolated bladder strips in organ baths, in which spontaneous bladder contractility and the response to a non-subtype selective muscarinic agonist was evaluated. Suburothelial and intramuscular IC were found and characterized in neonatal rat bladder. IM-treatment induced a significant decrease in numbers of IC based on specific immunohistochemical markers, and electron microscopy revealed evidence of IC cell injury. These morphological alterations were observed on intramuscular IC only and not on IC in the suburothelium. Isolated muscle strips from IM-treated animals had a lower contractile frequency and an altered response to muscarinic agonists. The present study shows the presence of regional subpopulations of IC in neonatal rat bladder, provides evidence for a dependence on KIT of the development of intramuscular IC and supports the hypothesis that a poor development of networks of intramuscular IC might have repercussions on spontaneous and muscarinic-induced bladder contractility. © 2013 Wiley Periodicals, Inc.
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Maroun, Mouna; Ioannides, Pericles J.; Bergman, Krista L.; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L.
2013-01-01
Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. PMID:23714419
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Li, Yong-Guang; Dong, Zhi-Feng; Chen, Kan-Kai; He, Ya-Ping; Dai, Xiao-Yan; Li, Shuai; Li, Jing-Bo; Zhu, Wei; Wei, Meng
2017-11-04
Insulin is involved in the development of diabetic heart disease and is important in the activities of mitochondrial complex I. However, the effect of insulin on cardiac mitochondrial nicotinamide adenine dinucleotide dehydrogenase (ubiquinone) 1 subunit of retinoic-interferon-induced mortality 19 (GRIM-19) has not been characterized. The aim of this study was to investigate the effect of insulin on the mitochondrial GRIM-19 in the hearts of rats with streptozotocin (STZ)-induced type 1 diabetes. Protein changes of GRIM-19 were evaluated by western blotting and reverse transcription-quantitative polymerase chain reaction. Furthermore, the effects of insulin on mitochondrial complex I were detected in HeLa cells and H9C2 cardiac myocytes. During the development of diabetic heart disease, the cardiac function did not change within the 8 weeks, but the mitochondrial morphology was altered. The hearts from the rats with STZ-induced diabetes exhibited reduced expression of GRIM-19. Prior to the overt cardiac dilatation, mitochondrial alterations were already present. Following subcutaneous insulin injection, it was demonstrated that GRIM-19 protein was altered, as well as the mitochondrial morphology. The phosphoinositide 3-kinase inhibitor LY294002 had an effect on insulin signaling in H9C2 cardiacmyocytes, and decreased the level of GRIM-19 by half compared with that in the insulin group. The results indicate that insulin is essential for the control of cardiac mitochondrial morphology and the GRIM-19 expression partly via PI3K/AKT signaling pathways. Copyright © 2017. Published by Elsevier Inc.
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Le Bé, Jean-Vincent; Silberberg, Gilad; Wang, Yun; Markram, Henry
2007-09-01
Neocortical pyramidal cells (PCs) project to various cortical and subcortical targets. In layer V, the population of thick tufted PCs (TTCs) projects to subcortical targets such as the tectum, brainstem, and spinal cord. Another population of layer V PCs projects via the corpus callosum to the contralateral neocortical hemisphere mediating information transfer between the hemispheres. This subpopulation (corticocallosally projecting cells [CCPs]) has been previously described in terms of their morphological properties, but less is known about their electrophysiological properties, and their synaptic connectivity is unknown. We studied the morphological, electrophysiological, and synaptic properties of CCPs by retrograde labeling with fluorescent microbeads in P13-P16 Wistar rats. CCPs were characterized by shorter, untufted apical dendrites, which reached only up to layers II/III, confirming previous reports. Synaptic connections between CCPs were different from those observed between TTCs, both in probability of occurrence and dynamic properties. We found that the CCP network is about 4 times less interconnected than the TTC network and the probability of release is 24% smaller, resulting in a more linear synaptic transmission. The study shows that layer V pyramidal neurons projecting to different targets form subnetworks with specialized connectivity profiles, in addition to the specialized morphological and electrophysiological intrinsic properties.
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The Characterization of Obese Polycystic Ovary Syndrome Rat Model Suitable for Exercise Intervention
Qiu, Shuwei; Jiang, Zhongli
2014-01-01
Objective To develop a new polycystic ovary syndrome (PCOS) rat model suitable for exercise intervention. Method Thirty six rats were randomly divided into three experimental groups: PCOS rats with high-fat diet (PF, n = 24), PCOS rats with ordinary diet (PO, n = 6), and control rats with ordinary diet (CO, n = 6). Two kinds of PCOS rat model were made by adjustment diet structure and testosterone injection for 28 days. After a successful animal model, PF model rats were randomly assigned to three groups: exercise with a continuation of high-fat diet (PF-EF, n = 6), sedentary with a continuation of high-fat diet (PF-SF, n = 6), exercise with an ordinary diet (PF-EO, n = 6). Fasting blood glucose (FBG) and insulin (FINS), estrogen (E2), progesterone (P), and testosterone (T) in serum were determined by RIA, and ovarian morphology was evaluated by Image-Pro plus 6.0. Results Body weight, Lee index, FINS increased significantly in PF rat model. Serum levels of E2 and T were significantly higher in PF and PO than in CO. Ovary organ index and ovarian areas were significant lower in PF than in CO. After intervention for 2 weeks, the levels of 1 h postprandial blood glucose (PBG1), 2 h postprandial blood glucose (PBG2), FINS and the serum levels of T decreased significantly in PF-EF rats and PF-EO rats. The ratio of FBG/FINS was significant higher in PF-EO rats than in PF-SF rats. Ovarian morphology showed that the numbers of preantral follicles and atretic follicles decreased significantly, and the numbers of antral follicles and corpora lutea increased significantly in the rats of PF-EF and PF-EO. Conclusion By combination of high-fat diet and testosterone injection, the obese PCOS rat model is conformable with the lifestyle habits of fatty foods and insufficient exercise, and has metabolic and reproductive characteristics of human PCOS. This model can be applied to study exercise intervention. PMID:24905232
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Sakai, Y; Yamashina, S; Furudate, S I
2000-05-01
Previous studies on the rdw rat have suggested that its dwarfism is caused primarily by dysfunction of the thyroid gland. In this study, rat thyroid glands were analyzed endocrinologically and morphologically to clarify the primary cause of dwarfism in the rdw rat. The rdw rat showed lowered thyroid hormone (T4 and T3) levels but elevated TSH in serum. The rdw thyroid gland was almost proportional in size and it was not goiter in gross inspection. Our histological investigation produced three results that may lend important evidence in understanding the problem in the thyroid gland of rdw rats. First of all, secretory granules could not be detected in the follicular epithelial cells of the rdw. Secondly, thyroglobulin was found at very low levels in the follicular lumen by immunohistochemical analysis. In contrast, it could be detected in a substantial quantity inside the dilated rER and in the huge vacuoles that are formed by swelling of the rough endoplasmic reticulum (rER) at the basal side of the follicular epithelial cells. Additionally, the nucleus of the follicular epithelial cells was pressed to the luminal side by the enlarged rER. These morphological changes would indicate that the transport of thyroglobulin is stopped at or before the formation of the secretory granules and thyroglobulin is not secreted into the follicular lumen. The rdw characterization strongly supports that rdw dwarfism is induced by hypothyroidism due to some defect(s) in the thyroid gland. Copyright 2000 Wiley-Liss, Inc.
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NASA Technical Reports Server (NTRS)
Bromage, Timothy G.; Doty, Stephen B.; Smolyar, Igor; Holton, Emily
1997-01-01
Our stated primary objective is to quantify the growth rate variability of rat lamellar bone exposed to micro- (near zero G: e.g., Cosmos 1887 & 2044; SLS-1 & SLS-2) and macrogravity (2G). The primary significance of the proposed work is that an elegant method will be established that unequivocally characterizes the morphological consequences of gravitational factors on developing bone. The integrity of this objective depends upon our successful preparation of thin sections suitable for imaging individual bone lamellae, and our imaging and quantitation of growth rate variability in populations of lamellae from individual bone samples.
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Fukuzato, Yoko; Matsuura, Tetsuro; Ozaki, Kiyokazu; Matsuura, Masahiro; Sano, Tomoya; Nakahara, Yutaka; Kodama, Yasushi; Nakagawa, Akihito; Okamura, Sumie; Suido, Hirohisa; Torii, Kayo; Makino, Taketoshi; Narama, Isao
2009-10-01
In our previous studies, WBN/KobSlc was characterized as a rat strain in which only males began to develop pancreatitis, and then presented with diabetic symptoms. In the course of studying their pancreatic inflammation, we detected molar caries in prediabetic males feeding on a standard diet (CRF-1) widely used for experimental animals. The purpose of this study is to confirm whether the WBN/KobSlc strain is caries-susceptible to the diet reported to be non-cariogenic, and to examine the effect of a prediabetic condition on their dental caries. For a morphological study, 25 male WBN/KobSlc rats aged 3.2-7.8 months and 24 females of the same strain aged 3.3-6.6 months were used, along with 10 males and 10 females of 8.2-month-old F344 rats. Marked dental caries were detected in the mandibular molars of male and female WBN/KobSlc rats regardless of pancreatitis, although no similar changes were observed in any teeth of the F344 strain fed the same diet. Soft X-ray examination revealed that the caries began in the crown and progressed horizontally and vertically, and that a severe radiolucent lesion extensively expanded to the entire crown, corresponding to a macroscopically deleted molar. The caries had gradually developed mainly in the second mandibular molar from more than 3.5 months of age, while none were seen in any rats before that time. The WBN/KobSlc rats were caries-susceptible even to the standard laboratory diet, and pancreatitis was not directly associated with the onset of dental caries in this strain.
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Bracher, Andreas; Doran, Stephen F.; Squadrito, Giuseppe L.; Fernandez, Solana; Postlethwait, Edward M.; Bowen, Larry; Matalon, Sadis
2012-01-01
We assessed the safety and efficacy of combined intravenous and aerosolized antioxidant administration to attenuate chlorine gas–induced airway alterations when administered after exposure. Adult male Sprague-Dawley rats were exposed to air or 400 parts per million (ppm) chlorine (a concentration likely to be encountered in the vicinity of industrial accidents) in environmental chambers for 30 minutes, and returned to room air, and they then received a single intravenous injection of ascorbic acid and deferoxamine or saline. At 1 hour and 15 hours after chlorine exposure, the rats were treated with aerosolized ascorbate and deferoxamine or vehicle. Lung antioxidant profiles, plasma ascorbate concentrations, airway morphology, and airway reactivity were evaluated at 24 hours and 7 days after chlorine exposure. At 24 hours after exposure, chlorine-exposed rats had significantly lower pulmonary ascorbate and reduced glutathione concentrations. Treatment with antioxidants restored depleted ascorbate in lungs and plasma. At 7 days after exposure, in chlorine-exposed, vehicle-treated rats, the thickness of the proximal airways was 60% greater than in control rats, with twice the amount of mucosubstances. Airway resistance in response to methacholine challenge was also significantly elevated. Combined treatment with intravenous and aerosolized antioxidants restored airway morphology, the amount of airway mucosubstances, and airway reactivity to control levels by 7 days after chlorine exposure. Our results demonstrate for the first time, to the best of our knowledge, that severe injury to major airways in rats exposed to chlorine, as characterized by epithelial hyperplasia, mucus accumulation, and airway hyperreactivity, can be reversed in a safe and efficacious manner by the post-exposure administration of ascorbate and deferoxamine. PMID:22162906
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Butkevich, Irina P; Khozhai, Ludmila I; Mikhailenko, Victor A; Otellin, Vladimir A
2003-11-13
Serotonin (5-HT) contributes to the prenatal development of the central nervous system, acting as a morphogen in the young embryo and later as a neurotransmitter. This biologically active agent influences both morphological and biochemical differentiation of raphe neurons, which give rise to the descending serotonergic paths that regulate the processing of acutely evoked nociceptive inputs. The involvement of 5-HT in the prenatal development of tonic nociceptive system has not been studied. In the present study we evaluated the effects of a single injection (400 mg/kg, 2 ml, i.p.) of the 5-HT synthesis inhibitor, para-chlorophenylalanine (pCPA), given to pregnant rats during the critical period fetal serotonin development. The functional integrity of the tonic nociceptive response was investigated in 25 day old rats using the classic formalin test. Morphological analysis of brain structures involved in formalin-induced pain and 5-HT levels in the heads of 12-day embryos were also evaluated. Embryonic levels of 5-HT were significantly lowered by the treatment. The juvenile rats from pCPA-treated females showed altered brain morphology and cell differentiation in the developing cortex, hippocampus, raphe nuclei, and substantia nigra. In the formalin test, there were significant decreases in the intensity and duration of the second phase of the formalin-induced response, characterizing persistent, tonic pain. The extent of impairments in the brain structures correlated positively with the level of decrease in the behavioral responses. The data demonstrate the involvement of 5-HT in the prenatal development of the tonic nociceptive system. The decreased tonic component of the behavioral response can be explained by lower activity of the descending excitatory serotonergic system originating in the raphe nuclei, resulting in decreased tonic pain processing organized at the level of the dorsal horn of the spinal cord.
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Romano-López, Antonio; Méndez-Díaz, Mónica; García, Fabio García; Regalado-Santiago, Citlalli; Ruiz-Contreras, Alejandra E; Prospéro-García, Oscar
2016-08-01
A considerable amount experimental studies have shown that maternal separation (MS) is associated with adult offspring abnormal behavior and cognition disorder. Accordingly, this experimental procedure has been proposed as a predictor for alcohol and drug dependence based on the neurodevelopmental soon after birth. Endocannabinoid system (eCBs) has been implicated in reward processes, including drug abuse and dependence. MS and associated stress causes changes in the eCBs that seem to facilitate alcohol consumption. In this study, we seek to evaluate potential morphological changes in neurons of the frontal cortex (FCx) and nucleus accumbens (NAcc), in the expression of receptors and enzymes of the endocannabinoid and dopamine systems and in second messengers, such as Akt, in adult rats subjected to MS and early stress (MS + ES; 2 × 180 min daily) vs. nonseparated rats (NMS). Results showed that MS + ES induces higher D2R expression and lower D3R, FAAH, and MAGL expression compared with NMS rats. Alterations in total dendritic length were also detected and were characterized by increases in the NAcc while there were decreases in the FCx. We believe MS + ES-induced changes in the dopaminergic and endocannabinergic systems and in the neuronal microstructure might be contributing to alcohol seeking behavior and, potential vulnerability to other drugs in rats. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 819-831, 2016. © 2015 Wiley Periodicals, Inc.
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Murărescu, Elena Doina; Eloae-Zugun, Fl; Mihailovici, Maria Sultana
2008-01-01
According to the GOLD 2006 definition, COPD is a preventable and treatable pathological situation characterized by the partially reversible airflow limitation determined by a variable proportion mixture of small airways disease (obliterative bronchiolitis) and parenchyma destruction (emphysema). A major impediment in the study of the COPD is represented by the fact the fundamental morphological changes that determine the major pulmonary dysfunction take place in the small, peripheral, airways, at the bronchiolo-alveolar attachments. That is why the experimental model of COPD developed progressively to the transgenic mouse. There are many experimental studies on the animal models that have obtained emphysema rapidly through intratraheal instillation of elastasis or bronchitis/bronchiolitis through intratraheal instillation of particles. It is accepted that the unnatural character of aggression, that does not permit the natural evolution of the inflammatory phenomenon, limits these models and tissue remodeling that take place in COPD patients. It is well known that cigarette smoking is a major cause of COPD. There have been reported some cases of COPD in never smoking patients exposed to air pollutants. We aimed to create an experimental model of COPD in rat through exposure to smoke resulted from solid combustibles burn for the same period and in the same conditions of cigarette smoke exposure and to compare the pulmonary morphological changes. Thirty Wistar rats were divided into three groups (n = 10): (1) the control group (C), (2) the cigarette smoke group (CS), and (3) the solid combustible smoke group (SCS). Apart from the control group, these were treated with solid combustibles smoke (SCS group) or cigarette smoke (CS group) for six months. Morphological and morphometry studies have been assessed. We have established a rat COPD model based on natural cigarette smoke exposure versus solid combustible burn resulted smoke, usable for a further approach in human non-smoker COPD investigation. Out procedures resulted in clear pulmonary morphological lesions that are characteristic for COPD. The achieved data support the idea that solid combustible burn resulted smoke determines emphysematous parenchyma lesions that are similar, but with an attenuated morphological appearance when comparing to the cigarette smoke exposure.
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Effects of electromagnetic radiation on spatial memory and synapses in rat hippocampal CA1☆
Li, Yuhong; Shi, Changhua; Lu, Guobing; Xu, Qian; Liu, Shaochen
2012-01-01
In this study, we investigated the effects of mobile phone radiation on spatial learning, reference memory, and morphology in related brain regions. After the near-field radiation (0.52–1.08 W/kg) was delivered to 8-week-old Wistar rats 2 hours per day for 1 month, behavioral changes were examined using the Morris water maze. Compared with the sham-irradiated rats, the irradiated rats exhibited impaired performance. Morphological changes were investigated by examining synaptic ultrastructural changes in the hippocampus. Using the physical dissector technique, the number of pyramidal neurons, the synaptic profiles, and the length of postsynaptic densities in the CA1 region were quantified stereologically. The morphological changes included mitochondrial degenerations, fewer synapses, and shorter postsynaptic densities in the radiated rats. These findings indicate that mobile phone radiation can significantly impair spatial learning and reference memory and induce morphological changes in the hippocampal CA1 region. PMID:25709623
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Liao, Zhi-Yin; Chen, Jin-Liang; Xiao, Ming-Han; Sun, Yue; Zhao, Yu-Xing; Pu, Die; Lv, An-Kang; Wang, Mei-Li; Zhou, Jing; Zhu, Shi-Yu; Zhao, Ke-Xiang; Xiao, Qian
2017-11-01
Sarcopenia is an age-related syndrome characterized by progressive loss of muscle mass and function. Exercise is an important strategy to prolong life and increase muscle mass, and resveratrol has been shown a variety beneficial effects on skeletal muscle. In the present study, we investigated the potential efficacy of using short-term exercise (six weeks), resveratrol (150mg/kg/day), or combined exercise+resveratrol (150mg/kg/day) on gastrocnemius muscle mass, grip strength, cross-sectional area and microscopic morphology in aged rats, and explored the potential mechanism at the apoptosis level. Six months old SD rats were used as young control group and 24months old SD rats were adopted as aged group. After six weeks intervention, the data provide evidence that exercise, resveratrol or their combination significantly increase the relative grip strength and muscle mass in aged rats (P<0.05). Electron microscopy discovered a significant increase in sarcomere length, I-band and H-zone in aged rats (P<0.05), and exercise, resveratrol or their combination significantly reduced the increasement (P<0.05). Moreover, light microscopy revealed a significant increase on Feret's diameter and cross-sectional area (CSA) in aged rats (P<0.05), but exercise and resveratrol did not show significant effects on them (P>0.05). Furthermore, exercise, resveratrol or their combination significantly increased the expression of p-AMPK and SIRT1, decreased the expression of acetyl P53 and Bax/Bcl-2 ratio in aged rats (P<0.05). These findings show that aged rats show significant changes in gastrocnemius muscle morphology and ultrastructure, and the protective effects of exercise, resveratrol and their combination are probably associated with anti-apoptotic signaling pathways through activation of AMPK/Sirt1. Copyright © 2017 Elsevier Inc. All rights reserved.
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de Araujo, Daniele Ribeiro; Padula, Cristina; Cereda, Cíntia Maria Saia; Tófoli, Giovana Radomille; Brito, Rui Barbosa; de Paula, Eneida; Nicoli, Sara; Santi, Patrizia
2010-08-01
The aim of this work was to develop anesthetic bioadhesive films containing benzocaine and study their in vitro skin permeation and in vivo performance, in comparison with commercial formulations. Films containing 3% and 5% w/w of benzocaine were prepared and characterized by weight, drug content, thickness and morphology. In vitro permeation assays were performed in vertical diffusion cells using full-thickness pig ear skin as barrier. Intensity and duration of analgesia were evaluated in rats by tail-flick test, and skin histological analysis was carried out. Tail-flick test showed that the duration of benzocaine-induced analgesia was significantly prolonged with the films compared to commercial creams, in agreement with the higher in vitro permeation. Histological analysis of the rat tail skin did not reveal morphological tissue changes nor cell infiltration signs after application of the commercial creams or films. Results from our study indicate that the films developed in this work can be considered as innovative dermal/transdermal therapeutic systems for benzocaine local delivery.
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Assessing heterogeneity of peroxisomes: isolation of two subpopulations from rat liver.
Islinger, Markus; Abdolzade-Bavil, Afsaneh; Liebler, Sven; Weber, Gerhardt; Völkl, Alfred
2012-01-01
Peroxisomes exhibit a heterogeneous morphological appearance in rat liver tissue. In this respect, the isolation and subsequent biochemical characterization of peroxisome species from different subcellular prefractions should help to solve the question of whether peroxisomes indeed diverge into functionally specialized subgroups in one tissue. As a means to address this question, we provide a detailed separation protocol for the isolation of peroxisomes from both the light (LM-Po) and the heavy (HM-Po) mitochondrial prefraction for their subsequent comparative analysis. Both isolation strategies rely on centrifugation in individually adapted Optiprep gradients. In case of the heavy mitochondrial fraction, free flow electrophoresis is appended as an additional separation step to yield peroxisomes of sufficient purity. In view of their morphology, peroxisomes isolated from both fractions are surrounded by a continuous single membrane and contain a gray-opaque inner matrix. However, beyond this overall similar appearance, HM-Po exhibit a smaller average diameter, float at lower density, and show a more negative average membrane charge when compared to LM-Po.
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Maroun, Mouna; Ioannides, Pericles J; Bergman, Krista L; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L
2013-08-01
Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.
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Schuelert, N; Gorodetskaya, N; Just, S; Doods, H; Corradini, L
2015-04-16
Diabetic polyneuropathy (DPN) is a devastating complication of diabetes. The underlying pathogenesis of DPN is still elusive and an effective treatment devoid of side effects presents a challenge. There is evidence that in type-1 and -2 diabetes, metabolic and morphological changes lead to peripheral nerve damage and altered central nociceptive transmission, which may contribute to neuropathic pain symptoms. We characterized the electrophysiological response properties of spinal wide dynamic range (WDR) neurons in three diabetic models. The streptozotocin (STZ) model was used as a drug-induced model of type-1 diabetes, and the BioBreeding/Worcester (BB/Wor) and Zucker diabetic fatty (ZDF) rat models were used for genetic DPN models. Data were compared to the respective control group (BB/Wor diabetic-resistant, Zucker lean (ZL) and saline-injected Wistar rat). Response properties of WDR neurons to mechanical stimulation and spontaneous activity were assessed. We found abnormal response properties of spinal WDR neurons in all diabetic rats but not controls. Profound differences between models were observed. In BB/Wor diabetic rats evoked responses were increased, while in ZDF rats spontaneous activity was increased and in STZ rats mainly after discharges were increased. The abnormal response properties of neurons might indicate differential pathological, diabetes-induced, changes in spinal neuronal transmission. This study shows for the first time that specific electrophysiological response properties are characteristic for certain models of DPN and that these might reflect the diverse and complex symptomatology of DPN in the clinic. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
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Boudreau, Mary D.; Imam, Mohammed S.; Paredes, Angel M.; Bryant, Matthew S.; Cunningham, Candice K.; Felton, Robert P.; Jones, Margie Y.; Davis, Kelly J.; Olson, Greg R.
2016-01-01
There are concerns within the regulatory and research communities regarding the health impact associated with consumer exposure to silver nanoparticles (AgNPs). This study evaluated particulate and ionic forms of silver and particle size for differences in silver accumulation, distribution, morphology, and toxicity when administered daily by oral gavage to Sprague Dawley rats for 13 weeks. Test materials and dose formulations were characterized by transmission electron microscopy (TEM), dynamic light scattering, and inductively coupled mass spectrometry (ICP-MS). Seven-week-old rats (10 rats per sex per group) were randomly assigned to treatments: AgNP (10, 75, and 110 nm) at 9, 18, and 36 mg/kg body weight (bw); silver acetate (AgOAc) at 100, 200, and 400 mg/kg bw; and controls (2 mM sodium citrate (CIT) or water). At termination, complete necropsies were conducted, histopathology, hematology, serum chemistry, micronuclei, and reproductive system analyses were performed, and silver accumulations and distributions were determined. Rats exposed to AgNP did not show significant changes in body weights or intakes of feed and water relative to controls, and blood, reproductive system, and genetic tests were similar to controls. Differences in the distributional pattern and morphology of silver deposits were observed by TEM: AgNP appeared predominantly within cells, while AgOAc had an affinity for extracellular membranes. Significant dose-dependent and AgNP size-dependent accumulations were detected in tissues by ICP-MS. In addition, sex differences in silver accumulations were noted for a number of tissues and organs, with accumulations being significantly higher in female rats, especially in the kidney, liver, jejunum, and colon. PMID:26732888
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Reproductive toxicity assessment of chronic dietary exposure to soy isoflavones in male rats.
Faqi, Ali S; Johnson, William D; Morrissey, Robert L; McCormick, David L
2004-06-01
Epidemiologic and experimental data suggest that consumption of diets that are rich in isoflavones may decrease cancer risk in the breast, prostate, and other tissues. Isoflavones such as genistein and daidzein are structurally similar to endogenous estrogens, and demonstrate both estrogenic and weak anti-estrogenic activities; these activities may underlie the impaired fertility and reproductive tract disorders reported in animals exposed to high doses of isoflavones. To identify possible effects of isoflavones on male fertility, we evaluated reproductive parameters in Wistar-Unilever rats receiving dietary exposure to PTI G-2535, a characterized mixture of soy-derived isoflavones containing 45% genistein, 23% daidzein, and 4% glycitein. Beginning at 10 weeks of age, rats received chronic dietary exposure to the soy isoflavone mixture (200 or 2000 mg/kg diet) for a minimum of 12 months. Controls received unsupplemented chow diet only for the same period. Dietary exposure to isoflavones induced no gross toxicity or alterations in body weight gain. Absolute and relative weights of the testis and epididymis in groups receiving high or low doses of isoflavones were comparable to those of controls, and histopathologic evaluations demonstrated that testicular morphology was similar in all study groups. Isoflavone exposure had no significant effects on spermatid count, sperm production, or sperm morphology in any group. These data suggest that the reproductive system of adult male rats is relatively insensitive to isoflavone toxicity at dose levels that demonstrate significant activity in cancer chemoprevention, and that male reproductive function is unlikely to be affected by long-term administration of isoflavones for cancer prevention or other purposes. The results of this study conducted in adult male rats differ from the significant alterations in reproductive parameters that have been reported in female rats receiving prenatal or juvenile exposure to isoflavones.
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Environmental enrichment alters dentate granule cell morphology in oldest-old rat.
Darmopil, Sanja; Petanjek, Zdravko; Mohammed, Abdul H; Bogdanović, Nenad
2009-08-01
The hippocampus of aged rats shows marked age-related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague-Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n = 7) or enriched (n = 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi-Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age-related dendritic regression and synaptic loss, thus preserving memory functions.
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Venâncio, Daniel P.; Andersen, Monica L.; Vilamaior, Patricia S. L.; Santos, Fernanda C.; Zager, Adriano; Tufik, Sérgio; Taboga, Sebastião R.; De Mello, Marco T.
2012-01-01
We investigated the effect of 96 h paradoxical sleep deprivation (PSD) and 21-day sleep restriction (SR) on prostate morphology using stereological assays in male rats. After euthanasia, the rat ventral prostate was removed, weighed, and prepared for conventional light microscopy. Microscopic analysis of the prostate reveals that morphology of this gland was altered after 96 h of PSD and 21 days of SR, with the most important alterations occurring in the epithelium and stroma in the course of both procedures compared with the control group. Both 96 h PSD and 21-day SR rats showed lower serum testosterone and higher corticosterone levels than control rats. The significance of our result referring to the sleep deprivation was responsible for deep morphological alterations in ventral prostate tissue, like to castration microscopic modifications. This result is due to the marked alterations in hormonal status caused by PSD and SR. PMID:22927719
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Comparison of effects of albendazole sulfoxide on in vitro produced bovine embryos and rat embryos.
Piscopo, S E; Smoak, I W
1997-09-01
To evaluate and compare effects of albendazole sulfoxide (ABZSO) on rat embryos and bovine embryos produced in vitro. In vitro produced bovine embryos. Rat embryos recovered from naturally bred Sprague-Dawley rats. 4- and 8-cell bovine embryos were randomly allocated to ABZSO or vehicle control groups. After 48 hours, embryos were evaluated for cell number and blastomere morphology. Rat embryos of similar stages, flushed from the uterine tube on gestational day 2-5, were randomly allocated to treatment or control groups. After 24 hours, embryos were evaluated as described previously. 44% of control bovine embryos divided in culture (> or = 16-cell stage). Fifteen percent of the controls had morphologic abnormalities, including disparity in blastomere size and cytoplasmic vacuoles and stippling. Treated (> or = 1 microgram of ABZSO/ml) bovine embryos differed (P < 0.0001) from controls, with 4% development and 93% abnormal morphology. Forty-five percent of control rat embryos divided in culture. Treated (> or = 500 ng of ABZSO/ml) rat embryos differed (P < 0.0003) from controls with regard to ability to divide. There were no consistent morphologic abnormalities in rat embryos. In vitro produced bovine embryos were susceptible to ABZSO at a concentration > or = 1 microgram/ ml, resulting in decreased ability to divide and presence of gross morphologic abnormalities. Rat embryos produced in vivo and exposed in vitro to ABZSO at a concentration > or = 500 ng/ml had decreased ability to divide in culture. Despite severe effects of ABZSO (> or = 1 microgram/ml) on bovine embryo development in vitro, it is beyond the scope of this study to speculate whether a therapeutic dosage of albendazole (10 mg/kg of body weight) would result in necessary concentrations of ABZSO in vivo to disrupt embryogenesis.
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Wang, Haipeng; Yu, Xiaojun; Xu, Guohui; Xu, Guangtao; Gao, Guishan; Xu, Xiaohu
2011-01-01
Traumatic subarachnoid hemorrhage (TSAH) related to alcohol abuse is a notable risk factor. Here, we investigated the vascular morphology and biomechanics of TSAH in rat models of acute alcoholic intoxication and chronic alcoholism rats to explore the possible mechanisms of TSAH. Sixty male Sprague-Dawley rats were divided into acute alcoholic intoxication and chronic alcoholism groups. Edible spirituous liquor (56% vol/vol) was intragastrically given (15 mL/kg) once to the rats in the acute group, and given twice daily (8 mL/kg for 2 weeks and 12 mL/kg for another 2 weeks) to rats in the chronic group. A self-made instrument was used to inflict head injury. Whole brain, arterial blood, and thoracic aorta of rats were sampled for morphologic and biomechanical examination. Compared with the acute alcoholic rats, the chronic alcoholic rats showed significant morphologic and biomechanical changes: (1) decreased body weight (p<0.05), (2) higher morbidity and mortality from TSAH (p<0.01), (3) greater mean thickness of vascular wall of subarachnoid small arteries and each layer thickness of thoracic aorta (p<0.05), (4) decreased failure load and corresponding extensibility (60 kPa and limit load) of thoracic aorta, and (5) increased elastic modulus (30 kPa, range in physiologic stress) (p<0.05). Chronic alcoholism can induce the morphologic and biomechanical changes in cerebral vessels and thoracic aorta. The synergistic effect of alcohol abuse and minor blow may be one of the mechanisms of TSAH. High blood pressure from long-term alcohol abuse is also a notable factor.
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Bhaskaran, Manoj; Cornwell, Paul D; Sorden, Steven D; Elwell, Michael R; Russell, Natalie R; Pritt, Michael L; Vahle, John L
2018-01-01
Inhibitors of Bruton's tyrosine kinase (BTK) are under development as potential therapies for various autoimmune diseases. In repeat-dose toxicity studies, small-molecule BTK inhibitors (BTKi) have been reported to cause a constellation of histologic effects at the pancreatic endocrine-exocrine interface in male rats; however, similar findings were not reported in other species. Since the BTKi-induced pancreatic effect is morphologically similar to well-documented spontaneous changes (predominantly characterized by insular/peri-insular hemorrhage, pigment deposition, chronic inflammation, and fibrosis) that are known to vary by rat strain, we investigated potential strain-dependent differences in the pancreatic effects of a small-molecule BTKi, LY3337641. Following 13 weeks of LY3337641 treatment, Crl:CD(SD) rats were most sensitive, Crl:WI(Han) rats were of intermediate sensitivity, and Hsd:SD rats were least sensitive. These strain differences appear to be related to differences in rate of weight gain across strains and sexes; however, a definitive mechanism was not determined. This study demonstrated that BTKi-induced pancreatic effects were highly dependent on rat strain and correlated with differences in the incidence and severity of the spontaneous background change. When considered with the lack of pancreas effects in nonrat species, these changes in rats are unlikely predictive of similar changes in humans administered a BTK inhibitor.
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[Morphological study of the adrenals of rats exposed on the Kosmos-690 satellite].
Savina, E A; Alekseev, E I
1979-01-01
Adrenals of 12 rats flown aboard the biosatellite Cosmos-690 and 30 rats used in the ground-based experiments Control-1 and Control-2 were studied morphologically. The animals were sacrificed on the 2nd and 27th days after completion of the experiments (i. e., on the 12 and 37th days after irradiation at a total dose of 800 rad). A comparative study of morphological changes in the adrenals of flight and control rats did not show any distinct differences. It is therefore concluded that space flight factors did not produce a significant effect on the adrenal response to irradiation at a dose of 800 rad.
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Mohamad Zaid, Siti Sarah; Kassim, Normadiah M.; Othman, Shatrah
2015-01-01
Bisphenol A (BPA) is an endocrine disrupting chemical (EDC) that can disrupt the normal functions of the reproductive system. The objective of the study is to investigate the potential protective effects of Tualang honey against BPA-induced uterine toxicity in pubertal rats. The rats were administered with BPA by oral gavage over a period of six weeks. Uterine toxicity in BPA-exposed rats was determined by the degree of the morphological abnormalities, increased lipid peroxidation, and dysregulated expression and distribution of ERα, ERβ, and C3 as compared to the control rats. Concurrent treatment of rats with BPA and Tualang honey significantly improved the uterine morphological abnormalities, reduced lipid peroxidation, and normalized ERα, ERβ, and C3 expressions and distribution. There were no abnormal changes observed in rats treated with Tualang honey alone, comparable with the control rats. In conclusion, Tualang honey has potential roles in protecting the uterus from BPA-induced toxicity, possibly accounted for by its phytochemical properties. PMID:26788107
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Lima, Cássia Borges; Soares, Geórgia de Sousa Ferreira; Vitor, Suênia Marcele; Castellano, Bernardo; Andrade da Costa, Belmira Lara da Silveira; Guedes, Rubem Carlos Araújo
2013-09-17
Monosodium glutamate (MSG) is a neuroexcitatory amino acid used in human food to enhance flavor. MSG can affect the morphological and electrophysiological organization of the brain. This effect is more severe during brain development. Here, we investigated the electrophysiological and morphological effects of MSG in the developing rat brain by characterizing changes in the excitability-related phenomenon of cortical spreading depression (CSD) and microglial reaction. From postnatal days 1-14, Wistar rat pups received 2 or 4 g/kg MSG (groups MSG-2 and MSG-4, respectively; n=9 in each group), saline (n=10) or no treatment (naïve group; n=5) every other day. At 45-60 days, CSD was recorded on two cortical points for 4h. The CSD parameters velocity, and amplitude and duration of the negative potential change were calculated. Fixative-perfused brain sections were immunolabeled with anti-IBA-1 antibodies to identify and quantify cortical microglia. MSG-4 rats presented significantly higher velocities (4.59 ± 0.34 mm/min) than the controls (saline, 3.84 ± 0.20mm/min; naïve, 3.71 ± 0.8mm/min) and MSG-2 group (3.75 ± 0.10mm/min). The amplitude (8.8 ± 2.2 to 11.2 ± 1.9 mV) and duration (58.2 ± 7.1 to 73.6 ± 6.0s) of the negative slow potential shift was similar in all groups. MSG-treatment dose-dependently increased the microglial immunolabeling. The results demonstrate a novel, dose-dependent action of MSG in the developing brain, characterized by acceleration of CSD and significant microglial reaction in the cerebral cortex. The CSD effect indicates that MSG can influence cortical excitability, during brain development, as evaluated by CSD acceleration. Data suggest caution when consuming MSG, especially in developing organisms. © 2013.
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Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Bae, Chun Sik; Park, Hae Ran; Jung, Uhee; Jo, Sung Kee
2009-12-01
Estradiol valerate (EV)-induced polycystic ovaries (PCOs) in rats cause the anovulation and cystic ovarian morphology. We investigated whether treatment with HemoHIM influences the ovarian morphology and the expression of nerve growth factor (NGF) in an EV-induced PCO rat model. PCO was induced by a single intramuscular injection of EV (4 mg, dissolved in sesame oil) in adult cycling rats. HemoHIM was either administered orally (100 mg/kg of body weight/day) for 35 consecutive days or injected intraperitoneally (50 mg/kg of body weight) every other day after EV injection. Ovarian morphology was almost normalized, and NGF was normalized in the PCO + HemoHIM group. HemoHIM lowered the high numbers of antral follicles and increased the number of corpora lutea in PCOs. The results are consistent with a beneficial effect of HemoHIM in the prevention and treatment of PCO syndrome.
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Intrinsic physiological properties of rat retinal ganglion cells with a comparative analysis.
Wong, Raymond C S; Cloherty, Shaun L; Ibbotson, Michael R; O'Brien, Brendan J
2012-10-01
Mammalian retina contains 15-20 different retinal ganglion cell (RGC) types, each of which is responsible for encoding different aspects of the visual scene. The encoding is defined by a combination of RGC synaptic inputs, the neurotransmitter systems used, and their intrinsic physiological properties. Each cell's intrinsic properties are defined by its morphology and membrane characteristics, including the complement and localization of the ion channels expressed. In this study, we examined the hypothesis that the intrinsic properties of individual RGC types are conserved among mammalian species. To do so, we measured the intrinsic properties of 16 morphologically defined rat RGC types and compared these data with cat RGC types. Our data demonstrate that in the rat different morphologically defined RGC types have distinct patterns of intrinsic properties. Variation in these properties across cell types was comparable to that found for cat RGC types. When presumed morphological homologs in rat and cat retina were compared directly, some RGC types had very similar properties. The rat A2 cell exhibited patterns of intrinsic properties nearly identical to the cat alpha cell. In contrast, rat D2 cells (ON-OFF directionally selective) had a very different pattern of intrinsic properties than the cat iota cell. Our data suggest that the intrinsic properties of RGCs with similar morphology and suspected visual function may be subject to variation due to the behavioral needs of the species.
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ERIC Educational Resources Information Center
Gale, James B.
This study describes the effects of several fixatives and buffers on the morphology of mitochondria from resting and exhausted rats. Rats were run to exhaustion and adjacent portions from the left ventricle or from the soleus were treated with the following fixation procedures: (a) glutaraldehyde buffered with cacodylate, S-collidine, or phosphate…
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Isolation and characterization of dental epithelial cells derived from amelogenesis imperfecta rat.
Adiningrat, A; Tanimura, A; Miyoshi, K; Hagita, H; Yanuaryska, R D; Arinawati, D Y; Horiguchi, T; Noma, T
2016-03-01
Disruption of the third zinc finger domain of specificity protein 6 (SP6) presents an enamel-specific defect in a rat model of amelogenesis imperfecta (AMI rats). To understand the molecular basis of amelogenesis imperfecta caused by the Sp6 mutation, we established and characterized AMI-derived rat dental epithelial (ARE) cells. ARE cell clones were isolated from the mandibular incisors of AMI rats, and amelogenesis-related gene expression was analyzed by reverse transcription polymerase chain reaction (RT-PCR). Localization of wild-type SP6 (SP6WT) and mutant-type SP6 (SP6AMI) was analyzed by immunocytochemistry. SP6 transcriptional activity was monitored by rho-associated protein kinase 1 (Rock1) promoter activity with its specific binding to the promoter region in dental (G5 and ARE) and non-dental (COS-7) epithelial cells. Isolated ARE cells were varied in morphology and gene expression. Both SP6WT and SP6AMI were mainly detected in nuclei. The promoter analysis revealed that SP6WT and SP6AMI enhanced Rock1 promoter activity in G5 cells but that enhancement by SP6AMI was weaker, whereas no enhancement was observed in the ARE and COS-7 cells, even though SP6WT and SP6AMI bound to the promoter in all instances. ARE cell clones can provide a useful in vitro model to study the mechanism of SP6-mediated amelogenesis imperfecta. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Vidal, Blanca; Vázquez-Roque, Rubén A; Gnecco, Dino; Enríquez, Raúl G; Floran, Benjamin; Díaz, Alfonso; Flores, Gonzalo
2017-03-01
Curcuma is a natural compound that has shown neuroprotective properties, and has been reported to prevent aging and improve memory. While the mechanism(s) underlying these effects are unclear, they may be related to increases in neural plasticity. Morphological changes have been reported in neuronal dendrites in the limbic system in animals and elderly humans with cognitive impairment. In this regard, there is a need to use alternative therapies that delay the onset of morphologies and behavioral characteristics of aging. Therefore, the objective of this study was to evaluate the effect of curcuma on cognitive processes and dendritic morphology of neurons in the prefrontal cortex (PFC), the CA1 and CA3 regions of the dorsal hippocampus, the dentate gyrus, and the basolateral amygdala (BLA) of aged rats. 18-month-old rats were administered curcuma (100 mg/kg) daily for 60 days. After treatment, recognition memory was assessed using the novel object recognition test. Curcuma-treated rats showed a significant increase in the exploration quotient. Dendritic morphology was assessed by Golgi-Cox staining and followed by Sholl analysis. Curcuma-treated rats showed a significant increase in dendritic spine density and dendritic length in pyramidal neurons of the PFC, the CA1 and CA3, and the BLA. The preservation of dendritic morphology was positively correlated with cognitive improvements. Our results suggest that curcuma induces modification of dendritic morphology in the aforementioned regions. These changes may explain how curcuma slows the aging process that has already begun in these animals, preventing deterioration in neuronal morphology of the limbic system and recognition memory. © 2016 Wiley Periodicals, Inc.
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Characterization of dystrophin deficient rats: a new model for Duchenne muscular dystrophy.
Larcher, Thibaut; Lafoux, Aude; Tesson, Laurent; Remy, Séverine; Thepenier, Virginie; François, Virginie; Le Guiner, Caroline; Goubin, Helicia; Dutilleul, Maéva; Guigand, Lydie; Toumaniantz, Gilles; De Cian, Anne; Boix, Charlotte; Renaud, Jean-Baptiste; Cherel, Yan; Giovannangeli, Carine; Concordet, Jean-Paul; Anegon, Ignacio; Huchet, Corinne
2014-01-01
A few animal models of Duchenne muscular dystrophy (DMD) are available, large ones such as pigs or dogs being expensive and difficult to handle. Mdx (X-linked muscular dystrophy) mice only partially mimic the human disease, with limited chronic muscular lesions and muscle weakness. Their small size also imposes limitations on analyses. A rat model could represent a useful alternative since rats are small animals but 10 times bigger than mice and could better reflect the lesions and functional abnormalities observed in DMD patients. Two lines of Dmd mutated-rats (Dmdmdx) were generated using TALENs targeting exon 23. Muscles of animals of both lines showed undetectable levels of dystrophin by western blot and less than 5% of dystrophin positive fibers by immunohistochemistry. At 3 months, limb and diaphragm muscles from Dmdmdx rats displayed severe necrosis and regeneration. At 7 months, these muscles also showed severe fibrosis and some adipose tissue infiltration. Dmdmdx rats showed significant reduction in muscle strength and a decrease in spontaneous motor activity. Furthermore, heart morphology was indicative of dilated cardiomyopathy associated histologically with necrotic and fibrotic changes. Echocardiography showed significant concentric remodeling and alteration of diastolic function. In conclusion, Dmdmdx rats represent a new faithful small animal model of DMD.
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Guo, Xiufang; Das, Mainak; Rumsey, John; Gonzalez, Mercedes; Stancescu, Maria; Hickman, James
2010-12-01
To date, the coculture of motoneurons (MNs) and skeletal muscle in a defined in vitro system has only been described in one study and that was between rat MNs and rat skeletal muscle. No in vitro studies have demonstrated human MN to rat muscle synapse formation, although numerous studies have attempted to implant human stem cells into rat models to determine if they could be of therapeutic use in disease or spinal injury models, although with little evidence of neuromuscular junction (NMJ) formation. In this report, MNs differentiated from human spinal cord stem cells, together with rat skeletal myotubes, were used to build a coculture system to demonstrate that NMJ formation between human MNs and rat skeletal muscles is possible. The culture was characterized by morphology, immunocytochemistry, and electrophysiology, while NMJ formation was demonstrated by immunocytochemistry and videography. This defined system provides a highly controlled reproducible model for studying the formation, regulation, maintenance, and repair of NMJs. The in vitro coculture system developed here will be an important model system to study NMJ development, the physiological and functional mechanism of synaptic transmission, and NMJ- or synapse-related disorders such as amyotrophic lateral sclerosis, as well as for drug screening and therapy design.
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O'Malley, Dervla; Julio-Pieper, Marcela; Gibney, Sinead M; Dinan, Timothy G; Cryan, John F
2010-03-01
Stress and anxiety are important causal and exacerbating factors in functional gastro-intestinal (GI) disorders such as irritable bowel syndrome. Stress affects GI motility, faecal transit and visceral pain sensitivity. Additionally, permeability and function of the gut epithelium, which acts as a barrier between the external environment and the body's internal milieu is altered by stress. However, the effects of an enhanced stress response on colonic morphology require further investigation. We have used two animal models of stress and anxiety, the maternally separated (MS) and Wistar Kyoto (WKY) rats to examine colonic morphology. These rats exhibit increased anxiety behaviours, visceral hypersensitivity and increased stress-induced defecation in the open field arena. At a morphological level, increased mucus secretion and an associated elevation in the number of mucosal goblet cells was observed in the high anxiety rats. Additionally, the mucosal layer was flattened in MS and WKY rats, a finding indicative of mild mucosal damage. Furthermore, the muscular layer of the distal colon in these animals was thickened, an observation that may have implications for faecal transit and visceral pain perception. This study provides evidence of altered colonic function and morphology in two animal models with a heightened response to stress.
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Johnson, M D; Yee, A G
1995-08-01
Recent electrophysiological investigations in this laboratory have shown that cultured mesopontine serotonergic neurons from neonatal rats evoke serotonergic and/or glutamatergic responses in themselves and in non-serotonergic neurons. Serotonergic nerve terminals in vivo are heterogeneous with respect to vesicle type, synaptic structure, and the frequency with which they form conventional synaptic contacts, but the functional correlates of this heterogeneity are unclear. We have therefore examined the ultrastructure of electrophysiologically-characterized synapses formed by cultured serotonergic neurons, and have compared the findings with the ultrastructural characteristics of serotonergic synapses reported in vivo. Dissociated rat serotonergic neurons in microcultures were identified by serotonin immunocytochemistry or by uptake of the autofluorescent serotonin analogue 5,7-dihydroxytryptamine, and were subsequently processed for electron microscopy. Unlabeled axon terminals formed numerous synapses on serotonin-immunoreactive somata and dendrites. Serotonin-immunoreactive axon terminals formed synapses on the somata, dendrites and somatodendritic spine-like appendages of serotonergic and non-serotonergic neurons. In microcultures containing a solitary serotonergic neuron that evoked glutamatergic or serotonergic/glutamatergic autaptic responses, both symmetric and asymmetric synapses were present. In addition to large dense core vesicles, individual neurons contained either microcanaliculi and microvesicles, clear round vesicles, or clear pleiomorphic vesicles. For a given cell, however, the subtypes of vesicles present in each axon terminal were similar. Thus, dissociated serotonergic and non-serotonergic raphe neurons formed functional, morphological synapses in culture. A direct examination of both the synaptic physiology and ultrastructure of single cultured serotonergic neurons indicated that these cells released serotonin and glutamate at synapses that were morphologically similar to synapses formed by serotonergic neurons in vivo. The findings also suggested that individual serotonergic neurons differ with respect to synaptic vesicle morphology, and are capable of simultaneously forming symmetric and asymmetric synapses with target cells.
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Saito, Yasuhiko; Zhang, Yue; Yanagawa, Yuchio
2015-04-01
Although it has been proposed that neurons that contain both acetylcholine (ACh) and γ-aminobutyric acid (GABA) are present in the prepositus hypoglossi nucleus (PHN), these neurons have not been characterized because of the difficulty in identifying them. In the present study, PHN neurons that express both choline acetyltransferase and the vesicular GABA transporter (VGAT) were identified using double-transgenic rats, in which the cholinergic and inhibitory neurons express the fluorescent proteins tdTomato and Venus, respectively. To characterize the neurons that express both tdTomato and Venus (D+ neurons), the afterhyperpolarization (AHP) profiles and firing patterns of these neurons were investigated via whole-cell recordings of brainstem slice preparations. Regarding the three AHP profiles and four firing patterns that the D+ neurons exhibited, an AHP with an afterdepolarization and a firing pattern that exhibited a delay in the generation of the first spike were the preferential properties of these neurons. In the three morphological types classified, the multipolar type that exhibited radiating dendrites was predominant among the D+ neurons. Immunocytochemical analysis revealed that the VGAT-immunopositive axonal boutons that expressed tdTomato were primarily located in the dorsal cap of inferior olive (IO) and the PHN. Although the PHN receives cholinergic inputs from the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus, D+ neurons were absent from these brain areas. Together, these results suggest that PHN neurons that co-express ACh and GABA exhibit specific electrophysiological and morphological properties, and innervate the dorsal cap of the IO and the PHN. © 2015 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O
2004-12-01
Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.
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Pan, Feng; Mi, Jing-Yi; Zhang, Yan; Pan, Xiao-Yun; Rui, Yong-Jun
2016-06-01
The failure to accept reinnervation is considered to be one of the reasons for the poor motor functional recovery of intrinsic hand muscles (IHMs) after nerve injury. Rat could be a suitable model to be used in simulating motor function recovery of the IHMs after nerve injury as to the similarities in function and anatomy of the muscles between human and rat. However, few studies have reported the muscle fiber types composition and endplate morphologic characteristics of intrinsic forepaw muscles (IFMs) in the rat. In this study, the myosin heavy chain isoforms and acetylcholine receptors were stained by immunofluorescence to show the muscle fiber types composition and endplates on type-identified fibers of the lumbrical muscles (LMs), interosseus muscles (IMs), abductor digiti minimi (AM) and flexor pollicis brevis (FM) in rat forepaw. The majority of IFMs fibers were labeled positively for fast-switch fiber. However, the IMs were composed of only slow-switch fiber. With the exception of the IMs, the other IFMs had a part of hybrid fibers. Two-dimensional morphological characteristics of endplates on I and IIa muscle fiber had no significant differences among the IFMs. The LMs is the most suitable IFMs of rat to stimulate reinnervation of the IHMs after nerve injury. Gaining greater insight into the muscle fiber types composition and endplate morphology in the IFMs of rat may help understand the pathological and functional changes of IFMs in rat model stimulating reinnervation of IHMs after peripheral nerve injury.
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Selvas, Abraham; Coria, Santiago M; Kastanauskaite, Asta; Fernaud-Espinosa, Isabel; DeFelipe, Javier; Ambrosio, Emilio; Miguéns, Miguel
2017-01-01
We previously showed that cocaine self-administration increases spine density in CA1 hippocampal neurons in Lewis (LEW) but not in Fischer 344 (F344) rats. Dendritic spine morphology is intimately related to its function. Thus, we conducted a 3D morphological analysis of CA1 dendrites and dendritic spines in these two strains of rats. Strain-specific differences were observed prior to cocaine self-administration: LEW rats had significantly larger dendritic diameters but lower spine density than the F344 strain. After cocaine self-administration, proximal dendritic volume, dendritic surface area and spine density were increased in LEW rats, where a higher percentage of larger spines were also observed. In addition, we found a strong positive correlation between dendritic volume and spine morphology, and a moderate correlation between dendritic volume and spine density in cocaine self-administered LEW rats, an effect that was not evident in any other condition. By contrast, after cocaine self-administration, F334 rats showed decreased spine head volumes. Our findings suggest that genetic differences could play a key role in the structural plasticity induced by cocaine in CA1 pyramidal neurons. These cocaine-induced alterations could be related to differences in the memory processing of drug reward cues that could potentially explain differential individual vulnerability to cocaine addiction. © 2015 Society for the Study of Addiction.
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Katharesan, Viythia; Lewis, Martin David; Vink, Robert; Johnson, Ian Paul
2016-01-01
An overall increase in inflammatory cytokines with age in both the blood and the central nervous system (CNS) has been proposed to explain many aspects of ageing, including decreased motor function and neurodegeneration. This study tests the hypothesis that age-related increases in inflammatory cytokines in the blood and CNS lead to facial motor neuron degeneration. Groups of 3-5 female Sprague-Dawley rats aged 3, 12-18, and 24 months were used. Twelve cytokines interleukin (IL)-1α, IL-β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p70, IL-13, tumor necrosis factor-α (TNFα), interferon-γ, and granulocyte macrophage-colony stimulating factor were measured in blood plasma and compared with those in the brainstem after first flushing blood from its vessels. The open-field test was used to measure exploratory behavior, and the morphology of the peripheral target muscle of facial motor neurons quantified. Total numbers of facial motor neurons were determined stereologically in separate groups of 3- and 24-month-old rats. Ageing rats showed a significant 30-42% decrease in blood plasma (peripheral) concentrations of IL-12p70 and TNFα and a significant 43-49% increase in brainstem (central) concentrations of IL-1α, IL-2, IL-4, IL-10, and TNFα. They also showed significant reductions in motor neuron number in the right but not left facial nucleus, reduced exploratory behavior, and increase in peripheral target muscle size. Marginal age-related facial motoneuronal loss occurs in the ageing rat and is characterized by complex changes in the inflammatory signature, rather than a general increase in inflammatory cytokines.
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Clofibrate prevents and reverses the hemodynamic manifestations of hyperthyroidism in rats.
Rodríguez-Gómez, Isabel; Cruz, Antonio; Moreno, Juan Manuel; Soler, Agatángelo; Osuna, Antonio; Vargas, Félix
2008-03-01
This study analyzed the effects of the chronic administration of clofibrate, a peroxisome proliferator-activated receptor-alpha (PPARalpha) agonist, on the development and established hemodynamic, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. The prevention study used four groups of male Wistar rats: control, clofibrate (240 mg/kg/day by gavage), T(4)(75 microg thyroxine/rat/day s.c.), and T(4)+clofibrate. All treatments were maintained for 3 weeks. Body weight (BW), tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, temperature, SBP, pulse pressure (PP) and HR were recorded in conscious rats, and morphologic, metabolic, plasma, and renal variables were measured. The reversion study used two groups of rats, T(4)(treated for 6 weeks) and T(4)+clofibrate, measuring their hemodynamic variables and temperature for 3 weeks. T(4) increased BP, HR, PP, and temperature when compared with control rats. Clofibrate prevented and reversed the increase in SBP, HR, PP, and temperature produced by T(4) administration, reduced plasma thyroid hormone levels, and increased plasma thyroid-stimulating hormone values and phenol-uridine diphosphate-glucuronosyl-transferase (UGT) activity. However, clofibrate did not modify the cardiac or renal hypertrophy, polyphagia, polydipsia, or proteinuria of hyperthyroid rats. In normal rats, clofibrate treatment did not significantly change thyroid hormone levels, phenol-UGT activity, or any hemodynamic, morphologic, or renal variables. Chronic clofibrate treatment suppressed the hemodynamic manifestations and increased temperature of hyperthyroidism, an effect that can be produced by direct antithyroid effects. However, clofibrate administration did not modify the morphologic, metabolic, or renal alterations of hyperthyroid rats, indicating specificity in the antithyroid actions of clofibrate.
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Sperm motility and morphology changes in rats exposed to cadmium and diazinon.
Adamkovicova, Maria; Toman, Robert; Martiniakova, Monika; Omelka, Radoslav; Babosova, Ramona; Krajcovicova, Vladimira; Grosskopf, Birgit; Massanyi, Peter
2016-08-08
Humans are ubiquitously exposed to multiple environmental contaminants. Consequences of combined action on the reproductive system remain unknown. This study aimed to assess single and joint effects of cadmium and diazinon exposure on sperm quality parameters. Male adult Wistar rats were randomized into 4 groups of ten animals each. Group A was used as a control, animals from group B were exposed to cadmium (30 mg/L), rats from group C were administered with diazinon (40 mg/L), and rats from group D were exposed simultaneously to cadmium (30 mg/L) and diazinon (40 mg/L) via drinking water for 90 days. Sperm morphology and motility were evaluated using a bright field microscope and a computer-assisted semen analysis. The percentage of motile spermatozoa and morphologically normal sperm was markedly reduced in rats from the group B. Rats from the C group showed an increase in velocity parameters, amplitude of lateral head displacement, decrease in beat-cross frequency, and an increase in abnormal sperm morphology. Simultaneous coexposure to cadmium and diazinon increased distance and velocity parameters, and amplitude of lateral head displacement. Reductions were observed in straightness, linearity, wobble, and beat-cross frequency. The decreased normal sperm morphology rates were related to defects of the sperm tail. Exposure to cadmium and diazinon at relatively low doses impairs sperm quality and can reduce male fertility. Cadmium and diazinon caused significant changes on sperm morphology with varying effects on motility patterns. These parameters were significantly higher in the group D as compared to the group C. The findings have important implications for reproductive risk assessment of combined exposures to multiple chemicals.
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Nguyen, Thi Thuong Thuong; Paul, Narayan Chandra
2016-01-01
During fungal diversity surveys of the order Eurotiales in Korea, two fungal strains, EML-DG33-1 and EML-NCP50, were isolated from samples of rat dung and fig tree leaf collected at a garden located in Gwangju in 2014. To complete the National Species List of Korea, it is a prerequisite to verify whether many questionable species, which were previously recorded but not confirmed, indeed present in Korea. Herein, the isolates were confirmed as undescribed species, Paecilomyces variotii and Talaromyces amestolkiae based on the combination of morphological and phylogenetic analyses of multigenes including the rDNA internal transcribed spacer, β-tubulin, and RNA polymerase II subunit 2. PMID:28154482
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Taupin, P; Zini, S; Cesselin, F; Ben-Ari, Y; Roisin, M P
1994-04-01
A method for preparation of hippocampal mossy fiber synaptosomes directly from the postnuclear pellet is presented. This method represents an adaptation of that previously described for the isolation of synaptosomes by centrifugation through Percoll gradients directly from the supernatant fraction. We have characterized by electron microscopy two fractions, PII and PIII, enriched in mossy fiber synaptosomes; fraction PIII had 75% mossy fiber synaptosomes with well-preserved morphology (large size 3 microns, complex morphology, high synaptic vesicle density, multisynapses), whereas fraction PII contained 12%. These fractions were enriched in lactate dehydrogenase activity indicating that the integrity of synaptosomes was preserved. Compared with the other synaptosomal fractions, these fractions showed greater levels of dynorphin A (1-8) immunoreactivity and endogenous zinc, which are particularly concentrated in hippocampal mossy fiber terminals. Furthermore, we prepared synaptosomes from adult hippocampus after neonatal irradiation, which destroys the majority of granule cells and associated mossy fibers. The levels of dynorphin and zinc decreased by 88 and 70% in fraction PII and by 95 and 90%, respectively, in PIII. These results suggest that the rapid Percoll procedure is convenient for the purification of mossy fiber synaptosomes.
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Dreon, Marcos S; Fernández, Patricia E; Gimeno, Eduardo J; Heras, Horacio
2014-06-01
The spread of the invasive snail Pomacea canaliculata is expanding the rat lungworm disease beyond its native range. Their toxic eggs have virtually no predators and unusual defenses including a neurotoxic lectin and a proteinase inhibitor, presumably advertised by a warning coloration. We explored the effect of egg perivitellin fluid (PVF) ingestion on the rat small intestine morphology and physiology. Through a combination of biochemical, histochemical, histopathological, scanning electron microscopy, cell culture and feeding experiments, we analyzed intestinal morphology, growth rate, hemaglutinating activity, cytotoxicity and cell proliferation after oral administration of PVF to rats. PVF adversely affects small intestine metabolism and morphology and consequently the standard growth rate, presumably by lectin-like proteins, as suggested by PVF hemaglutinating activity and its cytotoxic effect on Caco-2 cell culture. Short-term effects of ingested PVF were studied in growing rats. PVF-supplemented diet induced the appearance of shorter and wider villi as well as fused villi. This was associated with changes in glycoconjugate expression, increased cell proliferation at crypt base, and hypertrophic mucosal growth. This resulted in a decreased absorptive surface after 3 days of treatment and a diminished rat growth rate that reverted to normal after the fourth day of treatment. Longer exposure to PVF induced a time-dependent lengthening of the small intestine while switching to a control diet restored intestine length and morphology after 4 days. Ingestion of PVF rapidly limits the ability of potential predators to absorb nutrients by inducing large, reversible changes in intestinal morphology and growth rate. The occurrence of toxins that affect intestinal morphology and absorption is a strategy against predation not recognized among animals before. Remarkably, this defense is rather similar to the toxic effect of plant antipredator strategies. This defense mechanism may explain the near absence of predators of apple snail eggs.
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Jangde, Rajendra; Srivastava, Shikha; Singh, Manju R; Singh, Deependra
2018-05-03
The present work aim to prepare and evaluate multiphase hydrogel system incorporated with quercetin loaded liposomes (QLH), for wound healing. The quercetin loaded liposomal hydrogel were prepared by taking 15% carbopol and varying gelatin ratio. The clear and transparent hydrogel was obtained by taking ratio of gelatin to carbapol (6/4) compared to other ratios. The best prepared hydrogel were characterized for surface morphology, water vapor transmission rate (WVTR), swelling ratio, hemocompatibility, stability, in-vitro release and in-vivo studies. The evaluated results of (QLH) for surface morphology, WVTR, swelling ratio, hemocompatibility and in-vitro release were found to be significant compared to other prepared formulations. Consequently, on basis of optimized hydrogel was selected to study wound healing activity in albino rats. The results demonstrated accelerated wound-healing with significant decrease in wound closure time compared to conventional dosage form. The results of in-vitro and in-vivo promises reliable mode of treatment for connective tissue disorder as wound healing. Copyright © 2018. Published by Elsevier B.V.
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Proliferative and morphologic changes in rat colon following bypass surgery.
Barkla, D H; Tutton, P J
1985-06-01
In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence.
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NASA Astrophysics Data System (ADS)
Liang, Feng; Zhang, Guilin; Xiao, Xianghui; Cai, Zhonghou; Lai, Barry; Hwu, Yeukuang; Yan, Chonghuai; Xu, Jian; Li, Yulan; Tan, Mingguang; Zhang, Chuanfu; Li, Yan
2010-09-01
The hippocampus, a major component of the brain, is one of the target nervous organs in lead poisoning. In this work, a rat's hippocampal injury caused by lead was studied. The lead concentrations in blood, bone and hippocampus collected from rats subject to lead poisoning were quantified by Inductively Coupled Plasma Mass Spectrometry while morphological information and elemental distributions in the hippocampus were obtained with synchrotron radiation X-ray phase contrast imaging and synchrotron radiation micro-beam X-ray fluorescence, respectively. For comparison, identical characterization of the specimens from the rats in the control group was done in parallel. Results show that the ratios between the lead content in the treated group and that in the control group of the hippocampus, bone, and blood are about 2.66, 236, and 39.6, respectively. Analysis also revealed that some health elements such as S, K, Cl and P increase in the regions with high lead content in the treated hippocampus. Morphological differences between the normal and lead-exposed hippocampus specimens in some local areas were observed. Explicitly, the structure of the lead-exposed hippocampus was tortuous and irregular, and the density of the neurons in the Dentate Gyrus was significantly lower than that from the control group. The study shows that the synchrotron radiation methods are very powerful for investigating structural injury caused by heavy metals in the nervous system.
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Kalman, Eszter; Keay, Kevin A
2014-12-01
Physical and psychological trauma which results in mood disorders and the disruption of complex behaviours is associated with reductions in hippocampal volume. Clinical evaluation of neuropathic pain reveals mood and behavioural change in a significant number of patients. A rat model of neuropathic injury results in complex behavioural changes in a subpopulation (~30%) of injured rats; these changes are co-morbid with a range of other 'disabilities'. The specific objective of this study was to determine in rats the morphology of the hippocampus and dentate gyrus in individuals with and without complex behavioural disruptions following a constriction injury of the sciatic nerve, and to determine whether rats that develop disabilities following nerve injury have a reduced hippocampal volume compared with injured rats with no disabilities. The social behaviours of nerve-injured rats were evaluated before and after nerve injury. The morphology of the hippocampus of rats with and without behavioural disruptions was compared in serial histological sections. Single-housing and repeated social-interaction testing had no effect on the morphology of either the hippocampus or the dentate gyrus. Rats with transient or ongoing disability identified by behavioural disruption following sciatic nerve injury, show bilateral reductions in hippocampal volume, and lateralised reduction in the dentate gyrus (left side). Disabled rats display a combination of behavioural and physiological changes, which resemble many of the criteria used clinically to diagnose mood disorders. They also show reductions in the volume of the hippocampus similar to people with clinically diagnosed mood disorders. The sciatic nerve injury model reveals a similarity to the human neuropathic pain presentation presenting an anatomically specific focus for the investigation of the neural mechanisms underpinning the co-morbidity of chronic pain and mood disorder. © 2014 Anatomical Society.
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D1 Receptors Regulate Dendritic Morphology in Normal and Stressed Prelimbic Cortex
Lin, Grant L.; Borders, Candace B.; Lundewall, Leslie J.; Wellman, Cara L.
2014-01-01
Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3 h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. PMID:25305546
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D1 receptors regulate dendritic morphology in normal and stressed prelimbic cortex.
Lin, Grant L; Borders, Candace B; Lundewall, Leslie J; Wellman, Cara L
2015-01-01
Both stress and dysfunction of prefrontal cortex are linked to psychological disorders, and structure and function of medial prefrontal cortex (mPFC) are altered by stress. Chronic restraint stress causes dendritic retraction in the prelimbic region (PL) of mPFC in rats. Dopamine release in mPFC increases during stress, and chronic administration of dopaminergic agonists results in dendritic remodeling. Thus, stress-induced alterations in dopaminergic transmission in PL may contribute to dendritic remodeling. We examined the effects of dopamine D1 receptor (D1R) blockade in PL during daily restraint stress on dendritic morphology in PL. Rats either underwent daily restraint stress (3h/day, 10 days) or remained unstressed. In each group, rats received daily infusions of either the D1R antagonist SCH23390 or vehicle into PL prior to restraint; unstressed and stressed rats that had not undergone surgery were also examined. On the final day of restraint, rats were euthanized and brains were processed for Golgi histology. Pyramidal neurons in PL were reconstructed and dendritic morphology was quantified. Vehicle-infused stressed rats demonstrated dendritic retraction compared to unstressed rats, and D1R blockade in PL prevented this effect. Moreover, in unstressed rats, D1R blockade produced dendritic retraction. These effects were not due to attenuation of the HPA axis response to acute stress: plasma corticosterone levels in a separate group of rats that underwent acute restraint stress with or without D1R blockade were not significantly different. These findings indicate that dopaminergic transmission in mPFC during stress contributes directly to the stress-induced retraction of apical dendrites, while dopamine transmission in the absence of stress is important in maintaining normal dendritic morphology. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Apaijai, Nattayaporn; Pintana, Hiranya; Chattipakorn, Siriporn C; Chattipakorn, Nipon
2013-01-01
Background and Purpose Long-term high-fat diet (HFD) consumption has been shown to cause insulin resistance, which is characterized by hyperinsulinaemia with metabolic inflexibility. Insulin resistance is associated with cardiac sympathovagal imbalance, cardiac dysfunction and cardiac mitochondrial dysfunction. Dipeptidyl peptidase-4 (DPP-4) inhibitors, vildagliptin and sitagliptin, are oral anti-diabetic drugs often prescribed in patients with cardiovascular disease. Therefore, in this study, we sought to determine the effects of vildagliptin and sitagliptin in a murine model of insulin resistance. Experimental Approach Male Wistar rats weighing 180–200 g, were fed either a normal diet (20% energy from fat) or a HFD (59% energy from fat) for 12 weeks. These rats were then divided into three subgroups to receive vildagliptin (3 mg·kg−1·day−1), sitagliptin (30 mg·kg−1·day−1) or vehicle for another 21 days. Metabolic parameters, oxidative stress, heart rate variability (HRV), cardiac function and cardiac mitochondrial function were determined. Key Results Rats that received HFD developed insulin resistance characterized by increased body weight, plasma insulin, total cholesterol and oxidative stress levels along with a decreased high-density lipoprotein (HDL) level. Moreover, cardiac dysfunction, depressed HRV, cardiac mitochondrial dysfunction and cardiac mitochondrial morphology changes were observed in HFD rats. Both vildagliptin and sitagliptin decreased plasma insulin, total cholesterol and oxidative stress as well as increased HDL level. Furthermore, vildagliptin and sitagliptin attenuated cardiac dysfunction, prevented cardiac mitochondrial dysfunction and completely restored HRV. Conclusions and Implications Both vildagliptin and sitagliptin share similar efficacy in cardioprotection in obese insulin-resistant rats. PMID:23488656
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Cardiovascular-renal and metabolic characterization of a rat model of polycystic ovary syndrome.
Yanes, Licy L; Romero, Damian G; Moulana, Mohaddetheh; Lima, Roberta; Davis, Deborah D; Zhang, Huimin; Lockhart, Rachel; Racusen, Lorraine C; Reckelhoff, Jane F
2011-04-01
Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease when PCOS first occurs and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS have not been elucidated. This study characterized the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Female Sprague-Dawley rats (aged 4-6 weeks) were implanted with dihydrotestosterone or placebo pellets lasting 90 days. After 10 to 12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein, and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, and oral glucose tolerance test), inflammation (plasma tumor necrosis factor-α), oxidative stress (mRNA expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits, p22(phox), p47(phox), gp91(phox), and NOX4), nitrate/nitrite excretion and mRNA expression of components of the renin-angiotensin system (angiotensinogen, angiotensin-I-converting enzyme [ACE], and AT1 receptor) were determined. Plasma dihydrotestosterone increased 3-fold in hyperandrogenemic female (HAF) rats, whereas plasma estradiol levels did not differ compared with control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model to study the mechanisms responsible for PCOS-mediated hypertension. Copyright © 2011 Elsevier HS Journals, Inc. All rights reserved.
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Chen, X C; Liu, H; Li, H; Cheng, Y; Yang, L; Liu, Y F
2016-06-27
In this study, a dynamic three-dimensional cell culture technology was used to expand and differentiate rat pancreatic duct-derived stem cells (PDSCs) into islet-like cell clusters that can secrete insulin. PDSCs were isolated from rat pancreatic tissues by in situ collagenase digestion and density gradient centrifugation. Using a dynamic three-dimensional culture technique, the cells were expanded and differentiated into functional islet-like cell clusters, which were characterized by morphological and phenotype analyses. After maintaining 1 x 108 isolated rat PDSCs in a dynamic three-dimensional cell culture for 7 days, 1.5 x 109 cells could be harvested. Passaged PDSCs expressed markers of pancreatic endocrine progenitors, including CD29 (86.17%), CD73 (90.73%), CD90 (84.13%), CD105 (78.28%), and Pdx-1. Following 14 additional days of culture in serum-free medium with nicotinamide, keratinocyte growth factor (KGF), and b fibroblast growth factor (FGF), the cells were differentiated into islet-like cell clusters (ICCs). The ICC morphology reflected that of fused cell clusters. During the late stage of differentiation, representative clusters were non-adherent and expressed insulin indicated by dithizone (DTZ)-positive staining. Insulin was detected in the extracellular fluid and cytoplasm of ICCs after 14 days of differentiation. Additionally, insulin levels were significantly higher at this time compared with the levels exhibited by PDSCs before differentiation (P < 0.01). By using a dynamic three-dimensional cell culture system, PDSCs can be expanded in vitro and can differentiate into functional islet-like cell clusters.
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Mitigation of heat stress-related complications by a yeast fermentate product.
Giblot Ducray, Henri Alexandre; Globa, Ludmila; Pustovyy, Oleg; Reeves, Stuart; Robinson, Larry; Vodyanoy, Vitaly; Sorokulova, Iryna
2016-08-01
Heat stress results in a multitude of biological and physiological responses which can become lethal if not properly managed. It has been shown that heat stress causes significant adverse effects in both human and animals. Different approaches have been proposed to mitigate the adverse effects caused by heat stress, among which are special diet and probiotics. We characterized the effect of the yeast fermentate EpiCor (EH) on the prevention of heat stress-related complications in rats. We found that increasing the body temperature of animals from 37.1±0.2 to 40.6±0.2°C by exposure to heat (45°C for 25min) resulted in significant morphological changes in the intestine. Villi height and total mucosal thickness decreased in heat-stressed rats pre-treated with PBS in comparison with control animals not exposed to the heat. Oral treatment of rats with EH before heat stress prevented the traumatic effects of heat on the intestine. Changes in intestinal morphology of heat-stressed rats, pre-treated with PBS resulted in significant elevation of lipopolysaccharides (LPS) level in the serum of these animals. Pre-treatment with EH was effective in the prevention of LPS release into the bloodstream of heat-stressed rats. Our study revealed that elevation of body temperature also resulted in a significant increase of the concentration of vesicles released by erythrocytes in rats, pre-treated with PBS. This is an indication of a pathological impact of heat on the erythrocyte structure. Treatment of rats with EH completely protected their erythrocytes from this heat-induced pathology. Finally, exposure to heat stress conditions resulted in a significant increase of white blood cells in rats. In the group of animals pre-treated with EH before heat stress, the white blood cell count remained the same as in non-heated controls. These results showed the protective effect of the EH product in the prevention of complications, caused by heat stress. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Persistent estrus rat models of polycystic ovary disease: an update.
Singh, Krishna B
2005-10-01
To critically review published articles on polycystic ovary (PCO) disease in rat models, with a focus on delineating its pathophysiology. Review of the English-language literature published from 1966 to March 2005 was performed through PubMed search. Keywords or phrases used were persistent estrus, chronic anovulation, polycystic ovary, polycystic ovary disease, and polycystic ovary syndrome. Articles were also located via bibliographies of published literature. University Health Sciences Center. Articles on persistent estrus and PCO in rats were selected and reviewed regarding the methods for induction of PCO disease. Changes in the reproductive cycle, ovarian morphology, hormonal parameters, and factors associated with the development of PCO disease in rat models were analyzed. Principal methods for inducing PCO in the rat include exposure to constant light, anterior hypothalamic and amygdaloidal lesions, and the use of androgens, estrogens, antiprogestin, and mifepristone. The validated rat PCO models provide useful information on morphologic and hormonal disturbances in the pathogenesis of chronic anovulation in this condition. These studies have aimed to replicate the morphologic and hormonal characteristics observed in the human PCO syndrome. The implications of these studies to human condition are discussed.
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Du, Fang; Ding, Ye; Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling
2015-01-01
This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage.
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Zou, Jun; Li, Zhili; Tian, Jijing; She, Ruiping; Wang, Desheng; Wang, Huijuan; Lv, Dongqiang; Chang, Lingling
2015-01-01
This study investigated the effects of long-term simulated weightlessness on liver morphology, enzymes, glycogen, and apoptosis related proteins by using two-month rat-tail suspension model (TS), and liver injury improvement by rat-tail suspension with resistance training model (TS&RT). Microscopically the livers of TS rats showed massive granular degeneration, chronic inflammation, and portal fibrosis. Mitochondrial and endoplasmic reticulum swelling and loss of membrane integrity were observed by transmission electron microscopy (TEM). The similar, but milder, morphological changes were observed in the livers of TS&RT rats. Serum biochemistry analysis revealed that the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were significantly higher (p<0.05) in TS rats than in controls. The levels of ALT and AST in TS&RT rats were slightly lower than in RT rats, but they were insignificantly higher than in controls. However, both TS and TS&RT rats had significantly lower levels (p<0.05) of serum glucose and hepatic glycogen than in controls. Immunohistochemistry demonstrated that the expressions of Bax, Bcl-2, and active caspase-3 were higher in TS rats than in TS&RT and control rats. Real-time polymerase chain reaction (real-time PCR) showed that TS rats had higher mRNA levels (P < 0.05) of glucose-regulated protein 78 (GRP78) and caspase-12 transcription than in control rats; whereas mRNA expressions of C/EBP homologous protein (CHOP) and c-Jun N-terminal kinase (JNK) were slightly higher in TS rats. TS&RT rats showed no significant differences of above 4 mRNAs compared with the control group. Our results demonstrated that long-term weightlessness caused hepatic injury, and may trigger hepatic apoptosis. Resistance training slightly improved hepatic damage. PMID:26000905
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Wan, Changrong; Yin, Peng; Xu, Xiaolong; Liu, Mingjiang; He, Shasha; Song, Shixiu; Liu, Fenghua; Xu, Jianqin
2014-04-01
The present study investigated the effects of simulated transport stress on morphology and gene expression in the small intestine of laboratory rats. Sprague Dawley rats were subjected to 35°C and 0.1×g on a constant temperature shaker for physiological, biochemical, morphological and microarray analysis before and after treatment. The treatment induced obvious stress responses with significant decreases in body weight (P<0.01), increases in rectal temperature, serum corticosterone (CORT), serum glucose (GLU), creatine kinase (CK) and lactate dehydrogenase (LDH) levels (P<0.01), as well as expression of Hsp27/70/90 mRNA (P<0.05; P<0.01). The rat jejunum was severely damaged and apoptotic after mimicking transport stress, which may mainly be related to cell death, oxidation reduction and hormone imbalance determined by microarray analysis. The bioinformatics analysis from the present study would provide insight into the potential mechanisms underlying transport stress-induced injury in the rat small intestine. Copyright © 2014 Elsevier Ltd. All rights reserved.
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Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.
Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao
2013-11-01
The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.
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Gingerich, Aaron; Pang, Lan; Hanson, Jarod; Dlugolenski, Daniel; Streich, Rebecca; Lafontaine, Eric R; Nagy, Tamás; Tripp, Ralph A; Rada, Balázs
2016-01-01
Our aim was to study whether an extracellular, oxidative antimicrobial mechanism inherent to tracheal epithelial cells is capable of inactivating influenza H1N2 virus. Epithelial cells were isolated from tracheas of male Sprague-Dawley rats. Both primary human and rat tracheobronchial epithelial cells were differentiated in air-liquid interface cultures. A/swine/Illinois/02860/09 (swH1N2) influenza A virions were added to the apical side of airway cells for 1 h in the presence or absence of lactoperoxidase or thiocyanate. Characterization of rat epithelial cells (morphology, Duox expression) occurred via western blotting, PCR, hydrogen peroxide production measurement and histology. The number of viable virions was determined by plaque assays. Statistical difference of the results was analyzed by ANOVA and Tukey's test. Our data show that rat tracheobronchial epithelial cells develop a differentiated, polarized monolayer with high transepithelial electrical resistance, mucin production and expression of dual oxidases. Influenza A virions are inactivated by human and rat epithelial cells via a dual oxidase-, lactoperoxidase- and thiocyanate-dependent mechanism. Differentiated air-liquid interface cultures of rat tracheal epithelial cells provide a novel model to study airway epithelium-influenza interactions. The dual oxidase/lactoperoxidase/thiocyanate extracellular oxidative system producing hypothiocyanite is a fast and potent anti-influenza mechanism inactivating H1N2 viruses prior to infection of the epithelium.
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Zhu, Changlai; Li, Feng; Zhou, Xinyang; Lin, Lin; Zhang, Tianyi
2014-05-01
Bacterial cellulose (BC) is a natural biomaterial with unique properties suitable for tissue engineering applications, but it has not yet been used for preparing nerve conduits to repair peripheral nerve injuries. The objectives of this study were to prepare and characterize the Kampuchea-synthesized bacterial cellulose (KBC) and further evaluate the biocompatibility of KBC with peripheral nerve cells and tissues in vitro and in vivo. KBC membranes were composed of interwoven ribbons of about 20-100 nm in width, and had a high purity and the same crystallinity as that of cellulose Iα. The results from light and scanning electron microscopy, MTT assay, flow cytometry, and RT-PCR indicated that no significant differences in the morphology and cell function were observed between Schwann cells (SCs) cultured on KBC membranes and glass slips. We also fabricated a nerve conduit using KBC, which was implanted into the spatium intermusculare of rats. At 1, 3, and 6 weeks post-implantation, clinical chemistry and histochemistry showed that there were no significant differences in blood counts, serum biochemical parameters, and tissue reactions between implanted rats and sham-operated rats. Collectively, our data indicated that KBC possessed good biocompatibility with primary cultured SCs and KBC did not exert hematological and histological toxic effects on nerve tissues in vivo. Copyright © 2013 Wiley Periodicals, Inc.
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Response of the iron-deficient erythrocyte in the rat to hyperoxia
NASA Technical Reports Server (NTRS)
Larkin, E. C.; Kimzey, S. L.; Siler, K.
1978-01-01
Normal and iron-deficient rats were exposed to 90% O2 at 760 Torr for 24 or 48 h. Erythrocyte response to hyperoxia was monitored by potassium (rubidium) influx studies, by storage stress, and by ultrastructural studies. Normal rat erythrocytes exhibited morphological changes and decrease of ouabain-sensitive potassium influx compared to unexposed controls. Both components of erythrocyte potassium influx were affected by iron deficiency. Erythrocytes from unexposed iron-deficient rats showed a 50% increase in ouabain-sensitive potassium influx compared to controls. Iron-deficient rats exposed to hyperoxia for 24 or 48 h, had erythrocytes with morphological changes. Erythrocytes of iron-deficient rats exposed for 24 h showned no influx change; those exposed for 48 h showed a decrease of ouabain-sensitive influx compared to erythrocytes of controls.
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Nitric Oxide Signaling in Hypergravity-Induced Neuronal Plasticity
NASA Technical Reports Server (NTRS)
Holstein, Gay R.
2003-01-01
The goal of this research project was to identify the neurons and circuits in the vestibular nuclei and nucleus prepositus hypoglossi that utilize nitric oxide (NO) for intercellular signaling during gravity-induced plasticity. This objective was pursued using histochemical and immunocytochemical approaches to localize NO-producing neurons and characterize the fine morphology of the cells in ground-based studies of normal rats, rats adapted to hypergravity, and rats adapted to hypergravity and then re-adapted to the 1G environment. NO-producing neurons were identified and studied using four methodologies: i) immunocytochemistry employing polyclonal antibodies directed against neuronal nitric oxide synthase (nNOS), to provide an indication of the capacity of a cell for NO production; ii) immunocytochemistry employing a monoclonal antibody directed against L-citrulline, to provide an indirect index of the enzyme's activity; iii) histochemistry based on the NADPH-diaphorase reaction, for fuI1 cytological visualization of neurons; and iv) double immunofluorescence to co-localize nNOS and L-citrulline in individual vestibular nuclei (VN) and neurons.
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Genome wide identification of Staufen2-bound mRNAs in embryonic rat brains.
Maher-Laporte, Marjolaine; DesGroseillers, Luc
2010-05-01
Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Staufen2 is an mRNA-binding protein expressed in the cell bodies and cellular processes of different brain cells. It is notably involved in the transport of dendritic mRNAs along microtubules. Its knockdown expression was shown to change spine morphology and impair synaptic functions. However, the identity of Staufen2-bound mRNAs in brain cells is still completely unknown. As a mean to identify these mRNAs, we immunoprecipitated Staufen2-containing mRNPs from embryonic rat brains and used a genome wide approach to identify Staufen2-associated mRNAs. The genome wide approach identified 1780 mRNAs in Staufen2-containing mRNPs that code for proteins involved in cellular processes such as post-translational protein modifications, RNA metabolism, intracellular transport and translation. These results represent an additional and important step in the characterization of Staufen2- mediated neuronal functions in rat brains.
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El-Nahas, Amira E; Allam, Ahmed N; Abdelmonsif, Doaa A; El-Kamel, Amal H
2017-11-01
The objectives of this study were to formulate, characterize silymarin-loaded Eudragit nanoparticles (SNPs) and evaluate their hepatoprotective and cytotoxic effects after oral administration. SNPs were prepared by nanoprecipitation technique and were evaluated for particle size, entrapment efficiency, TEM, solid-state characterization, and in vitro drug release. The hepatoprotective activity was evaluated after oral administration of selected SNPs in carbon tetrachloride-intoxicated rats. Potential in vivo acute cytotoxicity study was also assessed. The selected SNPs contained 50 mg silymarin and 50 mg Eudragit polymers (1:1 w/w Eudragit RS 100 & Eudragit LS 100). Morphology of the selected SNPs (particle size of 84.70 nm and entrapment efficiency of 83.45% with 100% drug release after 12 h) revealed spherical and uniformly distributed nanoparticles. DSC and FT-IR studies suggested the presence of silymarin in an amorphous state and absence of chemical interaction. The hepatoprotective evaluation of the selected SNPs in CCl 4 -intoxicated rats revealed significant improvement in the activities of different biochemical parameters (P ≤ 0.01) compared to the marketed product. The histopathological studies suggested that the selected SNPs produced better hepatoprotective effect in CCl 4 -intoxicated rats compared with the commercially marketed product. Toxicity study revealed no evident toxic effect for blank or silymarin-loaded nanoparticles at the dose level of 50 mg/kg body weight. The obtained results suggested that the selected SNPs were safe and potentially offered enhancement in the pharmacological hepatoprotective properties of silymarin.
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Tokiwa, Toshihiro; Harunari, Tsunehito; Tanikawa, Tsutomu; Akao, Nobuaki; Ohta, Nobuo
2011-09-01
We collected 24 brown rats, Rattus norvegicus, in Kanagawa Prefecture in Japan and found one rat harboring a dioctophymatid nematode. A single male and a female worm were recovered from the abdominal cavity and were identified as Dioctophyme renale based on morphologic features and a BLAST DNA sequence analysis. We describe the morphological features of the adult worms and eggs from this extremely rare case of D. renale infection in a brown rat. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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Oliveira, Vitor Antunes; Favero, Gaia; Stacchiotti, Alessandra; Giugno, Lorena; Buffoli, Barbara; de Oliveira, Claudia Sirlene; Lavazza, Antonio; Albanese, Massimo; Rodella, Luigi Fabrizio; Pereira, Maria Ester; Rezzani, Rita
2017-05-01
This work investigated the effects of mercury chloride (HgCl 2 ) acute exposure on virgin, pregnant and lactating rats by determination of renal and hepatic morphological and ultrastructural parameters and the expression of oxidative stress and stress tolerance markers, due to kidney and liver are the organs that more accumulate inorganic mercury. Adult Wistar rats virgin (90 days old), pregnant (18 th gestation day) and lactating (7 th lactation day) were injected once with HgCl 2 (5 mg/kg) or saline (controls). We observed that HgCl 2 exposure of virgin rats caused significant inflammatory infiltration and severe morphological variations, like glomeruli atrophy, dilatation of Bowman's capsule, tubular degeneration and hepatocytes alteration. Moreover, virgin rats presented mitochondrial modification, important oxidative stress and increase in stress tolerance proteins at both kidney and liver level, compared with virgin controls. In detail, virgin rats exposed to HgCl 2 presented significantly elevated level of inducible nitric oxide synthase, heat shock protein 27 and glucose regulated proteins 75 expressions at both renal tubular and hepatocytes level, respect untreated virgin rats. Interestingly, pregnant and lactating rats exposed to HgCl 2 presented weak renal and liver morphological alterations, showing weak inflammatory infiltration and no significant difference in structural mitochondrial transmembrane protein, oxidative stress markers and stress tolerance proteins expressions respect controls (virgin, pregnant and lactating rats). Although, both control and HgCl 2 -exposed pregnant and lactating rats showed renal glomeruli greater in diameter respect virgin rats. In conclusion, we believe that virgin rats are more sensitive to HgCl 2 toxicity respect pregnant and lactating rats. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1500-1512, 2017. © 2016 Wiley Periodicals, Inc.
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Cortical astrocytes exposed to tributyltin undergo morphological changes in vitro.
Mizuhashi, S; Ikegaya, Y; Nishiyama, N; Matsuki, N
2000-11-01
We investigated the effect of tributyltin (TBT), an endocrine-disrupting chemical, on the morphology and viability of cultured rat cortical astrocytes. Cultured astrocytes exhibited smooth and planiform morphology under normal conditions. Following exposure to TBT, however, they showed rapid morphological changes that are characterized by asteriated cell bodies and process formation in a time- and concentration-dependent manner. Higher concentrations of TBT produced progressive cell death of the astrocytes. In serum-free medium, TBT at a concentration as low as 200 nM induced the stellation. Pharmacological studies revealed that the morphological changes were alleviated by application of diverse free radical scavengers or antioxidants such as catalase, superoxide dismutase, Trolox, ascorbic acid and N-acetyl-L-cysteine, suggesting that TBT-induced stellation is caused by oxidative stress involving free radicals, particularly reactive oxygen species. Furthermore, we found that the astrocyte stellation was abolished by treatment with inhibitors of phospholipase C, mitogen-activated protein kinase kinase or tyrosine phosphatase. The data suggest that TBT causes the stellation through intracellular signaling cascades rather than its non-specific toxicity. These findings provide an important insight for reconciling the problems in assumed aversive actions of this environmental pollutant for mammals.
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González-Trujano, María Eva; Alvarado-Vásquez, Noé; Mendoza-Sotelo, José; López, Guadalupe; Estrada-Camarena, Erika; Martínez-Mota, Lucia; Moreno, Julia
2012-08-01
Biochemical markers associated with the prognosis of depression in humans are being described in the literature, whereas experimental studies in animal models in search for antidepressant strategies are lacking. The aim of this study was to evaluate platelet morphology, platelet activity and nitric oxide (NO) synthesis as possible biomarkers of depressive-like behavior by using FST alone and in the presence of fluoxetine. Naïve rats were compared to those receiving vehicle or fluoxetine at 10mg/kg i.p. in acute, subchronic and chronic administration in the FST. After behavioral assessment, platelets were isolated from blood samples and analyzed by flow cytometry to determine the platelet mitochondrial membrane potential and NO synthesis. In addition, HPLC and electron microscopy were used to examine 5-HT and tryptophan levels and morphology of platelets, respectively. Rats receiving vehicle and exposed to FST showed depressive-like behavior at all the times tested; after chronic FST rats showed a similar pattern of alteration in platelet morphology and in the studied as possible biochemical markers as those previously recognized in depressive humans. Depressive-like behavior in rats exposed to FST was prevented in the presence of fluoxetine administration at all the times tested and associated with the prevention of alterations in platelet morphology, platelet activity and NO synthesis, and/or in 5-HT concentrations. The results of the present study suggest that platelet function and morphology might be relevant markers for the prognosis of depression and the search for functional treatments. Besides, the relevance of FST as model to study this psychiatric illness is reinforced. Copyright © 2012 Elsevier Inc. All rights reserved.
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Rojo, Concepción; Leguey, Ignacio; Kastanauskaite, Asta; Bielza, Concha; Larrañaga, Pedro; DeFelipe, Javier; Benavides-Piccione, Ruth
2016-06-01
Pyramidal cell structure varies between different cortical areas and species, indicating that the cortical circuits that these cells participate in are likely to be characterized by different functional capabilities. Structural differences between cortical layers have been traditionally reported using either the Golgi method or intracellular labeling, but the structure of pyramidal cells has not previously been systematically analyzed across all cortical layers at a particular age. In the present study, we investigated the dendritic architecture of complete basal arbors of pyramidal neurons in layers II, III, IV, Va, Vb, and VI of the hindlimb somatosensory cortical region of postnatal day 14 rats. We found that the characteristics of basal dendritic morphologies are statistically different in each cortical layer. The variations in size and branching pattern that exist between pyramidal cells of different cortical layers probably reflect the particular functional properties that are characteristic of the cortical circuit in which they participate. This new set of complete basal dendritic arbors of 3D-reconstructed pyramidal cell morphologies across each cortical layer will provide new insights into interlaminar information processing in the cerebral cortex. © The Author 2016. Published by Oxford University Press.
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Carter, Angela N.; Born, Heather A.; Levine, Amber T.; Dao, An T.; Zhao, Amanda J.; Lee, Wai L.
2017-01-01
Numerous studies have shown epilepsy-associated cognitive deficits, but less is known about the effects of one single generalized seizure. Recent studies demonstrate that a single, self-limited seizure can result in memory deficits and induces hyperactive phosphoinositide 3-kinase/Akt (protein kinase B)/mechanistic target of rapamycin (PI3K/Akt/mTOR) signaling. However, the effect of a single seizure on subcellular structures such as dendritic spines and the role of aberrant PI3K/Akt/mTOR signaling in these seizure-induced changes are unclear. Using the pentylenetetrazole (PTZ) model, we induced a single generalized seizure in rats and: (1) further characterized short- and long-term hippocampal and amygdala-dependent memory deficits, (2) evaluated whether there are changes in dendritic spines, and (3) determined whether inhibiting hyperactive PI3K/Akt/mTOR signaling rescued these alterations. Using the PI3K inhibitor wortmannin (Wort), we partially rescued short- and long-term memory deficits and altered spine morphology. These studies provide evidence that pathological PI3K/Akt/mTOR signaling plays a role in seizure-induced memory deficits as well as aberrant spine morphology. PMID:28612047
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Influence of long-term treatment of the rat with clebopride on the morphology of the mammary gland.
de Lima, T C; Morato, G S; Loch, S; Tames, D R
1990-01-01
The substituted benzamides or orthopramides are used to treat gastrointestinal and psychotic disorders. The orthopramide clebopride, a potent dopaminergic antagonist, blocks emesis in dogs and stereotyped behavior in rodents. Since the release of prolactin is inhibited by dopamine, antidopaminergic drugs may be useful to increase lactation in nursing mothers. The present work examines the morphological and histological alterations produced by long-term treatment of puerperal and virgin female rats with clebopride. Clebopride induced significant hyperplasia of parenchymal secretory units and stimulated milk secretion in both groups of rats. However, only in virgin rats was mammary weight significantly increased.
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Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat
Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan
2014-01-01
The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome. PMID:25285307
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Yang, Fan; Zhao, Jian F; Shou, Qi Y; Huang, Xiao J; Chen, Gang; Yang, Ke B; Zhang, Shi G; Lv, Bo D; Fu, Hui Y
2014-01-01
Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis. We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats. Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats. CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.
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Waldvogel, H J; Kubota, Y; Trevallyan, S C; Kawaguchi, Y; Fritschy, J M; Mohler, H; Faull, R L
1997-10-01
The distribution, morphology and chemical characteristics of neurons immunoreactive for the alpha1-subunit of the GABA(A) receptor in the striatum of the basal ganglia in the rat brain were investigated at the light, confocal and electron microscope levels using single, double and triple immunohistochemical labelling techniques. The results showed that alpha1-subunit immunoreactive neurons were sparsely distributed throughout the rat striatum. Double and triple labelling results showed that all the alpha1-subunit-immunoreactive neurons were positive for glutamate decarboxylase and immunoreactive for the beta2,3 and gamma2 subunits of the GABA(A) receptor. Three types of alpha1-subunit-immunoreactive neurons were identified in the striatum on the basis of cellular morphology and chemical characteristics. The most numerous alpha1-subunit-immunoreactive neurons were medium-sized, aspiny neurons with a widely branching dendritic tree. They were parvalbumin-negative and were located mainly in the dorsolateral regions of the striatum. Electron microscopy showed that these neurons had an indented nuclear membrane, typical of striatal interneurons, and were surrounded by small numbers of axon terminals which established alpha1-subunit-immunoreactive synaptic contacts with the soma and dendrites. These cells were classified as type 1 alpha1-subunit-immunoreactive neurons and comprised 75% of the total population of alpha1-subunit-immunoreactive neurons in the striatum. The remaining alpha1-subunit-immunoreactive neurons comprised of a heterogeneous population of large-sized neurons localized in the ventral and medial regions of the striatum. The most numerous large-sized cells were parvalbumin-negative, had two to three relatively short branching dendrites and were designated type 2 alpha1-subunit-immunoreactive neurons. Electron microscopy showed that the type 2 neurons were characterized by a highly convoluted nuclear membrane and were sparsely covered with small axon terminals. The type 2 neurons comprised 20% of the total population of alpha1-subunit-immunoreactive neurons. The remaining large-sized alpha1-immunoreactive cells were designated type 3 cells; they were positive for parvalbumin and were distinguished by long branching dendrites extending dorsally for 600-800 microm into the striatum. These neurons comprised 5% of the total population of alpha1-subunit-immunoreactive neurons and were surrounded by enkephalin-immunoreactive terminals. Electron microscopy showed that the alpha1-subunit type 3 neurons had an indented nuclear membrane and were densely covered with small axon terminals which established alpha1-subunit-immunoreactive symmetrical synaptic contacts with the soma and dendrites. These results provide a detailed characterization of the distribution, morphology and chemical characteristics of the alpha1-subunit-immunoreactive neurons in the rat striatum and suggest that the type 1 and type 2 neurons comprise of separate populations of striatal interneurons while the type 3 neurons may represent the large striatonigral projection neurons described by Bolam et al. [Bolam J. P., Somogyi P., Totterdell S. and Smith A. D. (1981) Neuroscience 6, 2141-2157.].
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Hasegawa, Tomoka; Li, Minqi; Hara, Kuniko; Sasaki, Muneteru; Tabata, Chihiro; de Freitas, Paulo Henrique Luiz; Hongo, Hiromi; Suzuki, Reiko; Kobayashi, Masatoshi; Inoue, Kiichiro; Yamamoto, Tsuneyuki; Oohata, Noboru; Oda, Kimimitsu; Akiyama, Yasuhiro; Amizuka, Norio
2011-08-01
Osteogenic disorder shionogi (ODS) rats carry a hereditary defect in ascorbic acid synthesis, mimicking human scurvy when fed with an ascorbic acid-deficient (aa-def) diet. As aa-def ODS rats were shown to feature disordered bone formation, we have examined the bone mineralization in this rat model. A fibrous tissue layer surrounding the trabeculae of tibial metaphyses was found in aa-def ODS rats, and this layer showed intense alkaline phosphatase activity and proliferating cell nuclear antigen-immunopositivity. Many osteoblasts detached from the bone surfaces and were characterized by round-shaped rough endoplasmic reticulum (rER), suggesting accumulation of malformed collagen inside the rER. Accordingly, fine, fragile fibrillar collagenous structures without evident striation were found in aa-def bones, which may result from misassembling of the triple helices of collagenous α-chains. Despite a marked reduction in bone formation, ascorbic acid deprivation seemed to have no effect on mineralization: while reduced in number, normal matrix vesicles and mineralized nodules could be seen in aa-def bones. Fine needle-like mineral crystals extended from these mineralized nodules, and were apparently bound to collagenous fibrillar structures. In summary, collagen mineralization seems unaffected by ascorbic acid deficiency in spite of the fine, fragile collagenous fibrils identified in the bones of our animal model.
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Ketamine-induced apoptosis in cultured rat cortical neurons
DOE Office of Scientific and Technical Information (OSTI.GOV)
Takadera, Tsuneo; Ishida, Akira; Ohyashiki, Takao
2006-01-15
Recent data suggest that anesthetic drugs cause neurodegeneration during development. Ketamine is frequently used in infants and toddlers for elective surgeries. The purpose of this study is to determine whether glycogen synthase kinase-3 (GSK-3) is involved in ketamine-induced apoptosis. Ketamine increased apoptotic cell death with morphological changes which were characterized by cell shrinkage, nuclear condensation or fragmentation. In addition, insulin growth factor-1 completely blocked the ketamine-induced apoptotic cell death. Ketamine decreased Akt phosphorylation. GSK-3 is known as a downstream target of Akt. The selective inhibitors of GSK-3 prevented the ketamine-induced apoptosis. Moreover, caspase-3 activation was accompanied by the ketamine-induced cellmore » death and inhibited by the GSK-3 inhibitors. These results suggest that activation of GSK-3 is involved in ketamine-induced apoptosis in rat cortical neurons.« less
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Proliferative and morphologic changes in rat colon following bypass surgery.
Barkla, D. H.; Tutton, P. J.
1985-01-01
In this study the proliferative and morphologic changes that occur in the colon of normal and dimethylhydrazine-treated rats following surgical bypass of the middle third of the colon are reported. Proliferative changes were measured by estimating accumulated mitotic indexes following vinblastine treatment and morphologic changes were observed with the use of light microscopy and scanning electron microscopy. Data were collected on Days 0, 7, 14, 30, and 72 after surgery. The results show that surgical bypass produces contrasting effects in the segments proximal to and distal to the suture line. In the proximal segment there was morphologic evidence of hyperplasia, although proliferative activity was unchanged except for an increase at 7 days in normal rats. In the distal segment there was a long-lived increase in the mitotic index, although morphologic changes were not seen. The results for DMH-treated rats were similar to those in normal rats. Groups of isolated dysplastic epithelial cells were often seen in the submucosa adjacent to sutures up to 72 days after surgery. Increased lymphoid infiltration was seen in segments proximal to but not distal to the suture line. It is hypothesized that the different responses of the proximal and distal segments may be related to the different embryologic origins of those segments. It is also hypothesized that the seeding of the submucosa with epithelial cells during suturing may be a factor in tumor recurrence. Images Figure 19 Figure 20 Figure 21 Figure 22 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 PMID:4014432
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Almabhouh, F A; Osman, K; Siti Fatimah, I; Sergey, G; Gnanou, J; Singh, H J
2015-09-01
Altered epididymal sperm count and morphology following leptin treatment has been reported recently. This study examined the effects of 42 days of leptin treatment on sperm count and morphology and their reversibility during a subsequent 56-day recovery period. Twelve-week-old male Sprague-Dawley rats were randomised into four leptin and four saline-treated control groups (n = 6). Intraperitoneal injections of leptin were given daily (60 μg Kg(-1) body weight) for 42 days. Controls received 0.1 ml of 0.9% saline. Leptin-treated animals and their respective age-matched controls were euthanised on either day 1, 21, 42 or 56 of recovery for collection of epididymal spermatozoa. Sperm concentration was determined using a Makler counting chamber. Spermatozoa were analysed for 8-hydroxy-2-deoxyguanosine and DNA fragmentation (Comet assay). Data were analysed using anova. Sperm concentration was significantly lower but fraction of abnormal spermatozoa, and levels of 8-hydroxy-2-deoxyguanosine were significantly higher in leptin-treated rats on day 1 of recovery. Comet assays revealed significant DNA fragmentation in leptin-treated rats. These differences were reduced by day 56 of recovery. It appears that 42 days of leptin treatment to Sprague-Dawley rats has significant adverse effects on sperm count and morphology that reverse following discontinuation of leptin treatment. © 2014 Blackwell Verlag GmbH.
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Souza, Joyce G R; Garcia, Juberlan S; Gomes, Ana Paula N; Machado-Silva, José Roberto; Maldonado, Arnaldo
2017-12-01
Echinostoma paraensei (Digenea: Echinostomatidae) lives in the duodenum and bile duct of rodents and is reported as a useful model for studies on the biology of flatworms. Here, we compared the growth and development of pre and post ovigerous worms collected 3, 7, 14 and 21 days post infection from experimentally infected hamster (permissive host) and Wistar rat (less permissive hosts). Linear measurements and ratios were examined by light (morphology and morphometry) and confocal laser scanning microscopy. At day 3, either worm from hamsters or rats were small with poorly developed gonads. At seven day, worms increased in size and morphometric differences between hosts are statistically significant after this time. In addition, adult worms (14 and 21 days of age) harvested from hamster showed developed gonads and vitelline glands laterally distributed on the body, whereas worms from rat showed atrophied reproductive system characterized by underdeveloped vitelline glands and stunted ovary. The worm rate recovery in rat decreased from 29.3% (day 7) to 20.6% (day 14) and 8% (day 21), whilst it remained around 37% in hamster. In conclusion, this is the first appointment demonstrating that low permissiveness influences the reproductive system of echinostome since the immature stages of development. The phenotypic analysis evidenced that hamster provides a more favorable microenvironment for gonads development than rat, confirming golden hamster as a permissive host, whereas Wistar rat is less permissive host. Copyright © 2017 Elsevier Inc. All rights reserved.
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A dysmorphology score system for assessing embryo abnormalities in rat whole embryo culture.
Zhang, Cindy X; Danberry, Tracy; Jacobs, Mary Ann; Augustine-Rauch, Karen
2010-12-01
The rodent whole embryo culture (WEC) system is a well-established model for characterizing developmental toxicity of test compounds and conducting mechanistic studies. Laboratories have taken various approaches in describing type and severity of developmental findings of organogenesis-stage rodent embryos, but the Brown and Fabro morphological score system is commonly used as a quantitative approach. The associated score criteria is based upon developmental stage and growth parameters, where a series of embryonic structures are assessed and assigned respective scores relative to their gestational stage, with a Total Morphological Score (TMS) assigned to the embryo. This score system is beneficial because it assesses a series of stage-specific anatomical landmarks, facilitating harmonized evaluation across laboratories. Although the TMS provides a quantitative approach to assess growth and determine developmental delay, it is limited to its ability to identify and/or delineate subtle or structure-specific abnormalities. Because of this, the TMS may not be sufficiently sensitive for identifying compounds that induce structure or organ-selective effects. This study describes a distinct morphological score system called the "Dysmorphology Score System (DMS system)" that has been developed for assessing gestation day 11 (approximately 20-26 somite stage) rat embryos using numerical scores to differentiate normal from abnormal morphology and define the respective severity of dysmorphology of specific embryonic structures and organ systems. This method can also be used in scoring mouse embryos of the equivalent developmental stage. The DMS system enhances capabilities to rank-order compounds based upon teratogenic potency, conduct structure- relationships of chemicals, and develop statistical prediction models to support abbreviated developmental toxicity screens. © 2010 Wiley-Liss, Inc.
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Omelchenko, N; Sesack, S R
2007-05-25
Dopamine and GABA neurons in the ventral tegmental area project to the nucleus accumbens and prefrontal cortex and modulate locomotor and reward behaviors as well as cognitive and affective processes. Both midbrain cell types receive synapses from glutamate afferents that provide an essential control of behaviorally-linked activity patterns, although the sources of glutamate inputs have not yet been completely characterized. We used antibodies against the vesicular glutamate transporter subtypes 1 and 2 (VGlut1 and VGlut2) to investigate the morphology and synaptic organization of axons containing these proteins as putative markers of glutamate afferents from cortical versus subcortical sites, respectively, in rats. We also characterized the ventral tegmental area cell populations receiving VGlut1+ or VGlut2+ synapses according to their transmitter phenotype (dopamine or GABA) and major projection target (nucleus accumbens or prefrontal cortex). By light and electron microscopic examination, VGlut2+ as opposed to VGlut1+ axon terminals were more numerous, had a larger average size, synapsed more proximally, and were more likely to form convergent synapses onto the same target. Both axon types formed predominantly asymmetric synapses, although VGlut2+ terminals more often formed synapses with symmetric morphology. No absolute selectivity was observed for VGlut1+ or VGlut2+ axons to target any particular cell population. However, the synapses onto mesoaccumbens neurons more often involved VGlut2+ terminals, whereas mesoprefrontal neurons received relatively equal synaptic inputs from VGlut1+ and VGlut2+ profiles. The distinct morphological features of VGlut1 and VGlut2 positive axons suggest that glutamate inputs from presumed cortical and subcortical sources, respectively, differ in the nature and intensity of their physiological actions on midbrain neurons. More specifically, our findings imply that subcortical glutamate inputs to the ventral tegmental area expressing VGlut2 predominate over cortical sources of excitation expressing VGlut1 and are more likely to drive the behaviorally-linked bursts in dopamine cells that signal future expectancy or attentional shifting.
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Cai, Huan; Daimon, Caitlin M.; Cong, Wei-na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen
2014-01-01
Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste–related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste–related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR. PMID:24077597
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Cai, Huan; Daimon, Caitlin M; Cong, Wei-Na; Wang, Rui; Chirdon, Patrick; de Cabo, Rafael; Sévigny, Jean; Maudsley, Stuart; Martin, Bronwen
2014-05-01
Calorie restriction (CR) is a lifestyle intervention employed to reduce body weight and improve metabolic functions primarily via reduction of ingested carbohydrates and fats. Taste perception is highly related to functional metabolic status and body adiposity. We have previously shown that sweet taste perception diminishes with age; however, relatively little is known about the effects of various lengths of CR upon taste cell morphology and function. We investigated the effects of CR on taste bud morphology and expression of sweet taste-related modulators in 5-, 17-, and 30-month-old rats. In ad libitum (AL) and CR rats, we consistently found the following parameters altered significantly with advancing age: reduction of taste bud size and taste cell numbers per taste bud and reduced expression of sonic hedgehog, type 1 taste receptor 3 (T1r3), α-gustducin, and glucagon-like peptide-1 (GLP-1). In the oldest rats, CR affected a significant reduction of tongue T1r3, GLP-1, and α-gustducin expression compared with age-matched AL rats. Leptin receptor immunopositive cells were elevated in 17- and 30-month-old CR rats compared with age-matched AL rats. These alterations of sweet taste-related modulators, specifically during advanced aging, suggest that sweet taste perception may be altered in response to different lengths of CR.
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Preparation and evaluation of biocomposites as wound dressing material.
Ramnath, V; Sekar, S; Sankar, S; Sankaranarayanan, C; Sastry, T P
2012-12-01
Collagen was isolated from the chrome containing leather waste (CCLW) which is a major solid waste in leather industry. Composite films were made using sago starch (SG), soya protein (SY), and collagen (C) and were cross linked with glutaraldehyde (G).The films prepared were characterized for their physico chemical properties like tensile strength, infrared spectra, thermogravimetric analysis, surface morphology, and water absorption studies. Better mechanical properties and surface morphology were observed for SG-SY-G-C films compared to other films prepared using collagen. The composite films prepared were used as wound dressing material on the experimental wounds of rats and healing pattern was evaluated using planimetric, biochemical, and histopathological studies. These studies have revealed better wound healing capacity of SG-SY-G-C film and utilization of CCLW in the preparation of value added product like wound dressing material.
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Hyberbaric oxygen increases atresia in normal & steroid induced PCO rat ovaries
2012-01-01
Background In this study, we investigated the effect of hyperbaric oxygen therapy (HBOT) on the morphology of estradiol valerate (EV) induced polycystic ovary (PCO) to find a new treatment modality for improvement of PCO. Methods The rats were divided into four groups. Group1, control; group 2, PCO group; group 3, PCO with HBOT group and group 4, normal ovary with HBOT. PCO was induced by a single intramuscular injection of 4 mg EV in adult cycling rats. Other rats with normal ovaries had oil injection as placebo. HBOT was applied to third and fourth groups for six weeks. Histopathologic evaluation of ovaries of all groups were performed & compared. Results Six weeks of HBOT was resulted in increase in follicular atresia, decrease in the number of primary, secondary, tertiary follicles and decrease in the number of fresh corpus luteum in normal rat ovary. HBOT on polycystic rat ovary, resulted in significant increase in atretic follicles which were already present. Conclusions HBOT of six weeks itself, changed ovarian morphology in favor of atresia both in PCO group and control group. This result of aggravated follicular atresia after HBOT on EV induced PCO may be due to long-term exposure in our protocol which with this state seems to be inapplicable in the improvement of PCO morphology. PMID:22309835
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Nash, P; Eriksson, U J
2007-01-01
Previously maternal and fetal alterations resembling human pre-eclampsia were induced in pregnant rats by injections of the angiogenesis inhibitor Suramin. These alterations were aggravated by maternal diabetes and partly rectified by vitamin E supplementation. In the present study we evaluated the morphology of placentae and kidneys in this model. Non-diabetic and streptozotocin-induced diabetic pregnant rats of two rat strains (U and H) were treated with Suramin or saline, and given standard or vitamin E-enriched food. On gestational day 20 one placenta and the left kidney of the mother were collected for morphological and stereological analysis. In the placental trophospongium Suramin treatment caused cysts, which were further enhanced by maternal diabetes. Vitamin E treatment had no effect on the vacuolization. In the placental labyrinth of the non-diabetic rats Suramin treatment restricted maternal placental blood volume and increased the interface between maternal and fetal circulation. These changes were reversed by vitamin E treatment. Diabetes increased slightly the interface between the circulations in both rat strains. Suramin treatment decreased the interface, and vitamin E further decreased the interface in the diabetic U rats, whereas neither treatment affected the maternal-fetal interface in the diabetic H rats. The kidneys of Suramin-treated and diabetic rats were heavier compared to controls. Suramin treatment and maternal diabetes damaged renal glomeruli to a similar extent. Vitamin E treatment diminished the Suramin- and diabetes-induced glomerular damage in U rats, but not in H rats. The average cell count per glomerulus was decreased by Suramin in the U rats. Vitamin E treatment did not affect cell number per glomerulus in any group. We conclude that Suramin-injected pregnant rats constitute a valid animal model for placental dysfunction and pre-eclampsia, also from the histological perspective. The present work supports the notion that one important effect of untreated maternal diabetes may be impaired placentation, leading to oxidative stress, morphological damage, and compromised placental function.
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Felix-Patrício, Bruno; Medeiros, Jorge L; De Souza, Diogo B; Costa, Waldemar S; Sampaio, Francisco J B
2015-01-01
Erectile dysfunction (ED) is frequently associated to hypertension and antihypertensive drugs; however, the penile morphological aspects on these situations are poorly known. Evaluate the penile morphology of untreated hypertensive rats and rats treated with enalapril or sildenafil alone or in combination to verify the hypothesis that morphological alterations promoted by hypertension on corpus cavernosum could be ameliorated by the use of angiotensin-converting enzyme inhibitors and/or phosphodiesterase type 5 inhibitors. Fifty male rats were assigned into five groups: normotensive rats, untreated spontaneously hypertensive rats (SHRs), and SHR treated with enalapril or sildenafil alone or in combination. Blood pressure was measured weekly. At the conclusion of the study, the rats were euthanized, and their penises were collected for histomorphometrical analysis. The cross-sectional areas of the penis, tunica albuginea, and corpus cavernosum were measured. The density of the corpus cavernosum structures was quantified. Both groups of SHR rats treated with enalapril became normotensive. Untreated SHR showed no difference in penile and cavernosal cross-sectional area compared with normotensive rats; however, those rats treated with enalapril or sildenafil alone demonstrated an increase in these parameters. Rats receiving combination therapy showed no cross-sectional area differences compared with normotensive rats. Cavernosal connective tissue density was increased, while the sinusoidal spaces were diminished in untreated SHR. All treatments were effective in maintaining connective tissue density in comparison with normotensive animals. Cavernosal smooth muscle density was similar in all groups, with the exception of the combination therapy group, which demonstrated a reduction in smooth muscle. Hypertension promoted structural alterations in the corpus cavernosum that may be related to ED. Enalapril- and sildenafil-treated animals had preservation of normal corpus cavernosum structure and an increase in penile and cavernosal cross-sectional area. The combination of these drugs showed less benefit than individual use. © 2014 International Society for Sexual Medicine.
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Effects of Arginase Inhibition in Hypertensive Hyperthyroid Rats.
Rodríguez-Gómez, Isabel; Manuel Moreno, Juan; Jimenez, Rosario; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Wangensteen, Rosemary; Vargas, Félix
2015-12-01
This study analyzed the effects of chronic administration of N[omega]-hydroxy-nor-l-arginine (nor-NOHA), an inhibitor of arginase, on the hemodynamic, oxidative stress, morphologic, metabolic, and renal manifestations of hyperthyroidism in rats. Four groups of male Wistar rats were used: control, nor-NOHA-treated (10 mg/kg/day), thyroxine (T4)-treated (75 μg/rat/day), and thyroxine- plus nor-NOHA-treated rats. All treatments were maintained for 4 weeks. Body weight, tail systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, morphologic, metabolic, plasma, and renal variables were measured. Arginase I and II protein abundance and arginase activity were measured in aorta, heart, and kidney. The T4 group showed increased arginase I and II protein abundance, arginase activity, SBP, HR, plasma nitrates/nitrites (NOx), brainstem and urinary isoprostanes, proteinuria and cardiac and renal hypertrophy in comparison to control rats. In hyperthyroid rats, chronic nor-NOHA prevented the increase in SBP and HR and decreased proteinuria in association with an increase in plasma NOx and a decrease in brainstem and urinary isoprostanes. In normal rats, nor-NOHA treatment did not significantly change any hemodynamic, morphologic, or renal variables. Acute nor-NOHA administration did not affect renal or systemic hemodynamic variables in normal or T4-treated rats. Hyperthyroidism in rats is associated with the increased expression and activity of arginase in aorta, heart, and kidney. Chronic arginase inhibition with nor-NOHA suppresses the characteristic hemodynamic manifestations of hyperthyroidism in association with a reduced oxidative stress. These results indicate an important role for arginase pathway alterations in the cardiovascular and renal abnormalities of hyperthyroidism. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
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A rat model of hypohidrotic ectodermal dysplasia carries a missense mutation in the Edaradd gene
2011-01-01
Background Hypohidrotic ectodermal dysplasia (HED) is a congenital disorder characterized by sparse hair, oligodontia, and inability to sweat. It is caused by mutations in any of three Eda pathway genes: ectodysplasin (Eda), Eda receptor (Edar), and Edar-associated death domain (Edaradd), which encode ligand, receptor, and intracellular adaptor molecule, respectively. The Eda signaling pathway activates NF-κB, which is central to ectodermal differentiation. Although the causative genes and the molecular pathway affecting HED have been identified, no curative treatment for HED has been established. Previously, we found a rat spontaneous mutation that caused defects in hair follicles and named it sparse-and-wavy (swh). Here, we have established the swh rat as the first rat model of HED and successfully identified the swh mutation. Results The swh/swh rat showed sparse hair, abnormal morphology of teeth, and absence of sweat glands. The ectoderm-derived glands, meibomian, preputial, and tongue glands, were absent. We mapped the swh mutation to the most telomeric part of rat Chr 7 and found a Pro153Ser missense mutation in the Edaradd gene. This mutation was located in the death domain of EDARADD, which is crucial for signal transduction and resulted in failure to activate NF-κB. Conclusions These findings suggest that swh is a loss-of-function mutation in the rat Edaradd and indicate that the swh/swh rat would be an excellent animal model of HED that could be used to investigate the pathological basis of the disease and the development of new therapies. PMID:22013926
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[Experiments using rats on Kosmos biosatellites: morphologic and biochemical studies].
Il'in, E A; Kaplanskiĭ, A S; Savina, E A
1989-01-01
Results of morphological and biochemical investigations of rats flown on Cosmos biosatellites are discussed. It is emphasized that most changes occurring during exposure to microgravity are directly or indirectly related to lower musculoskeletal loads which in turn produce deconditioning of different physiological systems and organism as a whole. It is concluded that this deconditioning is associated with both metabolic and structural changes.
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Molecular classification of spontaneous endometrial adenocarcinomas in BDII rats.
Samuelson, Emma; Hedberg, Carola; Nilsson, Staffan; Behboudi, Afrouz
2009-03-01
Female rats of the BDII/Han inbred strain are prone to spontaneously develop endometrial carcinomas (EC) that in cell biology and pathogenesis are very similar to those of human. Human EC are classified into two major groups: Type I displays endometroid histology, is hormone-dependent, and characterized by frequent microsatellite instability and PTEN, K-RAS, and CTNNB1 (beta-Catenin) mutations; Type II shows non-endometrioid histology, is hormone-unrelated, displays recurrent TP53 mutation, CDKN2A (P16) inactivation, over-expression of ERBB2 (Her2/neu), and reduced CDH1 (Cadherin 1 or E-Cadherin) expression. However, many human EC have overlapping clinical, morphologic, immunohistochemical, and molecular features of types I and II. The EC developed in BDII rats can be related to type I tumors, since they are hormone-related and histologically from endometrioid type. Here, we combined gene sequencing (Pten, Ifr1, and Ctnnb1) and real-time gene expression analysis (Pten, Cdh1, P16, Erbb2, Ctnnb1, Tp53, and Irf1) to further characterize molecular alterations in this tumor model with respect to different subtypes of EC in humans. No mutation in Pten and Ctnnb1 was detected, whereas three tumors displayed sequence aberrations of the Irf1 gene. Significant down regulation of Pten, Cdh1, p16, Erbb2, and Ctnnb1 gene products was found in the tumors. In conclusion, our data suggest that molecular features of spontaneous EC in BDII rats can be related to higher-grade human type I tumors and thus, this model represents an excellent experimental tool for research on this malignancy in human.
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Qian, Jingyi; Yeh, Bonnie; Rakshit, Kuntol; Colwell, Christopher S.
2015-01-01
There are clear epidemiological associations between circadian disruption, obesity, and pathogenesis of type 2 diabetes. The mechanisms driving these associations are unclear. In the current study, we hypothesized that continuous exposure to constant light (LL) compromises pancreatic β-cell functional and morphological adaption to diet-induced obesity leading to development of type 2 diabetes. To address this hypothesis, we studied wild type Sprague Dawley as well as Period-1 luciferase reporter transgenic rats (Per1-Luc) for 10 weeks under standard light-dark cycle (LD) or LL with concomitant ad libitum access to either standard chow or 60% high-fat diet (HFD). Exposure to HFD led to a comparable increase in food intake, body weight, and adiposity in both LD- and LL-treated rats. However, LL rats displayed profound loss of behavioral circadian rhythms as well as disrupted pancreatic islet clock function characterized by the impairment in the amplitude and the phase islet clock oscillations. Under LD cycle, HFD did not adversely alter diurnal glycemia, diurnal insulinemia, β-cell secretory function as well as β-cell survival, indicating successful adaptation to increased metabolic demand. In contrast, concomitant exposure to LL and HFD resulted in development of hyperglycemia characterized by loss of diurnal changes in insulin secretion, compromised β-cell function, and induction of β-cell apoptosis. This study suggests that circadian disruption and diet-induced obesity synergize to promote development of β-cell failure, likely mediated as a consequence of impaired islet clock function. PMID:26348474
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Age-related ultrastructural and monoamine oxidase changes in the rat optic nerve.
Taurone, S; Ripandelli, G; Minni, A; Lattanzi, R; Miglietta, S; Pepe, N; Fumagalli, L; Micera, A; Pastore, F S; Artico, M
2016-01-01
The aim of this paper is to study the morphology and the distribution of the monoamine oxidase enzymatic system in the optic nerve of 4 month-old Wistar (young) and 28 month-old Wistar (old) rats. The optic nerve was harvested from 20 young and old rats. The segment of optic nerve was divided longitudinally into two pieces, each 0.1 mm in length. The first piece was used for transmission electron microscopy. The second piece was stained with histochemical reaction for monoamine oxidase. The agerelated changes in the optic nerve of rats include micro-anatomical details, ultrastructure and monoamine oxidase histochemical staining. A strong decrease of the thin nerve fibers and a swelling of the thick ones can be observed in optic nerve fibers of old rats. Increased monoamine oxidase histochemical staining of the optic nerve of aged rats is well demonstrated. The increase of meningeal shealth and the decrease of thin nerve fibers of the optic nerve in old rats are well documented. Morphological, ultrastructural and histochemical changes observed in optic nerve fibers of the old rats show a close relation with aging.
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Papadeas, Sophia T.; Halloran, Christopher; McCown, Thomas J.; Breese, George R.; Blake, Bonita L.
2008-01-01
Rats lesioned with 6-hydroxydopamine (6-OHDA) as neonates exhibit behavioral and neurochemical abnormalities in adulthood that mimic Lesch-Nyhan disease, schizophrenia and other developmental disorders of frontostriatal circuit dysfunction. In these animals, a latent sensitivity to D1 agonists is maximally exposed by repeated administration of dopamine agonists in the post-pubertal period (D1 priming). In neonate-lesioned, adult rats primed with SKF-38393, we found selective, persistent alterations in the morphology of pyramidal neuron apical dendrites in the prelimbic area of the medial prefrontal cortex (mPFC). In these animals, dendrite bundling patterns and the typically straight trajectories of primary dendritic shafts were disrupted, whereas the diameter of higher-order oblique branches was increased. Although not present in neonate-lesioned rats treated with saline, these morphological changes persisted at least 21 days after repeated dosing with SKF-38393, and were not accompanied by markers of neurodegenerative change. A sustained increase in phospho-ERK immunoreactivity in wavy dendritic shafts over the same period suggested a relationship between prolonged ERK phosphorylation and dendritic remodeling in D1-primed rats. In support of this hypothesis, pretreatment with the MEK1/2-ERK1/2 pathway inhibitors PD98059 or SL327, prior to each priming dose of SKF-38393, prevented the morphological changes associated with D1 priming. Together, these findings demonstrate that repeated stimulation of D1 receptors in adulthood interacts with the developmental loss of dopamine to profoundly and persistently modify neuronal signaling and dendrite morphology in the mature prefrontal cortex. Furthermore, sustained elevation of ERK activity in mPFC pyramidal neurons may play a role in guiding these morphological changes in vivo. PMID:18785628
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Khavinson, V K; Konovalov, S S; Yuzhakov, V V; Popuchiev, V V; Kvetnoi, I M
2001-11-01
Immunohistochemical and morphometric analysis showed that epithalamin and epithalon produced similar effects on the functional morphology of the spleen in pinealectomized rats. Both peptides prevented hyperplasia of lymphoid cells in follicular germinative centers induced by pinealectomy and potentiated the decrease in extramedullary hemopoiesis. These findings confirm the data on functional relationships between the pineal gland and immune system. The effects of epithalamin and epithalon on cell and tissue homeostasis in the spleen of old pinealectomized rats can be regarded as a manifestation of the general regulatory effect of these peptides.
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Effect of chronic intake of liquid nutrition on stomach and duodenum morphology.
Vrabcova, Michaela; Mikuska, Livia; Vazan, Rastislav; Miko, Michal; Varga, Ivan; Mravec, Boris
2016-05-01
Changes in the quantity and/or quality of food intake have been shown to be associated with morphological and functional alterations of the gastrointestinal system. To examine this, we investigated the effect of chronic liquid nutrition intake (Fresubin) on stomach and duodenum morphology in Wistar rats fed liquid nutrition during different developmental periods. We used four groups of rats: a) control group (CON) fed pelleted chow for 130days; b) liquid nutrition group (LN) fed liquid nutrition for 130days; c) liquid nutrition juvenile group (LNJ) fed liquid nutrition for 70days and then pelleted food for 60days; d) liquid nutrition adult group (LNA) fed pelleted chow for 70days and then liquid nutrition for 60days. We found that LN and LNA rats showed a significant reduction of empty stomach mass compared to CON animals, while stomach and duodenal longitudinal muscle layer thickness did not differ between groups. Villus height was increased only in LNA animals, while villus width was increased in both LN and LNA rats. Crypt depth was reduced in LNJ. However, liquid nutrition intake did not affect villus height/crypt depth ratio, nor number of goblet cells. We found that chronic intake of liquid nutrition affects some morphological parameters of the stomach and duodenum but these changes were not homogenous between experimental groups. Interestingly, transition from liquid nutrition to solid food reversed the alterations of stomach weight as well as villus width induced by intake of liquid nutrition in LNA rats. Our data indicate that morphological and functional changes in the gastrointestinal system induced by qualitative and quantitative changes in food intake are at least partially reversible. Therefore, specific diets may be used potentially as adjuvant treatment for modulating the progression of gastrointestinal diseases by affecting stomach and small intestine morphology. Copyright © 2016 Elsevier GmbH. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Pérez Díaz, Matías F.F.; Acosta, Mariano; Mohamed, Fabián H.
We investigated the effects of cadmium exposition on thoracic aorta redox status and morphology, and the putative protective effect of soybeans in the diet. Male Wistar rats were separated into 6 groups: 3 fed with a diet containing casein and 3 containing soybeans, as protein source. Within each protein group, one was given tap water (control) and the other two tap water containing 15 and 100 ppm of Cd{sup 2+}, respectively, for two months. In rats fed with casein diet, 15 ppm of Cd induced an increase of thiobarbituric acid-reactive substances (TBARS), and of the catalase (CAT) and glutathione peroxidasemore » (GPx) activities, which were even higher with 100 ppm of Cd{sup 2+}, in aorta. Also, 100 ppm Cd{sup 2+} exposure increased superoxide dismutase (CuZnSOD) activity; CAT, GPX, SOD, Nrf2 and metallothioneine II mRNA expressions and CAT, GPx and NOX-2 protein levels, compared with control. Aorta endothelial and cytoplasmic alterations were observed. However, with the soybeans diet, 15 and 100 ppm of Cd{sup 2+} did not modify TBARS levels; CAT, GPX and Nrf2 mRNA expressions; CAT, GPx and NOX-2 protein; and the aorta morphology, compared with control. The soybean diet attenuates the redox changes and protects against morphological alterations induced, in a dose-dependent way, by Cd in aorta. - Highlights: • Under casein diet, 100 ppm Cd{sup 2+} in drinking water induces oxidative stress in aorta. • Under casein diet, 100 ppm Cd{sup 2+} increases Nrf2, MT II and NOX2 expressions in aorta. • Under casein diet, 100 ppm Cd{sup 2+} induces morphological changes in rat aorta. • The soybean diet attenuates the redox changes induced by Cd in rat aorta. • The soybean diet attenuates morphological alterations induced by Cd in rat aorta.« less
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Kozinets, G I; Korol'kov, V I; Britvan, I I; Bykova, I A; Spitsyna, N E
1983-01-01
Morphofunctional properties of peripheral blood cells of Cosmos-936 rats were examined, using morphological, interferometric and electron microscopic techniques. As follows from the morphological data, immediately after recovery the weightless rats showed symptoms of a stress reaction which disappeared by R+3. The centrifuged rats exhibited less expressed symptoms of this sort. The percentage of bone marrow cell distribution was shifted towards enhanced myelopoiesis and diminished erythropoiesis. By the end of the readaptation period the ratio of bone marrow cell composition returned to normal. Interferometric and electron microscopic examinations did not reveal any irreversible changes in the structure and function of cells that may be caused by zero-g.
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Fernández-Arjona, María Del Mar; Grondona, Jesús M; Granados-Durán, Pablo; Fernández-Llebrez, Pedro; López-Ávalos, María D
2017-01-01
It is known that microglia morphology and function are closely related, but only few studies have objectively described different morphological subtypes. To address this issue, morphological parameters of microglial cells were analyzed in a rat model of aseptic neuroinflammation. After the injection of a single dose of the enzyme neuraminidase (NA) within the lateral ventricle (LV) an acute inflammatory process occurs. Sections from NA-injected animals and sham controls were immunolabeled with the microglial marker IBA1, which highlights ramifications and features of the cell shape. Using images obtained by section scanning, individual microglial cells were sampled from various regions (septofimbrial nucleus, hippocampus and hypothalamus) at different times post-injection (2, 4 and 12 h). Each cell yielded a set of 15 morphological parameters by means of image analysis software. Five initial parameters (including fractal measures) were statistically different in cells from NA-injected rats (most of them IL-1β positive, i.e., M1-state) compared to those from control animals (none of them IL-1β positive, i.e., surveillant state). However, additional multimodal parameters were revealed more suitable for hierarchical cluster analysis (HCA). This method pointed out the classification of microglia population in four clusters. Furthermore, a linear discriminant analysis (LDA) suggested three specific parameters to objectively classify any microglia by a decision tree. In addition, a principal components analysis (PCA) revealed two extra valuable variables that allowed to further classifying microglia in a total of eight sub-clusters or types. The spatio-temporal distribution of these different morphotypes in our rat inflammation model allowed to relate specific morphotypes with microglial activation status and brain location. An objective method for microglia classification based on morphological parameters is proposed. Main points Microglia undergo a quantifiable morphological change upon neuraminidase induced inflammation.Hierarchical cluster and principal components analysis allow morphological classification of microglia.Brain location of microglia is a relevant factor.
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Fernández-Arjona, María del Mar; Grondona, Jesús M.; Granados-Durán, Pablo; Fernández-Llebrez, Pedro; López-Ávalos, María D.
2017-01-01
It is known that microglia morphology and function are closely related, but only few studies have objectively described different morphological subtypes. To address this issue, morphological parameters of microglial cells were analyzed in a rat model of aseptic neuroinflammation. After the injection of a single dose of the enzyme neuraminidase (NA) within the lateral ventricle (LV) an acute inflammatory process occurs. Sections from NA-injected animals and sham controls were immunolabeled with the microglial marker IBA1, which highlights ramifications and features of the cell shape. Using images obtained by section scanning, individual microglial cells were sampled from various regions (septofimbrial nucleus, hippocampus and hypothalamus) at different times post-injection (2, 4 and 12 h). Each cell yielded a set of 15 morphological parameters by means of image analysis software. Five initial parameters (including fractal measures) were statistically different in cells from NA-injected rats (most of them IL-1β positive, i.e., M1-state) compared to those from control animals (none of them IL-1β positive, i.e., surveillant state). However, additional multimodal parameters were revealed more suitable for hierarchical cluster analysis (HCA). This method pointed out the classification of microglia population in four clusters. Furthermore, a linear discriminant analysis (LDA) suggested three specific parameters to objectively classify any microglia by a decision tree. In addition, a principal components analysis (PCA) revealed two extra valuable variables that allowed to further classifying microglia in a total of eight sub-clusters or types. The spatio-temporal distribution of these different morphotypes in our rat inflammation model allowed to relate specific morphotypes with microglial activation status and brain location. An objective method for microglia classification based on morphological parameters is proposed. Main points Microglia undergo a quantifiable morphological change upon neuraminidase induced inflammation.Hierarchical cluster and principal components analysis allow morphological classification of microglia.Brain location of microglia is a relevant factor. PMID:28848398
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Fetotoxicity of 2,4-dichlorophenoxyacetic acid in rats and the protective role of vitamin E.
Mazhar, Fatma M; Moawad, Karima M; El-Dakdoky, Mai H; Amer, Amany S
2014-06-01
The present study was conducted to investigate the potential role of 2,4-dichlorophenoxyacetic acid (2,4-D) in inducing developmental toxicity and oxidative damage in pregnant rats and their fetuses as well as to assess the efficacy of vitamin E to prevent or alleviate such defects. Pregnant rats received 2,4-D (100 mg/kg bw) alone or in combination with vitamin E (100 mg/kg bw) daily from gestation day 1 to 19. The number of implantations, viable and resorbed fetuses and sex ratio were not statistically different among groups. However, fetuses maternally treated with 2,4-D were characterized by lower body weight and higher morphologic and skeletal defect rate. 2,4-D induced oxidative stress in the liver of mothers and fetuses which was indicated by a significant elevation of malondialdehyde level with reduction in catalase activity and total antioxidant capacity. Coadministration of vitamin E can counteract the deleterious effects of 2,4-D by successive reduction in the oxidative stress. © The Author(s) 2012.
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Non-proliferative and Proliferative Lesions of the Cardiovascular System of the Rat and Mouse
Berridge, Brian R.; Mowat, Vasanthi; Nagai, Hirofumi; Nyska, Abraham; Okazaki, Yoshimasa; Clements, Peter J.; Rinke, Matthias; Snyder, Paul W.; Boyle, Michael C.; Wells, Monique Y.
2016-01-01
The INHAND Project (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) is a joint initiative of the Societies of Toxicologic Pathology from Japan (JSTP), Europe (ESTP), Great Britain (BSTP) and North America (STP) to develop an internationally-accepted nomenclature for proliferative and non-proliferative lesions in laboratory animals. The primary purpose of this publication is to provide a standardized nomenclature for characterizing lesions observed in the cardiovascular (CV) system of rats and mice commonly used in drug or chemical safety assessment. The standardized nomenclature presented in this document is also available electronically for society members on the internet (http://goreni.org). Accurate and precise morphologic descriptions of changes in the CV system are important for understanding the mechanisms and pathogenesis of those changes, differentiation of natural and induced injuries and their ultimate functional consequence. Challenges in nomenclature are associated with lesions or pathologic processes that may present as a temporal or pathogenic spectrum or when natural and induced injuries share indistinguishable features. Specific nomenclature recommendations are offered to provide a consistent approach. PMID:27621537
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Huang, He; Ye, Jing; Pan, Wei; Zhong, Yun; Cheng, Chuanfang; You, Xiangyu; Liu, Benrong; Xiong, Longgen; Liu, Shiming
2014-01-01
Cardiac hypertrophy is characterized by thickening myocardium and decreasing in heart chamber volume in response to mechanical or pathological stress, but the underlying molecular mechanisms remain to be defined. This study investigated altered miRNA expression and autophagic activity in pathogenesis of cardiac hypertrophy. A rat model of myocardial hypertrophy was used and confirmed by heart morphology, induction of cardiomyocyte autophagy, altered expression of autophagy-related ATG9A, LC3 II/I and p62 proteins, and decrease in miR-34a expression. The in vitro data showed that in hypertrophic cardiomyocytes induced by Ang II, miR-34a expression was downregulated, whereas ATG9A expression was up-regulated. Moreover, miR-34a was able to bind to ATG9A 3′-UTR, but not to the mutated 3′-UTR and inhibited ATG9A protein expression and autophagic activity. The latter was evaluated by autophagy-related LC3 II/I and p62 levels, TEM, and flow cytometry in rat cardiomyocytes. In addition, ATG9A expression induced either by treatment of rat cardiomyocytes with Ang II or ATG9A cDNA transfection upregulated autophagic activity and cardiomyocyte hypertrophy in both morphology and expression of hypertrophy-related genes (i.e., ANP and β-MHC), whereas knockdown of ATG9A expression downregulated autophagic activity and cardiomyocyte hypertrophy. However, miR-34a antagonized Ang II-stimulated myocardial hypertrophy, whereas inhibition of miR-34a expression aggravated Ang II-stimulated myocardial hypertrophy (such as cardiomyocyte hypertrophy-related ANP and β-MHC expression and cardiomyocyte morphology). This study indicates that miR-34a plays a role in regulation of Ang II-induced cardiomyocyte hypertrophy by inhibition of ATG9A expression and autophagic activity. PMID:24728149
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Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner.
Bollinger, Justin L; Collins, Kaitlyn E; Patel, Rushi; Wellman, Cara L
2017-01-01
Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress-induced dendritic remodeling across OFC, BLA, and DHC. Together, these data suggest the potential for microglia-mediated sex differences in stress effects on neural structure, function, and behavior.
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Behavioral stress alters corticolimbic microglia in a sex- and brain region-specific manner
Bollinger, Justin L.; Collins, Kaitlyn E.; Patel, Rushi
2017-01-01
Women are more susceptible to numerous stress-linked psychological disorders (e.g., depression) characterized by dysfunction of corticolimbic brain regions critical for emotion regulation and cognitive function. Although sparsely investigated, a number of studies indicate sex differences in stress effects on neuronal structure, function, and behaviors associated with these regions. We recently demonstrated a basal sex difference in- and differential effects of stress on- microglial activation in medial prefrontal cortex (mPFC). The resident immune cells of the brain, microglia are implicated in synaptic and dendritic plasticity, and cognitive-behavioral function. Here, we examined the effects of acute (3h/day, 1 day) and chronic (3h/day, 10 days) restraint stress on microglial density and morphology, as well as immune factor expression in orbitofrontal cortex (OFC), basolateral amygdala (BLA), and dorsal hippocampus (DHC) in male and female rats. Microglia were visualized, classified based on their morphology, and stereologically counted. Microglia-associated transcripts (CD40, iNOS, Arg1, CX3CL1, CX3CR1, CD200, and CD200R) were assessed in brain punches from each region. Expression of genes linked with cellular stress, neuroimmune state, and neuron-microglia communication varied between unstressed male and female rats in a region-specific manner. In OFC, chronic stress upregulated a wider variety of immune factors in females than in males. Acute stress increased microglia-associated transcripts in BLA in males, whereas chronic stress altered immune factor expression in BLA more broadly in females. In DHC, chronic stress increased immune factor expression in males but not females. Moreover, acute and chronic stress differentially affected microglial morphological activation state in male and female rats across all brain regions investigated. In males, chronic stress altered microglial activation in a pattern consistent with microglial involvement in stress-induced dendritic remodeling across OFC, BLA, and DHC. Together, these data suggest the potential for microglia-mediated sex differences in stress effects on neural structure, function, and behavior. PMID:29194444
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Kaur, Navdeep; Garg, Tarun; Goyal, Amit K; Rath, Goutam
2016-09-01
The present study was designed to determine the role of curcumin-β-cyclodextrin-loaded sponge on burn wound healing in rats. Curcumin-β-cyclodextrin complex was prepared by the solvent evaporation encapsulation method. Molecular inclusion complex of curcumin-β-cyclodextrin was incorporated into gelatin sponge. The developed sponge was characterized for drug entrapment, drug release and morphology. The biological activity of optimized formulation was determined on burn wounds which were made on rats. The burn wound healing efficacy was analyzed through physical and histological changes observed at the wound sites. There was a significant decrease in rate of wound contraction in experimental groups then the control group. Curcumin-β-cyclodextrin-loaded sponge treated wound was found to heal in rate comparable to marketed formulation with no sign of adverse consequence. The result clearly substantiates the beneficial effects of curcumin-β-cyclodextrin-loaded sponge in the acceleration of wound healing.
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Abdel-Bar, Hend Mohamed; Osman, Rihab; Abdel-Reheem, Amal Youssef; Mortada, Nahed; Awad, Gehanne A S
2016-02-08
This work describes the development of a modified nanocomposite thermosensitive hydrogel for controlled cisplatin release and improved cytotoxicity with decreased side effects. The system was characterized in terms of physical properties, morphological architecture and in vitro cisplatin release. Cytotoxicity was tested against human colorectal carcinoma HCT-116. In vivo studies were conducted to evaluate the acute toxicity in terms of rats' survival rate and body weight loss. Nephro and hepatotoxicities were evaluated followed by histopathological alterations of various tissue organs. Nanocomposite thermosensitive hydrogel containing nanosized carrier conferred density and stiffness allowing a zero order drug release for 14 days. Enhanced cytotoxicity with 2-fold decrease in cisplatin IC50 was accomplished. A linear in vivo-in vitro correlation was proved for the system degradation. Higher animal survival rate and lower tissue toxicities proved the decreased toxicity of cisplatin nanocomposite compared to its solution.
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Costa, Evandro Luis de Oliveira; Azevedo, Geraldo Magela de; Petroianu, Andy
2014-06-01
To investigate the effects of ileal exclusion on hepatic and renal morphology in extra-hepatic cholestasis. Twenty four rats were distributed into three groups. Group 1 (control) underwent laparotomy and laparorrhaphy. The animals in groups 2 and 3 underwent hepatic duct ligature and kept in cholestasis for four weeks. After this period, the rats in groups 2 and 3 underwent internal biliary derivation. In Group 3, the last ten centimeters of the terminal ileum were by passed and excluded. Four weeks later, histological and biochemical analysis were performed in all animals of the three groups. In Group 1, no abnormalities regarding hepatic morphology were observed. All animals from groups 2 and 3 presented hepatic fibrosis. No difference was observed between the two groups. No morphological differences in renal histology could be identified among the three groups. There were differences in AST (p<0.05), ALT (p<0.05), direct bilirubin (p<0.05), ƔGT (p<0.05), urea (p<0.05) and creatinine (p<0.05) in Group 3 compared to control. The distal ileum exclusion had no influence upon the hepatic and renal morphological alterations, and biochemical liver and kidney tests have worsened.
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Silva-Gómez, Adriana B; Bravo-Duran, Dolores A; Eguibar, Jose R; Cortes, Carmen
2018-06-01
Myelin mutant taiep rats show a progressive demyelination in the central nervous system due to an abnormal accumulation of microtubules in the cytoplasm and the processes on their oligodendrocytes. Demyelination is associated with electrophysiological alterations and the mutant had a progressive astrocytosis. The illness is associated with change in cytokine levels and in the expression of different nitric oxide synthase and concomitantly lipoperoxidation in several areas of the brain. However, until now there has been no detailed anatomical analysis of neurons in this mutant. The aim of this study was to analyze the dendritic morphology in the hippocampus using Golgi-Cox staining and spatial memory through Morris water maze test in young adult (3 months old) taiep rats and compare them with normal Sprague-Dawley. Our results showed that taiep rats have altered dendritic tree morphology in pyramidal neurons in the CA1 field of the hippocampus, but not in the CA3 region. These morphological changes did not produce a concomitant deficit in spatial memory acquisition or recall at this early stage of the disease. Our results suggest that impairment of dendritic morphology in the CA1 field of the hippocampus is a landmark of the pathology of this progressive multiple sclerosis model. © 2018 Wiley Periodicals, Inc.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fowler, E.H.; Dodd, D.E.; Troup, C.M.
1987-06-01
The morphologic changes induced in the lungs of rats and guinea pigs exposed to high concentrations of MIC vapor (100, 600, and 1000 ppm in the rat and 25, 125, 225, and 675 ppm in the guinea pig) for a short time (15 min) in a static exposure chamber were evaluated at varying postexposure periods (0, 1, 2, and 4, and 16 hr). The 675 ppm-exposed guinea pigs were evaluated only immediately following removal from the chamber. Attention was primarily focused on the intrapulmonary conducting airways and the parenchyma (gas exchange region) of the lungs. The severity of morphologic changesmore » observed by light microscopy was directly correlated with exposure concentration and time postexposure in both species. Specifically, degenerative changes were observed in the bronchial, bronchiolar, and alveolar epithelium in both species. Quantitative differences were observed; 100 ppm of MIC in the rat resulted in much less damage than did 125 ppm of MIC in the guinea pig. Morphologic evidence of sloughing of large sheets of conducting airway epithelium with fibrin buildup and increased mucus production resulted in plugging of major airways and atelectasis. These observations support the hypothesis that tissue hypoxia was a major contributing factor resulting in death.« less
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de Leon, E B; Bortoluzzi, A; Rucatti, A; Nunes, R B; Saur, L; Rodrigues, M; Oliveira, U; Alves-Wagner, A B; Xavier, L L; Machado, U F; Schaan, B D; Dall'Ago, P
2011-02-01
Changes in skeletal muscle morphology and metabolism are associated with limited functional capacity in heart failure, which can be attenuated by neuromuscular electrical stimulation (ES). The purpose of the present study was to analyse the effects of ES upon GLUT-4 protein content, fibre structure and vessel density of the skeletal muscle in a rat model of HF subsequent to myocardial infarction. Forty-four male Wistar rats were assigned to one of four groups: sham (S), sham submitted to ES (S+ES), heart failure (HF) and heart failure submitted to ES (HF+ES). The rats in the ES groups were submitted to ES of the left leg during 20 days (2.5 kHz, once a day, 30 min, duty cycle 50%- 15 s contraction/15 s rest). After this period, the left tibialis anterior muscle was collected from all the rats for analysis. HF+ES rats showed lower values of lung congestion when compared with HF rats (P = 0.0001). Although muscle weight was lower in HF rats than in the S group, thus indicating hypotrophy, 20 days of ES led to their recovery (P < 0.0001). In both groups submitted to ES, there was an increase in muscle vessel density (P < 0.04). Additionally, heart failure determined a 49% reduction in GLUT-4 protein content (P < 0.03), which was recovered by ES (P < 0.01). In heart failure, ES improves morphological changes and raises GLUT-4 content in skeletal muscle. © 2010 The Authors. Acta Physiologica © 2010 Scandinavian Physiological Society.
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[Facial nerve injuries cause changes in central nervous system microglial cells].
Cerón, Jeimmy; Troncoso, Julieta
2016-12-01
Our research group has described both morphological and electrophysiological changes in motor cortex pyramidal neurons associated with contralateral facial nerve injury in rats. However, little is known about those neural changes, which occur together with changes in surrounding glial cells. To characterize the effect of the unilateral facial nerve injury on microglial proliferation and activation in the primary motor cortex. We performed immunohistochemical experiments in order to detect microglial cells in brain tissue of rats with unilateral facial nerve lesion sacrificed at different times after the injury. We caused two types of lesions: reversible (by crushing, which allows functional recovery), and irreversible (by section, which produces permanent paralysis). We compared the brain tissues of control animals (without surgical intervention) and sham-operated animals with animals with lesions sacrificed at 1, 3, 7, 21 or 35 days after the injury. In primary motor cortex, the microglial cells of irreversibly injured animals showed proliferation and activation between three and seven days post-lesion. The proliferation of microglial cells in reversibly injured animals was significant only three days after the lesion. Facial nerve injury causes changes in microglial cells in the primary motor cortex. These modifications could be involved in the generation of morphological and electrophysiological changes previously described in the pyramidal neurons of primary motor cortex that command facial movements.
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NASA Astrophysics Data System (ADS)
Xuan, Ruijiao; Zhao, Xinyan; Hu, Doudou; Jian, Jianbo; Wang, Tailing; Hu, Chunhong
2015-07-01
X-ray phase-contrast imaging (PCI) can substantially enhance contrast, and is particularly useful in differentiating biological soft tissues with small density differences. Combined with computed tomography (CT), PCI-CT enables the acquisition of accurate microstructures inside biological samples. In this study, liver microvasculature was visualized without contrast agents in vitro with PCI-CT using liver fibrosis samples induced by bile duct ligation (BDL) in rats. The histological section examination confirmed the correspondence of CT images with the microvascular morphology of the samples. By means of the PCI-CT and three-dimensional (3D) visualization technique, 3D microvascular structures in samples from different stages of liver fibrosis were clearly revealed. Different types of blood vessels, including portal veins and hepatic veins, in addition to ductular proliferation and bile ducts, could be distinguished with good sensitivity, excellent specificity and excellent accuracy. The study showed that PCI-CT could assess the morphological changes in liver microvasculature that result from fibrosis and allow characterization of the anatomical and pathological features of the microvasculature. With further development of PCI-CT technique, it may become a novel noninvasive imaging technique for the auxiliary analysis of liver fibrosis.
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Severe diffuse axon injury in chronic alcoholic rat medulla oblongata following a concussion blow.
Luo, Jianming; Chen, Guang; Wei, Lai; Qian, Hong; Lai, Xiaoping; Wang, Dian; Lv, Junyao; Yu, Xiaojun
2014-01-01
We investigated the axonal morphological changes and expression of both tau protein and β-APP following concussion to the medulla oblongata, in a rat model of chronic alcoholism. Fifty-nine male Sprague-Dawley rats were randomly divided into EtOH, EtOH-TBI and control groups (water group, water-TBI group). To establish chronic alcoholic rats, rats were intragastrically given edible spirituous liquor twice daily. Rats also received a blow on the occipital tuberosity with an iron pendulum. Morphological changes and expression of tau and β-APP proteins in the medulla oblongata were examined. (a) Nerve fibre thickening and twisting were observed in alcoholic rats, with nerve fibre changes becoming more significant following a concussion blow, which leads to some nerve fibres fracturing. (b) Transmission electron microscopy revealed that the nerve fibre myelin became loosened and displayed lamellar separation, which became more significant following concussion. (c) The integral optical density (IOD) sum value of β-APP of the EtOH-TBI group was lower than that in the EtOH group (P < 0.05); the Tau IOD sum value of the EtOH-TBI group was higher than that in the EtOH group (P < 0.05). (a) Chronic alcoholism caused nerve fibre and neuronal morphology damage in the rat medulla oblongata, with structural damage becoming more significant following concussion. (b) Concussion changed the expression of β-APP and tau protein in chronic alcoholic rat medulla oblongata, suggesting that chronic alcoholism can lead to severe axonal injury following a concussion blow. (c) The effect of chronic alcoholism may be synergistic the concussion blow to promote animal injury and death.
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Importance Rat Liver Morphology and Vasculature in Surgical Research.
Vdoviaková, Katarína; Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej
2016-12-02
BACKGROUND The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. MATERIAL AND METHODS Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. RESULTS We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. CONCLUSIONS Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations.
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Importance Rat Liver Morphology and Vasculature in Surgical Research
Vdoviaková, Katarína; Petrovová, Eva; Krešáková, Lenka; Maloveská, Marcela; Teleky, Jana; Jenčová, Janka; Živčák, Jozef; Jenča, Andrej
2016-01-01
Background The laboratory rat is one of the most popular experimental models for the experimental surgery of the liver. The objective of this study was to investigate the morphometric parameters, physiological data, differences in configuration of liver lobes, biliary system, and vasculature (arteries, veins, and lymphatic vessels) of the liver in laboratory rats. In addition, this study supports the anatomic literature and identified similarities and differences with human and other mammals. Material/Methods Forty laboratory rats were dissected to prepare corrosion casts of vascular system specimens (n=20), determine the lymph vessels and lymph nodes (n=10), and for macroscopic anatomical dissection (n=10) of the rat liver. The results are listed in percentages. The anatomical nomenclature of the liver morphology, its arteries, veins, lymph nodes, and lymphatic vessels are in accordance with Nomina Anatomica Veterinaria. Results We found many variations in origin, direction, and division of the arterial, venous, and lymphatic systems in rat livers, and found differences in morphometric parameters compared to results reported by other authors. The portal vein was formed by 4 tributaries in 23%, by 3 branches in 64%, and by 2 tributaries in 13%. The liver lymph was drained to the 2 different lymph nodes. The nomenclature and morphological characteristics of the rat liver vary among authors. Conclusions Our results may be useful for the planing of experimental surgery and for cooperation with other investigation methods to help fight liver diseases in human populations. PMID:27911356
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Goyal, H O; Braden, T D; Williams, C S; Dalvi, P; Mansour, M M; Mansour, M; Williams, J W; Bartol, F F; Wiley, A A; Birch, L; Prins, G S
2004-05-01
Objectives of the study were to determine developmental changes in morphology and expression of androgen receptor (AR) and estrogen receptor (ER)alpha in the body of the rat penis exposed neonatally to diethylstilbestrol (DES). Male pups received DES at a dose of 10 microg per rat on alternate days from Postnatal Day 2 to Postnatal Day 12. Controls received olive oil vehicle only. Tissue samples were collected on Days 18 (prepuberty), 41 (puberty), and 120 (adult) of age. DES-induced abnormalities were evident at 18 days of age and included smaller, lighter, and thinner penis, loss of cavernous spaces and associated smooth muscle cells, and increased deposition of fat cells in the corpora cavernosa penis. Fat cells virtually filled the entire area of the corpora cavernosa at puberty and adulthood. Plasma testosterone (T) was reduced to an undetectable level, while LH was unaltered in all treated groups. AR-positive cells were ubiquitous and their profile (incidence and staining intensity) did not differ between control and treated rats of the respective age groups. Conversely, ERalpha-positive cells were limited to the stroma of corpus spongiosus in all age groups of both control and treated rats, but the expression in treated rats at 18 days was up-regulated in stromal cells of corpora cavernosa, coincident with the presence of morphological abnormalities. Hence, this study reports for the first time DES-induced developmental, morphological abnormalities in the body of the penis and suggests that these abnormalities may have resulted from decreased T and/or overexpression of ERalpha.
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Oleuropein and hydroxytyrosol protect rats' pups against bisphenol A induced hypothyroidism.
Mahmoudi, Asma; Ghorbel, Hèla; Feki, Ines; Bouallagui, Zouhaier; Guermazi, Fadhel; Ayadi, Lobna; Sayadi, Sami
2018-04-27
Bisphenol A (BPA) can disturb the endocrine system and the organs that respond to endocrine signals in organisms, indirectly exposed during prenatal and/or early postnatal life. The present study was designed to assess the protective effect of phenolic compounds from olive leaves against BPA induced thyroid dysfunction and growth perturbation in young rats during lactation. The BPA disrupting effect on thyroid function was investigated by measuring changes in plasma levels of thyroid hormones. Free triiodothyronine (FT3) and thyroxine (FT4) were decreased in young rats breast-fed from mothers treated with bisphenol A. This effect was associated with an increase in the plasma level of thyroid-stimulating hormone (TSH). The histological and immunohistochemical study of the thyroid gland revealed a disturbance in morphological structure and thyroid cells function. Thyroid dysfunction led to a disruption in the skeletal bone growth of young rats. In fact, the infrared microspectroscopic analysis and histological examination of femoral bone showed significant changes in their histoarchitecture associated with a perturbation in the mechanism of bone tissue mineralization. The administration of oleuropein or hydroxytyrosol in BPA treated lactating mothers improved the thyroid cells function by enhancing thyroid hormone levels. Moreover, these phenolics increased the body growth characterized by an amelioration in the structure and the microstructure of femoral bone tissue. HPLC analysis of rats-breast milk indicated the presence of oleuropein and hydroxytyrosol, which could contribute to the protective effect against bisphenol A induced hypothyroidism in pups rats. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
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Dietary intake of high-dose biotin inhibits spermatogenesis in young rats.
Sawamura, Hiromi; Ikeda, Chieko; Shimada, Ryoko; Yoshii, Yui; Watanabe, Toshiaki
2015-02-01
To characterize a new function of the water-soluble vitamin, biotin, in reproduction and early growth in mammals, the effects of high dietary doses of biotin on early spermatogenesis were biochemically and histologically investigated in male rats. Weaned rats were fed a CE-2 (control) diet containing 0.00004% biotin, or a control diet supplemented with 0.01%, 0.1%, or 1.0% biotin. Pair-fed rats were fed a control diet that was equal in calories to the amount ingested by the 1.0% biotin group, because food intake was decreased in the 1.0% biotin group. Food intake and body weight gain were lower in the 1.0% biotin group than in the control group. The kidney, brain and testis weights were significantly lower in the 1.0% biotin group than in the pair-fed group after 6 weeks of feeding. The accumulation of biotin in the liver and testis increased in a dose-dependent manner. In the 1.0% biotin group, the number of mature sperm was markedly lower, that of sperm with morphologically abnormal heads, mainly consisting of round heads, had increased. In addition, the development of seminiferous tubules was inhibited, and few spermatogonia and no spermatocytes were histologically observed. These results demonstrated that the long-term intake of high-dose biotin inhibited spermatogenesis in young male rats. © 2014 Japanese Teratology Society.
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Harvey, Janice B.; Osborne, Tanasa S.; Hong, Hue-Hua L.; Bhusari, Sachin; Ton, Tai-Vu; Pandiri, Arun R.; Masinde, Tiwanda; Dunnick, June; Peddada, Shyamal; Elmore, Susan; Hoenerhoff, Mark J.
2015-01-01
Endometrial carcinoma is the most common gynecologic malignancy is the United States, and accounts for 6% of all cancers in women. The disease is classified as Type I or Type II based on clinicopathologic and molecular features. It is a multifactorial disease with a number of risk factors, including environmental exposures. How environmental exposures, such as flame retardants, may affect the incidence of endometrial cancer is a topic of current and ongoing interest. Tetrabromobisphenol A (TBBPA) is a widely used brominated flame retardant found in a variety of household products. A recent two-year National Toxicology Program carcinogenicity study found that exposure to TBBPA was associated with a marked increase in the development of uterine tumors, specifically uterine carcinomas, in Wistar Han rats. Molecularly, TBBPA-induced uterine carcinomas in Wistar Han rats were characterized by a marked increase in Tp53 mutation compared to spontaneous uterine carcinomas, as well as overexpression of Her2. Similar to spontaneous carcinomas, tumors in TBBPA-exposed rats were ERα positive and PR negative by immunohistochemistry. The morphologic and molecular features of uterine carcinomas in TBBPA-exposed rats resemble those of high-grade Type I tumors in women, and these data suggest that exposure to TBBPA may pose an increased cancer risk. PMID:26353976
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NASA Astrophysics Data System (ADS)
Lin, Jian; Wang, Zi; Zheng, Wei; Huang, Zhiwei
2014-02-01
Nonlinear optical microscopy (e.g., higher harmonic (second-/third- harmonic) generation (HHG), simulated Raman scattering (SRS)) has high diagnostic sensitivity and chemical specificity, making it a promising tool for label-free tissue and cell imaging. In this work, we report a development of a simultaneous SRS and HHG imaging technique for characterization of liver disease in a bile-duct-ligation rat-modal. HHG visualizes collagens formation and reveals the cell morphologic changes associated with liver fibrosis; whereas SRS identifies the distributions of hepatic fat cells formed in steatosis liver tissue. This work shows that the co-registration of SRS and HHG images can be an effective means for label-free diagnosis and characterization of liver steatosis/fibrosis at the cellular and molecular levels.
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Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid
Ruan, Zheng; Yang, Yuhui; Zhou, Yan; Wen, Yanmei; Ding, Sheng; Liu, Gang; Wu, Xin; Deng, Zeyuan; Assaad, Houssein; Wu, Guoyao
2016-01-01
This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution 1H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo. PMID:24927697
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Retinoic acid-induced lumbosacral neural tube defects: myeloschisis and hamartoma.
Cai, WeiSong; Zhao, HongYu; Guo, JunBin; Li, Yong; Yuan, ZhengWei; Wang, WeiLin
2007-05-01
To observe the morphological features of the lumbosacral neural tube defects (NTDs) induced by all-trans retinoic acid (atRA) and to explore the pathogenesis of these defects. Rat embryos with lumbosacral NTDs were obtained by treating pregnant rats with administration of atRA. Rat embryos were obtained by cesarean. Fetuses were sectioned and stained with hematoxylin-eosin (H&E). Relevant structures including caudal neural tube were examined. In the atRA-treated rats, about 48% embryos showed lumbosacral NTDs. There appeared a dorsally and rostrally situated, neural-plate-like structure (myeloschisis) and a ventrally and caudally located cell mass containing multiple canals (hamartoma) in the lumbosacral NTDs induced by atRA. Retinoic acid could disturb the notochord and tail bud development in the process of primary and secondary neurulation in rat embryos, which cause lumbosacral NTDs including myeloschisis and hamartoma. The morphology is very similar to that happens in humans.
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NASA Astrophysics Data System (ADS)
Sergio, L. P. S.; Trajano, L. A. S. N.; Thomé, A. M. C.; Mencalha, A. L.; Paoli, F.; Fonseca, A. S.
2018-06-01
Acute lung injury (ALI) is a potentially fatal disease characterized by uncontrolled hyperinflammatory responses in the lungs as a consequence of sepsis. ALI is divided into two sequential and time-dependent phases, exudative and fibroproliferative phases, with increased permeability of the alveolar barrier, causing edema and inflammation. However, there are no specific treatments for ALI. Low-power lasers have been successfully used in the resolution of acute inflammatory processes. The aim of this study was to evaluate the effects of low-power infrared laser exposure on alveolus and interalveolar septa of Wistar rats affected by ALI-induced by sepsis. Laser fluences, power, and the emission mode were those used in clinical protocols for the treatment of acute inflammation. Adult male Wistar rats were randomized into six groups: control, 10 J cm‑2, 20 J cm‑2, ALI, ALI + 10 J cm‑2, and ALI + 20 J cm‑2. ALI was induced by intraperitoneal Escherichia coli lipopolysaccharide (LPS). Lungs were removed and processed for hematoxylin–eosin staining. Morphological alterations induced by LPS in lung tissue were quantified by morphometry with a 32-point cyclic arcs test system in Stepanizer. Data showed that exposure to low-power infrared laser in both fluences reduced the thickening of interalveolar septa in lungs affected by ALI, increasing the alveolar space; however, inflammatory infiltrate was still observed. Our research showed that exposure to low-power infrared laser improves the lung parenchyma in Wistar rats affected by ALI, which could be an alternative approach for treatment of inflammatory lung injuries.
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Shyu, Jia-Fwu; Wang, Hwai-Shi; Shyr, Yi-Ming; Wang, Shin-E; Chen, Chia-Hsiang; Tan, Joo-Shin; Lin, Meng-Feng; Hsieh, Po-Shiuan; Sytwu, Huey-Kang; Chen, Tien-Hua
2011-03-01
Although islet transplantation holds promise for the treatment of diabetes, the scarcity of donor tissue remains a major drawback. The aim of this study is to generate insulin-producing cells from adult human pancreatic cells isolated from surgically resected pancreatic tissue. To isolate pancreatic endocrine precursor cells from 57 surgically resected pancreases, the cells were cultured and propagated in conditioned medium after which they were differentiated in Matrigel. The resultant cells were characterized using morphology, immunofluorescent studies, expression of differentiated pancreatic islet-specific genes using quantitative reverse transcription-PCR, and glucose-induced insulin secretion through analysis of C-peptide secretion. The relationships between propagation of insulin-producing cells and clinical variables of the donor were also analyzed. Finally, insulin-producing cell function was examined in streptozotocin-induced diabetic rats. Pancreatic endocrine precursor cells were successfully cultured; insulin-producing cells cultured from soft pancreas parenchyma had a significantly higher success rate. Morphological examination revealed islet-like cluster formation upon transfer to Matrigel. The presence of the neural stem cell marker nestin, duct cell marker cytokeratin 19, and endocrine cell markers C-peptide and pancreatic and duodenal homeobox 1, was also observed. In addition, glucose-stimulated C-peptide release was significantly increased in the insulin-producing cells. Furthermore, in diabetic rats, transplantation of insulin-producing cells reduced hyperglycemia. Isolated pancreatic endocrine precursor cells from surgically resected pancreatic tissue differentiated into insulin-producing cells and showed characteristics of functional endocrine cells. Thus, surgically resected pancreatic tissue may represent an alternative source of functional insulin-producing cells.
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Yadav, Vivek R; Suresh, Sarasija; Devi, Kshama; Yadav, Seema
2009-01-01
The purpose of the study was to prepare and evaluate the anti-inflammatory activity of cyclodextrin (CD) complex of curcumin for the treatment of inflammatory bowel disease (IBD) in colitis-induced rat model. Inclusion complexes of curcumin were prepared by common solvent and kneading methods. These complexes were further evaluated for increase in solubility of poorly soluble curcumin. The inclusion complexes were characterized for enhancement in solubility, in vitro dissolution, surface morphology, infrared, differential scanning calorimetry, and X-ray studies. Solubility, phase solubility, and in vitro dissolution studies showed that curcumin has higher affinity for hydroxypropyl-beta-CD (HPbetaCD) than other CDs. HPbetaCD complex of curcumin was further investigated for its antiangiogenic and anti-inflammatory activity using chick embryo and rat colitis model. HPbetaCD complex of curcumin proved to be a potent angioinhibitory compound, as demonstrated by inhibition of angiogenesis in chorioallantoic membrane assay. Curcumin- and HPbetaCD-treated rats showed a faster weight gain compared to dextran sulfate solution (DSS) controls. Whole colon length appeared to be significantly longer in HPbetaCD-treated rats than pure curcumin and DSS controls. An additional finding in the DSS-treated rats was the predominance of eosinophils in the chronic cell infiltrate. Decreased mast cell numbers in the mucosa of the colon of CD of curcumin- and pure-curcumin-treated rats was observed. This study concluded that the degree of colitis caused by administration of DSS was significantly attenuated by CD of curcumin. Being a nontoxic natural dietary product, curcumin could be useful in the therapeutic strategy for IBD patients.
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Fujiwara, Ken; Yatabe, Megumi; Tofrizal, Alimuddin; Jindatip, Depicha; Yashiro, Takashi; Nagai, Ryozo
2017-05-01
Macrophages are present throughout the anterior pituitary gland. However, the features and function of macrophages in the gland are poorly understood. Recent studies have indicated that there are two main macrophage classes: M1 (classically activated) and M2 (alternatively activated). In this study, we examine whether both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Our findings indicate that macrophages that are positive for CD68 (a pan-macrophage marker) were localized near capillaries in rat anterior pituitary gland. These macrophages were positive for iNOS or mannose receptor (MR), which are markers of M1 and M2 macrophages, respectively. To determine the morphological characteristics of M2 macrophages under pathological conditions, diethylstilbestrol (DES)-treated rats were used as an animal model of prolactinoma. After 2 weeks of DES treatment, a number of MR-immunopositive cells were present in the gland. Immunoelectron microscopy revealed that MR-immunopositive M2 macrophages had many small vesicles and moderately large vacuoles in cytoplasm. Phagosomes were sometimes present in cytoplasm. Interestingly, M2 macrophages in prolactinoma tissues did not usually exhibit distinct changes or differences during the normal, hyperplasia and adenoma stages. This study is the first to confirm that both M1 and M2 macrophages are present in the anterior pituitary gland of rats. Moreover, the number of M2 macrophages was greatly increased in rats with DES-induced prolactinoma. Future studies should attempt to characterize the functional role of M2 macrophages in the gland.
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Kolawole, T A; Oyeyemi, W A; Adigwe, C; Leko, B; Udeh, C; Dapper, D V
2015-12-20
Effect of honey on reproductive functions of male rats exposed to nicotine was examined in this study. Thirty-two adult male wistar rats (n=8/Group) were grouped as Control (distilled water), Nicotine (1.0mg/kg bwt), Honey (100mg/kg bwt) and Nicotine with Honey. The animals were orally treated for 35 days consecutively. Epididymis sperm motility, viability, morphology and counts were estimated, serum Follicle Stimulating Hormone (FSH), Leutinizing Hormone (LH) and Testosterone were assayed using ELISA method and testicular histology were also assessed. Significant reduction in percentage sperm motility, viability, morphology and counts were observed in nicotine group compared to control. Serum FSH, LH and testosterone levels were significantly reduced in nicotine group when compared with the control. There was significant improvement in sperm motility, viability, morphology, counts, FSH, LH and Testosterone in group co-treated with nicotine and honey relative to nicotine group. Also, the degenerative seminiferous tubule architecture due to nicotine was improved by honey. In conclusion, honey may suppress nicotine toxic effect on reproductive functions in male Wistar rats.
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Increased enterocyte production in gnotobiotic rats mono-associated with Lactobacillus rhamnosus GG.
Banasaz, M; Norin, E; Holma, R; Midtvedt, T
2002-06-01
There is increasing scientific and commercial interest in using beneficial microorganisms (i.e., probiotics) to enhance intestinal health. Of the numerous microbial strains examined, Lactobacillus rhamnosus GG has been most extensively studied. Daily intake of L. rhamnosus GG shortens the course of rotavirus infection by mechanisms that have not been fully elucidated. Comparative studies with germfree and conventional rats have shown that the microbial status of an animal influences the intestinal cell kinetics and morphology. The present study was undertaken to study whether establishment of L. rhamnosus GG as a mono-associate in germfree rats influences intestinal cell kinetics and morphology. L. rhamnosus GG was easily established in germfree rats. After 3 days of mono-association, the rate of mitoses in the upper part of the small intestine (jejunum 1) increased as much as 14 and 22% compared to the rates in germfree and conventional counterparts, respectively. The most striking alteration in morphology was an increase in the number of cells in the villi. We hypothesis that the compartmentalized effects of L. rhamnosus GG may represent a reparative event for the mucosa.
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Rattner, B.A.; Flickinger, Edward L.; Hoffman, D.J.
1993-01-01
Male cotton rats (Sigmodon hispidus) were studied at three industrial waste sites near Houston, Texas, to determine whether various morphological, biochemical, and histopathological indices provided evidence of contaminant exposure and toxic insult. Only modest changes were detected in cotton rats residing at waste sites compared with reference sites. No single parameter was consistently altered, except hepatic cytochrome P-450 concentration which was lower ( [Formula: see text] ) at two waste sites, and tended to be lower ( [Formula: see text] ) at a third waste site. Elevated petroleum hydrocarbon concentrations were detected in rats at one waste site, but contaminant burdens of rats from the other sites were unremarkable. Unlike rats captured in summer, those trapped in winter exhibited hepatocellular hypertrophy and up to a 65% increase in liver: body weight ratio, cytochrome P-450 concentration, and activities of aniline hydroxylase, aryl hydrocarbon hydroxylase, and glutathione S-transferase. Although genotoxicity has been previously documented in cotton rats residing at two of the waste sites, biomarkers in the present study provided little evidence of exposure and damage
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Oku, N; Matsunaga, S; Wada, S i; Watabe, S; Fusetani, N
2000-02-01
Three new isomalabaricane triterpenes, 29-hydroxystelliferin D (2), 3-epi-29-hydroxystelliferin E (3), and 3-epi-29-hydroxystelliferin A (4), were isolated from the marine sponge Stelletta globostellata. Their structures, including absolute stereochemistry, were determined on the basis of spectral data and chemical methods. Rat fibroblasts treated with 0.2 microM of 2-4 exhibited unusual morphological characteristics, followed by death in 5 days.
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Cerebral morphology and functional sparing after prenatal frontal cortex lesions in rats.
Kolb, B; Cioe, J; Muirhead, D
1998-03-01
Rats were given suction lesions of the presumptive frontal cortex on embryonic day 18 (E18) and subsequently tested, as adults, on tests of spatial navigation (Morris water task, radial arm maze), motor tasks (Whishaw reaching task, beam walking), and locomotor activity. Frontal cortical lesions at E18 affected cerebral morphogenesis, producing unusual morphological structures including abnormal patches of neurons in the cortex and white matter as well as neuronal bridges between the hemispheres. A small sample of E18 operates also had hydrocephaly. The animals with E18 lesions without hydrocephalus were behaviorally indistinguishable from littermate controls. The results demonstrate that animals with focal lesions of the presumptive frontal cortex have gross abnormalities in cerebral morphology but the lesions leave the functions normally subserved by the frontal cortex in adult rats unaffected. The results are discussed in the context of a hypothesis regarding the optimal times for functional recovery from cortical injury.
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Halliday, Amy J; Campbell, Toni E; Razal, Joselito M; McLean, Karen J; Nelson, Timothy S; Cook, Mark J; Wallace, Gordon G
2012-02-01
Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy. Copyright © 2011 Wiley Periodicals, Inc.
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A Novel Mouse Model of Penetrating Brain Injury
Cernak, Ibolja; Wing, Ian D.; Davidsson, Johan; Plantman, Stefan
2014-01-01
Penetrating traumatic brain injury (pTBI) has been difficult to model in small laboratory animals, such as rats or mice. Previously, we have established a non-fatal, rat model for pTBI using a modified air-rifle that accelerates a pellet, which hits a small probe that then penetrates the experimental animal’s brain. Knockout and transgenic strains of mice offer attractive tools to study biological reactions induced by TBI. Hence, in the present study, we adapted and modified our model to be used with mice. The technical characterization of the impact device included depth and speed of impact, as well as dimensions of the temporary cavity formed in a brain surrogate material after impact. Biologically, we have focused on three distinct levels of severity (mild, moderate, and severe), and characterized the acute phase response to injury in terms of tissue destruction, neural degeneration, and gliosis. Functional outcome was assessed by measuring bodyweight and motor performance on rotarod. The results showed that this model is capable of reproducing major morphological and neurological changes of pTBI; as such, we recommend its utilization in research studies aiming to unravel the biological events underlying injury and regeneration after pTBI. PMID:25374559
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GLUTAMATE NEUROTOXICITY IN THE DEVELOPING RAT COCHLEA: PHYSIOLOGICAL AND MORPHOLOGICAL APPROACHES
The neurotoxic effects of exogenous glutamate were studied in the rat cochlea. lutamate-treated rats (4g/kg/day ip, postnatal days 2 through 9) exhibited electrophysiologically-measured elevations in high frequency thresholds usually associated with hair cell loss in the basal re...
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SIGNIFICANCE OF INCORPORATING MEASURES OF SPERM PRODUCTION AND FUNCTION INTO RAT TOXICOLOGY STUDIES
The rat is the preferred species for reproductive toxicity testing. The inclusion of measures of rat sperm quality, such as motility and morphology, into reproductive test protocols often increases the sensitivity of the test to detect effects, and provides the toxicologist and ...
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Sexual behavior and testis morphology in the BACHD rat model
Novati, Arianna; Yu-Taeger, Libo; Gonzalez Menendez, Irene; Quintanilla Martinez, Leticia
2018-01-01
Background Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by a mutation in the huntingtin (HTT) gene, which results in brain neurodegeneration and peripheral pathology affecting different organs including testis. Patients with HD suffer from motor and cognitive impairment, and multiple psychiatric symptoms. Among behavioral abnormalities in HD, sexual disturbances have often been reported, but scarcely investigated in animal models. The BACHD rat model of HD carries the human full-length mutated HTT (mHTT) genomic sequence with 97 CAG-CAA repeats and displays HD-like alterations at neuropathological and behavioral level. Objective This study aims to phenotype the BACHD rats’ sexual behavior and performance as well as testis morphology because alterations in these aspects have been associated to HD. Methods Two rat cohorts at the age of 3 and 7 months were subjected to mating tests to assess different parameters of sexual behavior. Histological analyses for testis morphology were performed in different rat cohorts at 1.5, 7 and 12 months of age whereas immunohistochemical analyses were carried out at 7 and 12 months of age to visualize the presence of mHTT in testicular tissue. Furthermore, western blot analyses were used to assess HTT and mHTT expression levels in striatum and testis at three months of age. Results At 3 months, BACHD rats showed a decreased time exploring the female anogenital area (AGA), decreased latency to mount, increased number of intromissions and ejaculations and enhanced hit rate. At 7 months, all sexual parameters were comparable between genotypes with the exception that BACHD rats explored the AGA less than wild type rats. Testis analyses did not reveal any morphological alteration at any of the examined ages, but showed presence of mHTT limited to Sertoli cells in transgenic rats at both 7 and 12 months. BACHD rat HTT and mHTT expression levels in testis were lower than striatum at 3 months of age. Conclusions The testis phenotype in the BACHD rat model does not mimic the changes observed in human HD testis. The altered sexual behavior in BACHD rats at three months of age could be to a certain extent representative of and share common underlying pathways with some of the sexual disturbances in HD patients. Further investigating the biological causes of the sexual phenotype in BACHD rats may therefore contribute to clarifying the mechanisms at the base of sexual behavior changes in HD. PMID:29883458
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Panda, Shasanka Shekhar; Bajpai, Minu; Mallick, Saumyaranjan; Sharma, Mehar C
2014-01-01
The objective of the following study is to determine and to compare the different morphological parameters with duration of obstruction created experimentally in unilateral upper ureters of rats. Unilateral upper ureteric obstruction was created in 60 adult Wistar rats that were reversed after predetermined intervals. Rats were sacrificed and ipsilateral kidneys were subjected for analysis of morphological parameters such as renal height, cranio-caudal diameter, antero-posterior diameter, lateral diameter, volume of the pelvis and average cortical thickness: Renal height. Renal height and cranio-caudal diameter of renal pelvis after ipsilateral upper ureteric obstruction started rising as early as 7 days of creating obstruction and were affected earlier than antero-posterior and lateral diameter and also were reversed earlier than other parameters after reversal of obstruction. Renal cortical thickness and volume of the pelvis were affected after prolonged obstruction (> 3 weeks) and were the late parameters to be reversed after reversal of obstruction. Cranio-caudal diameter and renal height were the early morphological parameters to be affected and reversed after reversal of obstruction in experimentally created ipsilateral upper ureteric obstruction.
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Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats.
Ren, Yi-Ming; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin
2018-01-01
To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies.
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Wang, Tao; Ren, Xiaobao; Xiong, Jianqiong; Zhang, Lei; Qu, Jifu; Xu, Wenyue
2011-04-01
Spinal cord injury (SCI) remains a formidable challenge in the clinic. In the current study, we examined the effects of the TLX gene on the proliferation and neuronal differentiation of dermal multipotent stem cells (DMSCs) in vitro and the potential of these cells to improve SCI in rats in vivo. DMSCs were stably transfected with TLX-expressing plasmid (TLX/DMSCs). Cell proliferation was examined using the MTT assay, and neuronal differentiation was characterized by morphological observation combined with immunocytochemical/immunofluorescent staining. The in vivo functions of these cells were evaluated by transplantation into rats with SCI, followed by analysis of hindlimb locomotion and post-mortem histology. Compared to parental DMSCs, TLX/DMSCs showed enhanced proliferation and preferential differentiation into NF200-positive neurons in contrast to GFAP-positive astrocytes. When the undifferentiated cells were transplanted into rats with SCI injury, TLX/DMSCs led to significant improvement in locomotor recovery and healing of SCI, as evidenced by reduction in scar tissues and cavities, increase in continuous nerve fibers/axons and enrichment of NF200-positive neurons on the histological level. In conclusion, TLX promotes the proliferation and neuronal differentiation of DMSCs and thus, may serve as a promising therapy for SCI in the clinic.
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Early neurovascular dysfunction in a transgenic rat model of Alzheimer's disease.
Joo, Illsung L; Lai, Aaron Y; Bazzigaluppi, Paolo; Koletar, Margaret M; Dorr, Adrienne; Brown, Mary E; Thomason, Lynsie A M; Sled, John G; McLaurin, JoAnne; Stefanovic, Bojana
2017-04-12
Alzheimer's disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans.
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da Silva, Fernando B. R.; Cunha, Polyane A.; Ribera, Paula C.; Barros, Mayara A.; Cartágenes, Sabrina C.; Fernandes, Luanna M. P.; Teixeira, Francisco B.; Fontes-Júnior, Enéas A.; Prediger, Rui D.; Lima, Rafael R.; Maia, Cristiane S. F.
2018-01-01
Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures’ morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.
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da Silva, Fernando B R; Cunha, Polyane A; Ribera, Paula C; Barros, Mayara A; Cartágenes, Sabrina C; Fernandes, Luanna M P; Teixeira, Francisco B; Fontes-Júnior, Enéas A; Prediger, Rui D; Lima, Rafael R; Maia, Cristiane S F
2018-01-01
Over the last years, heavy ethanol consumption by teenagers/younger adults has increased considerably among females. However, few studies have addressed the long-term impact on brain structures' morphology and function of chronic exposure to high ethanol doses from adolescence to adulthood in females. In line with this idea, in the current study we investigated whether heavy chronic ethanol exposure during adolescence to adulthood may induce motor impairments and morphological and cellular alterations in the cerebellum of female rats. Adolescent female Wistar rats (35 days old) were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) during 55 days by gavage. At 90 days of age, motor function of animals was assessed using open field (OF), pole, beam walking and rotarod tests. Following completion of behavioral tests, morphological and immunohistochemical analyses of the cerebellum were performed. Chronic ethanol exposure impaired significantly motor performance of female rats, inducing spontaneous locomotor activity deficits, bradykinesia, incoordination and motor learning disruption. Moreover, histological analysis revealed that ethanol exposure induced atrophy and neuronal loss in the cerebellum. These findings indicate that heavy ethanol exposure during adolescence is associated with long-lasting cerebellar degeneration and motor impairments in female rats.
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Molecular composition of staufen2-containing ribonucleoproteins in embryonic rat brain.
Maher-Laporte, Marjolaine; Berthiaume, Frédéric; Moreau, Mireille; Julien, Louis-André; Lapointe, Gabriel; Mourez, Michael; DesGroseillers, Luc
2010-06-28
Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Numerous mRNA-binding and regulatory proteins within mRNPs finely regulate the fate of bound-mRNAs. Their specific combination defines different types of mRNPs that in turn are related to specific synaptic functions. One of these mRNA-binding proteins, Staufen2 (Stau2), was shown to transport dendritic mRNAs along microtubules. Its knockdown expression in neurons was shown to change spine morphology and synaptic functions. To further understand the molecular mechanisms by which Stau2 modulates synaptic function in neurons, it is important to identify and characterize protein co-factors that regulate the fate of Stau2-containing mRNPs. To this end, a proteomic approach was used to identify co-immunoprecipitated proteins in Staufen2-containing mRNPs isolated from embryonic rat brains. The proteomic approach identified mRNA-binding proteins (PABPC1, hnRNP H1, YB1 and hsc70), proteins of the cytoskeleton (alpha- and beta-tubulin) and RUFY3 a poorly characterized protein. While PABPC1 and YB1 associate with Stau2-containing mRNPs through RNAs, hsc70 is directly bound to Stau2 and this interaction is regulated by ATP. PABPC1 and YB1 proteins formed puncta in dendrites of embryonic rat hippocampal neurons. However, they poorly co-localized with Stau2 in the large dendritic complexes suggesting that they are rather components of Stau2-containing mRNA particles. All together, these results represent a further step in the characterization of Stau2-containing mRNPs in neurons and provide new tools to study and understand how Stau2-containing mRNPs are transported, translationally silenced during transport and/or locally expressed according to cell needs.
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Effects of zinc deficiency on the vallate papillae and taste buds in rats.
Chou, H C; Chien, C L; Huang, H L; Lu, K S
2001-05-01
Zinc deficiency is associated with multiple clinical complications, including taste disturbance, anorexia, growth retardation, skin changes, and hypogonadism. We investigated the zinc-deficiency-induced morphologic changes in the vallate taste buds of weanling and young adult male Wistar rats. A total of 24 weanling and 30 young adult rats were used. Each age group was further divided into a control group fed a zinc-adequate (50 ppm) diet, a zinc-deficient (< 1 ppm) diet group, and a zinc-adequate pair-fed group who were fed the same amount of food as that taken by the zinc-deficient group. Weanling rats were fed for 4 weeks and young adult rats were fed for 6 weeks. The morphometry and morphologic changes of vallate taste buds were analyzed using light and transmission electron microscopy. Light microscopy revealed no significant difference in papilla size and morphology among the various groups. In both weanling and young adult rats in the zinc-deficient diet and pair-fed groups, the number of taste buds per papilla (per animal) and the average profile area of the taste bud were significantly smaller than those of the corresponding controls (p < 0.05). Ultrastructural changes were seen only in the taste buds of weanling rats fed the zinc-deficient diet, with derangement of the architecture of the taste bud and widening of the intercellular space between taste bud cells. The proportion of type I taste bud cells in the taste buds of weanling rats fed the zinc-deficient diet decreased from 59% to 39%, and that of type II taste bud cells decreased from 25% to 12%. No obvious changes in the ultrastructure of type III taste bud cells were observed. The main effects of zinc deficiency in weanling and young adult rats and in adequate diet pair-fed rats were changes in the number and size of taste buds, and fine structure changes in the taste bud cells, especially during the accelerated growth stage after weaning.
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Chee, K N; Vorontsova, I; Lim, J C; Kistler, J; Donaldson, P J
2010-05-04
To characterize the expression patterns of the Na+-K+-Cl(-) cotransporter (NKCC) 1 and NKCC2, and the Na+-Cl(-) cotransporter (NCC) in the rat lens and to determine if they play a role in regulating lens volume and transparency. RT-PCR was performed on RNA extracted from fiber cells to identify sodium dependent cotransporters expressed in the rat lens. Western blotting and immunohistochemistry, using NKCC1, NKCC2, and NCC antibodies, were used to verify expression at the protein level and to localize transporter expression. Organ cultured rat lenses were incubated in Artificial Aqueous Humor (AAH) of varying osmolarities or isotonic AAH that contained either the NKCC specific inhibitor bumetanide, or the NCC specific inhibitor thiazide for up to 18 h. Lens transparency was monitored with dark field microscopy, while tissue morphology and antibody labeling patterns were recorded using a confocal microscope. Molecular experiments showed that NKCC1 and NCC were expressed in the lens at both the transcript and protein levels, but NKCC2 was not. Immunohistochemistry showed that both NKCC1 and NCC were expressed in the lens cortex, but NCC expression was also found in the lens core. In the lens cortex the majority of labeling for both transporters was cytoplasmic in nature, while in the lens core, NCC labeling was associated with the membrane. Exposure of lenses to either hypotonic or hypertonic AAH had no noticeable effects on the predominantly cytoplasmic location of either transporter in the lens cortex. Incubation of lenses in isotonic AAH plus the NKCC inhibitor bumetanide for 18 h induced a cortical opacity that was initiated by a shrinkage of peripheral fiber cells and the dilation of the extracellular space between fiber cells in a deeper zone located some approximately 150 microm in from the capsule. In contrast, lenses incubated in isotonic AAH and the NCC inhibitor thiazide maintained both their transparency and their regular fiber cell morphology. We have confirmed the expression of NKCC1 in the rat lens and report for the first time the expression of NCC in lens fiber cells. The expression patterns of the two transporters and the differential effects of their specific inhibitors on fiber cell morphology indicate that these transporters play distinct roles in the lens. NKCC1 appears to mediate ion influx in the lens cortex while NCC may play a role in the lens nucleus.
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Wang, Tao; Guan, Rui-Li; Liu, Ming-Chao; Shen, Xue-Feng; Chen, Jing Yuan; Zhao, Ming-Gao; Luo, Wen-Jing
2016-08-01
Lead (Pb) is an environmental neurotoxic metal. Pb exposure may cause neurobehavioral changes, such as learning and memory impairment, and adolescence violence among children. Previous animal models have largely focused on the effects of Pb exposure during early development (from gestation to lactation period) on neurobehavior. In this study, we exposed Sprague-Dawley rats during the juvenile stage (from juvenile period to adult period). We investigated the synaptic function and structural changes and the relationship of these changes to neurobehavioral deficits in adult rats. Our results showed that juvenile Pb exposure caused fear-conditioned memory impairment and anxiety-like behavior, but locomotion and pain behavior were indistinguishable from the controls. Electrophysiological studies showed that long-term potentiation induction was affected in Pb-exposed rats, and this was probably due to excitatory synaptic transmission impairment in Pb-exposed rats. We found that NMDA and AMPA receptor-mediated current was inhibited, whereas the GABA synaptic transmission was normal in Pb-exposed rats. NR2A and phosphorylated GluR1 expression decreased. Moreover, morphological studies showed that density of dendritic spines declined by about 20 % in the Pb-treated group. The spine showed an immature form in Pb-exposed rats, as indicated by spine size measurements. However, the length and arborization of dendrites were unchanged. Our results suggested that juvenile Pb exposure in rats is associated with alterations in the glutamate receptor, which caused synaptic functional and morphological changes in hippocampal CA1 pyramidal neurons, thereby leading to behavioral changes.
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Influence of thyroid state on cardiac and renal capillary density and glomerular morphology in rats.
Rodríguez-Gómez, Isabel; Banegas, Inmaculada; Wangensteen, Rosemary; Quesada, Andrés; Jiménez, Rosario; Gómez-Morales, Mercedes; O'Valle, Francisco; Duarte, Juan; Vargas, Félix
2013-01-01
The purpose was to analyse the cardiac and renal capillary density and glomerular morphology resulting from a chronic excess or deficiency of thyroid hormones (THs) in rats. We performed histopathological, morphometrical and immunohistochemical analyses in hypothyroid and hyperthyroid rats to evaluate the density of mesenteric, renal and cardiac vessels at 4 weeks after induction of thyroid disorders. The main angiogenic factors in plasma, heart and kidney were measured as possible mediators of vascular changes. Mesenteric vessel branching was augmented and decreased in hyper- and hypothyroid rats respectively. The numerical density of CD31-positive capillaries was higher in left and right ventricles and in cortical and medullary kidney from both hyper- and hypothyroid rats vs controls. Numbers of podocytes and glomeruli per square millimetre were similar among groups. Glomerular area and percentage mesangium were greater in the hyperthyroid vs control or hypothyroid groups. No morphological renal lesions were observed in any group. Vascularisation of the mesenteric bed is related to TH levels, but an increased capillarity was observed in heart and kidney in both thyroid disorders. This increase may be produced by higher tissue levels of angiogenic factors in hypothyroid rats, whereas haemodynamic factors would predominate in hyperthyroid rats. Our results also indicate that the renal dysfunctions of thyroid disorders are not related to cortical or medullary microvascular rarefaction and that the proteinuria of hyperthyroidism is not secondary to a podocyte deficit. Finally, TH or its analogues may be useful to increase capillarity in renal diseases associated with microvascular rarefaction.
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Comparative Study in Laboratory Rats to Validate Sperm Quality Methods and Endpoints
NASA Technical Reports Server (NTRS)
Price, W. A.; Briggs, G. B.; Alexander, W. K.; Still, K. R.; Grasman, K. A.
2000-01-01
Abstract The Naval Health Research Center, Detachment (Toxicology) performs toxicity studies in laboratory animals to characterize the risk of exposure to chemicals of Navy interest. Research was conducted at the Toxicology Detachment at WPAFB, OH in collaboration with Wright State University, Department of Biological Sciences for the validation of new bioassay methods for evaluating reproductive toxicity. The Hamilton Thorne sperm analyzer was used to evaluate sperm damage produced by exposure to a known testicular toxic agent, methoxyacetic acid and by inhalation exposure to JP-8 and JP-5 in laboratory rats. Sperm quality parameters were evaluated (sperm concentration, motility, and morphology) to provide evidence of sperm damage. The Hamilton Thorne sperm analyzer utilizes a DNA specific fluorescent stain (similar to flow cytometry) and digitized optical computer analysis to detect sperm cell damage. The computer assisted sperm analysis (CASA) is a more rapid, robust, predictive and sensitive method for characterizing reproductive toxicity. The results presented in this poster report validation information showing exposure to methoxyacetic acid causes reproductive toxicity and inhalation exposure to JP-8 and JP-5 had no significant effects. The CASA method detects early changes that result in reproductive deficits and these data will be used in a continuing program to characterize the toxicity of chemicals, and combinations of chemicals, of military interest to formulate permissible exposure limits.
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Morphological evidence for parallel processing of information in rat macula.
Ross, M D
1988-01-01
Study of montages, tracings and reconstructions prepared from a series of 570 consecutive ultrathin sections shows that rat maculas are morphologically organized for parallel processing of linear acceleratory information. Type II cells of one terminal field distribute information to neighboring terminals as well. The findings are examined in light of physiological data which indicate that macular receptor fields have a preferred directional vector, and are interpreted by analogy to a computer technology known as an information network.
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Morphological and immunohistochemical diversity of endometrial stromal sarcoma in rats.
Kumabe, Shino; Sato, Junko; Tomonari, Yuki; Takahashi, Miwa; Inoue, Kaoru; Yoshida, Midori; Doi, Takuya; Wako, Yumi; Tsuchitani, Minoru
2018-04-01
To clarify the histopathological characteristics of rat endometrial stromal sarcoma (ESS), we morphologically reviewed 12 malignant uterine tumors protruding into the lumen in previous rat carcinogenicity studies. The 12 cases were classified into the following 6 types based on their morphological features: spindle cell and collagen rich type, pleomorphic/spindle cell and compact type, decidual alteration type, histiocytic and multinucleated giant cell mixture type, Antoni A-type schwannoma type, and Antoni B-type schwannoma type. Immunohistochemically, tumor cells in all cases exhibited focal or diffuse positive reactions for vimentin, and 11 of the 12 cases were positive for S-100. Interestingly, 9 cases were positive for desmin or αSMA, indicating tumor cells expressing smooth muscle properties. Both Antoni A- and B-type schwannoma types showed low reactions for both muscle markers. Positive results for estrogen receptor α in the 11 cases suggested that they were derived from endometrial stromal cells. On the basis of their immunohistochemical profiles, they were considered to be derived from endometrial stromal cells while they showed morphological variation. The detection of a basement membrane surrounding tumor cells might not be a definitive indicator for differential diagnosis of ESS from malignant schwannoma. In conclusion, ESS could exhibit wide morphological and immunohistochemical variation including features of schwannoma or smooth muscle tumor.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Yakovleva, V.I.
1978-10-26
This work is part of a comprehensive study of the biological effects of long-term radiation on rats flown aboard Kosmos-690 for 20.5 days. The results of morphological studies of the rat liver irradiated aboard the biosatellite are discussed.
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Liu, Lichuan; Di Paolo, Julie; Barbosa, Jim; Rong, Hong; Reif, Karin; Wong, Harvey
2011-07-01
Bruton's tyrosine kinase (BTK) plays a critical role in the development, differentiation, and proliferation of B-lineage cells, making it an attractive target for the treatment of rheumatoid arthritis. The objective of this study was to evaluate the antiarthritis effect of GDC-0834 [R-N-(3-(6-(4-(1,4-dimethyl-3-oxopiperazin-2-yl)phenylamino)-4-methyl-5-oxo-4,5-dihydropyrazin-2-yl)-2-methylphenyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-2-carboxamide], a potent and selective BTK inhibitor, and characterize the relationship between inhibition of BTK phosphorylation (pBTK) and efficacy. GDC-0834 inhibited BTK with an in vitro IC(50) of 5.9 and 6.4 nM in biochemical and cellular assays, respectively, and in vivo IC(50) of 1.1 and 5.6 μM in mouse and rat, respectively. Administration of GDC-0834 (30-100 mg/kg) in a rat collagen-induced arthritis (CIA) model resulted in a dose-dependent decrease of ankle swelling and reduction of morphologic pathology. An integrated disease progression pharmacokinetic/pharmacodynamic model where efficacy is driven by pBTK inhibition was fit to ankle-diameter time-course data. This model incorporated a transit model to characterize nondrug-related decreases in ankle swelling occurring at later stages of disease progression in CIA rats. The time course of ankle swelling in vehicle animals was described well by the base model. Simultaneous fitting of data from vehicle- and GDC-0834-treated groups showed that overall 73% inhibition of pBTK was needed to decrease the rate constant describing the ankle swelling increase (k(in)) by half. These findings suggest a high degree of pBTK inhibition is required for maximal activity of the pathway on inflammatory arthritis in rats.
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The effects of maternal protein-energy malnutrition and exposure to nitrofen on selected aspects of intestinal morphology and function were studied in the fetal rat. Pregnant rats were fed, throughout gestation, diets containing 24% or 6% casein as the sole source of protein. Red...
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The influence of hollyhock extract administration on testicular function in rats.
Papiez, Monika A
2004-11-01
It has been reported, recently that an aqueous extract from hollyhock flowers (Althaea rosea Cav. varietas nigra) induces weak metabolic changes in rat testes. In the present study, the in vivoinfluence of a methanolic extract was investigated on the metabolism and morphology of the rat testis. To this end, histochemical, morphometric and radioimmunological methods were used. The rats drank the extract at a dose of 100 mg/day for 7 weeks. The histochemical activities of glucose-6-phosphate dehydrogenase (G6PDH) and Delta(5)beta-hydroxysteroid dehydrogenase (Delta(5)betaHSD) increased significantly statistically in the Leydig cells of the experimental rats in comparison with controls. There were no significant changes in either the diameter of seminiferous tubules or the height of seminiferous epithelium after hollyhock administration. Further, only a small amount of hyperplasia of the interstitial tissue was observed. The morphological and histoenzymatic changes in the Leydig cells indicate that the methanolic hollyhock extract has a direct but small influence on rat testes. The insignificant changes in testicular testosterone and estradiol content suggest that the extract does not disturb steroidogenesis.
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Khavinson, V K; Yuzhakov, V V; Kvetnoi, I M; Malinin, V V; Popuchiev, V V; Fomina, N K
2001-03-01
Studies of the effects of vilon and epithalon on functional morphology of the thymus, spleen, and duodenum in intact rats and rats exposed to single whole-body gamma-irradiation in a dose of 6 Gy showed that vilon stimulated proliferative activity of thymocytes and enhanced proliferative potential of stem cells in the intestine, thus stimulating the postradiation recovery of critical organs. Epithalon decelerated metabolic processes in the duodenal mucosa and suppressed hemopoiesis and lymphopoiesis in the spleen.
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Li, Dongliang; Fan, Jingjing; He, Xiuhua; Zhang, Xia; Zhang, Zhiqiang; Zeng, Zhiyu; Ruan, Mei; Cai, Lirong
2015-01-01
To evaluate the therapeutic efficacy of rat bone marrow mesenchymal stem cells (BMSCs) induced into hepatocyte-like cells and of un-induced BMSCs in acute liver failure rats. BMSCs in highly homogenous passage 3 were cultured using the whole bone marrow adherent culture method. Hepatic-related characters were confirmed with morphology, RT-PCR analysis, glycogen staining and albumin (ALB) immunofluorescence assay. Carbon tetrachloride (CCl4) was injected intraperitoneally to establish an acute rat liver failure model. Hepatocyte-like cells or un-induced BMSCs were respectively injected into the models to examine rats' appearance, liver function assay and liver tissue pathology. Hepatocyte-like morphology, higher expression of cytokeratin 18 (CK18) mRNA and ALB protein, and glycogen accumulation were confirmed in the induced BMSCs. The transplanted DAPI-labeled BMSCs were localized in the liver tissue 3-14 days after transplantation. The levels of liver function indicators (AST, ALT, ALP, and TBIL) from transplanted rats were significant decreased and pathology was improved, indicating the recovery of liver function. However, the differences were statistically insignificant. Both hepatocyte-like cells and un-induced BMSCs had a similarly positively therapeutic efficacy on liver regeneration in rat liver failure model.
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Glisić, Radmila; Koko, Vesna; Todorović, Vera; Drndarević, Neda; Cvijić, Gordana
2006-09-11
The aim of our study was to investigate the morphological, immunohistochemical and ultrastructural changes of rat serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2 mg/kg dexamethasone, rats developed diabetes similar to human diabetes type 2. Stomach, small and large intestines were examined. Large serotonin positive EC cells appeared in the corpus mucosa epithelium of D group of rats, although these cells were not present in control (C) rats. Both volume fraction and the number of EC cells per mm(2) of mucosa were significantly increased only in the duodenum. However, the number of EC cells per circular sections of both antrum and small intestine was increased, but reduced both in the ascending and descending colon in D group. The dexamethasone treatment caused a strong reduction in number of granules in the antral EC cells, while it was gradually increased beginning from the jejunum to descending colon. The mean granular content was reduced in the antral EC cells but increased in the jejunal EC cells in D group. In conclusion, the present study showed that morphological changes in gut serotonin-producing EC cells occurred in diabetic rats.
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Bloemberg, Darin; Quadrilatero, Joe
2012-01-01
Skeletal muscle is a heterogeneous tissue comprised of fibers with different morphological, functional, and metabolic properties. Different muscles contain varying proportions of fiber types; therefore, accurate identification is important. A number of histochemical methods are used to determine muscle fiber type; however, these techniques have several disadvantages. Immunofluorescence analysis is a sensitive method that allows for simultaneous evaluation of multiple MHC isoforms on a large number of fibers on a single cross-section, and offers a more precise means of identifying fiber types. In this investigation we characterized pure and hybrid fiber type distribution in 10 rat and 10 mouse skeletal muscles, as well as human vastus lateralis (VL) using multicolor immunofluorescence analysis. In addition, we determined fiber type-specific cross-sectional area (CSA), succinate dehydrogenase (SDH) activity, and α-glycerophosphate dehydrogenase (GPD) activity. Using this procedure we were able to easily identify pure and hybrid fiber populations in rat, mouse, and human muscle. Hybrid fibers were identified in all species and made up a significant portion of the total population in some rat and mouse muscles. For example, rat mixed gastrocnemius (MG) contained 12.2% hybrid fibers whereas mouse white tibialis anterior (WTA) contained 12.1% hybrid fibers. Collectively, we outline a simple and time-efficient method for determining MHC expression in skeletal muscle of multiple species. In addition, we provide a useful resource of the pure and hybrid fiber type distribution, fiber CSA, and relative fiber type-specific SDH and GPD activity in a number of rat and mouse muscles.
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Gomes, Rodrigo Mello; Miranda, Rosiane Aparecida; Barella, Luiz Felipe; Malta, Ananda; Martins, Isabela Peixoto; Franco, Claudinéia Conationi da Silva; Pavanello, Audrei; Torrezan, Rosana; Natali, Maria Raquel Marçal; Lisboa, Patrícia Cristina; de Moura, Egberto Gaspar
2016-01-01
Metabolic malprogramming has been associated with low birth weight; however, the interplay between insulin secretion disruption and adrenal function upon lipid metabolism is unclear in adult offspring from protein-malnourished mothers during the last third of gestation. Thus, we aimed to study the effects of a maternal low-protein diet during the last third of pregnancy on adult offspring metabolism, including pancreatic islet function and morphophysiological aspects of the liver, adrenal gland, white adipose tissue, and pancreas. Virgin female Wistar rats (age 70 d) were mated and fed a protein-restricted diet (4%, intrauterine protein restricted [IUPR]) from day 14 of pregnancy until delivery, whereas control dams were fed a 20.5% protein diet. At age 91 d, their body composition, glucose-insulin homeostasis, ACTH, corticosterone, leptin, adiponectin, lipid profile, pancreatic islet function and liver, adrenal gland, and pancreas morphology were assessed. The birth weights of the IUPR rats were 20% lower than the control rats (P < .001). Adult IUPR rats were heavier, hyperphagic, hyperglycemic, hyperinsulinemic, hyperleptinemic, and hypercorticosteronemic (P < .05) with higher low-density lipoprotein cholesterol and lower high-density lipoprotein cholesterol, adiponectin, ACTH, and insulin sensitivity index levels (P < .01). The insulinotropic action of glucose and acetylcholine as well as muscarinic and adrenergic receptor function were impaired in the IUPR rats (P < .05). Maternal undernutrition during the last third of gestation disrupts the pancreatic islet insulinotropic response and induces obesity-associated complications. Such alterations lead to a high risk of metabolic syndrome, characterized by insulin resistance, visceral obesity, and lower high-density lipoprotein cholesterol. PMID:27007071
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Zhang, Lin; Chen, Wei; Dai, Yuee
2016-01-01
Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. PMID:27190278
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Barkla, D H; Tutton, P J
1987-04-01
Colostomies were formed in the midcolon of normal and DMH-treated rats. Changes in cell proliferation in the mucosa adjacent to the colostomy and in the defunctioned distal segment were measured at seven, 14, 30, and 72 days using a stathmokinetic technique. Animals were given intraperitoneal injections of vinblastine and sacrificed three hours later; counts of mitotic and nonmitotic cells were made in tissue sections, and three-hour accumulated mitotic indexes were estimated. The results show that, except at seven days in DMH-treated rats, cell proliferation was unchanged in the colon proximal to the colostomy. Morphologic evidence of hyperplasia was seen in some animals at seven and 14 days. The defunctioned segment showed rapid atrophy of both mucosa and muscularis and a gradual but progressive decrease in cell proliferation. The morphology of the mucosa adjacent to the suture line in both functioning and defunctioned segments in normal and DMH-treated rats was abnormal in many animals. Abnormalities that were seen included collections of dysplastic epithelial cells in the submucosa, focal adenomatous changes, and intramural carcinoma formation. Aggregates of lymphoid tissue often were associated with carcinomas.
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Zhang, Yongliang; Mi, Yiqun; Gang, Jiahong; Wang, Huamin
2016-02-01
To observe the effects of warm needling moxibustion on body mass, knee cartilage andmorphology in rats with knee osteoarthritis (KOA). Forty SD rats were randomly divided into a normalgroup, a model group, a medication group and a warm needling group, 10 rats in each one. Except the normalgroup, the rats in the remaining three groups were injected with papain to establish the model of KOA. After themodeling, rats in the model group did not receive any treatment; rats in the warm needling group were treated withwarm needling moxibustion at bilateral "Xiqian"; rats in the medication group were treated with intragastric administration of meloxicam; rats in the normal group were treated with 0. 9% NaCl solution (identical dose as medication group) and immobilized as the warm needling group. The treatment was given once a day for consecutive20 days. The body mass, scale of knee cartilage and morphological changes were observed in each group after'treatment. The increasing of body mass in the medication group and warm needling group was faster than!that in the model group, but slower than that in the normal group (all P<0. 05); the difference between medication group and warm needling group was not statistically significant (P>0. 05). The scale of knee cartilage in thewarm needling group and medication group was significantly lower than that in the model group (both P<0. 05),while the scale in the warm needling group was lower than that in the medication group (P<. 05). Regarding theknee morphology under micro-CT, the relief of knee degeneration and improvement of knee recovery in the warm needlinggroup were superior to those in the medication group. The warm needling moxibustion could effectively reduce the knee pain, improve the recovery of knee cartilage, which is a safe and effective treatment.
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Yildiz, Ahmet; Ozdemir, Ercan; Gulturk, Sefa; Erdal, Sena
2009-01-01
Creatine (Cr) has been shown to increase the total muscle mass. The purpose of this study was to investigate the effect of Cr supplementation on muscle morphology and swimming performance, using an animal model. Each rat was subjected to exercise 15-minute period daily for the 12 weeks. The rats were randomly divided into four groups: no Cr supplementation (CON), no Cr supplementation and incomplete food intake (lacking lysine and methionine in diet for rats) (INCO), Cr supplementation 1 g·kg-1·day-1 (CREAT-I) and Cr supplementation 2 g·kg-1·day-1 (CREAT-II). Three months later, all groups adult rats exercised in swimming pool chambers. Swimming time was recorded as minute for each rat. Following swimming performance period, the animals were killed by cervical dislocation and the gastrocnemius and diaphragm muscles were dissected. Serial slices of 5-7 μm were allocated paraffin wax and histochemical staining procedure of cross-sections was carried out with heamatoxylin-eosin technics. All groups gained body weight at the end of 12 weeks but there was no statistical difference among them. Swimming time values were statistical difference between CREAT-II and CON group as well as between CREAT-I and CON group (p < 0.05). In the INCO group was determined increased connective tissue cell of the muscle sample. In contrast, in the CREAT-I and CREAT-II group, the basic histological changes were large-scale muscle fibers and hypertrophic muscle cells. These results suggest that long-term creatine supplementation increased the number of muscle fibers and enhanced endurance swimming performance in rats. Key points There is no study about the effects of creatine long-term supplementation on muscle morphology and swimming performance in rats. Long-term creatine supplementation increase muscle hypertrophy (but not body weight) and enhance endurance swimming performance in rats. The quantitative analysis indicated that the number of muscle fibers per defined area increased in creatine supplementation groups. PMID:24149591
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Astrocytes from adult Wistar rats aged in vitro show changes in glial functions.
Souza, Débora Guerini; Bellaver, Bruna; Raupp, Gustavo Santos; Souza, Diogo Onofre; Quincozes-Santos, André
2015-11-01
Astrocytes, the most versatile cells of the central nervous system, play an important role in the regulation of neurotransmitter homeostasis, energy metabolism, antioxidant defenses and the anti-inflammatory response. Recently, our group characterized cortical astrocyte cultures from adult Wistar rats. In line with that work, we studied glial function using an experimental in vitro model of aging astrocytes (30 days in vitro after reaching confluence) from newborn (NB), adult (AD) and aged (AG) Wistar rats. We evaluated metabolic parameters, such as the glucose uptake, glutamine synthetase (GS) activity, and glutathione (GSH) content, as well as the GFAP, GLUT-1 and xCT expression. AD and AG astrocytes take up less glucose than NB astrocytes and had decreased GLUT1 expression levels. Furthermore, AD and AG astrocytes exhibited decreased GS activity compared to NB cells. Simultaneously, AD and AG astrocytes showed an increase in GSH levels, along with an increase in xCT expression. NB, AD and AG astrocytes presented similar morphology; however, differences in GFAP levels were observed. Taken together, these results improve the knowledge of cerebral senescence and represent an innovative tool for brain studies of aging. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Workforce Effects and the Evolution of Complex Sociality in Wild Damaraland Mole Rats.
Young, Andrew J; Jarvis, Jennifer U M; Barnaville, James; Bennett, Nigel C
2015-08-01
Explaining the evolution of eusocial and cooperatively breeding societies demands that we understand the effects of workforce size on the reproductive success of breeders. This challenge has yet to be addressed in the family that arguably exhibits the most extreme outcomes of vertebrate social evolution, the African mole rats (Bathyergidae), leaving the ultimate causes of their many unusual adaptations open to debate. Here we report-using a 14-year field study of wild Damaraland mole rats, Fukomys damarensis-that workers appear to have strong but unusual effects on offspring. Groups with larger workforces exhibited substantially higher rates of offspring recruitment while maintaining high juvenile survival rates, relationships that may have favored the evolution of the delayed dispersal, cooperation, morphological specialization, and unusual patterns of longevity that characterize such societies. Offspring reared by larger workforces also showed slower growth, however. That reduced offspring growth in larger groups has also been documented under ad lib. food conditions in the laboratory raises the possibility that this reflects socially induced growth restraint rather than simple constraints on resource availability. Our findings shed new light on the evolution of complex sociality in this enigmatic clade and highlight further departures from the norms reported for other cooperative vertebrates.
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Midrio, P; Faussone-Pellegrini, M S; Vannucchi, M G; Flake, A W
2004-10-01
A pacemaker system is required for peristalsis generation. The interstitial cells of Cajal (ICC) are considered the intestinal pacemaker, and are identified by expression of the c-kit gene--encoded protein. Gastroschisis is characterized by a severe gastrointestinal dysmotility in newborns. In spite of this clinical picture, few studies have focused on smooth muscle cells (SMC) morphology and none on ICC. Therefore, their morphology has been studied in fetuses at term in the rat model of gastroschisis. At 18.5 day's gestation (E18.5), 10 rat fetuses were killed, 10 underwent surgical creation of gastroschisis, and 10 underwent manipulation only. The small intestine of the latter 2 groups was harvested at E21.5. Specimens were processed for H&E, c-kit and actin (alpha smooth muscle antibody [alpha-SMA]) immunohistochemistry, and transmission electron microscopy (TEM). In the controls, SMC were c-kit+ and alpha-SMA+, with labeling intensity increasing by age. At E21.5, some cells around the Auerbach's plexus were more intensely c-kit+, and differentiating ICC were seen under TEM at this level. Gastroschisis fetuses had no c-kit+ cells referable to ICC. In the more damaged loops, SMC were very faintly c-kit+ and alpha-SMA+. Under TEM, there were few differentiated SMC and no presumptive ICC. In the less-damaged loops, SMC were faintly c-kit+ and alpha-SMA+ and had ultrastructural features intermediate between those of E18.5 and E21.5 controls; ICC were very immature. ICC and SMC differentiation is delayed in gastroschisis with the most damaged loops showing the most incomplete picture. These findings might help in understanding the delayed onset of peristalsis and the variable time-course of the recover seen in babies affected by gastroschisis.
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Chen, Zhongshan; Song, Yanping; Yao, Junping; Weng, Chuanhuang; Yin, Zheng Qin
2013-11-01
All know that retinitis pigmentosa (RP) is a group of hereditary retinal degenerative diseases characterized by progressive dysfunction of photoreceptors and associated with progressive cells loss; nevertheless, little is known about how rods and cones loss affects the surviving inner retinal neurons and networks. Retinal ganglion cells (RGCs) process and convey visual information from retina to visual centers in the brain. The healthy various ion channels determine the normal reception and projection of visual signals from RGCs. Previous work on the Royal College of Surgeons (RCS) rat, as a kind of classical RP animal model, indicated that, at late stages of retinal degeneration in RCS rat, RGCs were also morphologically and functionally affected. Here, retrograde labeling for RGCs with Fluorogold was performed to investigate the distribution, density, and morphological changes of RGCs during retinal degeneration. Then, patch clamp recording, western blot, and immunofluorescence staining were performed to study the channels of sodium and potassium properties of RGCs, so as to explore the molecular and proteinic basis for understanding the alterations of RGCs membrane properties and firing functions. We found that the resting membrane potential, input resistance, and capacitance of RGCs changed significantly at the late stage of retinal degeneration. Action potential could not be evoked in a part of RGCs. Inward sodium current and outward potassium current recording showed that sodium current was impaired severely but only slightly in potassium current. Expressions of sodium channel protein were impaired dramatically at the late stage of retinal degeneration. The results suggested that the density of RGCs decreased, process ramification impaired, and sodium ion channel proteins destructed, which led to the impairment of electrophysiological functions of RGCs and eventually resulted in the loss of visual function.
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Monserrat Hernández-Hernández, Elizabeth; Serrano-García, Carolina; Antonio Vázquez-Roque, Rubén; Díaz, Alfonso; Monroy, Elibeth; Rodríguez-Moreno, Antonio; Florán, Benjamin; Flores, Gonzalo
2016-05-01
Resveratrol may induce its neuroprotective effects by reducing oxidative damage and chronic inflammation apart from improving vascular function and activating longevity genes, it also has the ability to promote the activity of neurotrophic factors. Morphological changes in dendrites of the pyramidal neurons of the prefrontal cortex (PFC) and hippocampus have been reported in the brain of aging humans, or in humans with neurodegenerative diseases such as Alzheimer's disease. These changes are reflected particularly in the decrement of both the dendritic tree and spine density. Here we evaluated the effect of resveratrol on the dendrites of pyramidal neurons of the PFC (Layers 3 and 5), CA1- and CA3-dorsal hippocampus (DH) as well as CA1-ventral hippocampus, dentate gyrus (DG), and medium spiny neurons of the nucleus accumbens of aged rats. 18-month-old rats were administered resveratrol (20 mg/kg, orally) daily for 60 days. Dendritic morphology was studied by the Golgi-Cox stain procedure, followed by Sholl analysis on 20-month-old rats. In all resveratrol-treated rats, a significant increase in dendritic length and spine density in pyramidal neurons of the PFC, CA1, and CA3 of DH was observed. Interestingly, the enhancement in dendritic length was close to the soma in pyramidal neurons of the PFC, whereas in neurons of the DH and DG, the increase in dendritic length was further from the soma. Our results suggest that resveratrol induces modifications of dendritic morphology in the PFC, DH, and DG. These changes may explain the therapeutic effect of resveratrol in aging and in Alzheimer's disease. © 2016 Wiley Periodicals, Inc.
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Maternal deprivation decelerates postnatal morphological lung development of F344 rats.
Hupa, Katharina Luise; Schmiedl, Andreas; Pabst, Reinhard; Von Hörsten, Stephan; Stephan, Michael
2014-02-01
Intensive medical care at premature born infants is often associated with separation of neonates from their mothers. Here, early artificial prolonged separation of rat pups from their dams (Maternal Deprivation, MD) was used to study potential impact on morphological lung maturation. Furthermore, we investigated the influence of an endogenous deficiency of the neuropeptide-cleaving dipeptidyl peptidase IV (DPP4), since the effects of MD are known to be partly mediated via neuropeptidergic effects, hypothesizing that MD will lead to a retardation of postnatal lung development, DPP4-dependendly. We used wild type and CD26/DPP4 deficient rats. For MD, the dam was placed each day into a separate cage for 2 h, while the pups remained in the nest on their own. Morphological lung maturation and cell proliferation at the postnatal days 7, 10, 14, and 21 were determined morphometrically. Maternally deprived wild types showed a retarded postnatal lung development compared with untreated controls in both substrains. During alveolarization, an increased thickness of alveolar septa and a decreased surface of septa about 50% were found. At the end of the morphological lung maturation, the surface of the alveolar septa was decreased at about 25% and the septal thickness remained increased about 20%. The proliferation rate was also decreased about 50% on day 14. However, the MD induced effects were less pronounced in DPP4-deficient rats, due to a significant deceleration already induced by DPP4-deficiency. Thus, MD as a model for postnatal stress experience influences remarkably postnatal development of rats, which is significantly modulated by the DPP4-system. Copyright © 2013 Wiley Periodicals, Inc.
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Stamenković, Stefan; Dučić, Tanja; Stamenković, Vera; Kranz, Alexander; Andjus, Pavle R
2017-08-15
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor and cognitive domains of the CNS. Mutations in the Cu,Zn-superoxide dismutase (SOD1) cause 20% of familial ALS and provoke formation of intracellular aggregates and copper and zinc unbinding, leading to glial activation and neurodegeneration. Therefore, we investigated glial cell morphology, intracellular SOD1 distribution, and elemental composition in the brainstem and hippocampus of the hSOD1 G93A transgenic rat model of ALS. Immunostaining for astrocytes, microglia and SOD1 revealed glial proliferation and progressive tissue accumulation of SOD1 in both brain regions of ALS rats starting already at the presymptomatic stage. Glial cell morphology analysis in the brainstem of ALS rats revealed astrocyte activation occurring before disease symptoms onset, followed by activation of microglia. Hippocampal ALS astrocytes exhibited an identical reactive profile, while microglial morphology was unchanged. Additionally, ALS brainstem astrocytes demonstrated progressive SOD1 accumulation in the cell body and processes, while microglial SOD1 levels were reduced and its distribution limited to distal cell processes. In the hippocampus both glial cell types exhibited SOD1 accumulation in the cell body. X-ray fluorescence imaging revealed decreased P and increased Ca, Cl, K, Ni, Cu and Zn in the brainstem, and higher levels of Cl, Ni and Cu, but lower levels of Zn in the hippocampus of symptomatic ALS rats. These results bring new insights into the glial response during disease development and progression in motor as well as in non-motor CNS structures, and indicate disturbed tissue elemental homeostasis as a prominent hallmark of disease pathology. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.
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Smith, H K; Plyley, M J; Rodgers, C D; McKee, N H
1999-07-01
The extent and stability of the expression of developmental isoforms of myosin heavy chain (MHCd), and their association with cellular morphology, were determined in adult rat skeletal muscle fibres following injury induced by eccentrically-biased exercise. Adult female Wistar rats [274 (10) g] were either assigned as non-exercised controls or subjected to 30 min of treadmill exercise (grade, -16 degrees; speed, 15 m x min(-1)), and then sacrificed following 1, 2, 4, 7, or 12 days of recovery (n = 5-6 per group). Histologically and immunohistologically stained serial, transverse cryosections of the soleus (S), vastus intermedius (VI), and tibialis anterior (TA) muscles were examined using light microscopy and digital imaging. Fibres staining positively for MHCd (MHCd+) were seldom detected in the TA. In the VI and S, higher proportions of MHCd+ fibres (0.8% and 2.5%, respectively) were observed in rats at 4 and 7 days post-exercise, in comparison to all other groups combined (0.2%, 1.2%; P < or = 0.01). In S, MHCd+ fibres were observed less frequently by 12 days (0.7%) than at 7 days (2.6%) following exercise. The majority (85.1%) of the MHCd+ fibres had morphological characteristics indicative of either damage, degeneration, repair or regeneration. Most of the MHCd+ fibres also expressed adult slow, and/or fast myosin heavy chain. Quantitatively, the MHCd+ fibres were smaller (< 2500 microm2) and more angular than fibres not expressing MHCd. Thus, there was a transient increase in a small, but distinct population of MHCd+ fibres following unaccustomed, functional exercise in adult rat S and VI muscles. The observed close coupling of MHCd expression with morphological changes within muscle fibres suggests that these characteristics have a common, initial exercise-induced injury-related stimulus.
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Changes in intrinsic excitability of ganglion cells in degenerated retinas of RCS rats
Ren, Yi-Ming; Weng, Chuan-Huang; Zhao, Cong-Jian; Yin, Zheng-Qin
2018-01-01
AIM To evaluate the intrinsic excitability of retinal ganglion cells (RGCs) in degenerated retinas. METHODS The intrinsic excitability of various morphologically defined RGC types using a combination of patch-clamp recording and the Lucifer yellow tracer in retinal whole-mount preparations harvested from Royal College of Surgeons (RCS) rats, a common retinitis pigmentosa (RP) model, in a relatively late stage of retinal degeneration (P90) were investigated. Several parameters of RGC morphologies and action potentials (APs) were measured and compared to those of non-dystrophic control rats, including dendritic stratification, dendritic field diameter, peak amplitude, half width, resting membrane potential, AP threshold, depolarization to threshold, and firing rates. RESULTS Compared with non-dystrophic control RGCs, more depolarizations were required to reach the AP threshold in RCS RGCs with low spontaneous spike rates and in RCS OFF cells (especially A2o cells), and RCS RGCs maintained their dendritic morphologies, resting membrane potentials and capabilities to generate APs. CONCLUSION RGCs are relatively well preserved morphologically and functionally, and some cells are more susceptible to decreased excitability during retinal degeneration. These findings provide valuable considerations for optimizing RP therapeutic strategies. PMID:29862172
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Long-term enteral arginine supplementation in rats with intestinal ischemia and reperfusion.
Lee, Chien-Hsing; Hsiao, Chien-Chou; Hung, Ching-Yi; Chang, Yu-Jun; Lo, Hui-Chen
2012-06-01
The effects of short-term enteral arginine supplementation on intestinal ischemia-reperfusion (IR) injury have been widely studied, especially the ischemic preconditioning supplementation. The aim of this study was to investigate the effects of long-term intra-duodenal supplementation of arginine on intestinal morphology, arginine-associated amino acid metabolism, and inflammatory responses in rats with intestinal IR. Male Wistar rats with or without three hours of ileal ischemia underwent duodenal cannulation for continuous infusion of formula with 2% arginine or commercial protein powder for 7 d. The serological examinations, plasma amino acid and cytokine profiles, and intestinal morphology were assessed. Intestinal IR injury had significant impacts on the decreases in circulating red blood cells, hemoglobin, ileum mass, and villus height and crypt depth of the distal jejunum. In addition, arginine supplementation decreased serum cholesterol and increased plasma arginine concentrations. In rats with intestinal IR injury, arginine supplementation significantly decreased serum nitric oxide, plasma citrulline and ornithine, and the mucosal protein content of the ileum. These results suggest that long-term intra-duodenal arginine administration may not have observable benefits on intestinal morphology or inflammatory response in rats with intestinal ischemia and reperfusion injury. Therefore, the necessity of long-term arginine supplementation for patients with intestinal ischemia and reperfusion injury remains questionable and requires further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.
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Egger, Robert; Narayanan, Rajeevan T.; Helmstaedter, Moritz; de Kock, Christiaan P. J.; Oberlaender, Marcel
2012-01-01
The three-dimensional (3D) structure of neural circuits is commonly studied by reconstructing individual or small groups of neurons in separate preparations. Investigation of structural organization principles or quantification of dendritic and axonal innervation thus requires integration of many reconstructed morphologies into a common reference frame. Here we present a standardized 3D model of the rat vibrissal cortex and introduce an automated registration tool that allows for precise placement of single neuron reconstructions. We (1) developed an automated image processing pipeline to reconstruct 3D anatomical landmarks, i.e., the barrels in Layer 4, the pia and white matter surfaces and the blood vessel pattern from high-resolution images, (2) quantified these landmarks in 12 different rats, (3) generated an average 3D model of the vibrissal cortex and (4) used rigid transformations and stepwise linear scaling to register 94 neuron morphologies, reconstructed from in vivo stainings, to the standardized cortex model. We find that anatomical landmarks vary substantially across the vibrissal cortex within an individual rat. In contrast, the 3D layout of the entire vibrissal cortex remains remarkably preserved across animals. This allows for precise registration of individual neuron reconstructions with approximately 30 µm accuracy. Our approach could be used to reconstruct and standardize other anatomically defined brain areas and may ultimately lead to a precise digital reference atlas of the rat brain. PMID:23284282
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Morphology of the non-sensory tissue components in rat aging vomeronasal organ.
Eltony, S A; Elgayar, S A
2011-08-01
With 30 figures, 3 histograms and 3 tables The vomeronasal organ (VNO) is a chemosensory organ that detects environmental pheromones. The morphology of the 'non-sensory' epithelium (NSE) of the VNO and its lamina propria, as well as how it relates to ageing has received little attention. Histological, histochemical, morphometric and ultrastructural techniques were used to study the morphological structure of the rat NSE in five adult (3 months old) and five aged (2-2.5 years old) male albino rats. In adult rats, the NSE contained dark and light columnar cells with predominance of the latter. The surface of the epithelial cells was covered with microvilli and/or cilia. The lamina propria contained serous vomeronasal glands (VNGs), smooth muscles with numerous variable-sized mitochondria, vessels including lymphatic capillaries and nerve bundles. The following changes were detected in aged rats. The NSE exhibited an increase in number of dark columnar cells. Some cells revealed a prominent cell coat, dense aggregation of filaments in the luminal cytoplasm and appearance of multinucleated cells. Their surface revealed malformed configuration. Large mitochondria (2 μm), formed by fusion, were frequently observed in the smooth muscle cells of the lamina propria. Lipid droplets were frequently detected both in the VNGs acini and in the lymphatic endothelium. Ageing affected both the cells of the tissues and the extracellular matrix. © 2011 Blackwell Verlag GmbH.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Browne, E.S.; Bhalla, V.K.
1991-02-01
Rat testicular interstitial cells were separated by three different gradient-density procedures and, with each, two biochemically and morphologically distinct cell fractions were isolated. The lighter density cells in fraction-I bound iodine 125-labeled human chorionic gonadotropin (hCG) with high-affinity (apparent equilibrium dissociation constant, Kd, approximately 10{sup {minus} 10} M) without producing either cyclic adenosine monophosphate or testosterone in response to hormone action. The heavier-density cells displayed morphologic features typical of Leydig cells and produced cyclic adenosine monophosphate and testosterone in the presence of hCG without detectable {sup 125}I-labeled hCG high-affinity binding. These cell fractions were further characterized by studies using deglycosylatedmore » hCG, a known antagonist to hCG action. Cell concentration-dependent studies with purified Leydig cells revealed that maximal testosterone production was achieved when lower cell concentrations (0.5 x 10(6) cells/250 microliters) were used for in vitro hCG stimulation assays. Under these conditions, the {sup 125}I-labeled hCG binding was barely detectable (2.24 fmol; 2,698 sites/cell). Furthermore, these studies revealed that the hCG-specific binding in Leydig cells is overestimated by the classic method for nonspecific binding correction using excess unlabeled hormone. An alternate method is presented.« less
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Starek, A; Kamiński, M
1982-01-01
Rats exposed to cosmetic kerosene mists (odourless kerosene), concentration of 75 and 300 mg/m3 for 14 days, underwent morphological and cytoenzymatic liver tests and biochemical tests of lipids composition in this organ. In addition, lipids concentration and activity of test--enzymes in blood serum were determined. The findings were: passive congestion, fine--droplet fatty degeneration in I zones of clusters and increased number of Browicz--Kupffer's phagocytes near liver triads. Those changes were accompanied by: decreased activity of succinic dehydrogenese (SDH), tetrazolic NADPH--reductase (NADPH-r.t.) and glucose-6-phosphatase (G-6-P-ase) and increased activity of adenosine triphosphatase (Mg++-ATP-ase) and acid phosphatase (AcP). In blood serum medium increase of base phosphatase (AP), 5-nucleotidase (5-Nt) and leucyloaminepeptidase (LAP) and decreased activity of prothrombin (Pt) were found. In addition, it was demonstrated that liver steatosis was characterized by cumulation of free fatty acids, phospholipids and cholesterol esters with simultaneous decrease in triglycerides content in this organ. The obtained results indicate that changes induced by kerosene hydrocarbons in liver are focal and cumulate in I zones of liver clusters. The degree of lesion varies with the extent of exposure, and results from toxic effects of this preparation on hepatic cells lypoproteid membranes.
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Vulnerability of continence structures to injury by simulated childbirth
Phull, Hardeep S.; Pan, Hui Q.; Butler, Robert S.; Hansel, Donna E.
2011-01-01
The goal of this study was to examine acute morphological changes, edema, muscle damage, inflammation, and hypoxia in urethral and vaginal tissues with increasing duration of vaginal distension (VD) in a rat model. Twenty-nine virgin Sprague-Dawley rats underwent VD under anesthesia with the use of a modified Foley catheter inserted into the vagina and filled with saline for 0, 1, 4, or 6 h. Control animals were anesthetized for 4 h without catheter placement. Urogenital organs were harvested after intracardiac perfusion of fixative. Tissues were embedded, sectioned, and stained with Masson's trichrome or hematoxylin and eosin stains. Regions of hypoxia were measured by hypoxyprobe-1 immunohistochemistry. Within 1 h of VD, the urethra became vertically elongated and displaced anteriorly. Edema was most prominent in the external urethral sphincter (EUS) and urethral/vaginal septum within 4 h of VD, while muscle disruption and fragmentation of the EUS occurred after 6 h. Inflammatory damage was characterized by the presence of polymorphonuclear leukocytes in vessels and tissues after 4 h of VD, with the greatest degree of infiltration occurring in the EUS. Hypoxia localized mostly to the vaginal lamina propria, urethral smooth muscle, and EUS within 4 h of VD. Increasing duration of VD caused progressively greater tissue edema, muscle damage, and morphological changes in the urethra and vagina. The EUS underwent the greatest insult, demonstrating its vulnerability to childbirth injury. PMID:21613415
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Jindatip, Depicha; Fujiwara, Ken; Kouki, Tom; Yashiro, Takashi
2012-09-01
Pericytes are perivascular cells associated with microcirculation. Typically, they are localized close to the capillary wall, underneath the basement membrane, and have sparse cytoplasm and poorly developed cell organelles. However, the specific properties of pericytes vary by organ and the conditions within organs. We recently demonstrated that pericytes in rat anterior pituitary gland produce type I and III collagens. The present study attempted to determine the morphological characteristics of these pituitary pericytes. Castrated rats were used as a model of hormonal and vascular changes in the gland. Pericytes, as determined by desmin immunohistochemistry, were more numerous and stained more intensely in castrated rats. Transmission electron microscopy revealed that pituitary pericytes displayed the typical characteristics of pericytes. In pituitary sections from castrated rats, the Golgi apparatus of pericytes was well developed and the rough endoplasmic reticulum was elongated. Additionally, scanning electron microscopy revealed four pericyte shapes: oval, elongate, triangular, and multiangular. As compared with normal rats, the proportion of oval pericytes was lower, and the proportions of the other three shapes were higher, in castrated rats. These results suggest that pericytes change their fine structure and cell shape in response to hormonal and vascular changes in the anterior pituitary gland. In addition, a novel type of perivascular cell was found by desmin immunoelectron microscopy. The morphological properties of these cells were dissimilar to those of pericytes. The cells were localized in the perivascular space, had no basement membrane, and contained dilated rough endoplasmic reticulum. This new cell type will require further study of its origin and characteristics.
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Sumiyoshi, Akira; Taki, Yasuyuki; Nonaka, Hiroi; Takeuchi, Hikaru; Kawashima, Ryuta
2014-09-01
The effects of physical exercise on brain morphology in rodents have been well documented in histological studies. However, to further understand when and where morphological changes occur in the whole brain, a noninvasive neuroimaging method allowing an unbiased, comprehensive, and longitudinal investigation of brain morphology should be used. In this study, we investigated the effects of 7days of voluntary wheel running exercise on regional gray matter volume (rGMV) using longitudinal voxel-based morphometry (VBM) in rats. Eighteen pairs of adult male naïve Wistar rats were randomized to the exercise or control condition (one rat for each condition from each pair). Each rat was scanned in a 7.0-T MRI scanner at three time points: before exercise, after 7days of exercise, and after 7days of follow-up. The T2-weighted MRI images were segmented using the rat brain tissue priors that were recently published by our laboratory, and the intra- and inter-subject template creation steps were followed. Longitudinal VBM analysis revealed significant increases in rGMV in the motor, somatosensory, association, and visual cortices in the exercise group. Among these brain regions, rGMV changes in the motor cortex were positively correlated with the total distance that was run during the 7days of exercise. In addition, the effects of 7days of exercise on rGMV persisted after 7days of follow-up. These results support the utility of a longitudinal VBM study in rats and provide new insights into experience-dependent structural brain plasticity in naïve adult animals. Copyright © 2014 Elsevier Inc. All rights reserved.
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Hepatoprotective effects of setarud against carbon tetrachloride-induced liver injury in rats.
Khorshid, Hamid Reza Khorram; Azonov, Jahan A; Novitsky, Yury A; Farzamfar, Bardia; Shahhosseiny, Mohammad Hassan
2008-01-01
To assess the hepatoprotective activity of a new herbal drug "setarud" in experimental liver fibrosis, 48 male Wistar rats were divided into four groups: controls, carbon tetrachloride (CCl4) group, and two treatment groups that received CCl4 and setarud at doses of 0.02 or 0.04 g/Kg/day for 30 days. Body weight gain, biochemical liver tests, bile flow rate and composition, and changes in liver morphology in the four groups were studied. CCl4 administration led to morphological and biochemical evidence of liver injury as compared to untreated controls. Setarud administration led to significant protection against CCl4-induced changes in body weight gain, liver morphology, bile flow and concentration. It was also associated with significantly lower serum liver enzyme levels (p<0.01), higher serum albumin level, and reduced increase in narcotic-induced sleeping time. Thus, setarud showed protective activity against CCl4-induced hepatotoxicity in rats. Further studies of its efficacy in liver disease are warranted.
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Wang, Zhi-Yong; Wang, Jian-Wei; Qin, Li-Hua; Zhang, Wei-Guang; Zhang, Pei-Xun; Jiang, Bao-Guo
2018-06-01
To investigate the efficacy of chitin biological absorbable catheters in a rat model of autologous nerve transplantation. A segment of sciatic nerve was removed to produce a sciatic nerve defect, and the sural nerve was cut from the ipsilateral leg and used as a graft to bridge the defect, with or without use of a chitin biological absorbable catheter surrounding the graft. The number and morphology of regenerating myelinated fibers, nerve conduction velocity, nerve function index, triceps surae muscle morphology, and sensory function were evaluated at 9 and 12 months after surgery. All of the above parameters were improved in rats in which the nerve graft was bridged with chitin biological absorbable catheters compared with rats without catheters. The results of this study indicate that use of chitin biological absorbable catheters to surround sural nerve grafts bridging sciatic nerve defects promotes recovery of structural, motor, and sensory function and improves muscle fiber morphology. © 2018 John Wiley & Sons Ltd.
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Regional Differences in Rat Vaginal Smooth Muscle Contractility and Morphology
Skoczylas, Laura C.; Jallah, Zegbeh; Sugino, Yoshio; Stein, Suzan E.; Feola, Andrew; Yoshimura, Naoki
2013-01-01
The objective of this study was to define the regional differences in rat vaginal smooth muscle contractility and morphology. We evaluated circumferential segments from the proximal, middle, and distal rat vagina (n = 21) in vitro. Contractile responses to carbachol, phenylephrine, potassium chloride, and electrical field stimulation (EFS) were measured. Immunohistochemical analyses were also performed. The dose–response curves for carbachol- and phenylephrine-dependent contractions were different in the distal (P = .05, P = .04) compared to the proximal/middle regions. Adjusted for region-dependent changes in contractility, the distal vagina generated lower force in response to carbachol and higher force in response to phenylephrine. There was less force with increasing EFS frequency in the distal (P = .03), compared to the proximal/middle regions. Cholinergic versus adrenergic nerves were more frequent in the proximal region (P = .03). In summary, the results indicate that functional and morphological differences in smooth muscle and nerve fibers of the distal versus proximal/middle regions of the vagina exist. PMID:23298869
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Kerimoğlu, Gökçen; Hancı, Hatice; Baş, Orhan; Aslan, Ali; Erol, Hüseyin Serkan; Turgut, Alpgiray; Kaya, Haydar; Çankaya, Soner; Sönmez, Osman Fikret; Odacı, Ersan
2016-11-01
The central nervous system (CNS) begins developing in the intrauterine period, a process that continues until adulthood. Contact with chemical substances, drugs or environmental agents such as electromagnetic field (EMF) during adolescence therefore has the potential to disturb the development of the morphological architecture of components of the CNS (such as the hippocampus). The hippocampus is essential to such diverse functions as memory acquisition and integration and spatial maneuvering. EMF can result in severe damage to both the morphology of the hippocampus and its principal functions during adolescence. Although children and adolescents undergo greater exposure to EMF than adults, the information currently available regarding the effects of exposure to EMF during this period is as yet insufficient. This study investigated the 60-day-old male rat hippocampus following exposure to 900 megahertz (MHz) EMF throughout the adolescent period using stereological, histopathological and biochemical analysis techniques. Eighteen male Sprague Dawley rats aged 21days were assigned into control, sham and EMF groups on a random basis. No procedure was performed on the control group rats. The EMF group (EMFGr) was exposed to a 900-MHz EMF for 1h daily from beginning to end of adolescence. The sham group rats were held in the EMF cage but were not exposed to EMF. All rats were sacrificed at 60days of age. Their brains were extracted and halved. The left hemispheres were set aside for biochemical analyses and the right hemispheres were subjected to stereological and histopathological evaluation. Histopathological examination revealed increased numbers of pyknotic neurons with black or dark blue cytoplasm on EMFGr slides stained with cresyl violet. Stereological analyses revealed fewer pyramidal neurons in EMFGr than in the other two groups. Biochemical analyses showed an increase in malondialdehyde and glutathione levels, but a decrease in catalase levels in EMFGr. Our results indicate that oxidative stress-related morphological damage and pyramidal neuron loss may be observed in the rat hippocampus following exposure to 900-MHz EMF throughout the adolescent period. Copyright © 2016 Elsevier B.V. All rights reserved.
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The objective of the study was to assess the effects of developmental exposure to a commercial mixture of PCBs (Aroclor 1254) on neuronal dendritic morphology of hippocampal CA1 pyramidal neurons in postnatal day (PND) 22 and PND 60 male Long-Evans rats. Rat pups were born to mot...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hu, Jianzhong; Cao, Yong; Wu, Tianding
2014-10-15
Purpose: Understanding the three-dimensional (3D) morphology of the spinal cord microvasculature has been limited by the lack of an effective high-resolution imaging technique. In this study, synchrotron radiation microcomputed tomography (SRµCT), a novel imaging technique based on absorption imaging, was evaluated with regard to the detection of the 3D morphology of the rat spinal cord microvasculature. Methods: Ten Sprague-Dawley rats were used in this ex vivo study. After contrast agent perfusion, their spinal cords were isolated and scanned using conventional x-rays, conventional micro-CT (CµCT), and SRµCT. Results: Based on contrast agent perfusion, the microvasculature of the rat spinal cord wasmore » clearly visualized for the first time ex vivo in 3D by means of SRµCT scanning. Compared to conventional imaging techniques, SRµCT achieved higher resolution 3D vascular imaging, with the smallest vessel that could be distinguished approximately 7.4 μm in diameter. Additionally, a 3D pseudocolored image of the spinal cord microvasculature was generated in a single session of SRµCT imaging, which was conducive to detailed observation of the vessel morphology. Conclusions: The results of this study indicated that SRµCT scanning could provide higher resolution images of the vascular network of the spinal cord. This modality also has the potential to serve as a powerful imaging tool for the investigation of morphology changes in the 3D angioarchitecture of the neurovasculature in preclinical research.« less
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Aeolian Rat Tails (ARTs): A New Morphological Indicator of Abrasion Direction
NASA Astrophysics Data System (ADS)
Favaro, E. A.; Hugenholtz, C.; Barchyn, T.
2016-12-01
Aeolian rat tails (ARTs) are a previously undocumented aeolian abrasion feature observed on ignimbrite surfaces in the Puna Plateau of Northwest Argentina and bare morphological similarity to small-scale features on Mars. We describe the terrestrial features and present an evolutionary sequence from inception to demise. ARTs are regionally-ubiquitous and characterized by a windward abrasion-resistant lithic clast and a downwind-tapering tail. The size of ARTs is controlled by the diameter of the windward lithic clast, observed on the sub-decimeter to meter scale. Their distribution throughout the Campo de Piedra Pómez, and adjacent regions is determined by the ignimbrite clast content. ARTs develop under a uni-modal abrasion direction when lithic clasts are eroded out of the ignimbrite matrix, protrude from the surface, and shelter material directly behind the clast. As the surrounding material is eroded away, a downwind-tapered tail develops. Continued erosion of the adjacent surface leads to the undercutting of clasts, liberating them from the feature where, if small enough, the clasts can be transported downwind, leading to the destruction of the tail and ultimately the feature. This evolutionary sequence accounts not only for the morphology of the feature, but also the presence of loose clasts on the ignimbrite surface, which plays a role in the development of other enigmatic landforms in the area, such as periodic bedrock ridges, yardangs, and megaripples. The significance of the identification of ARTs is due to the necessity of uni-modal abrasion direction for their development, thereby making their orientation a diagnostic indicator of long-term aeolian abrasion direction. ARTs are likely analogs of features identified by MSL Curiosity Rover on Mars, possibly providing information on past and present wind regimes.
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Interconnected network motifs control podocyte morphology and kidney function.
Azeloglu, Evren U; Hardy, Simon V; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y; Fang, Wei; Xiong, Huabao; Neves, Susana R; Jain, Mohit R; Li, Hong; Ma'ayan, Avi; Gordon, Ronald E; He, John Cijiang; Iyengar, Ravi
2014-02-04
Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3',5'-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element-binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor-driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease.
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Interconnected Network Motifs Control Podocyte Morphology and Kidney Function
Azeloglu, Evren U.; Hardy, Simon V.; Eungdamrong, Narat John; Chen, Yibang; Jayaraman, Gomathi; Chuang, Peter Y.; Fang, Wei; Xiong, Huabao; Neves, Susana R.; Jain, Mohit R.; Li, Hong; Ma’ayan, Avi; Gordon, Ronald E.; He, John Cijiang; Iyengar, Ravi
2014-01-01
Podocytes are kidney cells with specialized morphology that is required for glomerular filtration. Diseases, such as diabetes, or drug exposure that causes disruption of the podocyte foot process morphology results in kidney pathophysiology. Proteomic analysis of glomeruli isolated from rats with puromycin-induced kidney disease and control rats indicated that protein kinase A (PKA), which is activated by adenosine 3′,5′-monophosphate (cAMP), is a key regulator of podocyte morphology and function. In podocytes, cAMP signaling activates cAMP response element–binding protein (CREB) to enhance expression of the gene encoding a differentiation marker, synaptopodin, a protein that associates with actin and promotes its bundling. We constructed and experimentally verified a β-adrenergic receptor–driven network with multiple feedback and feedforward motifs that controls CREB activity. To determine how the motifs interacted to regulate gene expression, we mapped multicompartment dynamical models, including information about protein subcellular localization, onto the network topology using Petri net formalisms. These computational analyses indicated that the juxtaposition of multiple feedback and feedforward motifs enabled the prolonged CREB activation necessary for synaptopodin expression and actin bundling. Drug-induced modulation of these motifs in diseased rats led to recovery of normal morphology and physiological function in vivo. Thus, analysis of regulatory motifs using network dynamics can provide insights into pathophysiology that enable predictions for drug intervention strategies to treat kidney disease. PMID:24497609
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Leguey, Ignacio; Bielza, Concha; Larrañaga, Pedro; Kastanauskaite, Asta; Rojo, Concepción; Benavides-Piccione, Ruth; DeFelipe, Javier
2016-09-01
The characterization of the structural design of cortical microcircuits is essential for understanding how they contribute to function in both health and disease. Since pyramidal neurons represent the most abundant neuronal type and their dendritic spines constitute the major postsynaptic elements of cortical excitatory synapses, our understanding of the synaptic organization of the neocortex largely depends on the available knowledge regarding the structure of pyramidal cells. Previous studies have identified several apparently common rules in dendritic geometry. We study the dendritic branching angles of pyramidal cells across layers to further shed light on the principles that determine the geometric shapes of these cells. We find that the dendritic branching angles of pyramidal cells from layers II-VI of the juvenile rat somatosensory cortex suggest common design principles, despite the particular morphological and functional features that are characteristic of pyramidal cells in each cortical layer. J. Comp. Neurol. 524:2567-2576, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
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Rapid approach to analyze biochemical variation in rat organs by ATR FTIR spectroscopy
NASA Astrophysics Data System (ADS)
Staniszewska, Emilia; Malek, Kamilla; Baranska, Malgorzata
2014-01-01
ATR FTIR spectra were collected from rat tissue homogenates (myocardium, brain, liver, lung, intestine, and kidney) to analyze their biochemical content. Based on the second derivative of an average spectral profile it was possible to assign bands e.g. to triglycerides and cholesterol esters, proteins, phosphate macromolecules (DNA, RNA, phospholipids, phosphorylated proteins) and others (glycogen, lactate). Peaks in the region of 1600-1700 cm-1 related to amide I mode revealed the secondary structure of proteins. The collected spectra do not characterize morphological structure of the investigated tissues but show their different composition. The comparison of spectral information gathered from FTIR spectra of the homogenates and those obtained previously from FTIR imaging of the tissue sections implicates that the presented here approach can be successfully employed in the investigations of biochemical variation in animal tissues. Moreover, it can be used in the pharmacological and pharmacokinetic studies to correlate the overall biochemical status of the tissue with the pathological changes it has undergone.
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Water maze performance of aged Sprague-Dawley rats in relation to retinal morphologic measures.
Spencer, R L; O'Steen, W K; McEwen, B S
1995-06-01
The spatial learning ability of aged male and female Sprague-Dawley rats was assessed using the Morris water maze. To determine the influence of age-related visual deficits on performance levels, retinal morphologic measures were correlated with water maze performance for each rat. Rats were first trained on the water maze task at 21 months of age and were retrained 3 or 4 times at 6-week intervals. After the last training session the rats were killed and their eyes were removed for histopathologic and morphometric evaluation of the retinas. There was a large degree of retinal degeneration in all of the aged Sprague-Dawley rats with an average decrease in the thickness of the retinal outer nuclear layer (photoreceptor nuclei containing layer) of 85% in old males and 95% in old females. Some rats, however, had less degeneration of the retinas than others, and the degree of retinal degeneration was strongly related to performance levels on the water maze task. Among the aged rats in this study with the least retinal degeneration, there was little evidence for a subset of rats that were unable, with extensive training, to learn a platform position. Of the 41 rats with the least retinal degeneration (out of a total of 81), only one was a clear non-learner on the water maze task, whereas, of the 27 rats with the most retinal degeneration, 20 were non-learners. These results illustrate the potentially serious confounding effects of deteriorating visual ability on attempts to assess cognitive functioning of aged albino rats on tasks requiring utilization of visual cues.
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The dorso-lateral recess of the hypothalamic ventricle in neonatal rats.
Menéndez, A; Alvarez-Uría, M
1987-10-01
Light and electron microscopy of the hypothalamic ventricle in neonatal rats demonstrate morphological specializations of the ventricular wall at the level of the premammillary region of the third ventricle. The morphological features are: (1) A ventricular recess that we have called the "hypothalamic dorso-lateral recess" (HDR). (2) The presence of intraventricular capillaries near the dorso-lateral recess. (3) The HDR possessing a specialized ependymal lining; this consists of non-ciliated cells with short microvilli and bleb-like processes. (4) The existence of cerebrospinal fluid-contacting neurons within the HDR. (5) The presence of numerous phagocytic supraependymal cells. The HDR is not found in adult rats. This indicates that the dorso-lateral recess may play a physiological role during development.
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Kolahian, Saeed; Sadri, Hassan; Larijani, Amir; Hamidian, Gholamreza; Davasaz, Afshin
2015-12-01
The objective was to study whether leucine, zinc, and chromium supplementations influence function and histological structure of testes in a rat model of type 2 diabetes. Seventy seven adult male rats were categorized into 11 groups of 7 animals each: (1) nondiabetic (negative control); (2) non-treated (positive control); (3) treated with insulin; (4) treated with glibenclamide; (5) treated with leucine; (6) treated with zinc; (7) treated with chromium; (8) treated with leucine + zinc; (9) treated with leucine + chromium; (10) treated with zinc + chromium; (11) treated with leucine + zinc + chromium. In the non-treated group, hyperglycemia severely damaged testes morphology as well as the spermatogenic process. Diabetes induction decreased testicular length, height, width, volume, total number of epididymal sperm, and number of live sperm. Seminiferous tubules of diabetic rats showed a decrease in diameter of tubules and height of epithelium. Diabetes induction decreased the number of cells (spermatogonia, spermatocyte, spermatid, and Sertoli) in cross sections of seminiferous tubules. Administration of nutritional supplements to the diabetic rats improved testes morphology and reversed, although not completely, impairment of spermatogenesis. Treatment with nutritional supplements increased testicular length, height, width, and volume. All treatments increased the number of live sperm and the total number of epididymal sperm. Furthermore, nutritional supplements increased diameter of tubules, height of epithelium, and the number of cells in seminiferous tubules. These alleviating effects were more pronounced in animals treated with the leucine-zinc-chromium combination. The present results demonstrate beneficial effects of zinc, leucine, and chromium supplements to improve testes morphology and to restore spermatogenesis in type 2 diabetic rats.
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Farrell, M R; Holland, F H; Shansky, R M; Brenhouse, H C
2016-09-01
Early life stress has been linked to depression, anxiety, and behavior disorders in adolescence and adulthood. The medial prefrontal cortex (mPFC) is implicated in stress-related psychopathology, is a target for stress hormones, and mediates social behavior. The present study investigated sex differences in early-life stress effects on juvenile social interaction and adolescent mPFC dendritic morphology in rats using a maternal separation (MS) paradigm. Half of the rat pups of each sex were separated from their mother for 4h a day between postnatal days 2 and 21, while the other half remained with their mother in the animal facilities and were exposed to minimal handling. At postnatal day 25 (P25; juvenility), rats underwent a social interaction test with an age and sex matched conspecific. Distance from conspecific, approach and avoidance behaviors, nose-to-nose contacts, and general locomotion were measured. Rats were euthanized at postnatal day 40 (P40; adolescence), and randomly selected infralimbic pyramidal neurons were filled with Lucifer yellow using iontophoretic microinjections, imaged in 3D, and then analyzed for dendritic arborization, spine density, and spine morphology. Early-life stress increased the latency to make nose-to-nose contact at P25 in females but not males. At P40, early-life stress increased infralimbic apical dendritic branch number and length and decreased thin spine density in stressed female rats. These results indicate that MS during the postnatal period influenced juvenile social behavior and mPFC dendritic arborization in a sex-specific manner. Copyright © 2016 Elsevier B.V. All rights reserved.
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Bors, Luca; Tóth, Kinga; Tóth, Estilla Zsófia; Bajza, Ágnes; Csorba, Attila; Szigeti, Krisztián; Máthé, Domokos; Perlaki, Gábor; Orsi, Gergely; Tóth, Gábor K; Erdő, Franciska
2018-05-01
Decreased beta-amyloid clearance in Alzheimer's disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Wang, Xianjin; Zhong, Shan; Xu, Tianyuan; Xia, Leilei; Zhang, Xiaohua; Zhu, Zhaowei; Zhang, Minguang; Shen, Zhoujun
2015-02-01
A variety of murine models of experimental prostatitis that mimic the phenotype of human chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) have been developed. However, there is still a lack of explicit diagnosis criteria about those animal model. Our study is to establish histopathological classification criteria, which will be conducive to evaluate the animal models. We firstly established a rat model of experimental autoimmune prostatitis that is considered a valid model for CP/CPPS. For modelling, male Sprague-Dawley rats were immunized with autologous prostate tissue homogenate supernatant emulsified with complete Freund's adjuvant by subcutaneous injection into abdominal flank and simultaneously immunized with pertussis-diphtheria-tetanus vaccine by intraperitoneal injection. Three immunizations were administered semimonthly. At the 45th day, animals were killed, and prostate tissues were examined for morphology. Histologically, the prostate tissues were characterized by lymphoproliferation, atrophy of acini, and chronic inflammatory cells infiltration in the stromal connective tissue around the acini or ducts. Finally, we built histopathological classification criteria incorporating inflammation locations (mesenchyme, glands, periglandular tissues), ranges (focal, multifocal, diffuse), and grades (grade I-IV). To verify the effectiveness and practicability of the histopathological classification criteria, we conducted the treatment study with one of the alpha blockers, tamsulosin. The histopathological classification criteria of rat model of CP/CPPS will serve for further research of the pathogenesis and treatment strategies of the disease.
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Early neurovascular dysfunction in a transgenic rat model of Alzheimer’s disease
Joo, Illsung L.; Lai, Aaron Y.; Bazzigaluppi, Paolo; Koletar, Margaret M.; Dorr, Adrienne; Brown, Mary E.; Thomason, Lynsie A. M.; Sled, John G.; McLaurin, JoAnne; Stefanovic, Bojana
2017-01-01
Alzheimer’s disease (AD), pathologically characterized by amyloid-β peptide (Aβ) accumulation, neurofibrillary tangle formation, and neurodegeneration, is thought to involve early-onset neurovascular abnormalities. Hitherto studies on AD-associated neurovascular injury have used animal models that exhibit only a subset of AD-like pathologies and demonstrated some Aβ-dependent vascular dysfunction and destabilization of neuronal network. The present work focuses on the early stage of disease progression and uses TgF344-AD rats that recapitulate a broader repertoire of AD-like pathologies to investigate the cerebrovascular and neuronal network functioning using in situ two-photon fluorescence microscopy and laminar array recordings of local field potentials, followed by pathological analyses of vascular wall morphology, tau hyperphosphorylation, and amyloid plaques. Concomitant to widespread amyloid deposition and tau hyperphosphorylation, cerebrovascular reactivity was strongly attenuated in cortical penetrating arterioles and venules of TgF344-AD rats in comparison to those in non-transgenic littermates. Blood flow elevation to hypercapnia was abolished in TgF344-AD rats. Concomitantly, the phase-amplitude coupling of the neuronal network was impaired, evidenced by decreased modulation of theta band phase on gamma band amplitude. These results demonstrate significant neurovascular network dysfunction at an early stage of AD-like pathology. Our study identifies early markers of pathology progression and call for development of combinatorial treatment plans. PMID:28401931
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2007-01-01
AFRL-HE-BR-TR-2007-0008 Characterization of Maze Performance in Adrenalectomized Sleep Disrupted Rats: A Comparison of Radial Arm Maze Performance ...Sept 2005-Dec 2006 To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Characterization of Maze Performance in Adrenalectomized Sleep Disrupted Rats...A Comparison of Radial Arm Maze Performance Between Adrenalectomized and Sham Adrenalectomized Sleep Disrupted Rats 5b. GRANT NUMBER FA86500-05
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Mikaelian, Igor; Cameron, Mark; Dalmas, Deidre A; Enerson, Bradley E; Gonzalez, Raymond J; Guionaud, Silvia; Hoffmann, Peter K; King, Nicholas M P; Lawton, Michael P; Scicchitano, Marshall S; Smith, Holly W; Thomas, Roberta A; Weaver, James L; Zabka, Tanja S
2014-06-01
Better biomarkers are needed to identify, characterize, and/or monitor drug-induced vascular injury (DIVI) in nonclinical species and patients. The Predictive Safety Testing Consortium (PSTC), a precompetitive collaboration of pharmaceutical companies and the U.S. Food and Drug Administration (FDA), formed the Vascular Injury Working Group (VIWG) to develop and qualify translatable biomarkers of DIVI. The VIWG focused its research on acute DIVI because early detection for clinical and nonclinical safety monitoring is desirable. The VIWG developed a strategy based on the premise that biomarkers of DIVI in rat would be translatable to humans due to the morphologic similarity of vascular injury between species regardless of mechanism. The histomorphologic lexicon for DIVI in rat defines degenerative and adaptive findings of the vascular endothelium and smooth muscles, and characterizes inflammatory components. We describe the mechanisms of these changes and their associations with candidate biomarkers for which advanced analytical method validation was completed. Further development is recommended for circulating microRNAs, endothelial microparticles, and imaging techniques. Recommendations for sample collection and processing, analytical methods, and confirmation of target localization using immunohistochemistry and in situ hybridization are described. The methods described are anticipated to aid in the identification and qualification of translational biomarkers for DIVI. © 2014 by The Author(s).
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NASA Technical Reports Server (NTRS)
Kirichek, L. T.; Zholudeva, V. I.
1979-01-01
Functional and morphological manifestations of adrenal cortex response to hypodynamia (2-hr immobilization on an operating table) under the influence of bromine preparations were studied. The sodium bromide was administered intraperitoneally in 100, 250, and 500 mg/kg doses once and repeatedly during ten days. The adrenal gland was evaluated functionally by ascorbic acid and cholesterol content and morphologically by coloring it with hematoxylin-eosin and Sudans for lipid revealing at freezing. Results are displayed in two tables and microphotographs. They are summarized as follows: the bromine weakens the functional state of the adrenal cortex in intact rats, causing changes similar to those under stress. During immobilization combined with preliminary bromine administration, a less pronounced stress reaction is noticeable.
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Liu, Yang; Hou, Zhongwei; Lu, Jun; Dong, Feng; Wang, Pei; Jia, Wenrui; Wang, Chaoyang
2015-07-01
To explore the effects of moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) on liver furiction and morphology in rat with precancerous lesion of hepatic cellular cancer MCC). A total of 60 male Wistar rats were randomly divided into a normal group (10 rats), a model group (20 rats), a 20-day treatment group (15 rats) and a 40-day treatment group (15 rats). HCC model was established by intraperitoneal injection of diethylnitrosamine (DEN). Rats in the normal group received no treatment. Rats in the model group were treated with fixation. Rats in the 20-day treatment group and 40-day treatment group were treated by moxibustion with seed-sized moxa cone at "Ganshu" (BL 18), once every other day, for 20 days and 40 days, respectively. Blood sample in each group was collected 1 d before model establishment, 20 d, 40 d and 84 d after model establishment. Chemical method was applied to test the activity of ALT (alamine aminotransferase), AST (aspartate transaminase) and GGT (glutamyl transpeptidase); at the end of model establishment, all the rats were sacrificed to observe the liver morphology changes. After the first therapeutic course, the. content of ALT and AST in the 20-day treatment group was significantly lower than that in the model group (all P<0. 05); after the second therapeutic course, the content of ALT, AST and GGT in the 40-day treatment group was insignificantly lower than that in the model group (all P>0. 05). Under light microscope, the slice of liver tissue indicated that primary tumor was induced in the model group, and the tumor cells were stained and irregular; the cytoplasm in the 20-day treatment group was even, and the tumor cells were few with several nodules alone. In the 40-day treatment group the liver morphology was normal and the staining was even; the tumor cells were few without nodules or a few. Conclusion Moxibustion with seed-sized moxa cone at "Ganshu" (BL 18) could reduce the serum content of ALT, AST and GGT in rats with HCC, which could protect the liver and: delay the DEN-induced precancerous lesion on some levels.
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Histological and morphometric analyses for rat carotid balloon injury model.
Tulis, David A
2007-01-01
Experiments aimed at analyzing the response of blood vessels to mechanical injury and ensuing remodeling responses often employ the highly characterized carotid artery balloon injury model in laboratory rats. This approach utilizes luminal insertion of a balloon embolectomy catheter into the common carotid artery with inflation and withdrawal resulting in an injury characterized by vascular endothelial cell (EC) denudation and medial wall distension. The adaptive response to this injury is typified by robust vascular smooth muscle cell (SMC) replication and migration, SMC apoptosis and necrosis, enhanced synthesis and deposition of extracellular matrix (ECM) components, partial vascular EC regeneration from the border zones, luminal narrowing, and establishment of a neointima in time-dependent fashion. Evaluation of these adaptive responses to blood vessel injury can include acute and longer term qualitative and quantitative measures including expression analyses, activity assays, immunostaining for a plethora of factors and signals, and morphometry of neointima formation and gross mural remodeling. This chapter presents a logical continuation of Chapter 1 that offers details for performing the rat carotid artery balloon injury model in a standard laboratory setting by providing commonly used protocols for performing histological and morphometric analyses in such studies. Moreover, procedures, caveats, and considerations included in this chapter are highly relevant for alternative animal vascular physiology/pathophysiology studies and in particular those related to mechanisms of vascular injury and repair. Included in this chapter are specifics for in situ perfusion-fixation, tissue harvesting and processing for both snap-frozen and paraffin-embedded protocols, specimen embedding and sectioning, slide preparation, several standard histological staining steps, and routine morphological assessment.
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NASA Astrophysics Data System (ADS)
Bhargava, Maneesh
Rationale: In rodent model systems, the sequential changes in lung morphology resulting from hyperoxic injury are well characterized, and are similar to changes in human acute respiratory distress syndrome (ARDS). In the injured lung, alveolar type two (AT2) epithelial cells play a critical role restoring the normal alveolar structure. Thus characterizing the changes in AT2 cells will provide insights into the mechanisms underpinning the recovery from lung injury. Methods: We applied an unbiased systems level proteomics approach to elucidate molecular mechanisms contributing to lung repair in a rat hyperoxic lung injury model. AT2 cells were isolated from rat lungs at predetermined intervals during hyperoxic injury and recovery. Protein expression profiles were determined by using iTRAQRTM with tandem mass spectrometry. Results: Of 959 distinct proteins identified, 183 significantly changed in abundance during the injury-recovery cycle. Gene Ontology enrichment analysis identified cell cycle, cell differentiation, cell metabolism, ion homeostasis, programmed cell death, ubiquitination, and cell migration to be significantly enriched by these proteins. Gene Set Enrichment Analysis of data acquired during lung repair revealed differential expression of gene sets that control multicellular organismal development, systems development, organ development, and chemical homeostasis. More detailed analysis identified activity in two regulatory pathways, JNK and miR 374. A Short Time-series Expression Miner (STEM) algorithm identified protein clusters with coherent changes during injury and repair. Conclusion: Coherent changes occur in the AT2 cell proteome in response to hyperoxic stress. These findings offer guidance regarding the specific molecular mechanisms governing repair of the injured lung.
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Sarkar, Gunjan; Saha, Nayan Ranjan; Roy, Indranil; Bhattacharyya, Amartya; Bose, Madhura; Mishra, Roshnara; Rana, Dipak; Bhattacharjee, Debashis; Chattopadhyay, Dipankar
2014-05-01
The aim of this work is to examine the effectiveness of mucilage/hydroxypropylmethylcellulose (HPMC) based transdermal patch (matrix type) as a drug delivery device. We have successfully extracted mucilage from Colocasia esculenta (Taro) corms and prepared diltiazem hydrochloride incorporated mucilage/HPMC based transdermal patches using various wt% of mucilage by the solvent evaporation technique. Characterization of both mucilage and transdermal patches has been done by several techniques such as Molisch's test, organoleptic evaluation of mucilage, mechanical, morphological and thermal analysis of transdermal patches. Skin irritation test is studied on hairless Albino rat skin showing that transdermal patches are apparently free of potentially hazardous skin irritation. Fourier transform infrared analysis shows that there is no interaction between drug, mucilage and HPMC while scanning electron microscopy shows the surface morphology of transdermal patches. In vitro drug release time of mucilage-HPMC based transdermal patches is prolonged with increasing mucilage concentration in the formulation. Copyright © 2014 Elsevier B.V. All rights reserved.
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Zhang, Lili; Wang, Haibo; Fan, Zhaomin; Han, Yuechen; Xu, Lei; Zhang, Haiyan
2011-01-01
To study the changes in facial nerve function, morphology and neurotrophic factor III (NT-3) expression following three types of facial nerve injury. Changes in facial nerve function (in terms of blink reflex (BF), vibrissae movement (VM) and position of nasal tip) were assessed in 45 rats in response to three types of facial nerve injury: partial section of the extratemporal segment (group one), partial section of the facial canal segment (group two) and complete transection of the facial canal segment lesion (group three). All facial nerves specimen were then cut into two parts at the site of the lesion after being taken from the lesion site on 1st, 7th, 21st post-surgery-days (PSD). Changes of morphology and NT-3 expression were evaluated using the improved trichrome stain and immunohistochemistry techniques ,respectively. Changes in facial nerve function: In group 1, all animals had no blink reflex (BF) and weak vibrissae movement (VM) at the 1st PSD; The blink reflex in 80% of the rats recovered partly and the vibrissae movement in 40% of the rats returned to normal at the 7th PSD; The facial nerve function in 600 of the rats was almost normal at the 21st PSD. In group 2, all left facial nerve paralyzed at the 1st PSD; The blink reflex partly recovered in 40% of the rats and the vibrissae movement was weak in 80% of the rats at the 7th PSD; 8000 of the rats'BF were almost normal and 40% of the rats' VM completely recovered at the 21st PSD. In group 3, The recovery couldn't happen at anytime. Changes in morphology: In group 1, the size of nerve fiber differed in facial canal segment and some of myelin sheath and axons degenerated at the 7th PSD; The fibres' degeneration turned into regeneration at the 21st PSD; In group 2, the morphologic changes in this group were familiar with the group 1 while the degenerated fibers were more and dispersed in transection at the 7th PSD; Regeneration of nerve fibers happened at the 21st PSD. In group 3, most of the fibers crumbled at the 7th PSD and no regeneration was seen at the 21st PSD. Changes in NT-3: Positive staining of NT-3 was largely observed in axons at the 7th PSD, although little NT-3 was seen in the normal fibers. Facial palsy of the rats in group 2 was more extensive than that in group 1 and their function partly recovers at the 21st PSD. The fibres' degeneration occurs not only dispersed throughout the injury site but also occurred throught the length of the nerve. NT-3 immunoreactivity increased in activated fibers after partial transection.
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Sakthivel, Muniyan; Elanchezhian, Rajan; Thomas, Philip A.
2010-01-01
Purpose To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. Methods Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS–PAGE) and confirmed immunologically by western blot. Results Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased αA- and βB1-crystallins in the soluble fraction and aggregation of αA-crystallin, in addition to the degraded fragment of βB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite-cataract group exhibited similar changes, except that there was also high molecular weight aggregation of αA-crystallin. Conclusions The results of this study suggest that there is loss, as well as aggregation, of αA-crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency. PMID:20300567
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Sakthivel, Muniyan; Elanchezhian, Rajan; Thomas, Philip A; Geraldine, Pitchairaj
2010-03-16
To determine putative alterations in the major lenticular proteins in Wistar rats of different ages and to compare these alterations with those occurring in rats with selenite-induced cataract. Lenticular transparency was determined by morphological examination using slit-lamp biomicroscopy. Alterations in lenticular protein were determined by sodium dodecyl sulfate-PAGE (SDS-PAGE) and confirmed immunologically by western blot. Morphological examination did not reveal observable opacities in the lenses of the rats of different age groups; however, dense nuclear opacities were noted in lenses of rats in the selenite-cataract group. Western blot assays revealed age-related changes in soluble and urea-soluble lenticular proteins. Decreased alphaA- and betaB1-crystallins in the soluble fraction and aggregation of alphaA-crystallin, in addition to the degraded fragment of betaB1-crystallin, in the urea-soluble fraction appeared to occur in relation to increasing age of the rats from which the lenses were taken; similarly, cytoskeletal proteins appeared to decline with increasing age. The lenses from rats in the selenite-cataract group exhibited similar changes, except that there was also high molecular weight aggregation of alphaA-crystallin. The results of this study suggest that there is loss, as well as aggregation, of alphaA-crystallin in the aging rat lens, although there is no accompanying loss of lenticular transparency.
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The morphology and classification of α ganglion cells in the rat retinae: a fractal analysis study.
Jelinek, Herbert F; Ristanović, Dušan; Milošević, Nebojša T
2011-09-30
Rat retinal ganglion cells have been proposed to consist of a varying number of subtypes. Dendritic morphology is an essential aspect of classification and a necessary step toward understanding structure-function relationships of retinal ganglion cells. This study aimed at using a heuristic classification procedure in combination with the box-counting analysis to classify the alpha ganglion cells in the rat retinae based on the dendritic branching pattern and to investigate morphological changes with retinal eccentricity. The cells could be divided into two groups: cells with simple dendritic pattern (box dimension lower than 1.390) and cells with complex dendritic pattern (box dimension higher than 1.390) according to their dendritic branching pattern complexity. Both were further divided into two subtypes due to the stratification within the inner plexiform layer. In the present study we have shown that the alpha rat RCGs can be classified further by their dendritic branching complexity and thus extend those of previous reports that fractal analysis can be successfully used in neuronal classification, particularly that the fractal dimension represents a robust and sensitive tool for the classification of retinal ganglion cells. A hypothesis of possible functional significance of our classification scheme is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.
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Yurttas, Canan; Schmitz, Christoph; Turgut, Mehmet; Strekalova, Tatyana; Steinbusch, Harry W M
2017-09-01
Bilateral olfactory bulbectomy (OBX) has been used as an animal model for major depression that results in behavioral, neurochemical, and neuroendocrinological changes were reversed by chronic treatment with antidepressants, including fluoxetine. However, both etiological and construct validities are lacking in OBX for rats. In the present study, we investigated the morphological changes in the hippocampi of rats undergoing OBX that were treated with fluoxetine (10mg/kg, p.o. once daily for 4 and 12 weeks) using stereological techniques. Our results revealed that OBX caused a reduction in the volumes of the CA1/2, CA3, and dentate gyrus regions 4 weeks after OBX without fluoxetine treatment. With fluoxetine treatment, these reductions were achieved 12 weeks after OBX and the volumes were comparable to normal control rats. Nevertheless, fluoxetine treatment did not reverse neuron loss in all hippocampal regions 12 weeks after OBX. Therefore, we suggest that the OBX rat model should not be used to detect the antidepressant activity of various pharmacological agents such as fluoxetine. Copyright © 2017 Elsevier Inc. All rights reserved.
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Alcohol and malnutrition in the pathogenesis of experimental alcoholic cardiomyopathy.
Rossi, M A
1980-02-01
In this study, the morphology and the catecholamine levels of the myocardium in both well-nourished and malnourished alcohol-fed rats were examined. Alcohol has been administered to rats for 16 weeks. Rats fed a diet containing alcohol corresponding to 40 per cent. of total calorific intake and inadequate amounts of calories and nutrients developed morphological changes in the heart, while the controls did not. In addition, an increase in cardiac noradrenaline concentration and heart: body weight ratio could be observed. There were no differences in myocardial morphology and catecholamine concentration between well-nourished rats fed alcohol as 35 per cent. of the calorific intake and pair-fed controls. A dispute exists about whether alcohol is directly toxic to the heart or indirectly injurious due to associated dietary deficiency. The present results, taken together, make the theory of cardiotoxicity of alcohol an unlikely one, at least in the case of the rat; and they offer considerable support for the hypothesis that the association between chronic consumption of alcoholic beverages and cardiomyopathy is a result of a primary multifactorial nutritional deficiency, resulting from displacement of nutrient-associated calories by the "empty" calories--devoid of protein, vitamins, and minerals--of alcohol, and/or a secondary nutritional deficiency due to injurious effects of alcohol on the liver, pancreas and intestine. It is suggested that continued exposure to high levels of catecholamine, directly related to malnutrition, may play a role in the development of myocardial pathology.
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Polymyxin B Nephrotoxicity: From Organ to Cell Damage
Pessoa, Edson Andrade
2016-01-01
Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p.) once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 μM, 75 μM and 375 μM polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B. PMID:27532263
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Schneider, G B; Benis, K A; Flay, N W; Ireland, R A; Popoff, S N
1995-06-01
Osteopetrosis is a heterogeneous group of bone diseases characterized by an excess accumulation of bone and a variety of immune defects. Osteopetrosis (op) and incisors absent (ia) are two nonallelic mutations in the rat which demonstrated these skeletal defects as a result of reduced bone resorption. Osteopetrotic (op) rats have severe sclerosis as a result of reduced numbers of osteoclasts which are structurally abnormal. The sclerosis in ia rats is not as severe as in op mutants; they have elevated numbers of osteoclasts, but they are also morphologically abnormal, lacking a ruffled border. Both of these mutations have defects in the inflammation-primed activation of macrophages. They demonstrate independent defects in the cascade involved in the conversion of vitamin D binding protein (DBP) to a potent macrophage activating factor (DBP-MAF). Because this factor may also play a role in the pathogenesis of osteoclastic dysfunction, the effects of ex vivo-generated DBP-MAF were evaluated on the skeletal system of these two mutations. Newborn ia and op rats and normal littermate controls were injected with DBP-MAF or vehicle once every 4 days from birth until 2 weeks of age, at which time bone samples were collected to evaluate a number of skeletal parameters. DBP-MAF treated op rats had an increased number of osteoclasts and the majority of them exhibited normal structure. There was also reduced bone volume in the treated op animals and an associated increased cellularity of the marrow spaces. The skeletal sclerosis was also corrected in the ia rats; the bone marrow cavity size was significantly enlarged and the majority of the osteoclasts appeared normal with extensive ruffled borders.
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Zhang, Lin; Chen, Wei; Dai, Yuee; Zhu, Ziyang; Liu, Qianqi
2016-07-01
Intrauterine growth retardation (IUGR) is a disorder that can result in permanent changes in the physiology and metabolism of the newborn, which increased the risk of disease in adulthood. Evidence supports IUGR as a risk factor for the development of diabetes mellitus, which could reflect changes in pancreas developmental pathways. We sought to characterize the IUGR-induced alterations of the complex pathways of pancreas development in a rat model of IUGR. We analyzed the pancreases of Sprague Dawley rats after inducing IUGR by feeding a maternal low calorie diet from gestational day 1 until term. IUGR altered the pancreatic structure, islet areas, and islet quantities and resulted in abnormal morphological changes during pancreatic development, as determined by HE staining and light microscopy. We identified multiple differentially expressed genes in the pancreas by RT-PCR. The genes of the insulin/FoxO1/Pdx1/MafA signaling pathway were first expressed at embryonic day 14 (E14). The expressions of insulin and MafA increased as the fetus grew while the expressions of FoxO1 and Pdx1 decreased. Compared with the control rats, the expressions of FoxO1, Pdx1, and MafA were lower in the IUGR rats, whereas insulin levels showed no change. Microarray profiling, in combination with quantitative real-time PCR, uncovered a subset of microRNAs that changed in their degree of expression throughout pancreatic development. In conclusion, our data support the hypothesis that IUGR influences the development of the rat pancreas. We also identified new pathways that appear to be programmed by IUGR. © 2016 by the Society for Experimental Biology and Medicine.
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Shayakhmetova, Ganna M; Bondarenko, Larysa B; Matvienko, Anatoliy V; Kovalenko, Valentina M
2014-09-01
The aim of the study was to investigate the correlation between spermatogenesis disorders and CYP2E1 mRNA contents in testes of rats with experimental alcoholism or type I diabetes. Two pathological states characterized by CYP2E1 induction were simulated on Wistar male rats: experimental alcoholism and type I diabetes. As controls for each state, equal number of animals (of the same age and weight) were used. Morphological evaluation of rat testes was carried out. The spermatogenic epithelium state was estimated by four points system. CYP2E1 mRNA expression was rated by method of reverse transcriptase polymerase chain reaction. Pearson correlation coefficients were used for describing relationships between variables. The presence of alcoholism and diabetes-mediated quantitative and qualitative changes in male rat spermatogenic epithelium in comparison with norm has been demonstrated. The increased levels of testes CYP2E1 have been fixed simultaneously. CYP2E1 mRNA content negatively strongly correlated with spermatogenic index value (r=-0.99; P<0.001) and positively strongly correlated with epithelium desquamation occurrence (r=0.99; P<0.001) in testes of rats with chronic alcoholism. The strong correlation between CYP2E1 mRNA content and number of spermatogonia (r=0.99; P<0.001) and "windows" occurrence (r=0.96; P<0.001) has been fixed in diabetic rats testes. Present investigation has demonstrated that the testicular failure following chronic ethanol consumption and diabetes type I in male rats accompanied CYP2E1 mRNA over-expression in testes. The correlation between the levels of CYP2E1 mRNA in testes and spermatogenesis disorders allow supposing the involvement of CYP2E1 into the non-specific pathogenetic mechanisms of male infertility under above-mentioned pathologies. Copyright © 2014 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.
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Hamilton, Derek A; Akers, Katherine G; Rice, James P; Johnson, Travis E; Candelaria-Cook, Felicha T; Maes, Levi I; Rosenberg, Martina; Valenzuela, C Fernando; Savage, Daniel D
2010-03-05
The goals of the present study were to characterize the effects of prenatal exposure to moderate levels of ethanol on adult social behavior, and to evaluate fetal-ethanol-related effects on dendritic morphology, structural plasticity and activity-related immediate early gene (IEG) expression in the agranular insular (AID) and prelimbic (Cg3) regions of frontal cortex. Baseline fetal-ethanol-related alterations in social behavior were limited to reductions in social investigation in males. Repeated experience with novel cage-mates resulted in comparable increases in wrestling and social investigation among saccharin- and ethanol-exposed females, whereas social behavioral effects among males were more evident in ethanol-exposed animals. Male ethanol-exposed rats also displayed profound increases in wrestling when social interaction was motivated by 24h of isolation. Baseline decreases in dendritic length and spine density in AID were observed in ethanol-exposed rats that were always housed with the same cage-mate. Modest experience-related decreases in dendritic length and spine density in AID were observed in saccharin-exposed rats housed with various cage-mates. In contrast, fetal-ethanol-exposed rats displayed experience-related increases in dendritic length in AID, and no experience-related changes in spine density. The only effect observed in Cg3 was a baseline increase in basilar dendritic length among male ethanol-exposed rats. Robust increases in activity-related IEG expression in AID (c-fos and Arc) and Cg3 (c-fos) were observed following social interaction in saccharin-exposed rats, however, activity-related increases in IEG expression were not observed in fetal-ethanol-exposed rats in either region. The results indicate that deficits in social behavior are among the long-lasting behavioral consequences of moderate ethanol exposure during brain development, and implicate AID, and to a lesser degree Cg3, in fetal-ethanol-related social behavior abnormalities. Copyright 2009 Elsevier B.V. All rights reserved.
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Grima, J; Silvestrini, B; Cheng, C Y
2001-05-01
The oral male contraceptive agent 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF2364) is a new analogue of indazole-carboxylic acid. AF2364 was orally administered to rats at 50 mg/kg body weight once weekly for five consecutive weeks. The effects on fertility efficacy, hormonal profile, organ weights, tissue morphology, and serum microchemistry were examined. Complete infertility was noted in rats 29 days after the initial dose of AF2364 and continued until 90 days. Fertility resumed in 25% of the group after 104 days and had resumed in 75% of the rats by the last mating at 197 days. Morphological examination of the testis showed rapid exfoliation of elongated spermatids and the generation of large multinucleated cells 6 days after the first treatment, with depletion of most germ cells after 40 days. Normal spermatogenesis was noted in 95% of the tubules in the animals that were fertile at 210 days. Morphological analysis of the epididymal compartments revealed reduced lumen size, whereas the prostate exhibited an increase in the glandular lumen with a reduction in epithelium height. No morphological changes were detected in the kidney, liver, and cerebrum by light microscopy. Kidney and liver function, as evaluated by serum chemistry, were not affected by the drug treatment. AF2364 did not alter the levels of FSH, and only minimal changes were noted for LH and testosterone, suggesting that the hypothalamic-pituitary-testicular axis was not affected. These results illustrate the potential of AF2364 as a male contraceptive.
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Krause Neto, Walter; Silva, Wellington de Assis; Ciena, Adriano P.; de Souza, Romeu R.; Anaruma, Carlos A.; Gama, Eliane F.
2017-01-01
The present study aimed to analyze the morphology of the peripheral nerve, postsynaptic compartment, skeletal muscles and weight-bearing capacity of Wistar rats at specific ages. Twenty rats were divided into groups: 10 months-old (ADULT) and 24 months-old (OLD). After euthanasia, we prepared and analyzed the tibial nerve using transmission electron microscopy and the soleus and plantaris muscles for cytofluorescence and histochemistry. For the comparison of the results between groups we used dependent and independent Student's t-test with level of significance set at p ≤ 0.05. For the tibial nerve, the OLD group presented the following alterations compared to the ADULT group: larger area and diameter of both myelinated fibers and axons, smaller area occupied by myelinated and unmyelinated axons, lower numerical density of myelinated fibers, and fewer myelinated fibers with normal morphology. Both aged soleus and plantaris end-plate showed greater total perimeter, stained perimeter, total area and stained area compared to ADULT group (p < 0.05). Yet, aged soleus end-plate presented greater dispersion than ADULT samples (p < 0.05). For the morphology of soleus and plantaris muscles, density of the interstitial volume was greater in the OLD group (p < 0.05). No statistical difference was found between groups in the weight-bearing tests. The results of the present study demonstrated that the aging process induces changes in the peripheral nerve and postsynaptic compartment without any change in skeletal muscles and ability to carry load in Wistar rats. PMID:29326543
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Peng, Qiuxian; Zhang, Qin; Xiao, Wei; Shao, Meng; Fan, Qin; Zhang, Hongwei; Zou, Yukai; Li, Xin; Xu, Wenxue; Mo, Zhixian; Cai, Hongbing
2014-07-18
Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertn group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver. Copyright © 2014. Published by Elsevier Inc.
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Yu, Qing; Su, Yi-xiang; Wang, Wen-wei; Li, An-le; Liu, Cun-li; Wang, Yi-long; Hu, Wan-li
2007-07-01
To study the effects of soybean isoflavone (SI) on born metabolism and morphology in animal model of osteoporosis rats. All 70 female Sprague-Dawley (SD) rats were randomly divided into 7 groups according to the levels of total cholesterol (TC) in serum: hyper-lipoid group, estrogen group, low-dose SI group, middle-dose SI group, high-dose SI group, sham group and normal control groups. Bilateral ovaries were extirpated except sham and normal control groups. Except the rats in normal control group, the other rats were fed with high fat diet. Body weight was weighted ad unam vice per week. The estrogen, different dose of SI or deionized water were fed with intragastric administration for 12 weeks. Vena caudalis serum were collected after being ovariectomized, administered for 4 w, 8 w and killed. Serum alkaline phosphatase (AKP) activity and bone density were measured etc. To interfere of estrogen and SI might recover AKP enzyme activity after its being ovariectomized. There almost sowed no differences between high dose SI intervention and estrogen on bone density and microstructure. Bone loss due to being ovariectomized was relieved after SI intervention. SI might protect cardiocyte myofilament and mitochondrial ultramicrostructure. There was mirror image in estrogen, high dose SI group resembling the normal control group, and there was obvious damage in hyper-lipoids group. There should be effects of high dose SI on bone metabolism and morphology in animal model of osteoporosis rats. Serum AKP enzyme activity and bone density should have significantly recovered, the serum level of calcium and phosphorus were maintained after high dose intervened but no significant effects for low dose of SI.
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Hamar, P; Peti-Peterdi, J; Szabó, A; Becker, G; Flach, R; Rosivall, L; Heemann, U
2001-01-01
Glomerulosclerosis is a common feature of many end-stage renal diseases. The contribution of cellular immune mechanisms has been implicated in the development of glomerulosclerosis. We investigated whether the inhibition of lymphocyte activation influences this process in an established rat model of renal hyperfiltration. After removal of two-thirds of their respective kidney mass, rats were treated with either tacrolimus (0.08 mg/kg/day) or vehicle until the end of the study (n = 10/group). The rats were pair-fed and proteinuria was assessed regularly. Twenty weeks after nephrectomy, creatinine clearance and systemic blood pressure were determined, and kidneys were harvested for morphological, immunohistological and PCR analysis. In control animals, renal function started to decline from week 12, as indicated by an elevated proteinuria. Interleukin (IL)-2 and IL-2 receptor synthesis was upregulated in control animals and inhibited by tacrolimus treatment. Transforming growth factor-beta (TGF-beta(1)), platelet-derived growth factor-AA (PDGF-AA) and macrophage chemoattractant protein-1 (MCP-1) mRNA levels were upregulated in control animals, but were significantly lower in immunosuppressed hosts. Additionally, tacrolimus treatment resulted in a significant reduction of proteinuria. Morphological analysis supported these functional results; glomerular sclerosis, tubular atrophy and intimal proliferation were more pronounced in controls than in the tacrolimus group. These morphological parameters were accompanied by reduced infiltration of CD5+ (rat T-cell marker) T cells, ED1+ (rat macrophage marker) macrophages, and less intense staining for laminin and fibronectin. A continuous treatment with tacrolimus - an inhibitor of lymphocyte proliferation - reduced the pace of glomerulosclerosis in the remnant kidney. Copyright 2001 S. Karger AG, Basel
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Kiss, David S; Zsarnovszky, Attila; Horvath, Krisztina; Gyorffy, Andrea; Bartha, Tibor; Hazai, Diana; Sotonyi, Peter; Somogyi, Virag; Frenyo, Laszlo V; Diano, Sabrina
2009-01-01
Background Based on its distribution in the brain, ecto-nucleoside triphosphate diphosphohydrolase 3 (NTPDase3) may play a role in the hypothalamic regulation of homeostatic systems, including feeding, sleep-wake behavior and reproduction. To further characterize the morphological attributes of NTPDase3-immunoreactive (IR) hypothalamic structures in the rat brain, here we investigated: 1.) The cellular and subcellular localization of NTPDase3; 2.) The effects of 17β-estradiol on the expression level of hypothalamic NTPDase3; and 3.) The effects of NTPDase inhibition in hypothalamic synaptosomal preparations. Methods Combined light- and electron microscopic analyses were carried out to characterize the cellular and subcellular localization of NTPDase3-immunoreactivity. The effects of estrogen on hypothalamic NTPDase3 expression was studied by western blot technique. Finally, the effects of NTPDase inhibition on mitochondrial respiration were investigated using a Clark-type oxygen electrode. Results Combined light- and electron microscopic analysis of immunostained hypothalamic slices revealed that NTPDase3-IR is linked to ribosomes and mitochondria, is predominantly present in excitatory axon terminals and in distinct segments of the perikaryal plasma membrane. Immunohistochemical labeling of NTPDase3 and glutamic acid decarboxylase (GAD) indicated that γ-amino-butyric-acid- (GABA) ergic hypothalamic neurons do not express NTPDase3, further suggesting that in the hypothalamus, NTPDase3 is predominantly present in excitatory neurons. We also investigated whether estrogen influences the expression level of NTPDase3 in the ventrobasal and lateral hypothalamus. A single subcutaneous injection of estrogen differentially increased NTPDase3 expression in the medial and lateral parts of the hypothalamus, indicating that this enzyme likely plays region-specific roles in estrogen-dependent hypothalamic regulatory mechanisms. Determination of mitochondrial respiration rates with and without the inhibition of NTPDases confirmed the presence of NTPDases, including NTPDase3 in neuronal mitochondria and showed that blockade of mitochondrial NTPDase functions decreases state 3 mitochondrial respiration rate and total mitochondrial respiratory capacity. Conclusion Altogether, these results suggest the possibility that NTPDases, among them NTPDase3, may play an estrogen-dependent modulatory role in the regulation of intracellular availability of ATP needed for excitatory neuronal functions including neurotransmission. PMID:19383175
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Retinoprotective effect of Epithalon in campbell rats of various ages.
Khavinson, V Kh; Razumovsky, M I; Trofimova, S V; Razumovskaya, A M
2003-05-01
We studied the retinoprotective effect of Epithalon administered to the offspring of Campbell rats during postnatal ontogeny and to mothers before mating and during pregnancy. After this treatment the morphological structure and functional activity of the retina were preserved for a longer period compared to control rats (by 2 times) and to the animals receiving the peptide only during postnatal ontogeny (by 30%).
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Davies, Kalina T.J.; Bennett, Nigel C.; Tsagkogeorga, Georgia; Rossiter, Stephen J.; Faulkes, Christopher G.
2015-01-01
During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein–protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. PMID:26318402
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Long-term sequelae of perinatal asphyxia in the aging rat.
Weitzdoerfer, R; Gerstl, N; Hoeger, H; Mosgoeller, W; Dreher, W; Engidawork, E; Overgaard-Larsen, J; Lubec, B
2002-03-01
Information on the consequences of perinatal asphyxia (PA) on brain morphology and function in the aging rat is missing although several groups have hypothesized that PA may be responsible for neurological and psychiatric deficits in the adult. We therefore decided to study the effects of PA on the central nervous system (CNS) in terms of morphology, immunohistochemistry, neurology and behavior in the aging animal. Hippocampus and cerebellum were evaluated morphologically by histological, immunohistochemical and magnetic resonance imaging and cerebellum also by stereological tests. Neurological function was tested by an observational test battery and rota rod test. Cognitive functions were examined by multiple-T-maze and the Morris water maze (MWM). Increased serotonin transporter (SERT) immunoreactivity in the CA2 region of the hippocampus and a significant difference in the escape latency, when the platform of the MWM was moved to a new location, were observed in asphyxiated rats. We showed that deteriorated cognitive functions accompanied by aberrant expression of hippocampal SERT and impaired relearning are long-term sequelae of perinatal asphyxia, a finding that may form the basis for understanding CNS pathology in the aging subject, animal or human.
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Ontogeny of the cranial system in Laonastes aenigmamus
Herrel, Anthony; Fabre, Anne-Claire; Hugot, Jean-Pierre; Keovichit, Kham; Adriaens, Dominique; Brabant, Loes; Van Hoorebeke, Luc; Cornette, Raphael
2012-01-01
Rodents, together with bats, are among the ecologically most diverse and most speciose groups of mammals. Moreover, rodents show elaborate specializations of the feeding apparatus in response to the predominantly fore-aft movements of the lower jaw. The Laotian rock rat Laonastes aenigmamus was recently discovered and originally thought to belong to a new family. The difficulties in classifying L. aenigmamus based on morphological characters stem from the fact that it presents a mixture of sciurognathous and hystricognathous characteristics, including the morphology of the jaw adductors. The origin of the unusual muscular organization in this species remains, however, unclear. Here, we investigate the development of the masticatory system in Laonastes to better understand the origin of its derived morphology relative to other rodents. Our analyses show that skull and mandible development is characterized by an overall elongation of the snout region. Muscle mass increases with positive allometry during development and growth, and so does the force-generating capacity of the jaw adductor muscles (i.e. physiological cross-sectional area). Whereas fetal crania and musculature are more similar to those of typical rodents, adults diverge in the elongation of the rostral part of the skull and the disproportionate development of the zygomaticomandibularis. Our data suggest a functional signal in the development of the unusual cranial morphology, possibly associated with the folivorous trophic ecology of the species. PMID:22607030
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Khavinson, V Kh; Razumovskii, M I; Trofimova, S V; Grigor'yan, R A; Chaban, T V; Oleinik, T L; Razumovskaya, A M
2002-01-01
The effect of peptide bioregulator Epithalon on the course of hereditary pigmentary retinal degeneration was studied in Campbell rats. Administration of epithalon starting from birth protected morphological structure, increased its bioelectrical activity, and improved its function.
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[Morphological studies of rat adrenal glands after space flight on "Kosmos-1667"].
Prodan, N G; Bara'nska, V
1989-01-01
Histological and histomorphometric examinations of rat adrenals after a 7-day flight revealed the following changes: blood congestion in the cortex and medulla, progressive delipoidization of the cortex, slight enlargement of the nuclear volume of glomerular and fascicular zones, vacuolization of the cytoplasm of medulla cells, reduction of the area of noradrenocyte islets and cell nuclei of the medulla; the adrenal weight remained however unchanged. It is concluded that an early period of adaptation to microgravity was accompanied by a weak stress-reaction. Upon return to Earth the rats developed an acute gravitational stress. From the morphological point of view the stress manifested as: increased volume of nuclei in fascicular cells, decreased content of lipids in them, and greater vacuolization of the cytoplasm of medulla cells. The lack of medulla hypertrophy, reduction of the area of noradrenocyte islets and nuclei of medulla cells suggest that 7-day exposure to microgravity did not exert of stimulating effect on the sympathetic system of rats.
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Cholecystokinin-producing (I) cells of intestinal mucosa in dexamethasone-treated rats.
Glišić, Radmila; Koko, Vesna; Cvijić, Gordana; Milošević, Maja Čakić; Obradović, Jasmina
2011-11-10
The aim of this study was to investigate the morphological, immunohistochemical and ultrastructural changes of cholecystokinin-producing (I) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2mg/kg dexamethasone, rats developed diabetes similar to human diabetes mellitus type 2. The mean diameter of the duodenum was significantly decreased due to significant reduction of volume fraction and profile area of lamina propria. There was a decrease in volume fraction and number of cholecystokinin (CCK)-producing cells per mm(2) of mucosa, as well as their numerical density, but without statistical significance. Also, dexamethasone induced appearance of hyperactive duodenal I-cells with small number of granules and dilated endoplasmic reticulum. In conclusion, the present study showed that morphological changes in duodenum cholecystokinin-producing (I) cells occurred in diabetic rats, in a manner which, suggests compensatory effort of CCK cells in diabetic condition. Copyright © 2011 Elsevier B.V. All rights reserved.
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CHARACTERIZATION OF THE COMPLETE FIBER NETWORK TOPOLOGY OF PLANAR FIBROUS TISSUES AND SCAFFOLDS
D'Amore, Antonio; Stella, John A.; Wagner, William R.; Sacks, Michael S.
2010-01-01
Understanding how engineered tissue scaffold architecture affects cell morphology, metabolism, phenotypic expression, as well as predicting material mechanical behavior have recently received increased attention. In the present study, an image-based analysis approach that provides an automated tool to characterize engineered tissue fiber network topology is presented. Micro-architectural features that fully defined fiber network topology were detected and quantified, which include fiber orientation, connectivity, intersection spatial density, and diameter. Algorithm performance was tested using scanning electron microscopy (SEM) images of electrospun poly(ester urethane)urea (ES-PEUU) scaffolds. SEM images of rabbit mesenchymal stem cell (MSC) seeded collagen gel scaffolds and decellularized rat carotid arteries were also analyzed to further evaluate the ability of the algorithm to capture fiber network morphology regardless of scaffold type and the evaluated size scale. The image analysis procedure was validated qualitatively and quantitatively, comparing fiber network topology manually detected by human operators (n=5) with that automatically detected by the algorithm. Correlation values between manual detected and algorithm detected results for the fiber angle distribution and for the fiber connectivity distribution were 0.86 and 0.93 respectively. Algorithm detected fiber intersections and fiber diameter values were comparable (within the mean ± standard deviation) with those detected by human operators. This automated approach identifies and quantifies fiber network morphology as demonstrated for three relevant scaffold types and provides a means to: (1) guarantee objectivity, (2) significantly reduce analysis time, and (3) potentiate broader analysis of scaffold architecture effects on cell behavior and tissue development both in vitro and in vivo. PMID:20398930
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Jaumard, Nicolas V; Leung, Jennifer; Gokhale, Akhilesh J; Guarino, Benjamin B; Welch, William C; Winkelstein, Beth A
2015-10-15
Basic science study measuring anatomical features of the cervical and lumbar spine in rat with normalized comparison with the human. The goal of this study is to comprehensively compare the rat and human cervical and lumbar spines to investigate whether the rat is an appropriate model for spine biomechanics investigations. Animal models have been used for a long time to investigate the effects of trauma, degenerative changes, and mechanical loading on the structure and function of the spine. Comparative studies have reported some mechanical properties and/or anatomical dimensions of the spine to be similar between various species. However, those studies are largely limited to the lumbar spine, and a comprehensive comparison of the rat and human spines is lacking. Spines were harvested from male Holtzman rats (n = 5) and were scanned using micro- computed tomography and digitally rendered in 3 dimensions to quantify the spinal bony anatomy, including the lateral width and anteroposterior depth of the vertebra, vertebral body, and spinal canal, as well as the vertebral body and intervertebral disc heights. Normalized measurements of the vertebra, vertebral body, and spinal canal of the rat were computed and compared with corresponding measurements from the literature for the human in the cervical and lumbar spinal regions. The vertebral dimensions of the rat spine vary more between spinal levels than in humans. Rat vertebrae are more slender than human vertebrae, but the width-to-depth axial aspect ratios are very similar in both species in both the cervical and lumbar regions, especially for the spinal canal. The similar spinal morphology in the axial plane between rats and humans supports using the rat spine as an appropriate surrogate for modeling axial and shear loading of the human spine.
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Tendilla-Beltrán, Hiram; Arroyo-García, Luis Enrique; Diaz, Alfonso; Camacho-Abrego, Israel; de la Cruz, Fidel; Rodríguez-Moreno, Antonio; Flores, Gonzalo
2016-11-01
Amphetamines (AMPH) are psychostimulants widely used for therapy as well as for recreational purposes. Previous results of our group showed that AMPH exposure in pregnant rats induces physiological and behavioral changes in the offspring at prepubertal and postpubertal ages. In addition, several reports have shown that AMPH are capable of modifying the morphology of neurons in some regions of the limbic system. These modifications can cause some psychiatric conditions. However, it is still unclear if there are changes to behavioral and morphological levels when low doses of AMPH are administered at a juvenile age. The aim of this study was to assess the effect of AMPH administration (1mg/kg) in Sprague-Dawley rats (postnatal day, PD21-PD35) on locomotor activity in a novel environment and compare the neuronal morphology of limbic system areas at three different ages: prepubertal (PD 36), pubertal (PD50) and postpubertal (PD 62). We found that AMPH altered locomotor activity in the prepubertal group, but did not have an effect on the other two age groups. The Golgi-Cox staining method was used to describe the neural morphology of five limbic regions: (Layers 3 and 5) the medial prefrontal cortex (mPFC), the dorsal and ventral hippocampus, the nucleus accumbens and the amygdala, showing that AMPH induced changes at pubertal ages in arborization and spine density of these neurons, but interestingly these changes did not persist at postpubertal ages. Our findings suggest that even early-life AMPH exposure does not induce long-term behavioral and morphological changes, however it causes alterations at pubertal ages in the limbic system networks, a stage of life strongly associated with the development of substance abuse behaviors. Copyright © 2016. Published by Elsevier B.V.
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Efficacy of grape seed and skin extract against doxorubicin-induced oxidative stress in rat liver.
Mokni, Meherzia; Hamlaoui, Sonia; Kadri, Safouen; Limam, Ferid; Amri, Mohamed; Marzouki, Lamjed; Aouani, Ezzedine
2015-11-01
Doxorubicin (Dox) is an anthracycline used in chemotherapy, although it causes toxicity and oxidative stress. Grape seed and skin extract (GSSE) is a mixture of polyphenolic compounds with antioxidant properties. To evaluate the hepato-toxicity of Dox on healthy rats as well as the protective effect of GSSE, rats were treated with GSSE (500mg/kg bw) during 8 days. At the 4th day of treatment, they received a single dose of Dox (20 mg/kg bw). After the treatment (9th day), livers were collected and processed for oxidative stress status. Dox increased MDA (+ 900%), decreased catalase (-60%) and increased peroxidase (+90%) and superoxide dismutase (+100%) activities. In this latter case Dox mainly increased the iron isoform. Furthermore Dox altered intracellular mediators as catalytic free iron (-75%), H₂O₂(-75%) and calcium (+30%). Dox also affected liver function by elevating plasma triacylglycerol and transaminases and liver morphology by altering its typical architecture. Importantly all Dox-induced liver disturbances were alleviated upon GSSE treatment. Dox induced liver toxicity and an oxidative stress mainly characterized by increased lipoperoxidation but not protein carbonylation. GSSE efficiently protected the liver from Dox-induced toxicity and appeared as a safe adjuvant that could be incorporated into chemotherapy protocols.
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Molecular characterization of insulin resistance and glycolytic metabolism in the rat uterus
Zhang, Yuehui; Sun, Xue; Sun, Xiaoyan; Meng, Fanci; Hu, Min; Li, Xin; Li, Wei; Wu, Xiao-Ke; Brännström, Mats; Shao, Ruijin; Billig, Håkan
2016-01-01
Peripheral insulin resistance and hyperandrogenism are the primary features of polycystic ovary syndrome (PCOS). However, how insulin resistance and hyperandrogenism affect uterine function and contribute to the pathogenesis of PCOS are open questions. We treated rats with insulin alone or in combination with human chorionic gonadotropin (hCG) and showed that peripheral insulin resistance and hyperandrogenism alter uterine morphology, cell phenotype, and cell function, especially in glandular epithelial cells. These defects are associated with an aberration in the PI3K/Akt signaling pathway that is used as an indicator for the onset of insulin resistance in classical metabolic tissues. Concomitantly, increased GSK3β (Ser-9) phosphorylation and decreased ERK1/2 phosphorylation in rats treated with insulin and hCG were also observed. We also profiled the expression of glucose transporter (Glut) isoform genes in the uterus under conditions of insulin resistance and/or hyperandrogenism. Finally, we determined the expression pattern of glycolytic enzymes and intermediates during insulin resistance and hyperandrogenism in the uterus. These findings suggest that the PI3K/Akt and MAPK/ERK signaling pathways play a role in the onset of uterine insulin resistance, and they also suggest that changes in specific Glut isoform expression and alterations to glycolytic metabolism contribute to the endometrial dysfunction observed in PCOS patients. PMID:27461373
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Blakeslee, Weston W.; Demos-Davies, Kimberly M.; Lemon, Douglas D.; Lutter, Katharina M.; Cavasin, Maria A.; Payne, Sam; Nunley, Karin; Long, Carlin S.; McKinsey, Timothy A.; Miyamoto, Shelley D.
2017-01-01
Background Histone deacetylase (HDAC) inhibitors are promising therapeutics for various forms of cardiac disease. The purpose of this study was to assess cardiac HDAC catalytic activity and expression in children with single ventricle heart disease of right ventricular morphology (SV), as well as in a rodent model of right ventricular hypertrophy (RVH). Methods Homogenates of RV explants from non-failing controls and SV children were assayed for HDAC catalytic activity and HDAC isoform expression. Postnatal 1-day old rat pups were placed in hypoxic conditions and echocardiographic analysis, gene expression, HDAC catalytic activity and isoform expression studies of the RV were performed. Results Class I, IIa, and IIb HDAC catalytic activity and protein expression were elevated in hearts of SV children. Hypoxic neonatal rats demonstrated RVH, abnormal gene expression and elevated class I and class IIb HDAC catalytic activity and protein expression in the RV compared to control. Conclusions These data suggest that myocardial HDAC adaptations occur in the SV heart and could represent a novel therapeutic target. While further characterization of the hypoxic neonatal rat is needed, this animal model may be suitable for pre-clinical investigations of pediatric RV disease and could serve as a useful model for future mechanistic studies. PMID:28549058
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VX-induced cell death involves activation of caspase-3 in cultured rat cortical neurons.
Tenn, Catherine C; Wang, Yushan
2007-05-01
Exposure of cell cultures to organophosphorous compounds such as VX can result in cell death. However, it is not clear whether VX-induced cell death is necrotic or involves programmed cell death mechanisms. Activation of caspases, a family of cysteine proteases, is often involved in cell death, and in particular, caspase-3 activation appears to be a key event in programmed cell death processes including apoptosis. In this study, we investigated VX-induced neuronal cell death, as well as the underlying mechanism in terms of its effect on caspase-3 activity. Primary cortical neuronal cultures were prepared from gestational days 17 to 19 Sprague Dawley rat fetuses. At maturation, the cells were treated with varying concentrations of VX and cell death was evaluated by lactate dehydrogenase (LDH) release. VX induced an increase in LDH release in a concentration-dependent manner. Morphological VX-induced cell death was also characterized by using nuclear staining with propidium iodide and Hoechst 33342. VX induced a concentration- and time-dependent increase in caspase-3 activation. Caspase-3 activation was also confirmed by the proteolytic cleavage of poly(ADP-ribose)polymerase (PARP), an endogenous caspase-3 substrate. These data suggested that in rat cortical neurons, VX-induced cell death via a programmed cell death pathway that involves changes in caspase-3 protease.
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Chen, Li-Jin; Wang, Yueh-Jan; Chen, Jeng-Rung; Tseng, Guo-Fang
2017-07-01
Hydrocephalus is a common neurological disorder in children characterized by abnormal dilation of cerebral ventricles as a result of the impairment of cerebrospinal fluid flow or absorption. Clinical presentation of hydrocephalus varies with chronicity and often shows cognitive dysfunction. Here we used a kaolin-induction method in rats and studied the effects of hydrocephalus on cerebral cortex and hippocampus, the two regions highly related to cognition. Hydrocephalus impaired rats' performance in Morris water maze task. Serial three-dimensional reconstruction from sections of the whole brain freshly froze in situ with skull shows that the volumes of both structures were reduced. Morphologically, pyramidal neurons of the somatosensory cortex and hippocampus appear to be distorted. Intracellular dye injection and subsequent three-dimensional reconstruction and analyses revealed that the dendritic arbors of layer III and V cortical pyramid neurons were reduced. The total dendritic length of CA1, but not CA3, pyramidal neurons was also reduced. Dendritic spine densities on both cortical and hippocampal pyramidal neurons were decreased, consistent with our concomitant findings that the expressions of both synaptophysin and postsynaptic density protein 95 were reduced. These cortical and hippocampal changes suggest reductions of excitatory connectivity, which could underlie the learning and memory deficits in hydrocephalus. © 2016 International Society of Neuropathology.
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Molecular Composition of Staufen2-Containing Ribonucleoproteins in Embryonic Rat Brain
Maher-Laporte, Marjolaine; Berthiaume, Frédéric; Moreau, Mireille; Julien, Louis-André; Lapointe, Gabriel; Mourez, Michael; DesGroseillers, Luc
2010-01-01
Messenger ribonucleoprotein particles (mRNPs) are used to transport mRNAs along neuronal dendrites to their site of translation. Numerous mRNA-binding and regulatory proteins within mRNPs finely regulate the fate of bound-mRNAs. Their specific combination defines different types of mRNPs that in turn are related to specific synaptic functions. One of these mRNA-binding proteins, Staufen2 (Stau2), was shown to transport dendritic mRNAs along microtubules. Its knockdown expression in neurons was shown to change spine morphology and synaptic functions. To further understand the molecular mechanisms by which Stau2 modulates synaptic function in neurons, it is important to identify and characterize protein co-factors that regulate the fate of Stau2-containing mRNPs. To this end, a proteomic approach was used to identify co-immunoprecipitated proteins in Staufen2-containing mRNPs isolated from embryonic rat brains. The proteomic approach identified mRNA-binding proteins (PABPC1, hnRNP H1, YB1 and hsc70), proteins of the cytoskeleton (α- and β-tubulin) and RUFY3 a poorly characterized protein. While PABPC1 and YB1 associate with Stau2-containing mRNPs through RNAs, hsc70 is directly bound to Stau2 and this interaction is regulated by ATP. PABPC1 and YB1 proteins formed puncta in dendrites of embryonic rat hippocampal neurons. However, they poorly co-localized with Stau2 in the large dendritic complexes suggesting that they are rather components of Stau2-containing mRNA particles. All together, these results represent a further step in the characterization of Stau2-containing mRNPs in neurons and provide new tools to study and understand how Stau2-containing mRNPs are transported, translationally silenced during transport and/or locally expressed according to cell needs. PMID:20596529
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Xiao, Lu-wei; Shen, Jin-wen; Wu, Cheng-liang
2006-07-01
To study the effect of Jingui Shenqi Pill (JSP) on morphology of spinal cell apoptosis in rats injured by 192Ir irradiation. One hundred and twenty rats were randomly divided into four groups: the model group, the JSP group, the prednisone group and the normal group. Corresponding pharmaceutics were given to rats once a day for 14 days respectively. Then except rats in the normal group, the others received 192Ir interstitial irradiation with the dosage of 22 Gy using back-fixing technology. The injured segments of spinal cord were taken out for HE staining, TUNEL examination and observation with electron microscope 8 hrs, 24 hrs and 4 weeks after irradiation. HE staining examination showed no obvious histological change in rats 8 and 24 hrs after irradiation, but pathological changes, as tissue rarefaction and hemorrhage did found in white matter of spinal cord shown by TUNEL 4 weeks later. Electron microscopic examination and TUNEL staining showed that as compared with the model group, the apoptotic index in the JSP and predinisone treated groups was significantly lower (P < 0.01) 8 hrs after radiation, but it showed insignificant difference between groups at the time points of 24 hrs and 4 weeks after radiation (P > 0.05). JSP could act against apoptosis of gliocyte in spinal cord of rats in early stage after brachytherapy, indicating that JSP possessing a prednisone-like action.
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Characterization of p75{sup +} ectomesenchymal stem cells from rat embryonic facial process tissue
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wen, Xiujie; Liu, Luchuan; Deng, Manjing
2012-10-12
Highlights: Black-Right-Pointing-Pointer Ectomesenchymal stem cells (EMSCs) were found to migrate to rat facial processes at E11.5. Black-Right-Pointing-Pointer We successfully sorted p75NTR positive EMSCs (p75{sup +} EMSCs). Black-Right-Pointing-Pointer p75{sup +} EMSCs up to nine passages showed relative stable proliferative activity. Black-Right-Pointing-Pointer We examined the in vitro multilineage potential of p75{sup +} EMSCs. Black-Right-Pointing-Pointer p75{sup +}EMSCs provide an in vitro model for tooth morphogenesis. -- Abstract: Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well.more » However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial-mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75{sup +} EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75{sup +} EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering.« less
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Barlow, Norman J; McIntyre, Barry S; Foster, Paul M D
2004-01-01
In utero exposure of male rats to the antiandrogen di(n-butyl) phthalate (DBP) leads to decreased anogenital distance (AGD) on postnatal day (PND) 1, increased areolae retention on PND 13, malformations in the male reproductive tract, and histologic testicular lesions including marked seminiferous epithelial degeneration and a low incidence of Leydig cell (LC) adenomas on PND 90. One objective of this study was to determine the incidence and persistence of decreased AGD, increased areolae retention, and LC adenomas in adult rats following in utero DBP exposure. A second objective was to determine whether AGD and areolae retention during the early postnatal period are associated with lesions in the male reproductive tract. Pregnant Crl:CD(SD)BR rats were gavaged with corn oil or DBP at 100 or 500 mg/kg/day, 10 dams per group. Three replicates of rats (n = 30 rats per replicate) were exposed from gestation day 12 to 21 and the male offspring allowed to mature to 6, 12, or 18 months of age. Gross malformations in the male reproductive tract and histologic lesions in the testes were similar to those previously described. However, testicular dysgenesis, a lesion of proliferating LCs and aberrant tubules that has not been previously described in DBP-exposed testes, was diagnosed. The incidence of this lesion was approximately 20% unilateral and 7-18% bilateral in the high-dose group and was similar among all ages examined, implicating a developmental alteration rather than an age-related change. AGD and areolae retention were found to be permanent changes following in utero exposure to 500 mg/kg/day of DBP. Decreased AGD was a sensitive predictor of lesions in the male reproductive tract, relatively small changes in AGD were associated with a significant incidence of male reproductive malformations. In utero DBP exposure induced proliferative developmental lesions, some of which would have been diagnosed as LC adenomas by the morphological criteria set forth by the Society of Toxicologic Pathology. However, these lesions were dissimilar to traditional LC adenomas as the LCs were poorly differentiated and the lesions contained aberrant seminiferous tubules. While the morphology and incidence of this DBP-induced testicular developmental lesion has been fully characterized by this study, the detailed pathogenesis warrants further investigation.
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Cao, Ming-hua; Li, Yong-yu; Xu, Jing; Feng, Ya-jing; Lin, Xu-hong; Li, Kun; Han, Tong; Chen, Chang-Jie
2012-01-01
Acute pancreatitis (AP), especially severe acute pancreatitis often causes extra-pancreatic complications, such as acute gastrointestinal mucosal lesion (AGML) which is accompanied by a considerably high mortality, yet the pathogenesis of AP-induced AGML is still not fully understood. In this report, we investigated the alterations of serum components and gastric endocrine and exocrine functions in rats with experimental acute pancreatitis, and studied the possible contributions of these alterations in the pathogenesis of AGML. In addition, we explored the intervention effects of cannabinoid receptor agonist HU210 and antagonist AM251 on isolated and serum-perfused rat stomach. Our results showed that the AGML occurred after 5 h of AP replication, and the body homeostasis was disturbed in AP rat, with increased levels of pancreatic enzymes, lipopolysaccharide (LPS), proinflammtory cytokines and chemokines in the blood, and an imbalance of the gastric secretion function. Perfusing the isolated rat stomach with the AP rat serum caused morphological changes in the stomach, accompanied with a significant increment of pepsin and [H+] release, and increased gastrin and decreased somatostatin secretion. HU210 reversed the AP-serum-induced rat pathological alterations, including the reversal of transformation of the gastric morphology to certain degree. The results from this study prove that the inflammatory responses and the imbalance of the gastric secretion during the development of AP are responsible for the pathogenesis of AGML, and suggest the therapeutic potential of HU210 for AGML associated with acute pancreatitis. PMID:23285225
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Guan, Y; Cui, L; Qu, Z; Lu, L; Wang, F; Wu, Y; Zhang, J; Gao, F; Tian, H; Xu, L; Xu, G; Li, W; Jin, Y; Xu, G-T
2013-11-01
For degenerative retinal diseases, like the acquired form exemplified by age-related macular degeneration (AMD), there is currently no cure. This study was to explore a stem cell therapy and a stem cell based gene therapy for sodium iodate (SI)-induced retinal degeneration in rats. Three cell types, i.e., rat mesenchymal stem cells (rMSCs) alone, erythropoietin (EPO) gene modified rMSCs (EPO-rMSCs) or doxycycline (DOX) inducible EPO expression rMSCs (Tet-on EPO-rMSCs), were transplanted into the subretinal spaces of SI-treated rats. The rMSCs were prepared for transplantation after 3 to 5 passages or modified with EPO gene. During the 8 weeks after the transplantation, the rats treated with rMSCs alone or with two types of EPO-rMSCs were all monitored with fundus examination, fundus fluorescein angiography (FFA) and electroretinogram. The transplantation efficiency of donor cells was examined for their survival, integration and differentiation. Following the transplantation, labeled donor cells were observed in subretinal space and adopted RPE morphology. EPO concentration in vitreous and retina of SI-treated rats which were transplanted with EPO-rMSCs or Tet-on EPO-rMSCs was markedly increased, in parallel with the improvement of retinal morphology and function. These findings suggest that rMSCs transplantation could be a new therapy for degenerative retinal diseases since it can protect and rescue RPE and retinal neurons, while EPO gene modification to rMSCs could be an even better option.
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Pancreatic effect of andrographolide isolated from Andrographis paniculata (Burm. f.) Nees.
Nugroho, Agung Endro; Rais, Ichwan Ridwan; Setiawan, Iwan; Pratiwi, Pramita Yuli; Hadibarata, Tony; Tegar, Maulana; Pramono, Suwidjiyo
2014-01-01
Andrographis paniculata (Burm. f.) Nees is a plant that originates from India and grows widely to Southeast which used for several purposes mainly as treatment of diabetes mellitus so the aim of this study was evaluate andrographolide for its pancreatic effect in neonatal streptozotocin (STZ)-induced diabetic rats, a model of type 2 diabetic rats. Diabetic condition was induced with an intraperitoneal injection of 90 mg kg(-1) streptozotocin in two-day-old rats. After three months, the neonatal STZ-induced diabetic rats were treated with andrographolide or andrographolide-enriched extract of A. paniculata (AEEAP) for 8 consecutive days. Pancreatic effect was evaluated by estimating mainly the preprandial and postprandial blood glucose levels and other parameters such as morphology of pancreatic islet, beta cells density and morphology and immunohistochemically pancreatic insulin. Andrographolide significantly (p < 0.05) decreased the levels of blood glucose and improved diabetic rat islet and beta cells. However, AEEAP exhibited moderate hypoglycaemic effects on the blood glucose levels. Moderate changes in beta cells were observed after AEEAP treatment. They could restore decreasing of pancreatic insulin contents. Based on these results andrographolide and AEEAP exhibited pancreatic actions in neonatal STZ-induced diabetic rats. The activity of andrographolide was more effective than this of AEEAP.
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Granholm, Ann-Charlotte; Bimonte-Nelson, Heather A.; Moore, Alfred B.; Nelson, Matthew E.; Freeman, Linnea R.; Sambamurti, Kumar
2009-01-01
Diets rich in cholesterol and/or saturated fats have been shown to be detrimental to cognitive performance. Therefore, we fed a cholesterol (2%) and saturated fat (hydrogenated coconut oil, Sat Fat 10%) diet to 16-month old rats for 8 weeks to explore the effects on the working memory performance of middle-aged rats. Lipid profiles revealed elevated plasma triglycerides, total cholesterol, HDL, and LDL for the Sat-Fat group as compared to an iso-caloric control diet (12% soybean oil). Weight gain and food consumption were similar in both groups. Sat-Fat treated rats committed more working memory errors in the water radial arm maze, especially at higher memory loads. Cholesterol, amyloid-β peptide of 40 (Aβ40) or 42 (Aβ42) residues, and nerve growth factor in cortical regions was unaffected, but hippocampal Map-2 staining was reduced in rats fed a Sat-Fat diet, indicating a loss of dendritic integrity. Map-2 reduction correlated with memory errors. Microglial activation, indicating inflammation and/or gliosis, was also observed in the hippocampus of Sat-Fat fed rats. These data suggest that saturated fat, hydrogenated fat and cholesterol can profoundly impair memory and hippocampal morphology. PMID:18560126
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Protective Effects of Lipoxin A4 in Testis Injury following Testicular Torsion and Detorsion in Rats
Zhou, Xian-Long; Yang, Qi-Sheng; Ni, Shao-Zhou; Tu, Xiao-Peng; Zhao, Yan; Xu, Bing; Pan, Zheng-Qi; Shen, Jun
2014-01-01
Purpose. To investigate the protective effects of lipoxin A4 (LXA4) in rat testis injury following testicular torsion/detorsion. Methods. A rat testicular torsion model has been established as described. Rats were randomly divided into 6 groups: sham group, torsion group, torsion/detorsion (T/D) group, and T/D plus LXA4-pretreated groups (3 subgroups). Rats in LXA4-pretreated groups received LXA4 injection (0.1, 1.0, and 10 μg/kg body weight in LXA4-pretreated subgroups 1–3, resp.) at a single dose 1 h before detorsion. Biochemical analysis, apoptosis assessment, and morphologic evaluation were carried out after orchiectomies. Results. GPx and SOD levels significantly increased and MDA levels significantly reduced in LXA4-pretreated groups compared to T/D group. LXA4 also reverted IL-2 and TNF-α to basal levels and improved the expression of IL-4 and IL-10 in LXA4-pretreated groups. Moreover, the expression of NF-κB was downregulated in LXA4-pretreated groups. LXA4 treatment also showed an improved testicular morphology and decreased apoptosis in testes. Conclusion. Lipoxin A4 protects rats against testes injury after torsion/detorsion via modulation of cytokines, oxidative stress, and NF-κB activity. PMID:24904198
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Inferior ectopic pupil and typical ocular coloboma in RCS rats.
Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro
2011-08-01
Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F(1) rats nor N(2) (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma.
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Inferior Ectopic Pupil and Typical Ocular Coloboma in RCS Rats
Tsuji, Naho; Ozaki, Kiyokazu; Narama, Isao; Matsuura, Tetsuro
2011-01-01
Ocular coloboma is sometimes accompanied by corectopia in humans and therefore ectopic pupil may indicate ocular coloboma in experimental animals. The RCS strain of rats has a low incidence of microphthalmia. We found that inferior ectopic pupil is associated exclusively with small-sized eyes in this strain. The objective of the current study was to evaluate whether inferior ectopic pupil is associated with iridal coloboma and other types of ocular coloboma in RCS rats. Both eyes of RCS rats were examined clinically, and those with inferior ectopic pupils underwent morphologic and morphometric examinations. In a prenatal study, coronal serial sections of eyeballs from fetuses at gestational day 16.5 were examined by using light microscopy. Ectopic pupils in RCS rats were found exclusively in an inferior position, where the iris was shortened. Fundic examination revealed severe chorioretinal coloboma in all cases of inferior ectopic pupil. The morphologic characteristics closely resembled those of chorioretinal coloboma in humans. Histopathologic examination of primordia showed incomplete closure of the optic fissure in 4 eyeballs of RCS fetuses. Neither F1 rats nor N2 (progeny of RCS × BN matings) displayed any ocular anomalies, including ectopic pupils. The RCS strain is a suitable model for human ocular coloboma, and inferior ectopic pupil appears to be a strong indicator of ocular coloboma. PMID:22330254
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Rader, Erik P; Miller, G Roger; Chetlin, Robert D; Wirth, Oliver; Baker, Brent A
2014-01-01
Investigation of volitional animal models of resistance training has been instrumental in our understanding of adaptive training. However, these studies have lacked reactive force measurements, a precise performance measure, and morphological analysis at a distinct phase of training – when initial strength gains precede muscle hypertrophy. Our aim was to expose rats to one month of training (70 or 700 g load) on a custom-designed weight-lifting apparatus for analysis of reactive forces and muscle morphology prior to muscle hypertrophy. Exclusively following 700 g load training, forces increased by 21% whereas muscle masses remained unaltered. For soleus (SOL) and tibialis anterior (TA) muscles, 700 g load training increased muscle fiber number per unit area by ∼20% and decreased muscle fiber area by ∼20%. Additionally, number of muscle fibers per section increased by 18% for SOL muscles. These results establish that distinct morphological alterations accompany early strength gains in a volitional animal model of load-dependent adaptive resistance training. PMID:25392697
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Morphologic and biomechanical changes of rat oesophagus in experimental diabetes
Zeng, Yan-Jun; Yang, Jian; Zhao, Jing-Bo; Liao, Dong-Hua; Zhang, En-Ping; Gregersen, Hans; Xu, Xiao-Hu; Xu, Hong; Xu, Chuan-Qing
2004-01-01
AIM: To study morphologic and biomechanical changes of oesophagus in diabetes rats. METHODS: Diabetes was induced by a single injection of streptozotocin (STZ). The type of diabetes mellitus induced by parenteral STZ administration in rats was insulin-dependent (type I). The samples were excised and studied in vitro using a self-developed biomaterial test machine. RESULTS: The body mass was decreased after 4 d with STZ treatment. The length of esophagus shortened after 4, 7, 14 d. The opening angle increased after 14 d. The shear, longitudinal and circumferential stiffness were obviously raised after 28 d of STZ treatment. CONCLUSION: The changes of passive biomechanical properties reflect intra-structural alteration of tissue to a certain extent. This alteration will lead to some dysfunction of movement. For example, tension of esophageal wall will change due to some obstructive disease. PMID:15300896
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Glimcher, M.E.; Garcia, R.I.; Szab'o, G.
1978-05-01
Scrotal skin of black Long-Evans rats and human thigh skin were maintained in vitro as organ cultures for as long as 14 days, and examined histologically using the combined skin splitting and Dopa techniques. Selected rat skin cultures received testosterone in the culture medium and/or were irradiated with ultraviolet light (290 to 320 nm uvl). With increased time in culture, scrotal melanocytes round up and there is an increase in epidermal pigmentation. Human skin behaves similarly; after eight days in vitro human melanocytes also become rounded, but remain strongly Dopa-positive. Addition of exogenous testosterone to cultured rat skin maintains dendriticmore » morphology of melanocytes, but cell body size is still reduced. uvl irradiation stimulates melanocytes in rat skin cultures, maintaining their dendritic morphology and increasing epidermal and dermal pigmentation. Cultured skin receiving both uvl and testosterone illustrates a synergistic effect. Electron microscopic examination of cultured rat skin shows the presence of large melanosome complexes in keratinocytes, much larger than those found in vivo. Melanocytes appear to be active as they contain an extensive Golgi zone, rough endoplasmic reticulum, and melanosomes in various stages of formation. Dermis contained many dermal melanocytes and macrophages laden with melanosomes, correlating with the increased visible dermal pigmentation in vitro. This uvl stimulation of melanocytes in our skin organ cultures contrasts with the lack of melanogenic stimulation found in melanoma cell cultures. Our findings suggest that the intact epidermal melanin unit may be necessary for uvl stimulation of melanocytes.« less
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Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed
2017-08-01
Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.
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Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa
2013-03-01
Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.
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Oyonarte, Rodrigo; Becerra, Daniela; Díaz-Zúñiga, Jaime; Rojas, Victor; Carrion, Flavio
2013-05-01
The aim of this study was to assess and describe the morphological effects of an intra-articular iniection of Mesenchymal Stem Cells (MSCs) and/or Low Intensity Pulsed Ultrasound (LIPUS) stimulation on the mandibular condyles of growing rats, using cone beam computed tomography (CBCT) and histology. Twenty-six young (23-day-old) rats were divided into 5 groups identified as LIPUS-stimulated (20 minutes daily using 50 mW/cm2, 1MHz, 0.2 millisecond pulses), MSCs injected (1 x 10(5) cells/kg), LIPUS + MSCs, medium inlected, and untreated controls. All treatments were performed in the left temporomandibular joint of each rat (TMJs). At day 21, CBCTs were obtained for cephalometric analysis and 3D reconstructions. After animal sacrifice, left and right TMJ sections were histologically prepared and examined. The Wilcoxon sign rank test and the Kruskal-Wallis 2 test were applied for statistical comparison. Imaging results showed that left condyles were wider in all LIPUS-treated groups (p < 0.05), while the LIPUS-only group had a greater left sagittal condylar length. LIPUS-treated groups displayed a lower midline shift to the right (p < 0.02). No significant differences were observed in the MSC group. Bone marrow morphology and vascularity differed between the groups as LIPUS-treated groups exhibited increased vascularity in the erosive cartilage zone. It was established that LIPUS and MSC application to the TMJ region of growing rats favoured transverse condylar growth, while LIPUS application alone may enhance sagittal condylar development.The MSC injection model had little effect on sagittal condylar growth.
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Action of Micrurus dumerilii carinicauda coral snake venom on the mammalian neuromuscular junction.
Serafim, Francine G; Reali, Marielga; Cruz-Höfling, Maria Alice; Fontana, Marcos D
2002-02-01
The venoms of coral snakes (mainly Micrurus species) have pre- and/or postsynaptic actions, but only a few of these have been studied in detail. We have investigated the effects of Micrurus dumerilii carinicauda coral snake venom on neurotransmission in rat isolated phrenic nerve-diaphragm muscle and chick biventer cervicis preparations stimulated directly or indirectly. M. d. carinicauda venom (5 or 10 microg/ml) produced neuromuscular blockade in rat (85-90% in 291.8+/-7.3 min and 108.3+/-13.8, respectively; n=5) and avian (95.0+/-2.0 min; 5 microg/ml, n=5) preparations. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially reversed the venom-induced neuromuscular blockade in rat nerve-muscle preparations. In neither preparation did the venom depress the twitch response elicited by direct muscle stimulation. The contractures induced by acetylcholine in chick preparations were inhibited by the venom (95-100%; n=4; p<0.05). In rat preparations, the venom produced a progressive decrease in the amplitude of miniature end-plate potentials (m.e.p.ps control frequency=69.3+/-5.0/min and control amplitude=0.4+/-0.2 mV) until these were abolished. Neostigmine (5.8 microM) and 3,4-diaminopyridine (230 microM) partially antagonized this blockade of m.e.p.ps. The resting membrane potential was not altered with the venom (10 microg/ml). M. d. carinicauda venom produced dose-dependent morphological changes in indirectly stimulated mammal preparations. Twenty-five per cent of muscle fibers were affected by a venom concentration of 5 microg/ml, whilst 60.7% were damaged by 10 microg of venom/ml. In biventer cervicis preparations, the morphological changes were slower in onset and were generally characterized by undulating fibers and, to a lesser extent, by zones of disintegrating myofibrils. A venom concentration of 5 microg/ml damaged 52.2% of the fibers. These findings indicate that M. d. carinicauda venom has neurotoxic and myotoxic effects and that the neuromuscular blockade involves mainly a postsynaptic action.
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Shuai, Shuping; Yue, Shanlan; Huang, Qingting; Wang, Wei; Yang, Junyi; Lan, Ke; Ye, Liming
2016-08-01
The purpose of this study was to develop and evaluate a novel amorphous solid dispersion system for tectorigenin (TG). TG is one of isoflavone aglycones extracted from Iris tectorum and flowers of Pueraria thunbergiana, but its poor water solubility and low membrane permeability have severely restricted the clinical application. To increase the aqueous solubility and oral bioavailability of TG, we prepared the solid dispersions of tectorigenin (TG-SD) using a simple solvent evaporation process with TG, polyvinylpyrrolidone (PVP) and PEG4000 at weight ratio of 7:54:9 after tested in several ratios. The prepared solid dispersions of tectorigenin are duly characterized for drug morphological conversion, in vitro dissolution and in vivo bioavailability. The X-ray diffraction (XRD), differential scanning calorimetry (DSC) and scanning electron microscopy (SEM) studies have indicated the morphological conversion of tectorigenin to amorphous form. In vitro release profiles revealed that the % release of TG-SD was achieved 4.35-fold higher than that of the pure drug after 150 min. The oral bioavailability of the solid dispersion in rats was also increased based on AUC0-t and C max of TG-SD, which were 4.8- and 13.1-fold higher than that of TG crystal, respectively. It is worth noting that physical mixture containing TG, PEG4000 and PVP produced a similar level of oral exposure as TG-SD, suggesting that PEG4000 and PVP were able to enhance bioavailability of TG in rats. However, with the reduction of particle size, TG-SD provided the fastest oral absorption compared to physical mixture and pure drug. These results demonstrated that the efficacy of solid dispersions for the enhancement of TG oral bioavailability was by increasing its aqueous solubility and the solid dispersion formulation could be a viable option for enhancing the oral bioavailability of TG.
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Olude, M A; Mustapha, O A; Olopade, J O
2017-03-06
This experiment was designed to investigate the morphological characterization of the brain cortices of African giant rats, AGR (Cricetomys gambianus, Waterhouse) across age groups as related to function. A total of 15 male AGR were used for this study comprising of 5 neonates, 5 juveniles and 5 adults. Brains were described as having typical rodent features; the falx cerebri, the dura modification of interest, was partly inserted between the lobes of the olfactory bulb and extended towards the corpus callosum. Gross parameters extrapolated include cerebral and cerebellar cortical dimensions using a oneway ANOVA (p≤0.05). Most values showed highest significant value bias for juveniles over adults and neonates. The average brain weight was 5.60±0.06g, 4.64±0.17g and 0.62±0.08g; cortex volume: 2.84±0.04cm3, 3.16±0.10cm3 and 0.23±0.02cm3 and antero-posterior dimensions: 11.93±0.26mm, 14.54±0.22mm and 6.00±0.16mm for adult, juvenile and neonates respectively. There was however adult bias in the cerebellum weight (0.83±0.02g, 0.76±0.02g and 0.04±0.02g); vermis length (13.23±0.32mm, 11.27±0.014mm and 0.24±0.02mm) and the antero-posterior length values (8.79±0.19mm, 6.97±0.03mm and 0.29±0.01mm) for adults, juveniles and neonates AGR respectively. Cortical parameters were related as a function of the brain development and plasticity, while age was described to play functional roles in intelligence determination of the AGR. The result of this study will be useful as baseline information for post mortem studies, medical imaging and useful as diagnostic tool for future research work on the AGR brain.
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Li, X L; Zhang, Z; Li, Z X; Deng, N J; Zeng, B; Chen, Y M
2017-04-09
Objective: To isolate the cariogenic Streptococcus mutans (Sm) strains and study the therapeutical effect of egg yolk antibody (IgY) of the Sm on dental caries development. Methods: Sm strains were isolated from the children's dental plaque samples. Morphological, biochemical and molecular biological methods were applied to identify the serotype, acid producing and adhesion abilities of isolated Sm strains. After inactivation one of the Sm strains was used as antigen to immune laying hens to collect and extract the specific anti-Sm IgY. The rats were infected with Sm (serotype e). After 16 weeks of infection, all the rats were found developing dental caries. The rats were then randomly divided into two groups. The rats in experimental group were supplied with diet containing anti-Sm IgY while the rats in control group with normal IgY. All rats were sacrificed after another 8 weeks' observation. The degree of caries for each rat was assessed using Keyes' method. Results: We isolated 7 Sm strains from the children's dental plaque samples in the present study. The numbers of serotype c, e, f, k were 3, 2, 0 and 2, respectively. All strains showed similar morphological and biochemical characters as standard UA159 Sm strain, and possessed strong capabilities of acid production and adherence. Interestingly, even the same serotypec strains, such as No.3 and No.7 strains, demonstrated significant difference on acid producing and adherence capabilities. After 16 weeks infection with serotype e strain, the rats' mandibular teeth were apparently decayed, and treatment with specific anti-Sm IgY obviously attenuated the development of caries in the experiment group rats (16.4±2.0) compared with that in the control group rats (30.2±9.3) ( P< 0.05) determined by Keyes' method. Conclusions: Seven cariogenic Sm strains of different serotypes were isolated, which possesses similar morphology and biochemical characters. Although belonging to the same serotype strains they always show significant difference in acid-producing and adherencec apabilities. Further experiment provides evidences that the serotype e strain could obviously induce caries independently, and employment of specific anti-Sm IgY as passive immunotherapy additive might effectively inhibit the further development of dental caries.
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Orendáčová, Judita; Orendáč, Martin; Mojžiš, Miroslav; Labun, Ján; Martončíková, Marcela; Saganová, Kamila; Lievajová, Kamila; Blaško, Juraj; Abdiová, Henrieta; Gálik, Ján; Račeková, Eniko
2011-11-01
The immediate effects of whole body electromagnetic radiation (EMR) were used to study postnatal neurogenesis in the subventricular zone (SVZ) and rostral migratory stream (RMS) of Wistar rats of both sexes. Newborn postnatal day 7 (P7) and young adult rats (P28) were exposed to pulsed electromagnetic fields (EMF) at a frequency of 2.45 GHz and mean power density of 2.8 mW/cm(2) for 2 h. Post-irradiation changes were studied using immunohistochemical localization of Fos and NADPH-d. We found that short-duration exposure induces increased Fos immunoreactivity selectively in cells of the SVZ of P7 and P28 rats. There were no Fos positive cells visible within the RMS of irradiated rats. These findings indicate that some differences exist in prerequisites of proliferating cells between the SVZ and RMS regardless of the age of the rats. Short-duration exposure also caused praecox maturation of NADPH-d positive cells within the RMS of P7 rats. The NADPH-d positive cells appeared several days earlier than in age-matched controls, and their number and morphology showed characteristics of adult rats. On the other hand, in the young adult P28 rats, EMR induced morphological signs typical of early postnatal age. These findings indicate that EMR causes age-related changes in the production of nitric oxide (NO), which may lead to different courses of the proliferation cascade in newborn and young adult neurogenesis. Copyright © 2010 Elsevier GmbH. All rights reserved.
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Roboon, J; Nudmamud-Thanoi, S; Thanoi, S
2017-02-01
Depression and antidepressant drugs induce adverse effects in male reproduction. Therefore, it is important to investigate alternative treatment for depression without adverse effects on the male reproductive system. The aim of this study was to determine the effect of pre-germinated brown rice (PGBR) on sperm quality, testicular structure and androgen receptor (AR) expression in rat model of depression. Male Sprague Dawley rats were divided into five groups including control (distilled water only), depression induced by forced swimming test (FST), FST + fluoxetine (antidepressant drug), FST + GABA (gamma-aminobutyric acid) (standard) and FST + PGBR. When compared with the control, sperm motility showed a significant decrease in FST + fluoxetine group. Sperm morphology also decreased significantly in depression and FST + fluoxetine groups. The morphological changes of seminiferous tubules showed significant increases in depression and FST + fluoxetine groups, while AR expression showed significant decreases in depression, FST + fluoxetine and FST + GABA groups. Interestingly, there were no significant differences in all sperm quality parameters, testicular structure and AR expression in FST + PGBR group. These findings reflect the recovery effects of PGBR treatment on sperm quality, morphological changes of seminiferous tubules and AR expression in stress-induced rats. Therefore, PGBR may potentially develop for the treatment for depression without adverse effect on male reproduction. © 2016 Blackwell Verlag GmbH.
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Takahashi, Haruka; Ishikawa, Hiroshi; Tanaka, Akira
2017-04-01
The purpose of this study was to evaluate the utility of human adipose stem cells derived from the buccal fat pad (hBFP-ASCs) for nerve regeneration. Parkinson's disease (PD) is a neurodegenerative disorder characterized by progressive death of dopaminergic neurons. PD is a candidate disease for cell replacement therapy because it has no fundamental therapeutic methods. We examined the properties of neural-related cells induced from hBFP-ASCs as a cell source for PD treatment. hBFP-ASCs were cultured in neurogenic differentiation medium for about 2 weeks. After the morphology of hBFP-ASCs changed to neural-like cells, the medium was replaced with neural maintenance medium. Cells differentiated from hBFP-ASCs showed neuron-like structures and expressed neuron markers (β3-tubulin, neurofilament 200, and microtubule-associated protein 2), an astrocyte marker (glial fibrillary acidic protein), or dopaminergic neuron-related marker (tyrosine hydroxylase). Induced neural cells were transplanted into a 6-hydroxydopamine (6-OHDA)-lesioned rat hemi-parkinsonian model. At 4 weeks after transplantation, 6-OHDA-lesioned rats were subjected to apomorphine-induced rotation analysis. The transplanted cells survived in the brain of rats as dopaminergic neural cells. No tumor formation was found after cell transplantation. We demonstrated differentiation of hBFP-ASCs into neural cells, and that transplantation of these neural cells improved the symptoms of model rats. Our results suggest that neurons differentiated from hBFP-ASCs would be applicable to cell replacement therapy of PD.
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The Neuroprotective Effect of Erythropoietin in Rat Hippocampus in an Endotoxic Shock Model.
Ramírez-Jirano, Luis Javier; Zenteno-Savín, Tania; Gaxiola-Robles, Ramón; Ramos-González, Elsy Janeth; Torres-Mendoza, Blanca Miriam; Bitzer-Quintero, Oscar Kurt
2016-01-01
Sepsis is characterized by an early systemic inflammation in response to infection. In the brain, inflammation is associated with expression of pro-inflammatory cytokines (e.g. tumor necrosis factor-α, interleukin-1β and interleukin-6, among others) that may induce an overproduction of reactive oxygen and nitrogen species. The constitutive expression of cytokines in the brain is low, but may be induced by various stimuli, including lipopolysaccharide, which causes neuronal damage. Erythropoietin, among other effects, acts as a multifunctional neurotrophic factor implicated in neurogenesis, angiogenesis, vascular permeability, and immune regulation in the central nervous system. In an experimental model of endotoxic shock, we studied the neuroprotective capacity of erythropoietin in the rat hippocampus and compared with melatonin, a neurohormone with an important antioxidant and immunomodulatory effect. In 21-day-old male Wistar rats divided into eight groups, we administered by intraperitoneal injection lipopolysaccharide, erythropoietin, melatonin, or combinations thereof. The hippocampus was dissected and morphological (histological analysis) and biochemical (cytokine levels) studies were conducted. The number of dead neuronal cells in histological sections in groups treated with lipopolysaccharide was higher compared to the erythropoietin group. There was a greater decrease (70%) in interleukin-1β concentrations in rats with endotoxic shock that received erythropoietin compared to the lipopolysaccharide group. The neuronal cell loss caused by endotoxic shock and interleukin-1β levels were reduced by the administration of the hematopoietic cytokine erythropoietin in this experimental model.
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Yong, Chul Soon; Oh, Yu-Kyoung; Kim, Yong-Il; Kim, Jong Oh; Yoo, Bong-Kyu; Rhee, Jong-Dal; Lee, Kang Choon; Kim, Dae-Duk; Park, Young-Joon; Kim, Chong-Kook; Choi, Han-Gon
2005-09-14
To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting point of various formulations composed of poloxamer 124 (P 124) and poloxamer 188 (P 188) were investigated. The dissolution and pharmacokinetic study of diclofenac sodium delivered by the poloxamer-based suppository were performed. Furthermore, the identification test in the rectum and morphology test of rectal tissues were carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous phases. Very small amounts of P 188 affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about 32 degrees C was a solid form at room temperature and instantly melted at physiological temperature. Very small amounts of P 188 hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. The poloxamer-based suppository gave significantly higher initial plasma concentrations and faster T(max) of diclofenac sodium than did conventional PEG-based suppository, indicating that the drug from poloxamer-based suppository could be absorbed faster than that from PEG-based one in rats. It retained in the rectum for at least 4 h and could not irritate or damage the rectal tissues of rats. Thus, the poloxamer-based solid suppository with P 124 and P 188 was a mucoadhesive, safe and effective rectal dosage form for diclofenac sodium.
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Tschernutter, M; Schlichtenbrede, F C; Howe, S; Balaggan, K S; Munro, P M; Bainbridge, J W B; Thrasher, A J; Smith, A J; Ali, R R
2005-04-01
The Royal College of Surgeons (RCS) rat is a well-characterized model of autosomal recessive retinitis pigmentosa (RP) due to a defect in the retinal pigment epithelium (RPE). It is homozygous for a null mutation in the gene encoding , a receptor tyrosine kinase found in RPE cells, that is required for phagocytosis of shed photoreceptor outer segments. The absence of Mertk results in accumulation of outer segment debris. This subsequently leads to progressive loss of photoreceptor cells. In order to evaluate the efficacy of lentiviral-mediated gene replacement therapy in the RCS rat, we produced recombinant VSV-G pseudotyped HIV-1-based lentiviruses containing a murine Mertk cDNA driven by a spleen focus forming virus (SFFV) promoter. The vector was subretinally injected into the right eye of 10-day-old RCS rats; the left eye was left untreated as an internal control. Here, we present a detailed assessment of the duration and extent of the morphological rescue and the resulting functional benefits. We examined animals at various time points over a period of 7 months by light and electron microscopy, and electroretinography. We observed correction of the phagocytic defect, slowing of photoreceptor cell loss and preservation of retinal function for up to 7 months. This study demonstrates the potential of gene therapy approaches for the treatment of retinal degenerations caused by defects specific to the RPE and supports the use of lentiviral vectors for the treatment of such disorders.
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A longitudinal study of skeletal muscle following spinal cord injury and locomotor training.
Liu, M; Bose, P; Walter, G A; Thompson, F J; Vandenborne, K
2008-07-01
Experimental rat model of spinal cord contusion injury (contusion SCI). The objectives of this study were (1) to characterize the longitudinal changes in rat lower hindlimb muscle morphology following contusion SCI by using magnetic resonance imaging and (2) to determine the therapeutic potential of two types of locomotor training, treadmill and cycling. University research setting. After moderate midthoracic contusion SCI, Sprague-Dawley rats were assigned to either treadmill training, cycle training or an untrained group. Lower hindlimb muscle size was examined prior to SCI and at 1-, 2-, 4-, 8-, and 12-week post injury. Following contusion SCI, we observed significant atrophy in all rat hindlimb muscles with the posterior muscles (triceps surae and flexor digitorum) showing greater atrophy than the anterior muscles (tibialis anterior and extensor digitorum). The greatest amount of atrophy was measured at 2-week post injury (range from 11 to 26%), and spontaneous recovery in muscle size was observed by 4 weeks post-SCI. Both cycling and treadmill training halted the atrophic process and accelerated the rate of recovery. The therapeutic influence of both training interventions was observed within 1 week of training and no significant difference was noted between the two interventions, except in the tibialis anterior muscle. Finally, a positive correlation was found between locomotor functional scores and hindlimb muscle size following SCI. Both treadmill and cycle training diminish the extent of atrophy and facilitate muscle plasticity after contusion SCI.
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Uslukaya, Omer; Turkoglu, Ahmet; Yazgan, Umit Can; Kaplan, Ibrahim; Ibiloglu, Ibrahim; Kapan, Murat; Gumus, Metehan
2016-12-01
Systemic damage in acute pancreatitis (AP) can be characterized by oxidative stress and the release of pro-inflammatory cytokines. Roflumilast has been shown to be a potent anti-inflammatory and antioxidant agent. In the present study, we aimed to investigate the effect of roflumilast in cerulein-induced AP. Thirty-two male rats were divided into four groups: group 1 (sham), group 2 (Roflumilast), group 3 (AP), and group 4 (AP + Roflumilast). AP was induced by injecting 4 × 75 μg/kg of body weight at an interval of 1 h. Rats were killed after 12 h following the last cerulein administration. AP was confirmed by measuring the serum amylase level and inflammatory features. Morphological changes were observed in the pancreas. Amylase levels were higher in the AP and AP + Roflumilast groups than the sham and Roflumilast groups. The serum levels of TNF-α, IL-1β, and IL-6 increased in the AP group, whereas they decreased in the Roflumilast group. The total oxidant activity (TOA) was higher and the total antioxidant capacity (TAC) was lower in the AP group. The administration of roflumilast decreased the TOA and increased the TAC in comparison with the AP group (p < 0.05 for both). Roflumilast significantly decreases oxidative stress and inflammatory mediators in the plasma, pancreas, and lung in cerulein-induced AP rats.
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What Plurals and Compounds Reveal about Constraints in Word Formation
ERIC Educational Resources Information Center
Jaensch, Carol; Heyer, Vera; Gordon, Peter; Clahsen, Harald
2014-01-01
Morphological systems are constrained in how they interact with each other. One case that has been widely studied in the psycholinguistic literature is the avoidance of plurals inside compounds (e.g. *"rats eater" vs. "rat eater") in English and other languages, the so-called "plurals-in-compounds effect." Several…
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MORPHOLOGIC ANALYSIS CORRELATES WITH GENE EXPRESSION CHANGES IN CULTURED F344 RAT MESOTHELIAL CELLS
The gene expression pattern of mesothelial cells in vitro was determined after 4 or 12 h exposure to the rat mesothelial, kidney and thyroid carcinogen, and oxidative stressor potassium bromate (KBr03). Gene expression changes observed using cDNA arrays indicated oxidative stres...
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A morphological defect, a cortical heterotopia, has been observed in the brains of rat pups exposed in utero to moderate doses of the thyroid hormone (TH) synthesis inhibitor propylthioruracil (PTU). TH insufficiency during late gestation/early postnatal period is required to ind...
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Boiko, O A; Lavrenchuk, H Yo; Lypska, A I; Talko, V V; Asmolkov, V S
2017-12-01
to investigate morphological changes in the primary thyroid cell culture of rat infants whose parents were prenatally exposed by radioisotope iodine 131. obtaining and culturing of thyroid tissue primary cell cultures of newborn rats, cytological (receipt and analysis of cell cultures agents for optical microscopy), biophysical (flow cytometry), statistics. It was shown that cells in thyroid primary culture of offspring rats prenatally exposed by radioisotopes of iodine 131 signs of destructive degenerative changes were observed mostly when animals of both sexes were irra diated. Increased number of two and three nuclear cells and induction of ring like cells is an evidence of signifi cant genotoxic violation and points to the genome instability in offspring of animals exposed by radioisotope iodine 131. Analysis and quantitative morphological parameters of cells in thyroid primary culture of newborn rats whose parents were exposed prenatally by radioisotopes of iodine 131 showed that upon exposure to radiation thy roid undergoes destructive changes at the cellular level and, even in the second generation of offspring, leads to disruption of its functions. O. A. Boiko, H. Yo. Lavrenchuk, A. I. Lypska, V. V. Talko, V. S. Asmolkov.
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Li, Xiaoou; Xie, Lili; He, Bing; Huang, Wei
2018-01-01
Objective To study the role of a disintegrin and metalloproteinase10 (ADAM10) in shedding neural cadherin (N-cadherin) and develop an approach to interfere the process of ventricular remodeling in adriamycin-induced cardiomyopathy (ACM) rats. Methods In a rat model of ACM, the effects of intraperitoneal injection of the lentiviral RNAi vector of ADAM10 on the morphology of cardiomyocytes and contractile function were observed by HE staining and color Doppler echocardiography. The expressions of N-cadherin and C-terminal fragment 1 (CTF1) were detected by Western blotting and immunohistochemistry. Results In the in vivo experiment, a large amount of fluorescence was seen in the isolated primary cardiomyocytes, which indicated that the transfection in the rat model was successful. In the treatment group, the morphology of cardiomyocytes and function of the heart were evidently improved, N-cadherin protein expression was remarkably up-regulated and CTF1 protein was obviously down-regulated compared with the model group. Conclusion Knock-down of ADAM10 increases N-cadherin expression and decreases CTF1 expression, thus improves cardiac function in the rat model of ACM.
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Xu, Zhi-ling; Wang, Qiang; Liu, Tian-lin; Guo, Li-ying; Jing, Feng-qiu; Liu, Hui
2006-04-01
To investigate the changes of bone sialoprotein (BSP) in developing dental tissues of rats exposed to fluoride. Twenty rats were randomly divided into two groups, one was with distilled water (control group), the other was with distilled water treated by fluoride (experimental group). When the fluorosis model was established, the changes of the expression of BSP were investigated and compared between the two groups. HE staining was used to observe the morphology of the cell, and immunohistochemisty assay was used to determine the expression of BSP in rat incisor. Student's t test was used for statistical analysis. The ameloblasts had normal morphology and arranged orderly. Immunoreactivitis of BSP was present in matured ameloblasts, dentinoblasts, cementoblasts, and the matrix in the control group. But in the experimental group the ameloblasts arranged in multiple layers, the enamel matrix was confused and the expression of BSP was significantly lower than that of the control group. Statistical analysis showed significant differences between the two groups (P<0.01). Fluoride can inhibit the expression of BSP in developing dental tissues of rats, and then inhibit differentiation of the tooth epithelial cells and secretion of matrix. This is a probable intracellular mechanism of dental fluorosis.
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Burgos, Carmen Mesas; Davey, Marcus G; Riley, John S; Jia, Huimin; Flake, Alan W; Peranteau, William H
2017-12-19
Lung and pulmonary vascular maldevelopment in congenital diaphragmatic hernia (CDH) results in significant morbidity and mortality. Retinoic acid (RA) and imatinib have been shown to improve pulmonary morphology following prenatal administration in the rat nitrofen-induced CDH model. It remains unclear if these changes translate into improved function. We evaluated the effect of prenatal RA and imatinib on postnatal lung function, structure, and pulmonary artery (PA) blood flow in the rat CDH model. Olive oil or nitrofen was administered alone or in combination with RA or imatinib to pregnant rats. Pups were assessed for PA blood flow by ultrasound and pulmonary function/morphology following delivery, intubation, and short-term ventilation. Neither RA nor imatinib had a negative effect on lung and body growth. RA accelerated lung maturation indicated by increased alveoli number and thinner interalveolar septa and was associated with decreased PA resistance and improved oxygenation. With the exception of a decreased PA pulsatility index, no significant changes in morphology and pulmonary function were noted following imatinib. Prenatal treatment with RA but not imatinib was associated with improved pulmonary morphology and function, and decreased pulmonary vascular resistance. This study highlights the potential of prenatal pharmacologic therapies, such as RA, for management of CDH. Copyright © 2017 Elsevier Inc. All rights reserved.
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de Oliveira Belém, Mônica; Cirilo, Carla Possani; de Santi-Rampazzo, Ana Paula; Schoffen, João Paulo Ferreira; Comar, Jurandir Fernando; Natali, Maria Raquel Marçal; de Almeida Araújo, Eduardo José
2015-09-01
During the aging process, the body's systems change structurally and loss of function can occur. Ingesting a smaller amount of food has been considered a plausible proposal for increased longevity with the quality of life. However, the effects of dietary restriction (DR) during aging are still poorly understood, especially for organs of the digestive system. This study aimed to describe the body weight, oxidative status and possible morphological changes of the intestinal wall of rats submitted to DR during the aging process (7 to 18months old). Twelve 7-month-old male Wistar rats fed ad libitum since birth were assigned to two groups: control group (CG, n=6) fed ad libitum from 7 to 18months old; and dietary restriction group (DRG, n=6) fed 50% of the amount of chow consumed by the CG from 7 to 18months old. The body weight, feed and water intake were monitored throughout the experiment. Blood, periepididymal adipose tissue (PAT) and retroperitoneal adipose tissue (RAT), and the small intestine were collected at 18months old. The blood was collected to evaluate its components and oxidative status. Sections from the duodenum and ileum were stained with HE, PAS and AB pH2.5 for morphometric analyses of the intestinal wall components, and to count intraepithelial lymphocytes (IELs), goblet cells and cells in mitosis in the epithelium. DR rats showed a reduction in weight, naso-anal length, PAT, RAT and intestinal length; however, they consumed more water. Blood parameters indicate that the DR rats remained well nourished. In addition, they showed lower lipid peroxidation. Hypertrophy of the duodenal mucosa and atrophy of the ileal mucosa were observed. The number of goblet cells and IELs was reduced, but the mitotic index remained unaltered in both duodenum and ileum. In conclusion, 50% dietary restriction for rats from 7 to 18months old contributed to improving their nutritional parameters but, to achieve this, adjustments were required in the structure of the body weight and morphology of the small intestine. Copyright © 2015 Elsevier Inc. All rights reserved.
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Wang, Yi-Lu; Liu, Miao; Shang, Man; Wang, Yao; Zhang, Qi; Wang, Shao-Xun; Wei, Su; Zhang, Kun-Wei; Liu, Chao; Wu, Yan-Na; Song, Jun-Qiu; Liu, Yan-Xia
2016-02-08
To investigate the effects of circulating microvesicles (MVs) derived from ischemic preconditioning (IPC) on myocardial ischemia/reperfusion (I/R) injury in rats and explore the underlying mechanism. To establish the IPC model, the rats were subjected to brief cycles of left anterior descending (LAD) coronary occlusion and reperfusion. The blood was drawn from abdominal aorta once the operation was finished. IPC-MVs were isolated by ultracentrifugation from the peripheral blood and characterized by flow cytometry. The myocardial I/R model of rats was established in vivo. Rats were injected via the femoral vein with IPC-MVs at 7 mg/kg. Morphological changes of myocardium were observed microscopically after HE staining. Apoptosis of myocardial cells was detected with TUNEL assay. Myocardial infarct size was detected by TTC staining. Moreover, activity of plasma lactate dehydrogenase (LDH) was tested by colorimetry. The activity of caspase 3 in myocardium was assayed with spectrophotometry. Expression levels of Bcl-2 and Bax protein were examined with Western blot. The concentration of IPC-MVs, which was detected by flow cytometry, was 4380±745 cells/ μ l. Compared with I/R group, IPC-MVs alleviated the damage of tissues in I/R injured rats significantly. The myocardial infarct size and the cardiomyocyte apoptotic index were obviously decreased after IPC-MVs treatment ( P <0.01, respectively). The activity of plasma LDH was significantly decreased in IPC-MVs treated rats ( P <0.01). Moreover, the activity of caspase 3 was markedly decreased after IPC-MVs treatment ( P <0.01). In addition, the expression of Bcl-2 was increased ( P <0.01), the expression of Bax was decreased ( P <0.01), the ratio of Bcl-2/Bax was significantly increased after IPC-MVs treatment ( P <0.01). IPC-MVs protected myocardial against I/R injury by up-regulating the expression of Bcl-2 protein, down-regulating the expression of Bax protein, increasing the ratio of Bcl-2/Bax and decreasing cleavage of caspase 3.
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OTOTOXICITY OF 3,3'-IMINODIPROPIONITRILE: FUNCTIONAL AND MORPHOLOGICAL EVIDENCE OF COCHLEAR DAMAGE
Previous reports suggested that IDPN may be ototoxic (Wolff et al. 1977; Crofton and Knight, 1991). The purpose of this research was to investigate the ototoxicity of IDPN using behavioral, physiological and morphological approaches. Three groups of adult rats were exposed to IDP...
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Zussy, Charleine; Brureau, Anthony; Keller, Emeline; Marchal, Stéphane; Blayo, Claire; Delair, Brice; Ixart, Guy; Maurice, Tangui; Givalois, Laurent
2013-01-01
Alzheimer’s disease (AD) is a neurodegenerative pathology associated with aging characterized by the presence of senile plaques and neurofibrillary tangles that finally result in synaptic and neuronal loss. The major component of senile plaques is an amyloid-β protein (Aβ). Recently, we characterized the effects of a single intracerebroventricular (icv) injection of Aβ fragment (25–35) oligomers (oAβ25–35) for up to 3 weeks in rats and established a clear parallel with numerous relevant signs of AD. To clarify the long-term effects of oAβ25–35 and its potential role in the pathogenesis of AD, we determined its physiological, behavioral, biochemical and morphological impacts 6 weeks after injection in rats. oAβ25–35 was still present in the brain after 6 weeks. oAβ25–35 injection did not affect general activity and temperature rhythms after 6 weeks, but decreased body weight, induced short- and long-term memory impairments, increased corticosterone plasma levels, brain oxidative (lipid peroxidation), mitochondrial (caspase-9 levels) and reticulum stress (caspase-12 levels), astroglial and microglial activation. It provoked cholinergic neuron loss and decreased brain-derived neurotrophic factor levels. It induced cell loss in the hippocampic CA subdivisions and decreased hippocampic neurogenesis. Moreover, oAβ25–35 injection resulted in increased APP expression, Aβ1–42 generation, and increased Tau phosphorylation. In conclusion, this in vivo study evidenced that the soluble oligomeric forms of short fragments of Aβ, endogenously identified in AD patient brains, not only provoked long-lasting pathological alterations comparable to the human disease, but may also directly contribute to the progressive increase in amyloid load and Tau pathology, involved in the AD physiopathology. PMID:23301030
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Patil, Chetan N; Racusen, Lorraine C; Reckelhoff, Jane F
2017-11-01
Polycystic ovary syndrome (PCOS) is the most common endocrine and reproductive disorder in premenopausal women, characterized by hyperandrogenemia, metabolic syndrome, and inflammation. Women who had PCOS during their reproductive years remain hyperandrogenemic after menopause. The consequence of chronic hyperandrogenemia with advanced aging has not been studied to our knowledge. We have characterized a model of hyperandrogenemia in female rats and have aged them to 22-25 months to mimic advanced aging in hyperandrogenemic women, and tested the hypothesis that chronic exposure to hyperandrogenemia with aging has a deleterious effect on renal function. Female rats were chronically implanted with dihydrotestosterone pellets (DHT 7.5 mg/90 days) that were changed every 85 days or placebo pellets, and renal function was measured by clearance methods. Aging DHT-treated females had a threefold higher level of DHT with significantly higher body weight, mean arterial pressure, left kidney weight, proteinuria, and kidney injury molecule-1 (KIM-1), than did age-matched controls. In addition, DHT-treated-old females had a 60% reduction in glomerular filtration rate, 40% reduction in renal plasma flow, and significant reduction in urinary nitrate and nitrite excretion (UNOxV), an index of nitric oxide production. Morphological examination of kidneys showed that old DHT-treated females had significant focal segmental glomerulosclerosis, global sclerosis, and interstitial fibrosis compared to controls. Thus chronic hyperandrogenemia that persists into old age in females is associated with renal injury. These data suggest that women with chronic hyperandrogenemia such as in PCOS may be at increased risk for development of chronic kidney disease with advanced age. © 2017 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.
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Histological and Morphometric Analyses for Rat Carotid Artery Balloon Injury Studies
Tulis, David Anthony
2010-01-01
i. Summary Experiments aimed at analyzing the response of blood vessels to mechanical injury and ensuing remodeling responses often employ the highly characterized carotid artery balloon injury model in laboratory rats. This approach utilizes luminal insertion of a balloon embolectomy catheter into the common carotid artery with inflation and withdrawal resulting in an injury characterized by vascular endothelial cell (EC) denudation and medial wall distension. The adaptive response to this injury is typified by robust vascular smooth muscle cell (SMC) replication and migration, SMC apoptosis and necrosis, enhanced synthesis and deposition of extracellular matrix (ECM) components, partial vascular EC regeneration from the border zones, luminal narrowing and establishment of a neointima in time-dependent fashion. Evaluation of these adaptive responses to blood vessel injury can include acute and longer-term qualitative and quantitative measures including expression analyses, activity assays, immunostaining for a plethora of factors and signals, and morphometry of neointima formation and gross mural remodeling. This chapter presents a logical continuation of Chapter in this series that offers details for performing the rat carotid artery balloon injury model in a standard laboratory setting by providing commonly used protocols for performing histological and morphometric analyses in such studies. Moreover, procedures, caveats, and considerations included in this chapter are highly relevant for alternative animal vascular physiology/pathophysiology studies and in particular those related to mechanisms of vascular injury and repair. Included in this chapter are specifics for in situ perfusion-fixation, tissue harvesting and processing for both snap-frozen and paraffin-embedded protocols, specimen embedding and sectioning, slide preparation, several standard histological staining steps, and routine morphological assessment. Included in Notes are important caveats and considerations for practical use of these methods. PMID:18287663
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Functional and morphological characterization of glutamate transporters in the rat locus coeruleus
Medrano, M C; Gerrikagoitia, I; Martínez-Millán, L; Mendiguren, A; Pineda, J
2013-01-01
Background and Purpose Excitatory amino acid transporters (EAATs) in the CNS contribute to the clearance of glutamate released during neurotransmission. The aim of this study was to explore the role of EAATs in the regulation of locus coeruleus (LC) neurons by glutamate. Experimental Approach We measured the effect of different EAAT subtype inhibitors/enhancers on glutamate- and KCl-induced activation of LC neurons in rat slices. EAAT2–3 expression in the LC was also characterized by immunohistochemistry. Key Results The EAAT2–5 inhibitor DL-threo-β-benzyloxaspartic acid (100 μM), but not the EAAT2, 4, 5 inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (100 μM) or the EAAT2 inhibitor dihydrokainic acid (DHK; 100 μM), enhanced the glutamate- and KCl-induced activation of the firing rate of LC neurons. These effects were blocked by ionotropic, but not metabotrobic, glutamate receptor antagonists. DHK (100 μM) was the only EAAT inhibitor that increased the spontaneous firing rate of LC cells, an effect that was due to inhibition of EAAT2 and subsequent AMPA receptor activation. Chronic treatment with ceftriaxone (200 mg·kg−1 i.p., once daily, 7 days), an EAAT2 expression enhancer, increased the actions of glutamate and DHK, suggesting a functional impact of EAAT2 up-regulation on the glutamatergic system. Immuhistochemical data revealed the presence of EAAT2 and EAAT3 surrounding noradrenergic neurons and EAAT2 on glial cells in the LC. Conclusions and Implications These results remark the importance of EAAT2 and EAAT3 in the regulation of rat LC by glutamate. Neuronal EAAT3 would be responsible for terminating the action of synaptically released glutamate, whereas glial EAAT2 would regulate tonic glutamate concentrations in this nucleus. PMID:23638698
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Jindatip, Depicha; Fujiwara, Ken; Horiguchi, Kotaro; Tsukada, Takehiro; Kouki, Tom; Yashiro, Takashi
2013-09-01
Pericytes are perivascular cells associated with capillaries. We previously demonstrated that pericytes, identified by desmin immunohistochemistry, produce type I and III collagens in the anterior pituitary gland of adult rats. In addition, we recently used desmin immunoelectron microscopy to characterize a novel type of perivascular cell, dubbed a desmin-immunopositive perivascular cell, in the anterior pituitary. These two types of perivascular cells differ in fine structure. The present study attempted to characterize the morphological features of pituitary pericytes and novel desmin-immunopositive perivascular cells during postnatal development, in particular their role in collagen synthesis. Desmin immunostaining revealed numerous perivascular cells at postnatal day 5 (P5) and P10. Transmission electron microscopy showed differences in the fine structure of the two cell types, starting at P5. Pericytes had well-developed rough endoplasmic reticulum and Golgi apparatus at P5 and P10. The novel desmin-immunopositive perivascular cells exhibited dilated cisternae of rough endoplasmic reticulum at P5-P30. In addition, during early postnatal development in the gland, a number of type I and III collagen-expressing cells were observed, as were high expression levels of these collagen mRNAs. We conclude that pituitary pericytes and novel desmin-immunopositive perivascular cells contain well-developed cell organelles and that they actively synthesize collagens during the early postnatal period.
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Arica, Betül; Kaş, H Süheyla; Moghdam, Amir; Akalan, Nejat; Hincal, A Atilla
2005-02-16
The purpose of this study was to prepare and characterize injectable carbidopa (CD)/levodopa (LD)-loaded Poly(L-lactides) (L-PLA), Poly(D,L-lactides) (D,L-PLA) and Poly(D,L-lactide-co-glycolide) (PLAGA) microspheres for the intracerebral treatment of Parkinson's disease. The microspheres were prepared by solvent evaporation method. The polymers' (L-PLA, D,L-PLA and PLAGA) concentrations were 10% (w/w) in the organic phase; the emulsifiers [sodium carboxymethylcellulose (NaCMC):sodium oleate (SO) and Polyvinyl alcohol (PVA):SO mixture (4:1 w/v)] concentrations were 0.75% in the aqueous phase. Microspheres were analyzed for morphological characteristics, size distribution, drug loading and in vitro release. The release profile of CD/LD from microspheres was characterized in the range of 12-35% within the first hour of the in vitro release experiment. The efficiency of CD- and LD-encapsulated microspheres to striatal transplantation and the altering of apomorphine-induced rotational behavior in the 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model were also tested. 6-OHDA/CD-LD-loaded microsphere groups exhibited lower rotation scores than 6-OHDA/Blank microsphere groups as early as 1 week postlesion. These benefits continued throughout the entire experimental period and they were statistically significant during the 1, 2 and 8 weeks (p<0.05). CD/LD-loaded microspheres were specifically prepared to apply as an injectable dosage forms for brain implantation.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Roman, Danielle, E-mail: danielle.roman@novartis.c
AUY922, a heat shock protein 90 inhibitor is associated with ocular adverse events (AEs). To provide a better understanding of ocular AEs in patients, 4 investigative studies were performed in a step-wise approach to assess retinal structure and function in pigmented (Brown Norway) and albino (Wistar) rats. In rats administered 30 mg/kg of AUY922, the AUC{sub 0–24} {sub h} and C{sub max} are comparable to that in patients at 70 mg/m{sup 2}. AUY922 at ≥ 30 mg/kg was poorly tolerated by rats with morbidity or mortality generally after the third weekly treatment. Electroretinography (ERG) changes were observed at doses ≥more » 30 mg/kg. The ERG changes were dose dependent, consistent with an effect on the photoreceptors, and fully reversible. The ERG effects could not be minimized by decreasing the C{sub max} while maintaining AUC. Histopathological changes were seen mainly when rats were administered AUY922 at 100 mg/kg. The 2-hour infusion of AUY922 at 100 mg/kg caused disorganization of the outer segment photoreceptor morphology in male Brown Norway rats; the severity of the disorganization increased with the number of administrations, but was reversible during a 4-week posttreatment period. There was no major difference in ocular response between Brown Norway and Wistar rats. No changes in serum iron levels, and no changes in rhodopsin, PDE6α, β-transducin concentrations, or retinal pigment epithelium-specific protein RPE65 expression were observed after single and multiple infusions of AUY922 at 100 mg/kg compared to vehicle-treated controls. AUY922 retinal toxicity in rats recapitulates and further characterizes that reported in patients and is shown to be reversible, while a precise molecular mechanism for the effect was not determined. - Highlights: • Ocular toxicity of AUY922 was assessed in Brown Norway and Wistar rats. • AUY922 at ≥ 30 mg/kg was generally not well tolerated by rats. • Electroretinography (ERG) changes were observed at doses ≥ 30 mg/kg. • ERG changes at doses ≥ 30 mg/kg were dose-dependent, and fully reversible.« less
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Vakhnin, V A; Briukhin, G V
2014-04-01
The aim of this work was studying of morphology of a brain and the analysis of behavior at posterity of females of rats with a chronic alcoholic intoxication. As object of research were taken 60-day animals received from mothers with chronic alcoholic injury of hepatobiliary systems. During certain time (1.5 months) the part of animals grew in standard conditions, and another--in the "enriched" environment. The behavior analysis was spent in the open field test. Also was carried out research of a thickness of a cortex and a molecular layer of a forebrain. Work included three series of experiments. It is established, that the posterity of mothers with chronic injury of the hepatobiliary systems is characterized by the lowered motorial and research activity, increased by emotional reactivity that is accompanied by changes of structure of a cortex. The long finding of "alcoholic" animals in the "enriched" environment within 1.5 months promoted increasing of motorial and research activity, emotional reactance, change of structure of a cortex.
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Bayraktar, T; Welker, E; Freund, T F; Zilles, K; Staiger, J F
2000-05-08
Vasoactive intestinal polypeptide (VIP) in neocortex affects neuronal excitability as well as cortical blood flow and metabolism. Interneurons immunoreactive for VIP (VIP-IR neurons) are characterized by their predominantly bipolar appearance and the radial orientation of their main dendrites. In order to determine whether the morphology of VIP-IR neurons is related to the functional organization of the cortex into vertical columns, we combined both immunostaining of neurons containing VIP and cytochrome oxidase histochemistry for visualizing barrels, morphological layer IV correlates of functional columns, in the primary somatosensory (barrel) cortex of rats. VIP-IR neurons were localized in supragranular (48%), granular (16%), and infragranular layers (36%) as well as in the white matter. In the granular layer, a clear trend that more neurons were located in interbarrel septa rather than in barrels could be observed, resulting in a neuronal density which was about one-third higher in the septal area. VIP-IR neurons from the different cortical layers were three-dimensionally reconstructed from serial sections by using a computer microscope system. The neurons were mostly bipolar. Striking morphological differences in both axonal and dendritic trees were found between neurons whose cell bodies were located in supragranular, granular, and the upper part of infragranular layers, and those whose cell bodies were located in the area below. The former had dendrites which often reached layer I, where they bifurcated several times, and axonal trees which were particularly oriented vertically, with a tangential extent smaller than the width of barrels. Therefore, these neurons were mostly confined to either a barrel- or septum-related column. By contrast, the dendrites of neurons of the latter group did not reach the granular layer. Furthermore, these neurons had axons with sometimes very long horizontal collaterals, which often spanned two, in one case three, barrel columns. It is proposed that the differential morphology of neurons with different locations as stated above parallels to some extent the divergence of input streaming into the corresponding layer-defined areas. As a possible consequence of this, VIP-IR neurons may be capable of adapting the excitability and metabolism of cortical compartments either in a spatially limited or more extensive way. Copyright 2000 Wiley-Liss, Inc.
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Neurophysiological and morphological techniques were used to describe changes in the optic tract and superior colliculus (SC) in response to monocular enucleation. Long-Evans, male, (250g) rats were implanted with chronic bipolar stimulating electrodes located in the optic chiasm...
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Effect of anti-GM2 antibodies on rat sciatic nerve: electrophysiological and morphological study.
Ortiz, Nicolau; Sabaté, M Mar; Garcia, Neus; Santafe, Manel M; Lanuza, M Angel; Tomàs, Marta; Tomàs, Josep
2009-03-31
We found that a monoclonal human IgM anti-GM2 was fixed in rat sciatic axons and Schwann cells and was able to activate human complement. The passive transfer of IgM and complement in sciatic nerves can induce an acute alteration in nerve conduction. When the transfer of IgM plus complement was repeated for 10 days, the compound action motor potential amplitude was very low and the morphological study showed axons and myelin damage. Without human complement, IgM can only slightly disorganize the myelin by separating some layers, probably by interfering with the functional role of gangliosides in the myelin package.
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Influences of rich in saturated and unsaturated fatty acids diets in rat myocardium.
Pinotti, Matheus Fécchio; Silva, Maeli Dal-Pai; Sugizaki, Mário Mateus; Novelli, Yeda Santana Diniz; Sant'ana, Lea Sílvia; Aragon, Flávio Ferrari; Padovani, Carlos Roberto; Novelli, Ethel Lourenzi Barbosa; Cicogna, Antonio Carlos
2007-03-01
To study the influence of saturated (SFA) and unsaturated fatty acid (UFA) rich diets on mechanical function, morphology and oxidative stress in rat myocardium. Male, 60-day-old Wistar rats were fed a control (n=8), a SFA (n=8), or a UFA-rich diet (n=8) for sixty days. Mechanical function was studied in isolated left ventricle papillary muscle under isometric and isotonic contractions, in basal conditions (1.25 mM calcium chloride) and after 5.2 mM calcium chloride and beta-adrenergic stimuli with 1.0 microM isoproterenol. Left ventricle fragments were used to study oxidative stress and morphology under light and electron microscopy. SFA and UFA-rich diets did not change myocardium mechanical function. Both diets caused oxidative stress, with high lipid hydroperoxide and low superoxide-dismutase concentrations. UFA rich diet decreased catalase expression and SFA rich diet decreased the amount of myocardial glutathione-peroxidase. Both diets promoted light ultrastructural injuries such as lipid deposits and cell membrane injuries. Results suggest that SFA and UFA rich diets do not alter isolated muscle mechanical function, but promote light myocardial morphological injuries and oxidative stress.
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Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity.
Awadalla, Eatemad A
2012-07-01
Paraquat has been demonstrated to be a highly toxic compound for humans and animals and many cases of acute poisoning and death have been reported over the past few decades. The current experiment aimed to examine if vitamin C (ascorbic acid) alleviates the morphological changes induced by paraquat (PQ) administration in the liver and kidney of male albino rats. Male adult rats received paraquat (PQ) (1.5 mg/kg body weight) daily for three weeks. Vitamin C (VC) at a dose of 20 mg/kg body weight was given concomitantly with PQ to rats. Animals were divided into three groups in this experiment (control, PQ and PQ+VC). The morphopathological manifestations were investigated in tissues from liver and kidney. As expected, PQ administration induced marked changes in the morphological structure of the liver and kidney in PQ demonstrated animals. Importantly, vitamin C administration restored PQ-induced changes in the studied organs. Vitamin C administration attenuated the morphological damages induced by PQ in the liver and kidney of experimental animals. Our results suggest an antitoxic effect of vitamin C against paraquat. Copyright © 2010 Elsevier GmbH. All rights reserved.
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The effect of increased ozone concentrations in the air on selected aspects of rat reproduction.
Jedlińska-Krakowska, M; Gizejewski, Z; Dietrich, G J; Jakubowski, K; Glogowski, J; Penkowski, A
2006-01-01
Five-month-old male rates were exposed to 0.5 ppm ozone for 50 days, 5 hours a day. A week before the completion of ozone exposure, a biological test was performed to determine the fertilization rate and the survival rate of newborns in both ozone-exposed and control animals. After 50 days, the rats were sacrificed with an overdose of halotane, and testes were collected to assess the morphology and motility of spermatozoa. Neither the morphology of spermatozoa nor motility parameters determined by the CASA (computer-assisted sperm analysis) system showed statistically significant differences between ozone-exposed and control males. The number of successful matings and the survival rate of newborns per litter within one year postpartum were also similar in both groups. However, sperm concentration was by 17% lower in ozone-exposed rats, compared with the control animals.
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Saccharomyces boulardii protease inhibits Clostridium difficile toxin A effects in the rat ileum.
Castagliuolo, I; LaMont, J T; Nikulasson, S T; Pothoulakis, C
1996-01-01
Saccharomyces boulardii, a nonpathogenic yeast, is effective in treating some patients with Clostridium difficile diarrhea and colitis. We have previously reported that S. boulardii inhibits rat ileal secretion in response to C. difficile toxin A possibly by releasing a protease that digests the intestinal receptor for this toxin (C. Pothoulakis, C. P. Kelly, M. A. Joshi, N. Gao, C. J. O'Keane, I. Castagliuolo, and J. T. LaMont, Gastroenterology 104: 1108-1115, 1993). The aim of this study was to purify and characterize this protease. S. boulardii protease was partially purified by gel filtration on Sephadex G-50 and octyl-Sepharose. The effect of S. boulardii protease on rat ileal secretion, epithelial permeability, and morphology in response to toxin A was examined in rat ileal loops in vivo. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the purified S. boulardii protease revealed a major band at 54 kDa. Pretreatment of rat ileal brush border (BB) membranes with partially purified protease reduced specific toxin A receptor binding (by 26%). Partially purified protease digested the toxin A molecule and significantly reduced its binding to BB membranes in vitro (by 42%). Preincubation of toxin A with S. boulardii protease inhibited ileal secretion (46% inhibition, P < 0.01), mannitol permeability (74% inhibition, P < 0.01), and histologic damage caused by toxin A. Thus, S. boulardii protease inhibits the intestinal effects of C. difficile toxin A by proteolysis of the toxin and inhibition of toxin A binding to its BB receptor. Our results may be relevant to the mechanism by which S. boulardii exerts its protective effects in C. difficile infection in humans. PMID:8945570
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Hemanth Kumar, B S; Mishra, Sushanta Kumar; Rana, Poonam; Singh, Sadhana; Khushu, Subash
2012-06-15
Depression is a complex psychiatric disorder characterized by anhedonia and feeling of sadness and chronic mild stress (CMS) seems to be a valuable animal model of depression. CMS animal model was induced and validated using behavioral studies. In the present study we investigated the neuro-metabolite changes occurring in prefrontal cortex and hippocampus during the onset of depression, in CMS rat model using in vivo proton magnetic resonance spectroscopy ((1)H MRS) at field strength of 7 T. Results showed that CMS caused depression-like behavior in rats, as indicated by the decrease in sucrose consumption and locomotor activity. (1)H MRS was performed in both control and CMS rats (n=10, in each group) and the quantitative assessment of the neurometabolites was done using LC model. Relative concentrations of all the metabolites along with the macromolecules were calculated for analysis. The results revealed a significant decrease of glutamate (Glu), glutamine (Gln), NAA+NAAG, Glx and GABA levels in both hippocampus and prefrontal cortex of CMS animals and an elevated level of myo-ionisitol (mI) and taurine (Tau) was observed only in hippocampus. These metabolite fluctuations revealed by proton MRS indicate that there might be change in the neuronal integrity of the glial cells and neurons within prefrontal cortex and hippocampus in CMS model of depression. The present study also suggests that there may be a degenerative process concerning the brain morphology in the CMS rats. The overall finding using (1)H MRS suggests that, there might be a major role of the glia and neuron in the onset of depression. Copyright © 2012 Elsevier B.V. All rights reserved.
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Davies, Kalina T J; Bennett, Nigel C; Tsagkogeorga, Georgia; Rossiter, Stephen J; Faulkes, Christopher G
2015-12-01
During their evolutionary radiation, mammals have colonized diverse habitats. Arguably the subterranean niche is the most inhospitable of these, characterized by reduced oxygen, elevated carbon dioxide, absence of light, scarcity of food, and a substrate that is energetically costly to burrow through. Of all lineages to have transitioned to a subterranean niche, African mole-rats are one of the most successful. Much of their ecological success can be attributed to a diet of plant storage organs, which has allowed them to colonize climatically varied habitats across sub-Saharan Africa, and has probably contributed to the evolution of their diverse social systems. Yet despite their many remarkable phenotypic specializations, little is known about molecular adaptations underlying these traits. To address this, we sequenced the transcriptomes of seven mole-rat taxa, including three solitary species, and combined new sequences with existing genomic data sets. Alignments of more than 13,000 protein-coding genes encompassed, for the first time, all six genera and the full spectrum of ecological and social variation in the clade. We detected positive selection within the mole-rat clade and along ancestral branches in approximately 700 genes including loci associated with tumorigenesis, aging, morphological development, and sociality. By combining these results with gene ontology annotation and protein-protein networks, we identified several clusters of functionally related genes. This family wide analysis of molecular evolution in mole-rats has identified a suite of positively selected genes, deepening our understanding of the extreme phenotypic traits exhibited by this group. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
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Jin, Yuan-Zhe; Wang, Guo-Feng; Wang, Qi; Zhang, Xue-Ying; Yan, Bin; Hu, Wei-Na
2014-12-01
This study aimed to investigate the effects of acetaldehyde (AA) and L-carnitine (LC) on morphology and enzyme activity of myocardial mitochondria in rats. Sixty-five Wistar rats were randomly divided into 4 groups: the control group (n = 20), the AA low-dose group (n = 15), the AA high-dose group (n = 15) and the AA + LC group (n = 15). Different doses (110 mg/kg and 220 mg/kg) AA was injected intraperitoneally once a day for 4 weeks. After 4 weeks administration, transmission electron microscope (TEM) observation of morphology of rat myocardial mitochondria was performed. Serum levels of succinate dehydrogenase (SDH), superoxide dismutase (SOD), malondialdehyde (MDA) and cardiac troponin I (cTnI) were detected to evaluate mitochondrial enzymes activities. Light micrograph of rat myocardiocytes in the control group showing normal architecture of myocytes. The numerical density and number of mitochondria in both low-dose and high-dose AA groups were lower than that of the control group. After administration of LC, the rats in the AA + LC group showed an obvious increase in the numerical density and number of mitochondria. TEM showed that both low-dose and high-dose AA could induce myocardial mitochondrial damage in rats in a dose-dependent manner, such as mitochondrial swelling, disruptions of crest and membrane, mitochondrial deficiency. The degree of mitochondrial damage of the AA + LC group was significantly decreased after administration of LC. Our results showed that serum levels of SDH and SOD in the AA + LC and control groups were also higher than those of the low-dose and high-dose AA groups; while the MDA level in the AA + LC and control groups were lower than that of the low-dose and high-dose AA groups. The low-dose AA, high-dose AA and AA + LC groups exhibited a higher level of serum cTnI than that of the control group. However, there was no significant difference in serum cTnI level among the low-dose AA, high-dose AA and AA + LC groups. Our findings indicate that AA may lead to myocardial mitochondrial damage and the induction of enzyme activity in rats, while administration of LC could alleviate AA-related damage of rat myocardial mitochondria.
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Inhibiting the CD38/cADPR pathway protected rats against sepsis associated brain injury.
Peng, Qian-Yi; Wang, Yi-Min; Chen, Cai-Xia; Zou, Yu; Zhang, Li-Na; Deng, Song-Yun; Ai, Yu-Hang
2018-01-01
The CD38/cADPR pathway has been found to play roles in various inflammatory conditions. However, whether CD38 plays a protective or detrimental effect in the central nervous system (CNS) is controversial. The aim of this study was to determine the effect of CD38/cADPR pathway in sepsis associated brain injury. Male Sprague-Dawley rats were undergone cecal ligation and puncture (CLP) or sham laparotomies. NAD + , cADPR and CD38 were measured in the hippocampus of septic rats at 0, 6, 12, 24, and 48h after CLP surgery. Rats were divided into the sham, CLP group, CLP+ CD38 expression lentivirus (CLP+ CD38 LV), CLP+ CD38 interference lentivirus (CLP+ CD38 Ri), CLP+ negative control lentivirus (CLP+NC) and the CLP+8-Br-cADPR groups. The Western blots of Bcl-2, Bax and iNOS, TUNEL assays, malondialdehyde (MDA) and superoxide dismutase (SOD) assays, transmission electron microscope analysis were performed in the hippocampus of rats. NAD + , cADPR and CD38 levels increased significantly in the hippocampus of septic rats as early as 12-24h after CLP surgery. CD38 knockdown or blocking cADPR with 8-Br-cADPR significantly reduced apoptosis, MDA and SOD activity, iNOS expression and ultrastructural morphology damages in the hippocampus of septic rats. In this study, we found that the CD38/cADPR pathway was activated in sepsis associated brain injury. Blocking this pathway protected the hippocampus from apoptosis, oxidative stress and ultrastructural morphology damages in septic rats. Copyright © 2017. Published by Elsevier B.V.
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Su, Jian; Sripanidkulchai, Kittisak; Hu, Ying; Wyss, J Michael; Sripanidkulchai, Bungorn
2012-10-01
The loss of sex hormones in postmenopausal women has been suggested to be involved in cognitive degenerative diseases, such as Alzheimer's disease. In the present study, ovariectomized (OVX) and control rats were tested for 4 months in a Morris water maze (MWM) task to track their memory status. Thereafter, postmortem frozen brain sections were analyzed to determine if changes in brain area volumes and neuronal density were related to changes in cognitive ability. A modified artificial-land-mark-based method was used to assure the fidelity of the three dimensions (3D) reconstructed structures. Volumetric areas of the hippocampus, cortex, caudate putamen (cpu), and cerebellum were estimated from the reconstructions, and neuron densities of CA1 and CA3 subregions of the hippocampus were measured in an adjacent second series of Nissl-stained sections. Compared to the control rats, OVX rats displayed memory impairments, beginning in the second month after the ovariectomy (p < .05). Assessments at the end of the study demonstrated that OVX (compared to control) rats displayed reduced brain volume in the hippocampus and neocortex and in the brain as a whole. In contrast, when compared to controls, the volumes of cpu and cerebellum of OVX rats increased slightly. CA3 neuron density of OVX (compared to controls) rats was significantly lower, but the CA1 neuron density was significantly higher. In conclusion, ovariectomy impaired spatial memory and led to morphological changes in cognitive centers of rat brain. The results demonstrate that the 3D reconstructed method is useful for the study of brain morphological abnormality in rats.
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Polov'ian, E S; Chemich, N D; Moskalenko, R A; Romaniuk, A N
2012-06-01
At the present stage of infectionist practice in the treatment of acute intestinal infections caused by opportunistic microorganisms, colloidal silver is used with a particle size of 25 nm as an alternative to conventional causal therapy. In 32 rats, distributed in 4 groups of 8 animals each (intact; healthy, got colloidal silver; with a modeled acute intestinal infection in the basic treatment and with the addition of colloidal silver), histological examination was performed of small and large intestine of rats. Oral administration of colloidal silver at a dose of 0.02 mg/day to intact rats did not lead to changes in morphometric parameters compared to the norm, and during early convalescence in rats with acute intestinal infections were observed destructive and compensatory changes in the intestine, which depended on the treatment regimen. With the introduction of colloidal silver decreased activity of the inflammatory process and the severity of morphological changes in tissues of small and large intestine, indicating that the positive effect of study drug compared with baseline therapy.
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A morphological study of diffuse axonal injury in a rat model by lateral head rotation trauma.
Xiaoshengi, He; Guitao, Yang; Xiang, Zhang; Zhou, Fei
2010-03-01
Morphology in diffuse axonal injury (DAI) by lateral head rotation was investigated. SD rats were divided into injury (n=9) and sham (n=3) groups. A device was used to produce lateral rotational acceleration of the rats' heads. At different survival times three rats were killed for light and electron microscopic examination of the brain tissue. Sagittal sections were made from medulla oblongata and immunolabelled for NF68. At post-traumatic 30 min, NF68 immunolabelling showed a small number ofswollen and irregular axons. Ultrastructurally slightly-separated myelin lamellae and disorderly arranged neurofilaments occurred. At 2 and 24 h axonal damage became more severe. Increases in immunolabelled axonal swellings, disconnected axons and axonal retraction bulbs appeared. EM provided evidence of myelin separation, peri-axonal spaces, blank areas in axoplasm, loss of microtubules, peripheral accumulation of mitochondria and clumped neurofilaments for DAI. A tendency was noted for greater labelling with NF68 as axonal damage increased. The disorderly arrangement of NFs occurred at early stage of post-traumatic axonal changes.
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Song, Chengfu; Zhao, Xiangdong
2018-05-15
In patients with cerebral infarction (CI), elevated serum uric acid (UA) level may exacerbate the occurrence and development of carotid atherosclerosis (AS). Our study intended to explore the underlying mechanism. We enrolled 86 patients with CI, and divided them into four groups: Non-AS, AS-mild, AS-moderate, and AS-severe groups; the levels of UA and oxidative stress-related factors in serum were detected. The middle cerebral artery occlusion (MCAO) model was used to stimulate CI in rats, and different doses of UA were administrated. The levels of oxidative stress-related factors in serum were detected. Hematoxylin & eosin (H&E) staining was used to observe the morphological alterations, and the apoptotic cell death detection kit was used to detect apoptotic cells. Increased UA concentration and enhanced oxidative stress were found in AS patients. H&E staining results showed that UA treatment exacerbated morphological damage in rats with MCAO, promoted oxidative stress, and enhanced vascular endothelial cell apoptosis in rats with MCAO. © 2017 The Author(s).
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Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats.
Shao, Shan-shan; Zhao, Yuan-fei; Song, Yong-feng; Xu, Chao; Yang, Jian-mei; Xuan, Shi-meng; Yan, Hui-li; Yu, Chun-xiao; Zhao, Meng; Xu, Jin; Zhao, Jia-jun
2014-11-01
Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification.
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Translational aspects of rectal evoked potentials: a comparative study in rats and humans
Nissen, Thomas Dahl; Graversen, Carina; Coen, Steven J.; Hultin, Leif; Aziz, Qasim; Lykkesfeldt, Jens; Drewes, Asbjørn Mohr
2013-01-01
Inconsistencies between species has stunted the progress of developing new analgesics. To increase the success of translating results between species, improved comparable models are required. Twelve rats received rectal balloon distensions on 2 different days separated by 24.3 (SD 24.6) days. Rectal balloon distensions were also performed in 18 humans (mean age: 34 yr; range: 21–56 yr; 12 men) on two separate occasions, separated by 9.3 (SD 5.5) days. In rats, cerebral evoked potentials (CEPs) were recorded by use of implanted skull-electrodes to distension pressure of 80 mmHg. In humans surface electrodes and individualized pressure, corresponding to pain detection threshold, were used. Comparison of morphology was assessed by wavelet analysis. Within- and between-day reproducibility was assessed in terms of latencies, amplitudes, and frequency content. In rats CEPs showed triphasic morphology. No differences in latencies, amplitudes, and power distribution were seen within or between days (all P ≥ 0.5). Peak-to-peak amplitude between the first positive and negative potential were the most reproducible characteristic within and between days (evaluated by intraclass correlation coefficients, ICC) (ICC = 0.99 and ICC = 9.98, respectively). In humans CEPs showed a triphasic morphology. No differences in latencies, amplitudes, or power distribution were seen within or between days (all P ≥ 0.2). Latency to the second negative potential (ICC = 0.98) and the second positive potential (ICC = 0.95) was the most reproducible characteristic within and between days. A unique and reliable translational platform was established assessing visceral sensitivity in rats and humans, which may improve the translational process of developing new drugs targeting visceral pain. PMID:23703652
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Ma, Zhengwei; Zhang, Xizhong
2003-07-01
To investigate the long-term effect of dietary fiber complex (DFC) on intestinal structure and function in hypercholesterolemic rats, 60 healthy SD rats were feed with food rich in lipids and hypercholesterolemic animal models were established. The animals were randomly divided into 5 groups. Rats were fed DFC at levels of 4%, 16%, or 64% for three month in the experimental groups. Wheat fiber was used in the hypercholesterolemic control (HC) group and rats feeding on normal food were used as normal control (NC). Morphology of the small intestine, reticum and caecum were observed by light and electron microscope examination. Intestinal function was measured physically. The results showed that (1) compared with NC group, fecal weight was significantly raised in DFC group of higher level (group D and E, P < 0.05); (2) the weights of small intestine wall in D and E group were significantly higher than those of NC and HC group and weights of caecum wall in E group were significantly higher than those of NC and HC group (P < 0.05); (3) widen villi and thickened muscle layer of small intestine were observed in DFC group of higher level. No demonstrable changes in reticulum morphology in any group of animals were found under the observation of light microscope (4) microvilla becoming short and/or absent, mitochondria swelling, impairment of the integrity of the cristae were commonly observed in DFC groups. Conclusions Long-term intake of DFC composed mainly of Hippophae rhamnoides L, Bran, oat bran and guar gum at higher levels might induce some morphological changes of intestine and caecum. Therefore, DFC might be used at low level as an effective cholesterol-lowering agent.
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Kolodziejczyk, L; Laszczyńska, M; Masiuk, M; Grabowska, M; Skrzydlewska, E
2015-01-01
We investigated the immunoexpression of the intermediate filament proteins, cytokeratin and desmin, and the morphological changes in the liver of rats during experimental fasciolosis at 4, 7 and 10 weeks post-infection. Rats were infected with 30 Fasciola hepatica metacercariae. Paraffin sections of the liver were stained using H & E, PAS and azan stains. Immunohistochemical reactions were performed using antibodies against cytokeratin and desmin. The experimental F. hepatica infection led to fibrosis and cirrhosis of the liver, and to inflammation of the common bile ducts. The expression of cytokeratin was increased in the epithelial cells of both the liver bile ductules at 4, 7 and 10 weeks post-infection and in the common bile ducts at 7 and 10 weeks post-infection compared to uninfected rats; expression in the common bile ducts was more intense. The myofibroblasts of the liver and smooth myocytes of the interlobular bile ducts and common bile ducts, showed a slight increase in desmin expression compared to the uninfected rats. The increased expression of cytokeratins in the hyperplastic rat common bile duct epithelium during the biliary phase of fasciolosis at 7 and 10 weeks post-infection may be explained by mechanical irritation by the parasite and an inflammatory reaction in the bile duct epithelium and in periductal fibrous tissue.
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Effects of streptozotocin-induced diabetes on taste buds in rat vallate papillae.
Pai, Man-Hui; Ko, Tsui-Ling; Chou, Hsiu-Chu
2007-01-01
Some studies have documented taste changes in patients with diabetes mellitus (DM). In order to understand the relationships between taste disorders caused by DM and the innervation and morphologic changes in the taste buds, we studied the vallate papillae and their taste buds in rats with DM. DM was induced in these rats with streptozotocin (STZ), which causes the death of beta cells of the pancreas. The rats were sacrificed and the vallate papillae were dissected for morphometric and quantitative immunohistochemical analyses. The innervations of the vallate papillae and taste buds in diabetic and control rats were detected using immunohistochemistry employing antibodies directed against protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP). The results showed that PGP 9.5- and CGRP-immunoreactive nerve fibers in the trench wall of diabetic vallate papillae, as well as taste cells in the taste buds, gradually decreased both intragemmally and intergemmally. The morphometry revealed no significant difference in papilla size between the control and diabetic groups, but there were fewer taste buds per papilla (per animal). The quantification of innervation in taste buds of the diabetic rats supported the visual assessment of immunohistochemical labeling, that the innervation of taste cells was significantly reduced in diabetic animals. These findings suggest that taste impairment in diabetic subjects may be caused by neuropathy defects and/or morphological changes in the taste buds.
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Morphologic examination of CD3-CD4(bright) cells in rat liver.
Yamamoto, Satoshi; Sato, Yosinobu; Abo, Toru; Hatakeyama, Katsuyosi
2002-01-01
Recently, we found CD3-CD4(bright) cells with comparative specificity for normal rat liver. In the current study, we investigated the type and form of both CD3-CD4(bright) cells and CD3-CD4(dull) cells in the rat liver. The surface phenotype of hepatic mononuclear cells in Lewis rats was identified by using monoclonal antibodies including anti-CD4, anti-CD3, and antimacrophage in conjunction with two- or three-color immunofluorescence analysis. CD3-CD4(bright) cells and CD3-CD4(dull) cells were examined morphologically using May-Giemsa staining and scanning electron microscopy. The distribution of CD3-CD4(bright) cells and CD3-CD4(dull) cells 48 hours after intravenous administration of liposome-encapsulated dichloromethylene diphosphate was also investigated. In comparison to CD3-CD4(dull) cells, CD3-CD4(bright) cells were slightly larger macrophages with abundant cytoplasmic granules, being present with comparative specificity for normal rat liver and showing negligible effects by intravenous liposome-encapsulated dichloromethylene diphosphate administration. These data suggest that in normal young rat liver these CD3-CD4(dull) and CD3-CD4(bright) cells may be dendritic cells and Kupffer cells that shift from the liver to the spleen or vice versa. These cells may also be able to locally proliferate in liver or spleen due to changes in the developing liver.
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Diet-induced effects on neuronal and glial elements in the middle-aged rat hippocampus
Freeman, Linnea R.; Haley-Zitlin, Vivian; Stevens, Cheryl; Granholm, Ann-Charlotte
2014-01-01
Consumption of a high-fat and/or high-cholesterol diet can have detrimental effects on the brain. In the present study, dietary treatment with saturated fats, trans fats, or cholesterol to middle-aged Fischer 344 rats resulted in alterations to serum triglyceride and cholesterol levels, organ weights, and hippocampal morphology. Previously, we demonstrated that a 10% hydrogenated coconut oil and 2% cholesterol diet resulted in worse performance on the 12-day water radial arm maze, increased cholesterol and triglyceride levels, and decreased dendritic microtubule associated protein 2 (MAP2) staining in the hippocampus. The diets administered herein were used to examine components from the previous diet and further examine their effects on hippocampal morphology. Specifically, neuronal morphology, dendritic integrity, fatty acid metabolism, microgliosis, and blood vessel structure in the hippocampus and/or adjacent structures were explored. Our results indicate alterations to peripheral and neural systems following each of the diets. PMID:21535919
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Andriamihaja, Mireille; Davila, Anne-Marie; Eklou-Lawson, Mamy; Petit, Nathalie; Delpal, Serge; Allek, Fadhila; Blais, Anne; Delteil, Corine; Tomé, Daniel; Blachier, François
2010-11-01
Hyperproteic diets are used in human nutrition to obtain body weight reduction. Although increased protein ingestion results in an increased transfer of proteins from the small to the large intestine, there is little information on the consequences of the use of such diets on the composition of large intestine content and on epithelial cell morphology and metabolism. Rats were fed for 15 days with either a normoproteic (NP, 14% protein) or a hyperproteic isocaloric diet (HP, 53% protein), and absorptive colonocytes were observed by electron microscopy or isolated for enzyme activity studies. The colonic luminal content was recovered for biochemical analysis. Absorbing colonocytes were characterized by a 1.7-fold reduction in the height of the brush-border membranes (P = 0.0001) after HP diet consumption when compared with NP. This coincided in the whole colon content of HP animals with a 1.8-fold higher mass content (P = 0.0020), a 2.2-fold higher water content (P = 0.0240), a 5.2-fold higher protease activity (P = 0.0104), a 5.5-fold higher ammonia content (P = 0.0008), and a more than twofold higher propionate, valerate, isobutyrate, and isovalerate content (P < 0.05). The basal oxygen consumption of colonocytes was similar in the NP and HP groups, but ammonia was found to provoke a dose-dependent decrease of oxygen consumption in the isolated absorbing colonocytes. The activity of glutamine synthetase (which condenses ammonia and glutamate) was found to be much higher in colonocytes than in small intestine enterocytes and was 1.6-fold higher (P = 0.0304) in colonocytes isolated from HP animals than NP. Glutaminase activity remained unchanged. Thus hyperproteic diet ingestion causes marked changes both in the luminal environment of colonocytes and in the characteristics of these cells, demonstrating that hyperproteic diet interferes with colonocyte metabolism and morphology. Possible causal relationships between energy metabolism, reduced height of colonocyte brush-border membranes, and reduced water absorption are discussed.
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Pollano, Antonella; Zalosnik, María I; Durando, Patricia E; Suárez, Marta M
2016-11-01
Early maternal separation (MS) may produce lasting effects in the dorsal hippocampus (DH) that can change its response to chronic stress in adulthood. Chronic stress affects DH morphology and function, but tianeptine (an anti-depressant) can reverse the stress-induced morphological impairments. Morphologic alterations of hippocampus can affect contextual memory. Therefore, we evaluated the effect of tianeptine in MS and chronically stressed rats on: 1) volume of the DH and its areas using stereology and 2) hippocampal-dependent memory using a fear conditioning test. Male Wistar rats were subjected to daily MS for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50 and 74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle, providing eight groups: AFR-unstressed/vehicle (n = 5 for stereology, n = 18 for fear conditioning test); AFR unstressed/tianeptine (n = 6 and n = 10); AFR-chronic stress/vehicle (n = 6 and n = 14); AFR-chronic stress/tianeptine (n = 6 and n = 10), MS-unstressed/vehicle (n = 5 and n = 19), MS-unstressed/tianeptine (n = 6 and n = 10), MS-chronic stress/vehicle (n = 6 and n = 18), and MS-chronic stress/tianeptine (n = 6 and n = 10). MS-chronic stress/tianeptine rats showed a diminished CA1 area than the corresponding MS-unstressed/tianeptine rats. The combination of stressors produced a freezing response similar to those of the control group during postconditioning. During retrieval, MS led to a diminished freezing response compared to the AFR-unstressed groups. Tianeptine had no effect on freezing behavior. Our results show that tianeptine can affect the CA1 area volume differently depending on the nature and quantity of stressors but cannot alter freezing to context.
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NASA Astrophysics Data System (ADS)
Zhong, Lingyun; Tong, Hengli; Lv, Mu; Deng, Yufen
2017-09-01
According to the theory of traditional Chinese Medicine (TCM), all Chinese materia medica need to be processed using Pao zhi which is a processing technology before being used in clinic. Ginger juice, made from dried or fresh ginger, is one of the main TCM processing accessories and always used to help change some Chinese materia medica’s properties for its warm or hot nature. The purpose of this paper is to discuss the influence of ginger juice on Rhizoma Coptidis (RC) by determining 5-hydroxytryptamine (5-HT) content and observing morphological changes in the harns tissue of rats. Raw Rhizoma Coptidis (RRC), fresh ginger juice processed Rhizoma Coptidis (FGJPRC), dried juice processed Rhizoma Coptidis (DGJPRC), dried ginger juice (DGJ) and fresh ginger juice (FGJ) were prepared using appropriate methods. Immunohistochemical staining was used to observe the distribution of 5-HT and fluorescence spectrophotometry was applied to determine 5-hydroxytryptamine content in the brain tissue of rats. 5 - HT in brain tissue of the rats of RRC group was distributed most densely, with the highest content. Compared to the blank group, RRC and different ginger processed RC groups could lead to increasing content of 5-HT in rat encephalon, and significant differences in RRC. Compared with the RRC, the 5-HT content in rat encephalon in DGJPRC, FGJPRC, FGJ and DGJ groups reduced, and DGJPRC, FGJPRC groups showed significant difference, FGJ and DGJ groups showed extreme significant differences. The research showed that processing with hot, warm accessories would moderate the cold nature of RC. The cold and hot nature of Traditional Chinese Materia Medica could be expressed by the difference of 5-HT contents and morphological changes of rats’ brain tissue. Simultaneously, the research showed the different excipient of ginger juice would have different effects on the processing of RC.
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Ameliorated effect of L-arginine supplementation on gingival morphology in cyclosporin-treated rats.
Fu, E; Tz-Chong, C; Liu, D; Chiu, S C
2000-11-01
The role of nitric oxide (NO) in the pathogenesis of cyclosporin (CsA)-induced gingival overgrowth is unknown. The purpose of the present study was to evaluate the effect of NO substrate (L-arginine) and blockade (N-nitro-L-arginine methylester-hydrochloride, L-NAME) on the gingival morphology in CsA-fed rats. Sixty CsA-fed (10 mg/kg/day) male Sprague-Dawley rats were assigned to 3 groups. Animals in 2 experimental groups received L-arginine (1% weight/weight) in rat chowder or L-NAME (50 mg/l) in drinking water, respectively, for 4 weeks. Rats in the control group were fed a normal diet and water. At week 0, 2, and 4, dental stone models were made from the mandibular anterior region and the gingival dimensions (width, depth, and height) were measured. The tail cuff blood pressure and the plasma nitrate level were also measured at week 4 to monitor the effects of L-arginine and L-NAME treatment. No significant difference in the gingival dimensions was noticed at week 0; however, significant differences were observed at weeks 2 and 4, except the buccolingual depth at week 2. While the magnitude of gingival dimensions was large, moderate, and small in control, L-NAME, and L-arginine groups, respectively, we found significantly reduced gingival dimensions in both L-arginine supplement and L-NAME groups. Nevertheless, the reduced gingival overgrowth in the L-NAME treatment group was far less than that in the exogenous NO treatment group. Plasma NO2-/NO3- concentrations were also significantly different; i.e., from the highest to the lowest levels were the L-arginine, CsA control, and L-NAME group, respectively. A significantly increased mean and diastolic blood pressure was found in the L-NAME group compared to the L-arginine group. Gingival morphology in CsA-fed rats was evaluated after NO substrate (L-arginine) and blockade (L-NAME) treatment for 4 weeks. Significantly decreased dimensions were noted in the L-arginine group compared to the CsA group at weeks 2 and 4. Although an inhibitory effect on the gingival morphology was also observed in the L-NAME group, another unknown mechanism might be involved. Within the limitations of the study, we suggest that NO may have an important role in the mechanism of CsA-induced gingival overgrowth.
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Tripathi, Anima; PremKumar, Karuppanan V; Pandey, Ashutosh N; Khatun, Sabana; Mishra, Surabhi Kirti; Shrivastav, Tulsidas G; Chaube, Shail K
2011-09-30
The present study was aimed to determine whether clomiphene citrate-induces generation of hydrogen peroxide in ovary, if so, whether melatonin could scavenge hydrogen peroxide and protect against clomiphene citrate-induced morphological apoptotic changes in rat eggs. For this purpose, forty five sexually immature female rats were given single intramuscular injection of 10 IU pregnant mare's serum gonadotropin for 48 h followed by single injections of 10 IU human chorionic gonadotropin and clomiphene citrate (10 mg/kg bw) with or without melatonin (20 mg/kg bw) for 16 h. The histology of ovary, ovulation rate, hydrogen peroxide concentration and catalase activity in ovary and morphological changes in ovulated eggs were analyzed. Co-administration of clomiphene citrate along with human chorionic gonadotropin significantly increased hydrogen peroxide concentration and inhibited catalase activity in ovary, inhibited ovulation rate and induced egg apoptosis. Supplementation of melatonin reduced hydrogen peroxide concentration and increased catalase activity in the ovary, delayed meiotic cell cycle progression in follicular oocytes as well as in ovulated eggs since extrusion of first polar body was still in progress even after ovulation and protected against clomiphene citrate-induced egg apoptosis. These results clearly suggest that the melatonin reduces oxidative stress by scavenging hydrogen peroxide produced in the ovary after clomiphene citrate treatment, slows down meiotic cell cycle progression in eggs and protects against clomiphene citrate-induced apoptosis in rat eggs. Copyright © 2011 Elsevier B.V. All rights reserved.
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Xiong, Ruo-Hong; Wen, Shi-Lei; Wang, Qiang; Zhou, Hong-Ying; Feng, Shi
2018-01-01
Female athletes may experience difficulties in achieving pregnancy due to athletic amenorrhea (AA); however, the underlying mechanisms of AA remain unknown. The present study focuses on the mitochondrial alteration and its function in detecting the possible mechanism of AA. An AA rat model was established by excessive swimming. Hematoxylin and eosin staining, and transmission electron microscopic methods were performed to evaluate the morphological changes of the ovary, immunohistochemical examinations and radioimmunoassays were used to detect the reproductive hormones and corresponding receptors. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to test the mtDNA copy number. PCR and western blot analysis were used to test the expression of ND2. The change of morphological features of the rat ovaries revealed evident abnormalities. Particularly, the features of the mitochondria were markedly altered. In addition, reproductive hormones in the serum and tissues of AA rats were also detected to evaluate the function of the ovaries, and the levels of these hormones were significantly decreased. Furthermore, the mitochondrial DNA copy number (mtDNA) and expression of NADH dehydrogenase subunit 2 (ND2) were quantitated by qPCR or western blot analysis. Accordingly, the mtDNA copy number and expression of ND2 expression were markedly reduced in the AA rats. In conclusion, mitochondrial dysfunction in AA may affect the cellular energy supply and, therefore, result in dysfunction of the ovary. Thus, mitochondrial dysfunction may be considered as a possible underlying mechanism for the occurrence of AA.
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Functional Evolution of the Feeding System in Rodents
Cox, Philip G.; Rayfield, Emily J.; Fagan, Michael J.; Herrel, Anthony; Pataky, Todd C.; Jeffery, Nathan
2012-01-01
The masticatory musculature of rodents has evolved to enable both gnawing at the incisors and chewing at the molars. In particular, the masseter muscle is highly specialised, having extended anteriorly to originate from the rostrum. All living rodents have achieved this masseteric expansion in one of three ways, known as the sciuromorph, hystricomorph and myomorph conditions. Here, we used finite element analysis (FEA) to investigate the biomechanical implications of these three morphologies, in a squirrel, guinea pig and rat. In particular, we wished to determine whether each of the three morphologies is better adapted for either gnawing or chewing. Results show that squirrels are more efficient at muscle-bite force transmission during incisor gnawing than guinea pigs, and that guinea pigs are more efficient at molar chewing than squirrels. This matches the known diet of nuts and seeds that squirrels gnaw, and of grasses that guinea pigs grind down with their molars. Surprisingly, results also indicate that rats are more efficient as well as more versatile feeders than both the squirrel and guinea pig. There seems to be no compromise in biting efficiency to accommodate the wider range of foodstuffs and the more general feeding behaviour adopted by rats. Our results show that the morphology of the skull and masticatory muscles have allowed squirrels to specialise as gnawers and guinea pigs as chewers, but that rats are high-performance generalists, which helps explain their overwhelming success as a group. PMID:22558427
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van der Schoor, Ciska; Oberholzer, Hester Magdalena; Bester, Megan Jean; van Rooy, Mia-Jeanne
2014-12-01
Sibutramine is used in the treatment of obesity due to its ability to influence feelings of hunger and satiety by inhibiting the re-uptake of serotonin and noradrenalin in the central nervous system (CNS). Sibutramine use has been associated with numerous adverse events in particular cardiovascular complications possibly due to the formation of thrombi. This ultrastructural descriptive study investigated the effect of sibutramine on blood coagulation, specifically the effect on morphology of platelets and fibrin networks using scanning electron microscopy. Male Sprague-Dawley rats treated with either a recommended therapeutic dose [low dosage 1.32 mg/kg] or a toxicological higher dose [high dosage 13.2 mg/kg] of sibutramine for 28 days were used and compared to control animals. Blood samples were collected and plasma smears were prepared for platelet evaluation. Following the addition of thrombin to the plasma samples, the morphology of the fibrin clots was evaluated. Platelet evaluation by scanning electron microscopy revealed morphology typical of a prothrombotic state with a characteristic excessive platelet activation in both low-dose (LD) and high-dose (HD) rats. The fibrin clots of sibutramine-treated rats, LD and HD revealed fused thick fibers with thin fibers forming a net-like structure over the thick fibers which differ considerably from the organized structure of the control animals. It can be concluded that sibutramine alters the ultrastructure of platelets and fibrin networks creating a prothrombotic state.
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Sayers, T J; Wiltrout, T A; Sowder, R; Munger, W L; Smyth, M J; Henderson, L E
1992-01-01
We have purified a protein from the granules of the rat NK leukemia cell line (RNK) that is cytostatic to a variety of tumor cells. This protein shows no species specificity because certain tumor cell lines of mouse, rat, and human origin were equally sensitive to its growth inhibitory effects. Treatment of sensitive cells resulted in a rounding of the cells followed by homotypic aggregation into large aggregates. The granule protein was distinct from cytolysin, Na-Cbz-Lys-thiobenzylester-esterase, or leukolexin. It had a molecular mass of 29 to 31 kDa, bound strongly to heparin, was inactivated by heating at 70 degrees C for 5 min or reduction, but was stable to trypsin treatment. By using molecular sieve chromatography, heparin agarose chromatography, and reverse phase HPLC, this protein was purified to homogeneity. The first 33 amino acids of the N-terminal amino acid sequence showed complete identity to the sequence predicted from a rat serine protease gene recently cloned and designated RNKP-1. Therefore we have purified a novel serine protease and demonstrated that it has effects on the growth and morphology of certain tumor cells. Other serine proteases that were structurally related and have substantial homology with RNKP-1 at the amino acid level showed neither growth inhibitory properties nor affected the morphology of the tumor target cells we used.
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The Characterization of Deqi during Moxibustion in Stroke Rats
Lv, Zhimai; Liu, Zhongyong; Huang, Dandan; Chen, Rixin; Xie, Dingyi
2013-01-01
The efficacy of acupuncture and moxibustion is closely related to Deqi phenomenons, which are some subjective feelings. However, no one has reported the objective characterization of Deqi. Our preliminary research has found a phenomenon of tail temperature increasing (TTI) obviously in some stroke rats by suspended moxibustion at the acupoint dà zhuī (DU 14), which is similar to one characterization of Deqi during moxibustion that moxibustion heat is transferred from the original moxibustion acupoint to the other areas of the body. We wonder whether TTI is the objective indicator of Deqi characterization in animals. The present study showed that the stroke rat's recovery was also associated with TTI phenomenon. This suggests that TTI phenomenon is one objective characterization of the Deqi in stroke rats. Application of the TTI phenomenon contributes to explore the physiological mechanism of Deqi. PMID:24194777
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The Characterization of Deqi during Moxibustion in Stroke Rats.
Lv, Zhimai; Liu, Zhongyong; Huang, Dandan; Chen, Rixin; Xie, Dingyi
2013-01-01
The efficacy of acupuncture and moxibustion is closely related to Deqi phenomenons, which are some subjective feelings. However, no one has reported the objective characterization of Deqi. Our preliminary research has found a phenomenon of tail temperature increasing (TTI) obviously in some stroke rats by suspended moxibustion at the acupoint dà zhuī (DU 14), which is similar to one characterization of Deqi during moxibustion that moxibustion heat is transferred from the original moxibustion acupoint to the other areas of the body. We wonder whether TTI is the objective indicator of Deqi characterization in animals. The present study showed that the stroke rat's recovery was also associated with TTI phenomenon. This suggests that TTI phenomenon is one objective characterization of the Deqi in stroke rats. Application of the TTI phenomenon contributes to explore the physiological mechanism of Deqi.
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Morphological Characterization of the Frontal and Parietal Bones of the Human Skull
2017-03-01
ARL-TR- 7962 ● MAR 2017 US Army Research Laboratory Morphological Characterization of the Frontal and Parietal Bones of the...Army Research Laboratory Morphological Characterization of the Frontal and Parietal Bones of the Human Skull by Stephen L Alexander SURVICE...
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Improving oral bioavailability of acyclovir using nanoparticulates of thiolated xyloglucan.
Madgulkar, Ashwini; Bhalekar, Mangesh R; Dikpati, Amrita A
2016-08-01
Acyclovir a BCS class III drug exhibits poor bioavailability due to limited permeability. The intention of this research work was to formulate and characterize thiolated xyloglucan polysaccharide nanoparticles (TH-NPs) of acyclovir with the purpose of increasing its oral bioavailability. Acyclovir-loaded TH-NPs were prepared using a cross-linking agent. Interactions of formulation excipients were reconnoitered using Fourier transform infrared spectroscopy (FT-IR). The formulated nanoparticles were lyophilised by the addition of a cryoprotectant and characterized for its particle size, morphology and stability and optimized using Box Behnken Design.The optimized TH-NP formulation exhibited particle size of 474.4±2.01 and an entrapment efficiency of 81.57%. A marked enhancement in the mucoadhesion was also observed. In-vivo study in a rat model proved that relative bioavailability of acyclovir TH-NPs is ∼2.575 fold greater than that of the marketed acyclovir drug suspension. Copyright © 2016 Elsevier B.V. All rights reserved.
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Garcia-Perez, E; Schönberger, T; Sumalla, M; Stierstorfer, B; Solà, R; Doods, H; Serra, J; Gorodetskaya, N
2018-04-20
Peripheral neuropathy is a common complication in type 2 diabetes mellitus (T2DM). The most common presentation is in the form of a distal axonal sensory-motor polyneuropathy that involves large and small nerve fibres in variable proportion. Zucker Diabetic Fatty (ZDF), Zucker Lean (ZL) and Wistar Han (WH) rats were used to assess the behavioural, morphological and electrophysiological effects that T2DM have on peripheral large and small nerve fibres of 6- to 40-week-old rats. ZDF rats presented mechanical hypersensitivity that initially worsened in parallel to the progression of diabetes and eventually reverted at later stages of the disease. The reversal from hypersensitivity to hyposensitivity paralleled a reduction in the number of intraepithelial skin nerve terminals and in the nerve fibre lengths. However, no increased levels of degeneration of dorsal root ganglion neurons were observed. Nerve conduction studies showed a reduction in sensory and motor nerve conduction velocity (CV) in hyperglycaemic ZDF rats. Microneurography showed significant alterations in several parameters of activity-dependent slowing (ADS) of mechano-insensitive C-nociceptors in ZDF rats. Surprisingly, some of these changes were also observed in ZL rats. Moreover, we found spontaneous activity in all three strains implying that C-nociceptors become hyperexcitable and spontaneously active not only in ageing hyperglycaemic ZDF rats but also in age-matched and apparently normoglycaemic ZL and WH rats fed with the same diet. ZDF rats presented a diabetic neuropathy involving large and small nerve fibres; additionally, ZL and WH rats also showed early small abnormalities in C-fibres, clearly detected by microneurography SIGNIFICANCE: This study provides a functional description of large and small nerve fibre function in a diabetic model that recapitulates many of the findings observed in patients suffering from type 2 diabetes mellitus. © 2018 European Pain Federation - EFIC®.
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Dose–response analysis of phthalate effects on gene expression in rat whole embryo culture
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robinson, Joshua F.; Department of Toxicogenomics, Maastricht University, Maastricht; Verhoef, Aart
2012-10-01
The rat postimplantation whole embryo culture (WEC) model serves as a potential screening tool for developmental toxicity. In this model, cultured rat embryos are exposed during early embryogenesis and evaluated for morphological effects. The integration of molecular-based markers may lead to improved objectivity, sensitivity and predictability of WEC in assessing developmental toxic properties of compounds. In this study, we investigated the concentration-dependent effects of two phthalates differing in potency, mono(2-ethylhexyl) phthalate (MEHP) and monomethyl phthalate (MMP, less toxic), on the transcriptome in WEC to examine gene expression in relation with dysmorphogenesis. MEHP was more potent than MMP in inducing genemore » expression changes as well as changes on morphology. MEHP induced significant enrichment of cholesterol/lipid/steroid (CLS) metabolism and apoptosis pathways which was associated with developmental toxicity. Regulation of genes within CLS metabolism pathways represented the most sensitive markers of MEHP exposure, more sensitive than classical morphological endpoints. As shown in direct comparisons with toxicogenomic in vivo studies, alterations in the regulation of CLS metabolism pathways has been previously identified to be associated with developmental toxicity due to phthalate exposure in utero. Our results support the application of WEC as a model to examine relative phthalate potency through gene expression and morphological responses. Additionally, our results further define the applicability domain of the WEC model for developmental toxicological investigations. -- Highlights: ► We examine the effect of two phthalates on gene expression and morphology in WEC. ► MEHP is more potent than MMP in inducing gene expression changes and dysmorphogenesis. ► MEHP significantly disrupts cholesterol metabolism pathways in a dose-dependent manner. ► Specific phthalate-related mechanisms in WEC are relevant to mechanisms in vivo.« less
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Padival, Mallika A.; Blume, Shannon R.; Vantrease, Jaime E.; Rosenkranz, J. Amiel
2015-01-01
Repeated stress can elicit symptoms of depression and anxiety. The amygdala is a significant contributor to the expression of emotion and the basolateral amygdala (BLA) is a major target for the effects of stress on emotion. The adolescent time period may be particularly susceptible to the effects of stress on emotion. While repeated stress has been demonstrated to modify the morphology of BLA neurons in adult rats, little is known about its effects on BLA neurons during adolescence. This study tests the effects of repeated stress during adolescence on BLA neuronal morphology, and whether these are similar to the effects of stress during adulthood. The BLA includes the basal (BA) and lateral (LAT) nuclei, which are differentially responsive to stress in adults. Therefore, effects of stress during adolescence were compared between the BA and LAT nuclei. Morphological features of reconstructed BLA neurons were examined using Golgi-Cox stained tissue from control or repeated restraint stress exposed rats. We found subtle dendritic growth coupled with loss of spines after repeated stress during adolescence. The magnitude and dendritic location of these differences varied between the BA and LAT nuclei in strong contrast to the stress-induced increases in spine number seen in adults. These results demonstrate that repeated stress during adolescence has markedly different effects on BLA neuronal morphology, and the extent of these changes are BLA nucleus-dependent. Moreover, altered neuroanatomy was associated with age-dependent effects of repeated stress on generalization of fear, and may point to the necessity for different approaches to target stress-induced changes in adolescents. PMID:25701125
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Cobalt treatment does not prevent glomerular morphological alterations in type 1 diabetic rats.
Singh, Gaaminepreet; Krishan, Pawan
2018-06-02
Early renal morphological alterations including glomerular hypertrophy and mesangial expansion occur in diabetic kidney disease and correlate with various clinical manifestations of diabetes. The present study was designed to investigate the influence of pharmacological modulation of HIF-1α (hypoxia inducible factor-1 alpha) protein levels, on these glomerular changes in rodent model of type 1 diabetes. Male wistar rats were made diabetic (Streptozotocin 45 mg/kg; i.p.) and afterwards treated with HIF activator cobalt chloride for 4 weeks. Renal function was assessed by serum creatinine, albumin, proteinuria levels, oxidative stress: reduced glutathione levels and catalase activity, and renal tissue HIF-1α protein levels were determined by ELISA assay. Histological analysis of kidney sections was done by haematoxylin and eosin (glomeruli diameter), periodic acid Schiff (mesangial expansion and glomerulosclerosis) and sirius red (fibrosis, tubular dilation) staining. Diabetes rats displayed reduced serum albumin levels, marked proteinuria, lower kidney reduced glutathione content, glomerular hypertrophy, glomerulosclerosis, mesangial expansion, tubular dilation and renal fibrosis. Cobalt chloride treatment normalised renal HIF-1α protein levels, reduced development of proteinuria and tubulo-interstitial fibrosis, but the glomerular morphological alterations such as glomerulosclerosis, mesangial expansion, increased glomerular diameter and tubular vacoulations were not abrogated in diabetic kidneys. Glomerular morphological abnormalities might precede the development of proteinuria and renal fibrosis in experimental model of type 1 diabetes. Pharmacological modulation of renal HIF-1α protein levels does not influence glomerular and tubular dilatory changes in diabetic kidney disease.
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Misa-Agustiño, Maria J; Jorge-Mora, Teresa; Jorge-Barreiro, Francisco J; Suarez-Quintanilla, Juan; Moreno-Piquero, Eduardo; Ares-Pena, Francisco J
2015-01-01
Non-ionizing radiation at 2.45 GHz may modify the morphology and expression of genes that codify heat shock proteins (HSP) in the thyroid gland. Diathermy is the therapeutic application of non-ionizing radiation to humans for its beneficial effects in rheumatological and musculo-skeletal pain processes. We used a diathermy model on laboratory rats subjected to maximum exposure in the left front leg, in order to study the effects of radiation on the nearby thyroid tissue. Fifty-six rats were individually exposed once or repeatedly (10 times in two weeks) for 30 min to 2.45 GHz radiation in a commercial chamber at different non-thermal specific absorption rates (SARs), which were calculated using the finite difference time domain technique. We used immunohistochemistry methods to study the expression of HSP-90 and morphological changes in thyroid gland tissues. Ninety minutes after radiation with the highest SAR, the central and peripheral follicles presented increased size and the thickness of the peripheral septa had decreased. Twenty-four hours after radiation, only peripheral follicles radiated at 12 W were found to be smaller. Peripheral follicles increased in size with repeated exposure at 3 W power. Morphological changes in the thyroid tissue may indicate a glandular response to acute or repeated stress from radiation in the hypothalamic–pituitary–thyroid axis. Further research is needed to determine if the effect of this physical agent over time may cause disease in the human thyroid gland. PMID:25649190
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1985-01-01
The endocytic compartments of the asialoglycoprotein (ASGP) pathway in rat hepatocytes were studied using a combined morphological and biochemical approach in the isolated perfused liver. Use of electron microscopic tracers and a temperature-shift protocol to synchronize ligand entry confirmed the route of ASGP internalization observed in our previous in vivo studies (1) and established conditions under which we could label the contents of successive compartments in the pathway for subcellular fractionation studies. Three endosomal compartments were demonstrated in which ASGPs appear after they enter the cell via coated pits and vesicles but before they reach their site of degradation in lysosomes. These three compartments could be distinguished by their location within the hepatocyte, by their morphological appearance in situ, and by their density in sucrose gradients. The distributions of ASGP receptors, both accessible and latent (revealed by detergent permeabilization), were also examined and compared with that of ligand during subcellular fractionation. Most accessible ASGP receptors co-distributed with conventional plasma membrane markers. However, hepatocytes contain a substantial intracellular pool of latent ASGP binding sites that exceeds the number of cell surface receptors and whose presence is not dependent on ASGP exposure. The distribution of these latent ASGP receptors on sucrose gradients (detected either immunologically or by binding assays) was coincident with that of ligand sequestered within the early endosome compartments. In addition, both early endosomes and the membrane vesicles containing latent ASGP receptors had high cholesterol content, because both shifted markedly in density upon exposure to digitonin. PMID:2866191
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Karasu, C; Ozansoy, G; Bozkurt, O; Erdoğan, D; Omeroğlu, S
1997-08-01
In this study, we evaluated the effects of vitamin E on the vascular reactivity and structure of thoracic aorta from streptozotocin (STZ)-diabetic rats. Plasma glucose, cholesterol, and triglyceride concentrations in rats were increased markedly by STZ-diabetes. The thiobarbituric acid (TBA) reactivity level as an index of lipid peroxidation was higher in both plasma and aorta of STZ-diabetic rats compared with controls. The rings of thoracic aorta with or without endothelium were mounted in organ chambers for measurement of isometric tension and were contracted by a single dose (10-5 mol/L) and then cumulative doses of noradrenaline ([NA] 10(-9) to 10(-5) mol/L). Pretreatment with methylene blue (MB) or removal of the endothelium resulted in a similar degree of enhancement in NA-induced contraction of control rings. STZ-diabetes increased the fast and slow components of NA-induced contraction in all experiments. The maximal contractile response of aorta to NA was also augmented by STZ-diabetes, whereas the sensitivity (pD2) remained unaltered. STZ-diabetes resulted in significant increases in the maximum contractile response and sensitivity of aorta to KCl. STZ-diabetic rats showed a significant reduction in the percentage of endothelial response (PER). A group of diabetic rats was treated from the time of diabetes induction with a 0.5% dietary supplement of vitamin E. Vitamin E supplementation of STZ-diabetic rats eliminated accumulation of lipid peroxides and returned plasma triglycerides toward normal levels. Diabetes-induced abnormal contractility and endothelial dysfunction were significantly but not completely prevented by vitamin E treatment. The endothelium-independent relaxation response to sodium nitroprusside (SNP) was not affected by diabetes or vitamin E treatment. Electron microscopic examination of thoracic aorta revealed that normal tissue organization was disrupted in STZ-diabetic rats, and that vitamin E treatment can protect the morphological integrity of aorta against STZ-diabetes. The results suggest the following: (1) The increased triglycerides/lipid peroxides may be an important reason for morphological or functional disruption of endothelium and enhanced activation of contractile mechanisms of vascular smooth muscle in STZ-diabetic rats. Both contribute to an increased responsiveness of diabetic aorta to vasoconstrictor agents. (2) Vitamin E treatment of STZ-diabetic rats can prevent the development of abnormal contractility and structure and endothelial dysfunction in aorta. (3) The triglyceride- and/or lipid peroxidation-lowering effect of vitamin E may be crucial for the protective effect of this vitamin on the vasculature.
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He, Xiao-Sheng; Xiang, Zhang; Zhou, Fei; Fu, Luo-An; Shuang, Wang
2004-05-01
The study investigated morphologically axonal calcium overloading and its relationship with axonal structural changes. Twelve SD rats were divided into an injury and a sham group. The rat model of traumatic axonal injury (TAI) by lateral head rotation was produced. The oxalate-pyroantimonate technique for calcium localization was used to process the rat's medulla oblongata tissues with thin sections observed electron-microscopically for axonal structure and calcium precipitates on it. The axonal damage in medulla oblongata appeared at 2 h post-injury, gradually became diffuse and severe, and continued to exist at 24 hours. At 2 hours, calcium precipitates were deposited on separated lamellae and axolemma, but were rarely distributed in the axoplasm. At 6 hours, calcium precipitates occurred on separated lamellae and axolemma in much higher density, but on axoplasm in extremely small amounts. Some axons, though lacking structural changes of the myelin sheath, sequestered plenty of calcium deposits on their swollen mitochondria. At 24 hours, damaged axons presented with much more severe lamellae separation and calcium deposits. Axonal calcium overloading developed in rat TAI model using lateral head rotation. This was significantly related to structural damage in the axons. These findings suggest the feasibility of using calcium antagonists in cope the management of human DAI in its very early stage.
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The rat caudal nerves: a model for experimental neuropathies.
Schaumburg, Herbert H; Zotova, Elena; Raine, Cedric S; Tar, Moses; Arezzo, Joseph
2010-06-01
This study provides a detailed investigation of the anatomy of the rat caudal nerve along its entire length, as well as correlated nerve conduction measures in both large and small diameter axons. It determines that rodent caudal nerves provide a simple, sensitive experimental model for evaluation of the pathophysiology of degeneration, recovery, and prevention of length-dependent distal axonopathy. After first defining the normal anatomy and electrophysiology of the rat caudal nerves, acrylamide monomer, a reliable axonal toxin, was administered at different doses for escalating time periods. Serial electrophysiological recordings were obtained, during intoxication, from multiple sites along caudal and distal sciatic nerves. Multiple sections of the caudal and sciatic nerves were examined with light and electron microscopy. The normal distribution of conduction velocities was determined and acrylamide-induced time- and dose-related slowing of velocities at the vulnerable ultraterminal region was documented. Degenerative morphological changes in the distal regions of the caudal nerves appeared well before changes in the distal sciatic nerves. Our study has shown that (1) rat caudal nerves have a complex neural structure that varies along a distal-to-proximal gradient and (2) correlative assessment of both morphology and electrophysiology of rat caudal nerves is easily achieved and provides a highly sensitive index of the onset and progression of the length-dependent distal axonopathy.
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NASA Technical Reports Server (NTRS)
Holton, E.; Hargens, A.; Gonsalves, M.; Berretta, D.; Doty, S.; Roberts, W.; Garetto, L.; Kaplansky, A.; Durnova, G.; Gott, S.
1990-01-01
Bone area, bone electrophysiology, bone vascularity, osteoblast morphology, and osteoblast histogenesis were studied in rats associated with Cosmos 1887. The results suggest that the synchronous animals were the only group with a significantly larger bone area than the basal group, that the bone electrical potential was more negative in flight than in the synchronous rats, that the endosteal osteoblasts from flight rats had greater numbers of transitional Golgi vesicles but no difference in the large Golgi saccules or the alkaline phosphatase activity, that the perioteal vasculature in the shaft of flight rats often showed very dense intraluminal deposits with adjacent degenerating osteocytes as well as lipid accumulations within the lumen of the vessels and sometimes degeneration of the vascular wall (this change was not present in the metaphyseal region of flight animals), and that the progenitor cells decreased in flight rats while the preosteoblasts increased compared to controls. Many of the results suggest that the animals were beginning to recover from the effects of spaceflight during the two day interval between landing and euthanasia; flight effects, such as the vascular changes, did not appear to recover.
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Effects of neonatal exposure to a glyphosate-based herbicide on female rat reproduction.
Ingaramo, Paola I; Varayoud, Jorgelina; Milesi, María M; Schimpf, Marlise Guerrero; Muñoz-de-Toro, Mónica; Luque, Enrique H
2016-11-01
In this study, we investigated whether neonatal exposure to a glyphosate-based herbicide (GBH) alters the reproductive performance and the molecular mechanisms involved in the decidualization process in adult rats. Newborn female rats received vehicle or 2 mg/kg/day of a GBH on postnatal days (PND) 1, 3, 5 and 7. On PND90, the rats were mated to evaluate (i) the reproductive performance on gestational day (GD) 19 and (ii) the ovarian steroid levels, uterine morphology, endometrial cell proliferation, apoptosis and cell cycle regulators, and endocrine pathways that regulate uterine decidualization (steroid receptors/COUP-TFII/Bmp2/Hoxa10) at the implantation sites (IS) on GD9. The GBH-exposed group showed a significant increase in the number of resorption sites on GD19, associated with an altered decidualization response. In fact, on GD9, the GBH-treated rats showed morphological changes at the IS, associated with a decreased expression of estrogen and progesterone receptors, a downregulation of COUP-TFII (Nr2f2) and Bmp2 mRNA and an increased expression of HOXA10 and the proliferation marker Ki67(Mki67) at the IS. We concluded that alterations in endometrial decidualization might be the mechanism of GBH-induced post-implantation embryo loss. © 2016 Society for Reproduction and Fertility.
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Effects of Calorie Restriction on Cardioprotection and Cardiovascular Health
Ahmet, Ismayil; Tae, Hyun-Jin; de Cabo, Rafael; Lakatta, Edward G.; Talan, Mark I.
2011-01-01
Multiple health benefits of calorie restriction (CR) and alternate day fasting (ADF) regimens are widely recognized. Experimental data concerning the effects of calorie restriction on cardiac health are more controversial, ranging from evidence that ADF protects heart from ischemic damage but results in developing of diastolic dysfunction, to reports that CR ameliorates the age-associated diastolic dysfunction. Here we investigated the effects of chronic CR on morphology and function of the cardiovascular system of aged rats and cardioprotective effect of CR against ischemic damage in the experimental rat model of MI. Cardiovascular fitness of 24-mo old Fisher 344 rats maintained through life on ad libitum (AL) or CR diets was extensively evaluated via echocardiography, dobutamine stress test, pressure-volume loop analyses, pulse wave velocity measurements, and histology. Groups of 2-mo old AL and 29-mo old CR rats were studied for comparison. Myocardial infarction (MI) was induced by a permanent ligation of the anterior descending coronary artery in 5-mo old rats maintained for 3 months on CR or AL. MI size was evaluated histologically 24 hrs following coronary ligation. Cardiac remodeling was followed-up via echocardiography. Age-associated changes in 24-mo old rats consisted of 33% increase of fibrosis in the myocardium and more than 2 fold increase of the collagen in the tunica media of the aorta. There was a significant decrease in the density and total number of cardiomyocytes, while their size was increased. These morphological changes were manifested in a decline of systolic and diastolic cardiac function, increase of left ventricular and aortic stiffness, and arterio-ventricular uncoupling. Tachycardic response to dobutamine challenge was absent in the old rats. Compared to AL rats, 24-mo old CR rats had reduced levels of cardiac and aortic fibrosis, increased density of cardiomyocytes that were smaller in size, attenuated diastolic dysfunction, normal systolic function and arterio-ventricular coupling. Tachycardic response to dobutamine was also intact in CR 24-mo old rats and aortic stiffness was reduced. Adjustment for body weight differences through ratiometric or allometric scaling did not affect the overall pattern of differences between AL and CR rats. Attenuation of morphological and functional age-associated changes in 24-mo old CR rats either was not observed at all or was smaller in 29-mo old CR rats. Size of MI induced by a permanent coronary ligation as well as post-MI cardiac remodeling and function were similar in CR and AL rats. CR does not increase tolerance of myocardium to ischemic damage, but attenuates the age-associated changes in the heart and major vessels. The attenuation of age-associated changes by CR cannot be explained by the effect of lower body weight but are attributable to more intimate cellular mechanisms of CR itself. Attenuation of age-associated changes by CR waned with advancing age, and is consistent with the idea that CR postponed senescence. PMID:21586294
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Effects of an ethanol-gasoline mixture: results of a 4-week inhalation study in rats.
Chu, I; Poon, R; Valli, V; Yagminas, A; Bowers, W J; Seegal, R; Vincent, R
2005-01-01
The inhalation toxicity of an ethanol-gasoline mixture was investigated in rats. Groups of 15 male and 15 female rats were exposed by inhalation to 6130 ppm ethanol, 500 ppm gasoline or a mixture of 85% ethanol and 15% gasoline (by volume, 6130 ppm ethanol and 500 ppm gasoline), 6 h a day, 5 days per week for 4 weeks. Control rats of both genders received HEPA/charcoal-filtered room air. Ten males and ten females from each group were killed after 4 weeks of treatment and the remaining rats were exposed to filtered room air for an additional 4 weeks to determine the reversibility of toxic injuries. Female rats treated with the mixture showed growth suppression, which was reversed after 4 weeks of recovery. Increased kidney weight and elevated liver microsomal ethoxyresorufin-O-deethylase (EROD) activity, urinary ascorbic acid, hippuric acid and blood lymphocytes were observed and most of the effects were associated with gasoline exposure. Combined exposure to ethanol and gasoline appeared to exert an additive effect on growth suppression. Inflammation of the upper respiratory tract was observed only in the ethanol-gasoline mixture groups, and exposure to either ethanol and gasoline had no effect on the organ, suggesting that an irritating effect was produced when the two liquids were mixed. Morphology in the adrenal gland was characterized by vacuolation of the cortical area. Although histological changes were generally mild in male and female rats and were reversed after 4 weeks, the changes tended to be more severe in male rats. Brain biogenic amine levels were altered in ethanol- and gasoline-treated groups; their levels varied with respect to gender and brain region. Although no general interactions were observed in the brain neurotransmitters, gasoline appeared to suppress dopamine concentrations in the nucleus accumbens region co-exposed to ethanol. It was concluded that treatment with ethanol and gasoline, at the levels studied, produced mild, reversible biochemical hematological and histological effects, with some indications of interactions when they were co-administered.
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Kim, Sung-Jo; Hwang, Eunmi; Yi, Sun Shin; Song, Ki Duk; Lee, Hak-Kyo; Heo, Tae-Hwe; Park, Sang-Kyu; Jung, Yun Joo; Jun, Hyun Sik
2017-08-01
Hippophae rhamnoides L., also known as sea buckthorn (SBT), possesses a wide range of biological and pharmacological activities. However, the underlying mechanism is largely unknown. The present study examined whether SBT leaf extract could inhibit proliferation and promote apoptosis of rat glioma C6 cells. The results revealed that the treatment with SBT leaf extract inhibited proliferation of rat C6 glioma cells in a dose-dependent manner. SBT-induced reduction of C6 glioma cell proliferation and viability was accompanied by a decrease in production of reactive oxygen species (ROS), which are critical for the proliferation of tumor cells. SBT treatment not only significantly upregulated the expression of the pro-apoptotic protein Bcl-2-associated X (Bax) but also promoted its localization in the nucleus. Although increased expression and nuclear translocation of Bax were observed in SBT-treated C6 glioma cells, the induced nuclear morphological change was distinct from that of typical apoptotic cells in that most of SBT-treated cells were characterized by convoluted nuclei with cavitations and clumps of chromatin. All of these results suggest that SBT leaf extract could inhibit the rapid proliferation of rat C6 glioma cells, possibly by inducing the early events of apoptosis. Thus, SBT may serve as a potential therapeutic candidate for the treatment of glioma.
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Solubilized liver extracellular matrix maintains primary rat hepatocyte phenotype in-vitro.
Loneker, Abigail E; Faulk, Denver M; Hussey, George S; D'Amore, Antonio; Badylak, Stephen F
2016-04-01
Whole organ engineering and cell-based regenerative medicine approaches are being investigated as potential therapeutic options for end-stage liver failure. However, a major challenge of these strategies is the loss of hepatic specific function after hepatocytes are removed from their native microenvironment. The objective of the present study was to determine if solubilized liver extracellular matrix (ECM), when used as a media supplement, can better maintain hepatocyte phenotype compared to type I collagen alone or solubilized ECM harvested from a non-liver tissue source. Liver extracellular matrix (LECM) from four different species was isolated via liver tissue decellularization, solubilized, and then used as a media supplement for primary rat hepatocytes (PRH). The four species of LECM investigated were human, porcine, canine and rat. Cell morphology, albumin secretion, and ammonia metabolism were used to assess maintenance of hepatocyte phenotype. Biochemical and mechanical characterization of each LECM were also conducted. Results showed that PRH's supplemented with canine and porcine LECM maintained their phenotype to a greater extent compared to all other groups. PRH's supplemented with canine and porcine LECM showed increased bile production, increased albumin production, and the formation of multinucleate cells. The findings of the present study suggest that solubilized liver ECM can support in-vitro hepatocyte culture and should be considered for therapeutic and diagnostic techniques that utilize hepatocytes. © 2016 Wiley Periodicals, Inc.
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Clostridium perfringens epsilon toxin increases the small intestinal permeability in mice and rats.
Goldstein, Jorge; Morris, Winston E; Loidl, César Fabián; Tironi-Farinati, Carla; Tironi-Farinatti, Carla; McClane, Bruce A; Uzal, Francisco A; Fernandez Miyakawa, Mariano E
2009-09-18
Epsilon toxin is a potent neurotoxin produced by Clostridium perfringens types B and D, an anaerobic bacterium that causes enterotoxaemia in ruminants. In the affected animal, it causes oedema of the lungs and brain by damaging the endothelial cells, inducing physiological and morphological changes. Although it is believed to compromise the intestinal barrier, thus entering the gut vasculature, little is known about the mechanism underlying this process. This study characterizes the effects of epsilon toxin on fluid transport and bioelectrical parameters in the small intestine of mice and rats. The enteropooling and the intestinal loop tests, together with the single-pass perfusion assay and in vitro and ex vivo analysis in Ussing's chamber, were all used in combination with histological and ultrastructural analysis of mice and rat small intestine, challenged with or without C. perfringens epsilon toxin. Luminal epsilon toxin induced a time and concentration dependent intestinal fluid accumulation and fall of the transepithelial resistance. Although no evident histological changes were observed, opening of the mucosa tight junction in combination with apoptotic changes in the lamina propria were seen with transmission electron microscopy. These results indicate that C. perfringens epsilon toxin alters the intestinal permeability, predominantly by opening the mucosa tight junction, increasing its permeability to macromolecules, and inducing further degenerative changes in the lamina propria of the bowel.
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Nekkanti, Vijaykumar; Venkatesan, Natarajan; Wang, Zhijun; Betageri, Guru V
2015-01-01
The objective of our investigational work was to develop a proliposomal formulation to improve the oral bioavailability of valsartan. Proliposomes were formulated by thin film hydration technique using different ratios of phospholipids:drug:cholesterol. The prepared proliposomes were evaluated for vesicle size, encapsulation efficiency, morphological properties, in vitro drug release, in vitro permeability and in vivo pharmacokinetics. In vitro drug-release studies were performed in simulated gastric fluid (pH 1.2) and purified water using dialysis bag method. In vitro drug permeation was studied using parallel artificial membrane permeation assay (PAMPA), Caco-2 monolayer and everted rat intestinal perfusion techniques. In vivo pharmacokinetic studies were conducted in male Sprague Dawley (SD) rats. Among the proliposomal formulations, F-V was found to have the highest encapsulation efficiency of 95.6 ± 2.9% with a vesicle size of 364.1 ± 14.9 nm. The in vitro dissolution studies indicated an improved drug release from proliposomal formulation, F-V in comparison to pure drug suspension in both, purified water and pH 1.2 dissolution media after 12 h. Permeability across PAMPA, Caco-2 cell and everted rat intestinal perfusion studies were higher with F-V formulation as compared to pure drug. Following single oral administration of F-V formulation, a relative bioavailability of 202.36% was achieved as compared to pure valsartan.
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Alayoubi, Alaadin; Sullivan, Ryan D; Lou, Hao; Patel, Hemlata; Mandrell, Timothy; Helms, Richard; Almoazen, Hassan
2016-06-01
The objective of this study was to evaluate the transdermal efficiency of iodide microemulsion in treating iodine deficiency using rats as an animal model. Animals were fed either iodine-deficient diet (20 μg/kg iodide) or control diet (200 μg/kg iodide) over a 17-month period. At month 14, iodide microemulsion was applied topically in iodine-deficient group and physiological evaluations of thyroid gland functions were characterized by monitoring the thyroid hormones (T3, T4), thyroid-stimulating hormone (TSH), iodide ion excretion in urine, and the overall rat body weights in both groups. Moreover, morphological evaluations of thyroid gland before and after treatment were performed by ultrasound imaging and through histological assessment. Prior to microemulsion treatment, the levels of T3, T4, and TSH in iodine-deficient group were statistically significant as compared to that in the control group. The levels of T3 and T4 increased while TSH level decreased significantly in iodine-deficient group within the first 4 weeks of treatment. After treatment, iodide concentration in urine increased significantly. There was no statistical difference in weight between the two groups. Ultrasound imaging and histological evaluations showed evidence of hyperplasia in iodine-deficient group. Topical iodide microemulsion has shown a promising potential as a novel delivery system to treat iodine deficiency.
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NASA Technical Reports Server (NTRS)
Gerus, A. I.
1980-01-01
The effect of hypodynamia on the vascular system of white rats with diaphragm deprivation was investigated. Morphological changes in the intraorganic blood stream of the diaphragm were determined. The capacity of the intraorganic vascular flow within the diaphragm muscles was established.
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[Morphological signs of survival cultured adult rat cardiomyocytes].
Chang, Hui; Zhang, Lin; Yu, Zhi-Bin
2011-02-01
To clarify the key morphological signs for the survival of adult rat cardiomyocytes in primary culture. The adult rat hearts were retrogradely superfused by Langendorff apparatus. Cardiomyocytes were digested by collagenase I and cultured in three groups: (1) Serum free medium + BA (Bongkrekic acid, apoptotic inhibitor), (2) 5% serum medium, and (3) 5% serum medium + BA. The morphological alterations were observed and the percentage of rod-shaped cardiomyocytes, the apoptotic rate of cells, the rate of pseudopodium formation and the nuclear distances of cardiomyocytes were detected during culture. (1) The percentage of rod-shaped cardiomyocytes decreased gradually in the first 3 days of cell culture. The percentage of rod-shaped cardiomyocytes cultured without fetal bovine serum (FBS) decreased more rapidly than those cultured with FBS. No differences were noticed between with and without the addition of apoptotic inhibitor BA. The apoptotic rate of cardiomyocytes increased in the first 3 days of cell culture, and the apoptotic rate of cells cultured without FBS increased more than that cultured with FBS. Also BA had no effect on apoptotic rate. (2) Cardiomyocytes cultured with FBS spread from the intercalated disk and extended pseudopodium on the second or third day of cell culture. Cardiomyocytes with thin membranous pseudopodium developed would survive and spread laterally at the 6th day of culture. Cells with the elongated morphology gradually spread extensively and took on a spheroidal shape. Myofibrils gradually lost their parallel. Cells cultured without FBS had no pseudopodium formation. The intercalated disk of cells gradually changed blunt. There was no effect on the rate of pseudopodium formation when added with apoptotic inhibitor BA. (3) Cytoskeletal remodeling occurred in survived cardiomyocytes. After 6 days of culture, cardiomyocytes exhibited characteristic of redifferentiation. (4) The distance between nuclei decreased in a single cardiomyocyte cultured with FBS for the cytoskeletal reconstruction, whereas it remained unchanged in cardiomyocytes cultured without FBS. We clarify the pseudopodium developed on the second or third day of cell culture will be the critical morphological signs of survival cultured adult rat cardiomyocytes. It is necessary to add FBS for the formation of pseudopodium.
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Dos Santos, Adriana Souza; de Almeida, Wellington; Popik, Bruno; Sbardelotto, Bruno Marques; Torrejais, Márcia Miranda; de Souza, Marcelo Alves; Centenaro, Lígia Aline
2017-08-01
In an attempt to propose an animal model that reproduces in rats the phenotype of cerebral palsy, this study evaluated the effects of maternal exposure to bacterial endotoxin associated with perinatal asphyxia and sensorimotor restriction on gait pattern, brain and spinal cord morphology. Two experimental groups were used: Control Group (CTG) - offspring of rats injected with saline during pregnancy and Cerebral Palsy Group (CPG) - offspring of rats injected with lipopolysaccharide during pregnancy, submitted to perinatal asphyxia and sensorimotor restriction for 30days. At 29days of age, the CPG exhibited coordination between limbs, weight-supported dorsal steps or weight-supported plantar steps with paw rotation. At 45days of age, CPG exhibited plantar stepping with the paw rotated in the balance phase. An increase in the number of glial cells in the primary somatosensory cortex and dorsal striatum were observed in the CPG, but the corpus callosum thickness and cross-sectional area of lateral ventricle were similar between studied groups. No changes were found in the number of motoneurons, glial cells and soma area of the motoneurons in the ventral horn of spinal cord. The combination of insults in the pre, peri and postnatal periods produced changes in hindlimbs gait pattern of animals similar to those observed in diplegic patients, but motor impairments were attenuated over time. Besides, the greater number of glial cells observed seems to be related to the formation of a glial scar in important sensorimotor brain areas. Copyright © 2017 ISDN. Published by Elsevier Ltd. All rights reserved.
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Lipopolysaccharide endotoxemia induces amyloid-β and p-tau formation in the rat brain.
Wang, Li-Ming; Wu, Qi; Kirk, Ryan A; Horn, Kevin P; Ebada Salem, Ahmed H; Hoffman, John M; Yap, Jeffrey T; Sonnen, Joshua A; Towner, Rheal A; Bozza, Fernando A; Rodrigues, Rosana S; Morton, Kathryn A
2018-01-01
Amyloid beta (Aβ) plaques are not specific to Alzheimer's disease and occur with aging and neurodegenerative disorders. Soluble brain Aβ may be neuroprotective and increases in response to neuroinflammation. Sepsis is associated with neurocognitive compromise. The objective was to determine, in a rat endotoxemia model of sepsis, whether neuroinflammation and soluble Aβ production are associated with Aβ plaque and hyperphosphorylated tau deposition in the brain. Male Sprague Dawley rats received a single intraperitoneal injection of 10 mg/kg of lipopolysaccharide endotoxin (LPS). Brain and blood levels of IL-1β, IL-6, and TNFα and cortical microglial density were measured in LPS-injected and control animals. Soluble brain Aβ and p-tau were compared and Aβ plaques were quantified and characterized. Brain uptake of [ 18 F]flutemetamol was measured by phosphor imaging. LPS endotoxemia resulted in elevations of cytokines in blood and brain. Microglial density was increased in LPS-treated rats relative to controls. LPS resulted in increased soluble Aβ and in p-tau levels in whole brain. Progressive increases in morphologically-diffuse Aβ plaques occurred throughout the interval of observation (to 7-9 days post LPS). LPS endotoxemia resulted in increased [ 18 F]flutemetamol in the cortex and increased cortex: white matter ratios of activity. In conclusion, LPS endotoxemia causes neuroinflammation, increased soluble Aβ and Aβ diffuse plaques in the brain. Aβ PET tracers may inform this neuropathology. Increased p-tau in the brain of LPS treated animals suggests that downstream consequences of Aβ plaque formation may occur. Further mechanistic and neurocognitive studies to understand the causes and consequences of LPS-induced neuropathology are warranted.
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Ototoxicity in rats exposed to ethylbenzene and to two technical xylene vapours for 13 weeks.
Gagnaire, François; Langlais, Cristina; Grossmann, Stéphane; Wild, Pascal
2007-02-01
Male Sprague-Dawley rats were exposed to ethylbenzene (200, 400, 600 and 800 ppm) and to two mixed xylenes (250, 500, 1,000 and 2,000 ppm total compounds) by inhalation, 6 h/day, 6 days/week for 13 weeks and sacrificed for morphological investigation 8 weeks after the end of exposure. Brainstem auditory-evoked responses were used to determine auditory thresholds at different frequencies. Ethylbenzene produced moderate to severe ototoxicity in rats exposed to the four concentrations studied. Increased thresholds were observed at 2, 4, 8 and 16 kHz in rats exposed to 400, 600 and 800 ppm ethylbenzene. Moderate to severe losses of outer hair cells of the organ of Corti occurred in animals exposed to the four concentrations studied. Exposure to both mixed xylenes produced ototoxicity characterized by increased auditory thresholds and losses of outer hair cells. Ototoxicity potentiation caused by ethylbenzene was observed. Depending on the mixed xylene studied and the area of the concentration-response curves taken into account, the concentrations of ethylbenzene in mixed xylenes necessary to cause a given ototoxicity were 1.7-2.8 times less than those of pure ethylbenzene. Given the high ototoxicity of ethylbenzene, the safety margin of less or equal to two (LOAEL/TWA) might be too small to protect workers from the potential risk of ototoxicity. Moreover, the enhanced ototoxicity of ethylbenzene and para-xylene observed in mixed xylenes should encourage the production of mixed xylenes with the lowest possible concentrations of ethylbenzene and para-xylene.
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Protective effects of propolis on methotrexate-induced testis injury in rat.
Sönmez, Mehmet Fatih; Çilenk, Kübra Tuğçe; Karabulut, Derya; Ünalmış, Sunay; Deligönül, Erkan; Öztürk, İsmet; Kaymak, Emin
2016-04-01
Propolis is an adhesive substance which is collected and used by honeybees. Propolis is a potent antioxidant and a free radical scavenger. This study was designed to determine whether propolis could protect against dysfunction and oxidative stress induced by methotrexate-induced injury in rat testis. A total of 40 male Wistar albino rats were divided into four groups: group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and 4 received 100mg/kg/day propolis (by oral gavage) for 15 days by the first day of the experimental protocol. Then the rats were decapitated under anesthesia, and their testes were removed. The histopathological and biochemical analysis along with apoptosis assessment of testis tissues were compared. Immunohistochemical analysis of Heat shock protein-70 (HSP-70) and Proliferating Cell Nuclear Antigen (PCNA) were performed. The phenolic characterization of propolis was performed by Liquid chromatography-mass spectrometry (LC-MS/MS). Methotrexate caused tended to increase in malondialdehyde level and in the number of apoptotic cells; it also caused a decrease in MSTD and JTBS, PCNA and HSP-70 expression and xanthine oxidase levels in group 2. Propolis prevented the rise in malondialdehyde, xanthine oxidase levels and HSP-70 expression and improved testicular morphology and JTBS. It was found that, methorexate gives rise to serious damage in the testes and propolis is a potent antioxidant agent in preventing testicular injury. Copyright © 2016. Published by Elsevier Masson SAS.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Hagland, Hanne R.; Nilsson, Linn I.H.; Burri, Lena
Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects,more » and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.« less
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Kudasova, E O; Vlasova, L F; Semenov, D E; Lushnikova, E L
2017-03-01
Morphological analysis of the subcutaneous fat was performed in rats after subcutaneous implantation of basic dental plastic materials with different hydrophobic and hydrophilic properties. It was shown that subcutaneous implantation of dental plastics with mostly hydrophobic surface and low biocompatibility induced destructive and inflammatory processes of various intensities, sometimes with allergic component; morphological signs of processes persisted for 6 weeks. Modification of basic plastics using glow-discharge plasma and enhancement of their hydrophilicity and biocompatibility significantly reduced the intensity of destructive and inflammatory processes and ensured more rapid (in 2 weeks) repair of the destroyed tissues with the formation of fibrous capsule around the implant.
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Il'in, E A; Serova, L V; Noskin, A D
1976-01-01
In 1974 a rat experiment was carried out onboard the Cosmos-605 biosatellite. Inflight Wistar rats were kept unrestrained in small cages. The cages were equipped with a feeder, water supply, light source and a ventilation device. The state of the animals was assessed with respect to their motor activity. The flight experiment was preceded by a number of preparatory runs and testinns that were completed with an end-to-end experiment in a biosatellite mockup. The flight experiment was paralleled by the ground-based synchroneous experiment which simulated almost entirely the flight profile. For each experiment rats were selected and trained during a month's observation. Postflight rats were exposed to clinical, physiological, morphological, cytochemical and biochemical investigations. Tissue examinations were performed on the 2nd-3rd day (20 rats) and 26-27th day (12 rats) after flight. Four rats were kept to study remote aftereffects.
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Rorabaugh, Jacki M; Chalermpalanupap, Termpanit; Botz-Zapp, Christian A; Fu, Vanessa M; Lembeck, Natalie A; Cohen, Robert M; Weinshenker, David
2017-11-01
See Grinberg and Heinsen (doi:10.1093/brain/awx261) for a scientific commentary on this article. Clinical evidence suggests that aberrant tau accumulation in the locus coeruleus and noradrenergic dysfunction may be a critical early step in Alzheimer’s disease progression. Yet, an accurate preclinical model of these phenotypes that includes early pretangle tau accrual in the locus coeruleus, loss of locus coeruleus innervation and deficits locus coeruleus/norepinephrine modulated behaviours, does not exist, hampering the identification of underlying mechanisms and the development of locus coeruleus-based therapies. Here, a transgenic rat (TgF344-AD) expressing disease-causing mutant amyloid precursor protein (APPsw) and presenilin-1 (PS1ΔE9) was characterized for histological and behavioural signs of locus coeruleus dysfunction reminiscent of mild cognitive impairment/early Alzheimer’s disease. In TgF344-AD rats, hyperphosphorylated tau was detected in the locus coeruleus prior to accrual in the medial entorhinal cortex or hippocampus, and tau pathology in the locus coeruleus was negatively correlated with noradrenergic innervation in the medial entorhinal cortex. Likewise, TgF344-AD rats displayed progressive loss of hippocampal norepinephrine levels and locus coeruleus fibres in the medial entorhinal cortex and dentate gyrus, with no frank noradrenergic cell body loss. Cultured mouse locus coeruleus neurons expressing hyperphosphorylation-prone mutant human tau had shorter neurites than control neurons, but similar cell viability, suggesting a causal link between pretangle tau accrual and altered locus coeruleus fibre morphology. TgF344-AD rats had impaired reversal learning in the Morris water maze compared to their wild-type littermates, which was rescued by chemogenetic locus coeruleus activation via designer receptors exclusively activated by designer drugs (DREADDs). Our results indicate that TgF344-AD rats uniquely meet several key criteria for a suitable model of locus coeruleus pathology and dysfunction early in Alzheimer’s disease progression, and suggest that a substantial window of opportunity for locus coeruleus/ norepinephrine-based therapeutics exists.
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Asfora, Kattyenne Kabbaz; Santos, Maria do Carmo Moreira da Silva; Montes, Marcos Antonio Japiassú Resende; de Castro, Célia Maria Machado Barbosa
2005-02-01
The purpose of this study was to evaluate the biocompatibility of the most used bleaching materials for pulpless teeth, sodium perborate and 30% hydrogen peroxide, in an experimental model of macrophages, through analysis of the adherence index and the cellular morphology. Inflammatory macrophages were obtained from peritoneal washed of Wistar rats. The evaluation of the adherence capacity of these cells to the plastic surface was conducted in Eppendorf tubes containing RPMI, after treatment with the bleaching agents diluted in 1:10, 1:100 and 1:1000 for 15 and 30 min, and incubation at 37 degrees C and humidified atmosphere of 5% CO(2) in air. The cellular morphology was verified after incubation of the cells treated with the bleaching agents in culture plaques and compared with normal cells in culture medium. Results showed that sodium perborate neither increased the adherence index, nor altered the cellular morphology when compared to the control group. The distribution, cellular morphology, cytoplasmatic and nuclear characteristics, reproduced the aspects observed in normal macrophages. However, the treatment with 30% hydrogen peroxide presented an increase in adherence index when compared to the control group (RPMI), in all dilutions, according to Mann-Whitney test (n=08 and p=0.001 for dilutions 1:10 and 1:100, and n=08 and p=0.004 for dilution 1:1000). The morphology of the cells treated with this product presented structural alterations proportionally greater, depending on the dilution of this bleaching agent, and even in the highest dilution (1:1000) the cells presented very evident alterations. This irreversible cellular damage as well as the elevation of the adherence index, characterizes the aggressive potential of 30% hydrogen peroxide, regardless of its dilution. Sodium perborate, on the other hand, showed biocompatibitity, since, no morphological nor functional alteration was observed in macrophages.
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Fan, Huailing; Ji, Feng; Lin, Ying; Zhang, Mulan; Qin, Wei; Zhou, Qi; Wu, Qiang
2016-03-01
The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt‑β‑catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague‑Dawley rats (4.5‑months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non‑acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three‑point‑bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme‑linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription‑quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, β‑catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt‑β‑catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt‑β‑catenin signaling pathway.
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FAN, HUAILING; JI, FENG; LIN, YING; ZHANG, MULAN; QIN, WEI; ZHOU, QI; WU, QIANG
2016-01-01
The present study aimed to investigate the effect of electroacupuncture stimulation at CV4 (also termed Guanyuan) on femoral osteocalcin also termed bone gla protein (BGP), alkaline phosphatase (ALP), bone mineral density (BMD) and biomechanics, as well as the Wnt-β-catenin signaling pathway in rats with postmenopausal osteoporosis. Female Sprague-Dawley rats (4.5-months old) were randomly divided into sham, Ovx, CV4 and mock groups (n=10/group). With the exception of those in the sham group, the rats were ovariectomized to induce postmenopausal osteoporosis. The rats in the CV4 and mock groups were given electroacupuncture at CV4 and non-acupoint, respectively. The rats in the Ovx model and sham groups underwent identical fixing procedures, but did not undergo electroacupuncture. Following treatment, hematoxylin and eosin staining was used to observe morphological changes in the left femoral trabecular bone, and a three-point-bending test was used to analyze femur biomechanics and determine the BMD. In addition, an enzyme-linked immunosorbent assay was used to measure the serum levels of ALP/BGP and reverse transcription-quantitative polymerase chain reaction was used detect the expression levels of Wnt3a, β-catenin and Runx2. In the present study, it was demonstrated that electroacupuncture at CV4 significantly improved the osteoporotic morphological changes that occurred in the ovariectomized rats, increased serum ALP and BGP levels, enhanced the maximum and fracture loads, increased BMD (P<0.01), and activated the Wnt-β-catenin signaling pathway. These findings demonstrated that electroacupuncture stimulation at CV4 affected bone formation and promoted bone metabolism in rats with postmenopausal osteoporosis, possibly by activating the Wnt-β-catenin signaling pathway. PMID:26846191
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Šumbera, Radim; Krásová, Jarmila; Lavrenchenko, Leonid A; Mengistu, Sewnet; Bekele, Afework; Mikula, Ondřej; Bryja, Josef
2018-09-01
Root-rats of the genus Tachyoryctes (Spalacidae) are subterranean herbivores occupying open humid habitats in the highlands of Eastern Africa. There is strong disagreement about species diversity of the genus, because some authors accept two species, while others more than ten. Species with relatively high surface activity, the giant root-rat Tachyoryctes macrocephalus, which is by far largest member of the genus, and the more fossorial African root-rat Tachyoryctes splendens, which eventually has been divided up to 12-13 species, represent two major morphological forms within the genus. In our study, we carried out a multilocus analysis of root-rats' genetic diversity based on samples from 41 localities representing most of Tachyoryctes geographic distribution. Using two mitochondrial and three nuclear genes, we found six main genetic clades possibly representing separate species. These clades were organised into three basal groups whose branching is not well resolved, probably due to fast radiation in the late Pliocene and early Pleistocene. Climatic changes in that time, i.e. fast and repeated changes between extremely dry and humid conditions, which both limited root-rat dispersal, probably stimulated their initial genetic diversification. Contrary to expectation based on the largest root-rat diversity in Kenya (up to eight species by some authors), we found the highest diversity in the Ethiopian highlands, because all but one putative species occur there. All individuals outside of Ethiopia belong to a single recently diverged and expanded clade. This species should bear the name T. annectens (Thomas, 1891), and all other names of taxa described from outside of Ethiopia should be considered its junior synonyms. However, to solve taxonomic issues, future detailed morphological analyses should be conducted on all main clades together with genetic analysis of material from areas of their supposed contact. One of the most interesting findings of the study is the internal position of T. macrocephalus in T. splendens sensu lato. This demonstrates the intriguing phenomenon of accelerated morphological evolution of rodents occupying the Afroalpine zone in Ethiopia. Finally, we discuss how the distribution of Tachyoryctes is influenced by competition with another group of subterranean herbivores on the continent, the African mole-rats. We assume that both groups do not compete directly as previously expected, but specialisation to different subterranean niches is the main factor responsible for their spatial segregation. Copyright © 2018 Elsevier Inc. All rights reserved.
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Narayanan, Sareesh Naduvil; Kumar, Raju Suresh; Karun, Kalesh M; Nayak, Satheesha B; Bhat, P Gopalakrishna
2015-10-01
The effects of chronic and repeated radiofrequency electromagnetic radiation (RFEMR) exposure on spatial cognition and hippocampal architecture were investigated in prepubescent rats. Four weeks old male Wistar rats were exposed to RF-EMR (900 MHz; SAR-1.15 W/kg with peak power density of 146.60 μW/cm(2)) for 1 h/day, for 28 days. Followed by this, spatial cognition was evaluated by Morris water maze test. To evaluate the hippocampal morphology; H&E staining, cresyl violet staining, and Golgi-Cox staining were performed on hippocampal sections. CA3 pyramidal neuron morphology and surviving neuron count (in CA3 region) were studied using H&E and cresyl violet stained sections. Dendritic arborization pattern of CA3 pyramidal neuron was investigated by concentric circle method. Progressive learning abilities were found to be decreased in RF-EMR exposed rats. Memory retention test performed 24 h after the last training revealed minor spatial memory deficit in RF-EMR exposed group. However, RF-EMR exposed rats exhibited poor spatial memory retention when tested 48 h after the final trial. Hirano bodies and Granulovacuolar bodies were absent in the CA3 pyramidal neurons of different groups studied. Nevertheless, RF-EMR exposure affected the viable cell count in dorsal hippocampal CA3 region. RF-EMR exposure influenced dendritic arborization pattern of both apical and basal dendritic trees in RF-EMR exposed rats. Structural changes found in the hippocampus of RF-EMR exposed rats could be one of the possible reasons for altered cognition.
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Copeland, D. D.; Talley, F. A.; Bigner, D. D.
1976-01-01
Groups of F-344 rats were inoculated with the Bratislava-77 strain of avian sarcoma virus (B-77 ASV) within 24 hours of birth, at 9 days of age, or between 97 and 119 days of age. Intracranial tumors developed in each age group. Multiple tumors with mixed histologic patterns developed in rats inoculated at 1 or 9 days of age. Solitary tumors with a uniform histologic pattern developed in rats inoculated as adults. On the basis of light and electron microscopic study, the majority of tumors in each age group were classified as astrocytomas and divided into either poorly differentiated, gemistocytic, pilocytic, or polymorphic varieties. The polymorphic astrocytomas were most common among neonatally inoculated rats, while the pilocytic astrocytomas were most common among rats inoculated as adults. Ultrastructural characteristics of astrocytes, including gap junctions and 7- to 9-nm filaments, were present in the majority of tumors in each age groups. Astrocytomas induced in adult rats were remarkable for the presence of extensive basement membrane alone the astrocytic cell surfaces. Intracytoplasmic virus-like particles (R particles) were common in the tumor cells. These virus-like particles are morphologically distinct from C-type B-77 ASV, and no morphologic evidence of C-type virus replication was observed in any of the tumors. Images Figure 16 Figure 17 Figure 1 Figure 2 Figure 18 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:179328
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Hormone-induced rat model of polycystic ovary syndrome: A systematic review.
Noroozzadeh, Mahsa; Behboudi-Gandevani, Samira; Zadeh-Vakili, Azita; Ramezani Tehrani, Fahimeh
2017-12-15
Despite polycystic ovary syndrome (PCOS) being one of the most common endocrine disorders affecting reproductive-aged women, the etiopathogenesis and mechanisms of this syndrome remain unclear. Considering the ethical limitations in human studies, animal models that reflect many features of PCOS are crucial resources to investigate this syndrome. We aimed to introduce the most suitable rat model of PCOS that closely mimics the endocrine, ovarian and metabolic disturbances of human PCOS phenotype, while maintaining normal reproductive system morphology in adulthood, in order to further more detailed investigations about PCOS. We searched Pubmed, Science direct, and Web of science between 1990 and 2016, for relevant English manuscripts, using keywords including the "Polycystic Ovary Syndrome AND Rat Model" to generate a subset of citations relevant to our research. Included were those articles that compared at least both ovarian histology or estrous cycle and reproductive hormonal profiles in hormone-induced rat model of PCOS and controls. Differences in the findings between hormone-induced PCOS rats appear to be a result of the degree of transplacental transfer of the steroid administered into the fetus, dose and type of hormone, route of administration and timing and duration of exposure. We conclude that prenatal hormone-induced rat model with a lower dose and shorter time of exposure during the critical period of fetal development that exhibits endocrine, ovarian and metabolic disturbances similar to PCOS in women, while maintaining normal reproductive system morphology in adulthood is more suitable than postnatal hormone-induced rat model to facilitate studies regarding PCOS. Copyright © 2017 Elsevier Inc. All rights reserved.
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Adamec, Robert; Hebert, Mark; Blundell, Jacqueline; Mervis, Ronald F.
2013-01-01
We investigated the neurobiological bases of variation in response to predator stress (PS). Sixteen days after treatment (PS or handling), rats were grouped according to anxiety in the elevated plus maze (EPM). Acoustic startle was also measured. We examined the structure of dendritic trees of basolateral amygdala (BLA) output neurons (stellate and pyramidal cells) and of dorsal hippocampal (DHC) dentate granule cells of less anxious (LA) and more (extremely) anxious (MA) stressed animals (PSLA and PSMA). Handled controls (HC) which were less anxious (HCLA) and spontaneously more anxious (HCMA) equivalently to predator stressed subgroups were also studied. Golgi analysis revealed BLA output neurons of HCMA rats exhibited longer, more branched dendrites with higher spine density than the other groups of rats, which did not differ. Finally, spine density of DHC granule cells was equally depressed in HCMA and PSMA rats relative to HCLA and PSLA rats. Total dendritic length of BLA pyramidal and stellate cells (positive predictor) and DHC spine density (negative predictor) together accounted for 96% of the variance of anxiety of handled rats. DHC spine density was a negative predictor of PSMA and PSLA anxiety, accounting for 70% of the variance. Data are discussed in the context of morphological differences as phenotypic markers of a genetic predisposition to anxiety in handled controls, and a possible genetic vulnerability to predator stress expressed as reduced spine density in the DHC. Significance of findings for animal models of anxiety and hyperarousal comorbidities of PTSD are discussed. PMID:21925210
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Dagnino-Subiabre, A; Terreros, G; Carmona-Fontaine, C; Zepeda, R; Orellana, J A; Díaz-Véliz, G; Mora, S; Aboitiz, F
2005-01-01
Chronic stress affects brain areas involved in learning and emotional responses. These alterations have been related with the development of cognitive deficits in major depression. The aim of this study was to determine the effect of chronic immobilization stress on the auditory and visual mesencephalic regions in the rat brain. We analyzed in Golgi preparations whether stress impairs the neuronal morphology of the inferior (auditory processing) and superior colliculi (visual processing). Afterward, we examined the effect of stress on acoustic and visual conditioning using an avoidance conditioning test. We found that stress induced dendritic atrophy in inferior colliculus neurons and did not affect neuronal morphology in the superior colliculus. Furthermore, stressed rats showed a stronger impairment in acoustic conditioning than in visual conditioning. Fifteen days post-stress the inferior colliculus neurons completely restored their dendritic structure, showing a high level of neural plasticity that is correlated with an improvement in acoustic learning. These results suggest that chronic stress has more deleterious effects in the subcortical auditory system than in the visual system and may affect the aversive system and fear-like behaviors. Our study opens a new approach to understand the pathophysiology of stress and stress-related disorders such as major depression.
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Whey versus soy protein diets and renal status in rats.
Aparicio, Virginia A; Nebot, Elena; Tassi, Mohamed; Camiletti-Moirón, Daniel; Sanchez-Gonzalez, Cristina; Porres, Jesús M; Aranda, Pilar
2014-09-01
Different dietary protein sources can promote different renal statuses. We examined the effects of whey protein (WP) and soy protein (SP) intake on plasma, urinary, and morphological renal parameters in rats. One hundred and twenty Wistar rats were randomly distributed into 2 experimental groups fed with either WP or SP diets over 12 weeks. These diets were based on commercial WP or SP isolates. The urinary calcium content was higher in the WP diet compared to the SP diet group (P<.001) whereas the urinary citrate level was lower (P<.001). The urinary pH was more acidic in the WP diet group compared to the SP diet group (P<.001); however, no differences were observed between the groups for any of the renal morphological parameters analyzed (all, P>.05) or other plasma renal markers such as albumin or urea concentrations. The increase of acid and urinary calcium and the lower urinary citrate level observed in the WP diet group could increase the incidence of nephrolithiasis compared to the SP diet group. Despite the WP showed poorer acid-base profile, no significant morphological renal changes were observed. These results suggest that the use of SP instead of WP appears to promote a more alkaline plasma and urinary profile, with their consequent renal advantages.
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Yashchenko, S G; Rybalko, S Yu
Pineal gland is one of the most important components of homeostasis - the supporting system of the body. It participates in the launch of stress responses, restriction of their development, prevention of adverse effects on the body. There was proved an impact of electromagnetic radiation on the epiphysis. However, morphological changes in the epiphysis under exposure to electromagnetic radiation of modern communication devices are studied not sufficiently. For the time present the population is daily exposed to electromagnetic radiation, including local irradiation on the brain. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. These date determined the task of this research - the study of the structure of rat pineal gland under the exposure to electromagnetic radiation from personal computers and mobile phones. Performed transmission electron microscopy revealed signs of degeneration of dark and light pinealocytes. These signs were manifested in the development of a complex of general and specific morphological changes. There was revealed the appearance of signs of aging and depletion transmission electron microscopy both in light and dark pinealocytes. These signs were manifested in the accumulation of lipofuscin granules and electron-dense "brain sand", the disappearance of nucleoli, cytoplasm vacuolization and mitochondrial cristae enlightenment.
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Kawabe, Yoshihiro; Mizobe, Kenich; Bando, Yasuhiko; Sakiyama, Koji; Taira, Fuyoko; Tomomura, Akito; Araki, Hisao; Amano, Osamu
2016-12-28
Myoepithelial cells (MECs) exist on the basal surface of acini in major exocrine glands, include myofilaments and various constructive proteins, and share characteristics with smooth muscle and epithelial cells. MECs project several ramified processes to invest acini, and possibly contract to compress acini to support the secretion by the glandular cells. However, the functional roles of MECs in salivary secretion are still unclear. We investigated morphological changes in immunostained MECs using the anti-α-smooth muscle actin (αSMA) antibody in operated or non-operated contralateral (NC) submandibular glands after partial or total resection. Furthermore, we investigated and discuss other salivary glands of rats. MECs in the parotid, sublingual and submandibular gland of adult rats exhibited different shapes and localizations. After surgery, in both operated and NC glands, the number of MECs and αSMA-immunopositive areas increased significantly. Three-dimensional analysis using a confocal laser-scanning microscope revealed that substantial and significant enhancement became evident in the number, length, and thickness of MEC-processes covering acini of the operated and NC submandibular glands. The preset findings indicate that MECs alter the morphology of their processes in operated and NC glands after surgery of the partial or total resection. It is suggested that MECs promote salivary secretion using elongated, thickened, and more ramified processes.
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Halevas, E; Nday, C M; Salifoglou, A
2016-10-01
Morphological alterations compromising inter-neuronal connectivity may be directly linked to learning-memory deficits in Central Nervous System neurodegenerative processes. Cu(II)-mediated oxidative stress plays a pivotal role in regulating redox reactions generating reactive oxygen species (ROS) and reactive nitrogen species (RNS), known contributors to Alzheimer's disease (AD) pathology. The antioxidant properties of flavonoid catechin have been well-documented in neurodegenerative processes. However, the impact that catechin encapsulation in nanoparticles may have on neuronal survival and morphological lesions has been poorly demonstrated. To investigate potential effects of nano-encapsulated catechin on neuronal survival and morphological aberrations in primary rat hippocampal neurons, poly(ethyleneglycol) (PEG) and cetyltrimethylammonium bromide (CTAB)-modified silica nanoparticles were synthesized. Catechin was loaded on silica nanoparticles in a concentration-dependent fashion, and release studies were carried out. Further physicochemical characterization of the new nano-materials included elemental analysis, particle size, z-potential, FT-IR, Brunauer-Emmett-Teller (BET), thermogravimetric (TGA), and scanning electron microscopy (SEM) analysis in order to optimize material composition linked to the delivery of loaded catechin in the hippocampal cellular milieu. The findings reveal that, under Cu(II)-induced oxidative stress, the loading ability of the PEGylated/CTAB silica nanoparticles was concentration-dependent, based on their catechin release profile. The overall bio-activity profile of the new hybrid nanoparticles a) denoted their enhanced protective activity against oxidative stress and hippocampal cell survival compared to previously reported quercetin, b) revealed that morphological lesions affecting neuronal integrity can be counterbalanced at high copper concentrations, and c) warrants in-depth perusal of molecular events underlying neuronal function and degeneration, collectively linked to preventive nanotechnology in neurodegeneration. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Bucharskaya, A. B.; Pakhomy, S. S.; Zlobina, O. V.; Maslyakova, G. N.; Matveeva, O. V.; Bugaeva, I. O.; Navolokin, N. A.; Khlebtsov, B. N.; Bogatyrev, V. A.; Khlebtsov, N. G.; Tuchin, V. V.
2016-03-01
The wide application of nanotechnologies in medicine requires the careful study of various aspects of their potential safety. The effects of prolonged peroral administration of gold nanoparticles on morphological changes in lymphoid organs and indicators of peripheral blood of laboratory animals were investigated in experiment. The gold nanospheres functionalized with thiolated polyethylene glycol sizes 2, 15 and 50 nm were administered orally for 15 days to outbred white rats at a dosage of 190 μg/kg of animal body weight. The standard histological and hematological staining were used for morphological study of lymphoid organs and bone marrow smears. The size-dependent decrease of the number of neutrophils and lymphocytes was noted in the study of peripheral blood, especially pronounced after administration of gold nanoparticles with size of 50 nm. The stimulation of myelocytic germ of hematopoiesis was recorded at morphological study of the bone marrow. The signs of strengthening of the processes of differentiation and maturation of cellular elements were found in lymph nodes, which were showed as the increasing number of immunoblasts and large lymphocytes. The quantitative changes of cellular component morphology of lymphoid organs due to activation of migration, proliferation and differentiation of immune cells indicate the presence of immunostimulation effect of gold nanoparticles.
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Tsai, Tsung-Chang; Huang, Hui-Pei; Chang, Yun-Ching; Wang, Chau-Jong
2014-02-19
A previous study reported that anthocyanins from roselle (Hibiscus sabdariffa L.) showed significant anticancer activity in human promyelocytic leukemia cells. To explore the antitumor effect of anthocyanin, a roselle bioactive polyphenol in a rat model of chemical-induced leukemia was assayed. Anthocyanin extract of roselle (Hibiscus anthocyanins, HAs) was supplemented in the diet (0.1 and 0.2%). This study was carried out to evaluate the protective effect of HAs on N-nitrosomethylurea (NMU)-induced leukemia of rats. The study employed male Sprague-Dawley rats (n = 48), and leukemia was induced by intravenous injection of 35 mg kg(-1) body weight of NMU dissolved in physiologic saline solution. The rats were divided into four groups (n = 12): control, NMU only, and HAs groups that received different doses of HAs (0.1 and 0.2%) daily, orally, after NMU injection. After 220 days, the animals were killed, and the following parameters were assessed: morphological observation, hematology examination, histopathological assessment, and biochemical assay. When compared with the NMU-only group, HAs significantly prevented loss of organ weight and ameliorated the impairment of morphology, hematology, and histopathology. Treatment with HAs caused reduction in the levels of AST, ALT, uric acid, and MPO. Also, the results showed that oral administration of HAs (0.2%) remarkably inhibited progression of NMU-induced leukemia by approximately 33.3% in rats. This is the first report to demonstrate that the sequential administration of HAs followed by NMU resulted in an antileukemic activity in vivo.
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MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis.
Zeng, LiHua; Ji, XiTuan; Zhang, YanJun; Miao, Xia; Zou, ChangXu; Lang, HaiYang; Zhang, Jie; Li, YuRong; Wang, XiaoWu; Qi, HongXing; Ren, DongQin; Guo, GuoZhen
2011-12-01
Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc-superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6 h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression.
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Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory
2009-01-01
Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017
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Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio
2015-01-01
Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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Light, Jacob G; Fransen, James W; Adekunle, Adewumi N; Adkins, Alice; Pangeni, Gobinda; Loudin, James; Mathieson, Keith; Palanker, Daniel V; McCall, Maureen A; Pardue, Machelle T
2014-11-01
Photovoltaic arrays (PVA) implanted into the subretinal space of patients with retinitis pigmentosa (RP) are designed to electrically stimulate the remaining inner retinal circuitry in response to incident light, thereby recreating a visual signal when photoreceptor function declines or is lost. Preservation of inner retinal circuitry is critical to the fidelity of this transmitted signal to ganglion cells and beyond to higher visual targets. Post-implantation loss of retinal interneurons or excessive glial scarring could diminish and/or eliminate PVA-evoked signal transmission. As such, assessing the morphology of the inner retina in RP animal models with subretinal PVAs is an important step in defining biocompatibility and predicting success of signal transmission. In this study, we used immunohistochemical methods to qualitatively and quantitatively compare inner retinal morphology after the implantation of a PVA in two RP models: the Royal College of Surgeons (RCS) or transgenic S334ter-line 3 (S334ter-3) rhodopsin mutant rat. Two PVA designs were compared. In the RCS rat, we implanted devices in the subretinal space at 4 weeks of age and histologically examined them at 8 weeks of age and found inner retinal morphology preservation with both PVA devices. In the S334ter-3 rat, we implanted devices at 6-12 weeks of age and again, inner retinal morphology was generally preserved with either PVA design 16-26 weeks post-implantation. Specifically, the length of rod bipolar cells and numbers of cholinergic amacrine cells were maintained along with their characteristic inner plexiform lamination patterns. Throughout the implanted retinas we found nonspecific glial reaction, but none showed additional glial scarring at the implant site. Our results indicate that subretinally implanted PVAs are well-tolerated in rodent RP models and that the inner retinal circuitry is preserved, consistent with our published results showing implant-evoked signal transmission. Published by Elsevier Ltd.
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Characterization of Two New Records of Zygomycete Species Belonging to Undiscovered Taxa in Korea.
Nguyen, Thi Thuong Thuong; Lee, Seo Hee; Bae, Sarah; Jeon, Sun Jeong; Mun, Hye Yeon; Lee, Hyang Burm
2016-03-01
During a biodiversity survey of undiscovered taxa in Korea, two zygomycetous fungal strains were isolated. The first strain, EML-FSDY6-1 was isolated from a soil sample collected at Dokdo Island in the East Sea of Korea in 2013, and the second strain, EML-DG-NH3-1 was isolated from a rat dung sample collected at Chonnam National University garden, Gwangju, Korea in 2014. Based on the morphological characteristics and phylogenetic analysis of the internal transcribed spacer, 18S and 28S rDNA, actin and translation elongation factor-1α genes. EML-FSDY6-1 and EML-DG-NH3-1 isolates were confirmed as zygomycete species, Absidia pseudocylindrospora and Absidia glauca, respectively. Neither species has previously been described in Korea.
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Characterization of Two New Records of Zygomycete Species Belonging to Undiscovered Taxa in Korea
Nguyen, Thi Thuong Thuong; Lee, Seo Hee; Bae, Sarah; Jeon, Sun Jeong; Mun, Hye Yeon
2016-01-01
During a biodiversity survey of undiscovered taxa in Korea, two zygomycetous fungal strains were isolated. The first strain, EML-FSDY6-1 was isolated from a soil sample collected at Dokdo Island in the East Sea of Korea in 2013, and the second strain, EML-DG-NH3-1 was isolated from a rat dung sample collected at Chonnam National University garden, Gwangju, Korea in 2014. Based on the morphological characteristics and phylogenetic analysis of the internal transcribed spacer, 18S and 28S rDNA, actin and translation elongation factor-1α genes. EML-FSDY6-1 and EML-DG-NH3-1 isolates were confirmed as zygomycete species, Absidia pseudocylindrospora and Absidia glauca, respectively. Neither species has previously been described in Korea. PMID:27103852
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Repeated dose 28-days oral toxicity study of Carica papaya L. leaf extract in Sprague Dawley rats.
Afzan, Adlin; Abdullah, Noor Rain; Halim, Siti Zaleha; Rashid, Badrul Amini; Semail, Raja Hazlini Raja; Abdullah, Noordini; Jantan, Ibrahim; Muhammad, Hussin; Ismail, Zakiah
2012-04-10
Carica papaya L. leaves have been used in ethnomedicine for the treatment of fevers and cancers. Despite its benefits, very few studies on their potential toxicity have been described. The aim of the present study was to characterize the chemical composition of the leaf extract from 'Sekaki' C. papaya cultivar by UPLC-TripleTOF-ESI-MS and to investigate the sub-acute oral toxicity in Sprague Dawley rats at doses of 0.01, 0.14 and 2 g/kg by examining the general behavior, clinical signs, hematological parameters, serum biochemistry and histopathology changes. A total of twelve compounds consisting of one piperidine alkaloid, two organic acids, six malic acid derivatives, and four flavonol glycosides were characterized or tentatively identified in the C. papaya leaf extract. In the sub-acute study, the C. papaya extract did not cause mortality nor were treatment-related changes in body weight, food intake, water level, and hematological parameters observed between treatment and control groups. Some biochemical parameters such as the total protein, HDL-cholesterol, AST, ALT and ALP were elevated in a non-dose dependent manner. Histopathological examination of all organs including liver did not reveal morphological alteration. Other parameters showed non-significant differences between treatment and control groups. The present results suggest that C. papaya leaf extract at a dose up to fourteen times the levels employed in practical use in traditional medicine in Malaysia could be considered safe as a medicinal agent.
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Mechanisms of Cdc42-mediated rat MSC differentiation on micro/nano-textured topography.
Li, Guangwen; Song, Yanyan; Shi, Mengqi; Du, Yuanhong; Wang, Wei; Zhang, Yumei
2017-02-01
Micro/nano-textured titanium surface topography promotes osteoblast differentiation and the Wnt/β-catenin signaling pathway. However, the response of rat bone mesenchymal stem cells (MSCs) to micro/nano-textured topography, and the underlying mechanisms of its effects, are not well understood. We hypothesized that cell division cycle 42 protein (Cdc42), a key member of the Rho GTPases family, may regulate rat MSCs morphology and osteogenic differentiation by micro/nano-textured topography, and that crosstalk between Cdc42 and Wnt/β-catenin is the underlying mechanism. To confirm the hypothesis, we first tested rat MSCs' morphology, cytoskeleton, and osteogenic differentiation on micro/nano-textured topography. We then examined the cells' Wnt pathway and Cdc42 signaling activity. The results show that micro/nano-textured topography enhances MSCs' osteogenic differentiation. In addition, the cells' morphology and cytoskeletal reorganization were dramatically different on smooth surfaces and micropitted/nanotubular topography. Ligands of the canonical Wnt pathway, as well as accumulation of β-catenin in the nucleus, were up-regulated by micro/nano-textured topography. Cdc42 protein expression was markedly increased under these conditions; conversely, Cdc42 silencing significantly depressed the enhancement of MSCs osteogenic differentiation by micro/nano-textured topography. Moreover, Cdc42si attenuated p-GSK3β activation and resulted in β-catenin cytoplasmic degradation on the micro/nano-textured topography. Our results indicate that Cdc42 is a key modulator of rat MSCs morphology and cytoskeletal reorganization, and that crosstalk between Cdc42 and Wnt/β-catenin signaling though GSK3β regulates MSCs osteogenic differentiation by implant topographical cues. Topographical modification at micro- and nanoscale is widely applied to enhance the tissue integration properties of biomaterials. However, the response of bone mesenchymal stem cells (MSCs) to the micro/nano-textured topography and the underlying mechanisms are not well understood. This study shows that the micropitted/nanotubular hierarchical topography produced by etching and anodic oxidation treatment drives fusiform cell morphology, cytoskeletal reorganization as well as better MSCs osteogenic differentiation. The cross-talk between Cdc42 pathway and Wnt/β-catenin pathway though GSK3β modulates the osteoinductive effect of the micro/nano-textured topography on MSCs. This finding sheds light on a novel mechanism involved in micro/nano-textured surface-mediated MSCs osteogenic differentiation and is a major step in the development of new surface modifications aiming to accelerate and enhance the process of osseointegration. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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The organization of the whisker representation within the neocortex of the rat is dependent on an intact periphery during development. To further investigate how alterations in the cortical map arise the authors examined the organization of thalamocortical afferents to the whiske...
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Central effects of ghrelin on the adrenal cortex: a morphological and hormonal study.
Milosević, Verica Lj; Stevanović, Darko M; Nesić, Dejan M; Sosić-Jurjević, Branka T; Ajdzanović, Vladimir Z; Starcević, Vesna P; Severs, Walter B
2010-06-01
Ghrelin, a growth hormone secretagogue that exerts an important role in appetite and weight regulation, participates in the activation of the hypothalamo-pituitary-adrenal (HPA) axis. Male Wistar rats (5/group) received daily for 5 days, via an ICV (intracerebroventricular) cannula, 5 microl phosphate buffered saline with or without 1 microg of rat ghrelin. Two hours after the last injection, blood and adrenal glands were collected from decapitated rats for blood hormone analyses and histologic and morphometric processing. Ghrelin treatment resulted in increased (p<0.05) body weight (13%), absolute whole adrenal gland weight (18%) and whole adrenal gland volume (20%). The absolute volumes of the entire adrenal cortex, ZG, ZF, and ZR also increased (p<0.05) after ghrelin by 20%, 21%, 21% and 11%, respectively. Ghrelin-treated rats had elevated (p<0.05) blood concentrations of ACTH, aldosterone and corticosterone (68%, 32% and 67%, respectively). The data clearly provide both morphological and hormonal status that ghrelin acts centrally to exert a global stimulatory effect on the adrenal cortex. Clarifying of the ghrelin precise role in the multiple networks affecting the stress hormone release, besides its well known energy and metabolic unbalance effects, remains a very important research goal.
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Benvegnu, Dalila M; Barcelos, Raquel C S; Roversi, Katiane; Boufleur, Nardelli; Pase, Camila S; Trevizol, Fabiola; Segat, Hecson J; Dias, Verônica T; Dolci, Geisa S; Antoniazzi, Caren T D; Reckziegel, Patricia; Lima, Fernanda; de Lima, Luiz A R; de Carvalho, Leandro M; da Silva Junior, Valdemiro A; Burger, Marilise E
2013-01-01
This study investigated the protective effect of pecan nut (Carya illinoensis) shell aqueous extract (AE) on the oxidative and morphological status of rat testis treated with cyclophosphamide (CP). Wistar rats received water or AE (5%) ad libitum for 37 days. On day 30, half of each group received a single intraperitoneal administration of vehicle or CP 200 mg/kg. After 7 days, the animals were killed and their testis removed. Rats treated with CP presented reduced levels of lactate dehydrogenase, vitamin C, and gluthatione, as well as decreased catalase activity, increased lipid peroxidation levels and superoxide dismutase activity, no alteration in carbonyl protein levels, and a loss of morphological testicular integrity. In contrast, cotreatment with pecan shell AE totally prevented the decrease of lactate dehydrogenase and vitamin C levels and catalase activity and partially prevented the depletion of gluthatione levels. Moreover, it totally prevented the increase in superoxide dismutase activity and lipid peroxidation levels and maintained testicular integrity. These findings show the protective role of pecan shell AE in CP-induced testicular toxicity. The use of this phytotherapy may be considered to minimize deleterious effects related to this chemotherapy.
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Cook, T L; Beppu, W J; Hitt, B A; Kosek, J C; Mazze, R I
1975-01-01
Twenty-five 5-month-old male Fischer-344 rats were randomly divided into 5 groups: Group I, no anesthesia; Group II, 1.4 precent sevoflurane for 2 hours; Group III, 0.1 percent phenobarbital, ad lib, in drinking water for 7 days; followed by 1.4 percent sevoflurane for 2 hours; Group IV, 0.25 percent methoxyflurane, 1 hour; Group V, phenobarbital in water as in Group III, followed by methoxyflurane as in group IV. Pre- and postanesthetic serum and urinary osmolality, Na+, K+, urea nitrogen (BUN), inorganic fluoride (F-) levels, and 24-hour urine volume were measured. Kidney tissue was obtained for examination by light and electron microscopy. Sevoflurane was metabolized to F- to a lesser extent than was methoxyflurane; treatment with phenobarbital-sevoflurane doubled urinary F- excretion, resulting in a value similar to that seen after methoxyflurane alone. There was no functional or morphologic evidence of renal abnormalities in either group of rats anesthetized with sevoflurane. Methoxyflurane dosage was sufficiently low that renal abnormalities did not occur except in rats treated also with phenobarbital; these animals developed polyuria and the morphologic lesion typically associated with F--induced nephrotoxicity.
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Nudmamud-Thanoi, Sutisa; Thanoi, Samur
2012-08-01
Pseudoephedrine, an over-the-counter drug, is commonly used for the treatments of asthma, nasal congestion, and obesity. Furthermore, it can be used as a psychostimulant drug if taken in large doses; however, there have been no reports on its effects on reproduction. The aim of this study was therefore to investigate the effects of pseudoephedrine administration on sperm morphology, sperm concentration and apoptotic activity in the rat testis. Rats were administered intraperitoneally (IP) with pseudoephedrine at 120 mg/kg for the acute group and 80 mg/kg, IP, once daily for 15 days for the chronic group, while a control group was treated with vehicle. The percentages of normal sperm morphology were significantly decreased in both acute and chronic groups when compared with controls while the total sperm count was significantly decreased in the acute group. Apoptotic activities were increased significantly in both pseudoephedrine-treated groups. The results indicate that pseudoephedrine can induce sperm abnormalities, decrease sperm numbers and increase apoptotic activity in the testis of rats if taken at high doses. The results of this study suggest that the users of pseudoephedrine in medical treatments need to be aware of its potential toxicity involving spermatogenesis.
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Low and high dietary folic acid levels perturb postnatal cerebellar morphology in growing rats.
Partearroyo, Teresa; Pérez-Miguelsanz, Juliana; Peña-Melián, Ángel; Maestro-de-Las-Casas, Carmen; Úbeda, Natalia; Varela-Moreiras, Gregorio
2016-06-01
The brain is particularly sensitive to folate metabolic disturbances, because methyl groups are critical for brain functions. This study aimed to investigate the effects of different dietary levels of folic acid (FA) on postnatal cerebellar morphology, including the architecture and organisation of the various layers. A total of forty male OFA rats (a Sprague-Dawley strain), 5 weeks old, were classified into the following four dietary groups: FA deficient (0 mg/kg FA); FA supplemented (8 mg/kg FA); FA supra-supplemented (40 mg/kg FA); and control (2 mg/kg FA) (all n 10 per group). Rats were fed ad libitum for 30 d. The cerebellum was quickly removed and processed for histological and immunohistochemical analysis. Slides were immunostained for glial fibrillary acidic protein (to label Bergmann glia), calbindin (to label Purkinje cells) and NeuN (to label post-mitotic neurons). Microscopic analysis revealed two types of defect: partial disappearance of fissures and/or neuronal ectopia, primarily in supra-supplemented animals (incidence of 80 %, P≤0·01), but also in deficient and supplemented groups (incidence of 40 %, P≤0·05), compared with control animals. The primary fissure was predominantly affected, sometimes accompanied by defects in the secondary fissure. Our findings show that growing rats fed an FA-modified diet, including both deficient and supplemented diets, have an increased risk of disturbances in cerebellar corticogenesis. Defects caused by these diets may have functional consequences in later life. The present study is the first to demonstrate that cerebellar morphological defects can arise from deficient, as well as high, FA levels in the diet.
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Del Cerro, M C R; Ortega, E; Gómez, F; Segovia, S; Pérez-Laso, C
2015-07-01
Environmental prenatal stress (EPS) has effects on fetuses that are long-lasting, altering their hormone levels, brain morphology and behavior when they reach maturity. In previous research, we demonstrated that EPS affects the expression of induced maternal behavior (MB), the neuroendocrine system, and morphology of the sexually dimorphic accessory olfactory bulb (AOB) involved in reproductive behavior patterns. The bed nucleus of the accessory olfactory tract (BAOT) is another vomeronasal (VN) structure that plays an inhibitory role in rats in the expression of induced maternal behavior in female and male virgins. In the present study, we have ascertained whether the behavioral, neuroendocrine, and neuromorphological alterations of the AOB found after EPS also appear in the BAOT. After applying EPS to pregnant rats during the late gestational period, in their female offspring at maturity we tested induced maternal behavior, BAOT morphology and plasma levels of testosterone (T), estradiol (E2), progesterone (P), adrenocorticotropic hormone (ACTH) and corticosterone (Cpd B). EPS: a) affected the induction of MB, showed a male-like pattern of care for pups, b) elevated plasma levels of Cpd B and reduced E2 in comparison with the controls, and c) significantly increased the number of BAOT neurons compared to the control females and comparable to the control male group. These findings provide further evidence that stress applied to pregnant rats produces long-lasting behavioral, endocrine and neuroanatomical alterations in the female offspring that are evident when they become mature. Copyright © 2015 Elsevier Inc. All rights reserved.
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[Protective effect of arctigenin in GK rats combined with hypertension macroangiopathy].
Feng, Qin; Sun, Bao-cun; Xia, Wen-kai
2015-03-01
To study the protective effect of Arctigenin in goto-kakizaki (GK) rats combined with hypertension macroangiopathy. Six-week-old GK rats were divided randomly according to blood glucose level into four groups: the model group and low, middle and high dose arctigenin groups (12.5, 25, 50 mg x kg(-1)), with Wistar rats as the normal group. All of GK rats were given high-glucose and high-fat diet. After 16 weeks, GK rats were orally administrated with 10 mg x kg(-1) x d(-1) N-Ω-nitro-L-arginine methyl ester for eight weeks. During the modeling, all of arctigenin groups were orally administrated with different dose of arctigenin twice a day; The model group and the normal group were given solvents. At the beginning, mid-term and end of the experiment, blood glucose was measured. At the end of the experiment, efforts were made to detect blood pressure, collect abdominal aortic blood after anesthesia, fix thoracic aorta after bloodletting to make paraffin sections, observe morphological characteristics and detect the expression of VEGF by immunohistochemistry. According to the results, the blood glucose rose in all GK rats, with no significant difference between the drug group and the model group. At the end of the experiment, the blood pressure significantly increased in GK rats, indicating that Arctigenin could notably reduce the blood pressure in GK rats in a dose-dependent manner. The blood routine test showed increases in both the total white blood cell count and differential blood count, MPV and PDW, abnormal blood platelet parameters and decrease in PLT in GK rats, suggesting that Arctigenin could remarkably reduce the total white blood cell count and differential blood count, MPV and PDW. The thoracic aortic morphological observation revealed obvious endangium lesions in GK rats, demonstrating that Arctigenin could ameliorate the lesion extent. VEGF immumohistochemical staining showed a higher VEGF expression in the model group but lower expression in Arctigenin groups. In conclusion, Arctigenin had a protective effect on aorta in GK rats. Its mechanism may be related to blood pressure lowering, anti-inflammation, improvement in blood platelet function and reduction of VEGF expression.
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Adrenergic nerve fibres and mast cells: correlation in rat thymus.
Artico, Marco; Cavallotti, Carlo; Cavallotti, Daniela
2002-10-21
The interactions between adrenergic nerve fibres and mast cells (MCs) were studied in the thymus of adult and old rats by morphological methods and by quantitative analysis of images (QAIs). The whole thymus was drawn in adult (12 months old) rats: normal, sympathectomized or electrostimulated. Thymuses from the above-mentioned animals were weighed, measured and dissected. Thymic slices were stained with eosin orange for detection of microanatomical details and with Bodian's method for identification of the whole nerve fibres. Thymic MCs were stained with Astrablau. Histofluorescence microscopy was used for staining of adrenergic nerve fibres. Finally, all morphological results were submitted to the QAIs and statistical analysis of data. Our results suggest that after surgical sympathectomy, the greater part of adrenergic nerve fibres disappear while related MCs appear to show less evident fluorescence and few granules. On the contrary, electrostimulation of the cervical superior ganglion induced an increase in the fluorescence of adrenergic nerve fibres and of related MCs.
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Regulation of Blood Volume During Spaceflight
NASA Technical Reports Server (NTRS)
Alfrey, Clarence P.
1997-01-01
The effects of spaceflight on erythropoiesis and blood volume in the rat were studied during the 14-day NASA Spacelab Life Sciences 2 (SLS-2) Shuttle mission. Measurements included red blood cell mass (RBCM), plasma volume (PV), iron utilization and iron utilization in response to an injection of erythropoietin. Red blood cell (RBC) survival, splenic sequestration and erythrocyte morphology were also evaluated. At landing, the RBCM adjusted for body weight was significantly lower in the flight animals than in the ground controls. While the PV was also decreased, the change was not statistically significant. Incorporation of iron into circulating RBCs was normal when measured after five days of spaceflight and the rat responded normally to the single in-flight injection of erythropoietin. No change in RBC morphology could be attributed to spaceflight. A normal survival was found for the RBC population that was represented by Cr-51 labeled RBCS. These results demonstrate that rats, like humans, return from spaceflight with a decreased RBCM and total blood volume.
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Damasceno, Débora Cristina; Sinzato, Yuri Karen; Ribeiro, Viviane Maria; Rudge, Marilza Vieira Cunha; Calderon, Iracema Mattos Paranhos
2015-01-01
The potential benefits and risks of physical exercise on fetal development during pregnancy remain unclear. The aim was to analyze maternal oxidative stress status and the placental morphometry to relate to intrauterine growth restriction (IUGR) from diabetic female rats submitted to swimming program after embryonic implantation. Pregnant Wistar rats were distributed into 4 groups (11 animals/group): control—nondiabetic sedentary rats, control exercised—nondiabetic exercised rats, diabetic—diabetic sedentary rats, and diabetic exercised—diabetic exercised rats. A swimming program was used as an exercise model. At the end of pregnancy, the maternal oxidative stress status, placental morphology, and fetal weight were analyzed. The swimming program was not efficient to reduce the hyperglycemia-induced oxidative stress. This fact impaired placental development, resulting in altered blood flow and energy reserves, which contributed to a deficient exchange of nutrients and oxygen for the fetal development, leading to IUGR. PMID:25361551
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Stimulation of Mucosal Mast Cell Growth in Normal and Nude Rat Bone Marrow Cultures
NASA Astrophysics Data System (ADS)
Haig, David M.; McMenamin, Christine; Gunneberg, Christian; Woodbury, Richard; Jarrett, Ellen E. E.
1983-07-01
Mast cells with the morphological and biochemical properties of mucosal mast cells (MMC) appear and proliferate to form the predominant cell type in rat bone marrow cultures stimulated with factors from antigen- or mitogen-activated lymphocytes. Conditioned media causing a selective proliferation of MMC were derived from mesenteric lymph node cells of Nippostrongylus brasiliensis-infected rats restimulated in vitro with specific antigen or from normal or infected rat mesenteric lymph node cells stimulated with concanavalin A. MMC growth factor is not produced by T-cell-depleted mesenteric lymph node cells or by the mesenteric lymph node cells of athymic rats. By contrast, MMC precursors are present in the bone marrow of athymic rats and are normally receptive to the growth factor produced by the lymphocytes of thymus-intact rats. The thymus dependence of MMC hyperplasia is thus based on the requirement of a thymus-independent precursor for a T-cell-derived growth promoter.
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Zinc deficiency during growth: influence on renal function and morphology.
Tomat, Analía Lorena; Costa, María Angeles; Girgulsky, Luciana Carolina; Veiras, Luciana; Weisstaub, Adriana Ruth; Inserra, Felipe; Balaszczuk, Ana María; Arranz, Cristina Teresa
2007-03-13
This study was designed to investigate the effects of moderate zinc deficiency during growth on renal morphology and function in adult life. Weaned male Wistar rats were divided into two groups and fed either a moderately zinc-deficient diet (zinc: 8 mg/kg, n=12) or a control diet (zinc: 30 mg/kg, n=12) for 60 days. We evaluated: renal parameters, NADPH-diaphorase and nitric oxide synthase activity in kidney, renal morphology and apoptotic cells in renal cortex. Zinc-deficient rats showed a decrease in glomerular filtration rate and no changes in sodium and potassium urinary excretion. Zinc deficiency decreased NADPH diaphorase activity in glomeruli and tubular segment of nephrons, and reduced activity of nitric oxide synthase in the renal medulla and cortex, showing that zinc plays an important role in preservation of the renal nitric oxide system. A reduction in nephron number, glomerular capillary area and number of glomerular nuclei in cortical and juxtamedullary areas was observed in zinc deficient kidneys. Sirius red staining and immunostaining for alpha-smooth muscle-actin and collagen III showed no signs of fibrosis in the renal cortex and medulla. An increase in the number of apoptotic cells in distal tubules and cortical collecting ducts neighboring glomeruli and, to a lesser extent, in the glomeruli was observed in zinc deficient rats. The major finding of our study is the emergence of moderate zinc deficiency during growth as a potential nutritional factor related to abnormalities in renal morphology and function that facilitates the development of cardiovascular and renal diseases in adult life.
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Wu, Guo-Hao; Chen, Ji; Li, Hang; Wu, Zhao-Han
2006-09-01
To investigate the effects of glucagon-like peptide 2 (GLP-2) on the morphology and functional adaptation of the residual small bowel in rat model of short bowel syndrome. Twenty rats with 75% of the midjejunoileum removed were randomly divided into two groups, and received intra-peritoneal injection of GLP-2(250 micro*gd*kg-1*d-1) or subcutaneous injection saline(0.5 ml, twice one day) after operation. On postoperative day 6, the morphological changes of the residual jejunum and ileum, the expression of proliferating cell nuclear antigen(PCNA), and the mRNA expressions of Na-D-glucose cotransporters (SGLT1) and peptide cotransporters (PEPT1) were determined. The intestinal glucose absorption data per unit length as well as per unit weight of ileum were measured by in vivo circulatory perfusion experiment. The morphological parameters of the residual gut such as the thickness of mucosa, height of villus, depth of crypt, and PCNA positive index were significantly higher, while the apoptosis rate per unit of mucosal square was significantly lower in GLP-2 treatment group than those in the control group. The expressions of mRNA SGTLl and PEPT1 in the residual ileum were significantly higher than those in the control group. There was no significant difference in glucose absorption rate per gram of mucosal wet weight between the two groups (P > 0.05). GLP-2 could improve morphological and functional adaptation of the residual small bowel by stimulating enterocyte proliferation and decreasing enterocyte apoptosis in short bowel syndrome.
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Baskaran, Xavierravi; Geo Vigila, Antony Varuvel; Parimelazhagan, Thangaraj; Muralidhara-Rao, Doulathabad; Zhang, Shouzhou
2016-01-01
The objective of the study was to characterize silver nanoparticles (Ag-NPs) and their bioactivities in early tracheophytes (Pteridophyta). Aqueous leaf extract of a critically endangered fern, Pteris tripartita Sw., was used for one-step green synthesis of Ag-NPs. The biosynthesized Ag-NPs were characterized using ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, and high-resolution transmission electron microscopy. Morphologically, the Ag-NPs showed hexagonal, spherical, and rod-shaped structures. Size distributions of Ag-NPs, calculated using Scherrer’s formula, showed an average size of 32 nm. Ag-NPs were studied for in vitro antioxidant, antimicrobial, and in vivo anti-inflammatory activities. Ag-NPs exhibited significant anti-inflammatory activity in carrageenan-induced paw volume tests performed in female Wistar albino rats. Furthermore, Ag-NPs showed significant antimicrobial activity against 12 different microorganisms in three different assays (disk diffusion, time course growth, and minimum inhibitory concentration). This study reports that colloidal Ag-NPs can be synthesized by simple, nonhazardous methods, and that biosynthesized Ag-NPs have significant therapeutic properties. PMID:27895478
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Portable image analysis system for characterizing aggregate morphology.
DOT National Transportation Integrated Search
2008-01-01
In the last decade, the application of image-based evaluation of particle shape, angularity and texture has been widely researched to characterize aggregate morphology. These efforts have been driven by the knowledge that the morphologic characterist...
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Tsujikawa, T; Bamba, T; Hosoda, S
1990-06-01
This study was undertaken to evaluate the effect of epidermal growth factor (EGF) on the morphological changes and polyamine metabolism in the atrophic small intestinal mucosa of rats caused by feeding elemental diet (ED; Elental, Ajinomoto, Tokyo) for several weeks. Four-week-old Wistar male rats were given ad libitum ED (1 kcal/ml) for 4 weeks. The body weight increased to the same extent as the control group fed a pellet diet. However, the small intestine became atrophic: the mucosal wet weight of the jejunum decreased to 70%, while that of the ileum decreased to 60%. EGF (10 micrograms/kg) was subcutaneously injected into these rats every 8 hours. Ornithine decarboxylase (ODC) activities of the jejunal and ileal mucosa rose within 12 hours of the initial EGF administration. Mucosal DNA specific activities tended to increase. Next, EGF (30 micrograms/kg/day) was intraperitoneally administered with a Mini-osmotic pump for one week. The wet weight, protein and DNA contents of the ileal mucosa increased significantly compared with those of the saline administered controls, while the crypt cell production rate (CCPR) also increased. Histologically, increases in both villus height and crypt depth were confirmed. These findings indicate that EGF causes mucosal proliferation through polyamine metabolism even in the atrophic small intestine of mature rats after ED administration for 4 weeks.
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Karacaoğlu, Elif; Selmanoğlu, Güldeniz
2010-05-01
Furan (C(4)H(4)O) is a volatile, colorless liquid and is used in some segments of the chemical manufacturing industry. It is found in variety of foods such as coffee, jarred and canned foods that undergo heat treatment. This study was designed to investigate the effect of furan exposure on reproductive system of male rats. Three to four weeks old rats were exposed to furan at 2, 4 and 8 mg/kg/day doses by orally for 90 days. Hematology, weights, histology and morphometry of reproductive organs, serum LH and testosterone levels, sperm count and morphology and apoptosis in testis were evaluated. Slight changes were observed in hematological parameters of furan-treated rats. The weights of seminal vesicle reduced significantly whereas the weights of prostate increased significantly in the highest furan dose group. LH and testosterone levels decreased in furan-treated rats. Histological examinations have revealed that furan caused impairments in testis, epididymis and prostate gland. Furan showed no effects on sperm counts and morphology. On the other hand apoptotic cells in testis increased significantly. According to morphometrical examination, the epithelial heights and lumen diameters of the reproductive organs have changed in treatment groups. These results indicate that subchronic furan treatment induces toxicity of the male reproductive system. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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Yoshida, Midori; Takahashi, Miwa; Inoue, Kaoru; Hayashi, Seigo; Maekawa, Akihiko; Nishikawa, Akiyoshi
2011-08-01
Neonatal exposure to estrogenic chemicals causes irreversible complex damage to the hypothalamus-pituitary-gonadal axis and reproductive system in females. Some lesions are noted after maturation as delayed adverse effects. We investigated the characteristics and dose dependence of delayed effects using female rats neonatally exposed to diethylstilbestrol (DES). Female Donryu rats were subcutaneously injected with a single dose of DES of 0 (control), 0.15, 1.5, 15, 150, or 1,500 µg/kg bw after birth. All except the lowest dose had estrogenic activity in a uterotrophic assay. All rats at 1500 µg/kg and some at 150 µg/kg showed abnormal morphologies in the genital tract, indicating they were androgenized before maturation. Although no morphological abnormalities were noted at 15 µg/kg or lower, onset of persistent estrus was significantly accelerated in the 1.5, 15, and 150 µg/kg groups with dose dependency, and the latest onset was from seventeen to twenty-one weeks of age at 1.5 µg/kg. The neonatal exposure to DES increased uterine adenocarcinoma development only at 150 µg/kg, although uterine anomalies were detected at 1,500 µg/kg. These results indicate that neonatal exposure to DES, which exerts estrogenic activity in vivo, induces delayed adverse effects in female rats in a dose-dependent manner. Early onset of persistent estrus appears to be the most sensitive parameter.
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Bulle, Saradamma; Reddy, Vaddi Damodara; Hebbani, Ananda Vardhan; Padmavathi, Pannuru; Challa, Chandrasekhar; Puvvada, Pavan Kumar; Repalle, Elisha; Nayakanti, Devanna; Aluganti Narasimhulu, Chandrakala; Nallanchakravarthula, Varadacharyulu
2016-12-01
The present study investigated the antioxidant potential of P. santalinus heartwood methanolic extract (PSE) against alcohol-induced nephro-toxicity. The results indicated an increase in the concentration of kidney damage plasma markers, urea and creatinine with a concomitant decrease in the concentration of uric acid in alcohol-administered rats. A significant decrease in plasma electrolytes and mineral levels with increased kidney thiobarbituric acid reactive substances (TBARS) and nitric oxide (NOx) levels was also observed. PSE treatment to alcohol-administered rats effectively prevented the elevation in TBARS and NOx levels. Decreased activity of Na + /K + -ATPase in alcohol administered rats was brought to near normal levels with treatment of PSE. Chronic alcohol consumption affects antioxidant enzymatic activity and reabsorption function of the kidney which is evident from the decreased level of GSH as well as the activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione s-transferase (GST). However, treatment with PSE to alcohol-administered rats significantly enhanced these enzymatic activities and reduced glutathione (GSH) content close to normal level. Alcohol-induced organ damage was evident from morphological changes in the kidney. Nevertheless, administration of PSE effectively restored these morphological changes to normal. The flavonoid and tannoid compounds might have protective activity against alcohol-induced oxidative/nitrosative stress mediated kidney damage. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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The effect of sibutramine on platelet morphology of Spraque-Dawley rats fed a high energy diet.
Oberholzer, Hester Magdalena; Van Der Schoor, Ciska; Pretorius, Etheresia
2013-06-01
The aim of this study was to investigate the effect of Sibutramine on platelet ultrastructure and discuss the morphological observations in relation to known physiological effects of the compound. Six-week-old, female Spraque-Dawley rats were used in this study. The animals were placed on a high energy diet after which sibutramine administration followed. Blood was drawn on the day of termination and platelet rich plasma was obtained to prepare plasma smears for analysis. Scanning electron microscopy was used to investigate the ultrastructure of the platelets. Platelets of the Sibutramine-treated animals showed smooth surface with limited pseudopodia formation when compared with that of the control animals. Higher magnification of the platelet surface showed membrane tears and swelling, typically seen in necrotic cells. It can therefore be concluded from these results that Sibutramine alters the membrane morphology of platelets to that typical of necrotic cells. Copyright © 2013 Wiley Periodicals, Inc.
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Starek, A; Kamiński, M
1982-01-01
The rats exposed for 14 weeks to odourless kerosene mists (concentration of 75 and 300 mg/m3) had their urinary chemical and morphotic composition determined. In addition, morphological and cytoenzymatic examinations of kidneys were carried out. The findings were: increased pH and protein concentration and single erythrocytes in urine and also: passive congestion of renal cortex and medulla, infiltrates composed of granulocytes and eosinophils and albuminous casts in renal tubules. Decreased activity of succinate dehydrogenase, glucoso-6-phosphatase, Mg++ stimulated adenosinotriphosphatase and increased activity of acid phosphatase were found. Those changes were localized in cortical part of the kidney especially in the main tubules epithelial cells. The observed functional, morphological and cytoenzymatic changes depended on the magnitude of exposure. The obtained results confirm that kerosene hydrocarbons may exhibit toxic effects on the kidney function and structure.
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Heterogeneous targeting of centrifugal inputs to the glomerular layer of the main olfactory bulb.
Gómez, C; Briñón, J G; Barbado, M V; Weruaga, E; Valero, J; Alonso, J R
2005-06-01
The centrifugal systems innervating the olfactory bulb are important elements in the functional regulation of the olfactory pathway. In this study, the selective innervation of specific glomeruli by serotonergic, noradrenergic and cholinergic centrifugal axons was analyzed. Thus, the morphology, distribution and density of positive axons were studied in the glomerular layer of the main olfactory bulb of the rat, using serotonin-, serotonin transporter- and dopamine-beta-hydroxylase-immunohistochemistry and acetylcholinesterase histochemistry in serial sections. Serotonin-, serotonin transporter-immunostaining and acetylcholinesterase-staining revealed a higher heterogeneity in the glomerular layer of the main olfactory bulb than previously reported. In this sense, four types of glomeruli could be identified according to their serotonergic innervation. The main distinctive feature of these four types of glomeruli was their serotonergic fibre density, although they also differed in their size, morphology and relative position throughout the rostro-caudal main olfactory bulb. In this sense, some specific regions of the glomerular layer were occupied by glomeruli with a particular morphology and a characteristic serotonergic innervation pattern that was consistent from animal to animal. Regarding the cholinergic system, we offer a new subclassification of glomeruli based on the distribution of cholinergic fibres in the glomerular structure. Finally, the serotonergic and cholinergic innervation patterns were compared in the glomerular layer. Sexual differences concerning the density of serotonergic fibres were observed in the atypical glomeruli (characterized by their strong cholinergic innervation). The present report provides new data on the heterogeneity of the centrifugal innervation of the glomerular layer that constitutes the morphological substrate supporting the existence of differential modulatory levels among the entire glomerular population.
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Borzacchiello, Assunta; Mayol, Laura; Ramires, Piera A; Pastorello, Andrea; Di Bartolo, Chiara; Ambrosio, Luigi; Milella, Evelina
2007-10-01
In this study the attention has been focused on the ester derivative of hyaluronic acid (HA), HYAFF11, as a potential three-dimensional scaffold in adipose tissue engineering. Different HYAFF11 sponges having different pore sizes, coated or not coated with HA, have been studied from a rheological and morphological point of view in order to correlate their structure to the macroscopic and degradation properties both in vitro and in vivo, using rat model. The in vitro results indicate that the HYAFF11 sponges possess proper structural and mechanical properties to be used as scaffolds for adipose tissue engineering and, among all the analysed samples, uncoated HYAFF11 large-pore sponges showed a longer lasting mechanical stability. From the in vivo results, it was observed that the elastic modulus of scaffolds seeded with preadipocytes, the biohybrid constructs, and explanted after 3 months of implantation in autologous rat model are over one order of magnitude higher than the corresponding values for the native tissue. These results could suggest that the implanted scaffolds can be invaded and populated by different cells, not only adipocytes, that can produce new matrix having different properties from that of adipose tissue.
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Kumar, Nagendra; Chaurasia, Sundeep; Patel, Ravi R; Khan, Gayasuddin; Kumar, Vikas; Mishra, Brahmeshwar
2017-03-01
Atorvastatin calcium (ATR), a second generation statin drug, was encapsulated in eudragit RSPO-based polymeric nanoparticles. The effect of independent variables (polymer content, stabilizer concentration, volume of chloroform and homogenization speed) on response variables (mean diameter particle size and entrapment efficiency) were investigated by employing central composite experimental design. All the independent variables were found to be significant for determining the response variables. Solid-state characterization study indicated the absence of physicochemical interaction between drug and polymer in formulation. Morphological study exhibited homogenous spherical shape of formulated nanoparticles. In vitro release study in phosphate buffer (pH 7.4) demonstrated sustained release profile over 24 h. Pharmacokinetic study in Charles Foster rats showed significant enhancement in oral bioavailability as compared to pure drug suspension. Efficacy study (lipid profile and blood glucose level) significantly justified the effectiveness of formulation having 50% less dose of ATR as compared to pure drug suspension. The effectiveness of formulation was further justified with an improved plasma safety profile of treated rats. Hence, ATR encapsulated eudragit RSPO nanoparticles can serve as potential drug delivery approach to enhance drug bioavailability, efficacy and safety profiles to alter existing marketed drug products.
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Moringa oleifera, a species with potential analgesic and anti-inflammatory activities.
Martínez-González, Claudia Lizbeth; Martínez, Laura; Martínez-Ortiz, Efraín J; González-Trujano, María Eva; Déciga-Campos, Myrna; Ventura-Martínez, Rosa; Díaz-Reval, Irene
2017-03-01
Moringa oleifera has long been used in large demand in folk medicine to treat pain. The present study was undertaken to examine the antinociceptive and anti-inflammatory spectrum of M. oleifera leaf extracts discriminating the constituents' nature by using different kind of experimental models in rats. Pharmacological evaluation of a non-polar and/or polar extracts at several doses (30-300mg/kg, p.o.) was explored through experimental nociception using formalin test, carrageenan-induced paw edema and arthritis with subcutaneous injection of collagen in rats. Basic morphology characterization was done by scanning electronic microscopy and laser scanning confocal microscopy. Not only polar (from 30 or 100mg/kg, p.o.) but also non-polar extract produced significant inhibition of the nociceptive behavior with major efficacy in the inflammatory response in different assessed experimental models. This antinociceptive activity involved constituents of different nature and depended on the intensity of the induced painful stimulus. Phytochemical analysis showed the presence of kaempferol-3-glucoside in the polar extract and fatty acids like chlorogenic acid, among others, in the non-polar extract. Data obtained with M. oleifera leaf extracts give evidence of its potential for pain treatment. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Radi, Zaher, E-mail: zaher.radi@pfizer.com; Bartholomew, Phillip, E-mail: phillip.m.bartholomew@pfizer.com; Elwell, Michael, E-mail: michael.elwell@covance.com
In humans, hibernoma is a very rare, benign neoplasm of brown adipose tissue (BAT) that typically occurs at subcutaneous locations and is successfully treated by surgical excision. No single cause has been accepted to explain these very rare human tumors. In contrast, spontaneous hibernoma in rats is rare, often malignant, usually occurs in the thoracic or abdominal cavity, and metastases are common. In recent years, there has been an increased incidence of spontaneous hibernomas in rat carcinogenicity studies, but overall the occurrence remains relatively low and highly variable across studies. There have only been four reported examples of pharmaceutical-induced hibernomamore » in rat carcinogenicity studies. These include phentolamine, an alpha-adrenergic antagonist; varenicline, a nicotine partial agonist; tofacitinib, a Janus kinase (JAK) inhibitor; and hydromorphone, an opiod analgesic. Potential non-genotoxic mechanisms that may contribute to the pathogenesis of BAT activation/proliferation and/or subsequent hibernoma development in rats include: (1) physiological stimuli, (2) sympathetic stimulation, (3) peroxisome proliferator-activated receptor (PPAR) agonism, and/or (4) interference or inhibition of JAK/Signal Transducer and Activator of Transcription (JAK/STAT) signaling. The evaluation of an apparent increase of hibernoma in rats from 2-year carcinogenicity studies of novel pharmaceutical therapeutics and its relevance to human safety risk assessment is complex. One should consider: the genotoxicity of the test article, dose/exposure and safety margins, and pathophysiologic and morphologic differences and similarities of hibernoma between rats and humans. Hibernomas observed to date in carcinogenicity studies of pharmaceutical agents do not appear to be relevant for human risk at therapeutic dosages. - Highlights: • Highly variable incidence of spontaneous hibernoma in carcinogenicity studies • Recent increase in the spontaneous incidence of hibernomas in Sprague–Dawley rats • Pharmaceutical-related hibernoma has been observed in rats, but not in humans. • Pathophysiologic and morphologic differences of hibernoma between rats and 7 humans. • Hibernomas are unlikely to be relevant to human risk assessment.« less
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COGNITIVE IMPAIRMENT AND MORPHOLOGICAL CHANGES IN THE DORSAL HIPPOCAMPUS OF VERY OLD FEMALE RATS
Morel, Gustavo R.; Andersen, Tomás; Pardo, Joaquín; Zuccolilli, Gustavo O.; Cambiaggi, Vanina L.; Hereñú, Claudia B.; Goya, Rodolfo G.
2015-01-01
The hippocampus, a medial temporal lobe structure necessary for the formation of spatial memory, is particularly affected by both normal and pathologic aging. In previous studies, we observed a significant age-related increase in dopaminergic neuron loss in the hypothalamus and the substantia nigra of female rats, which becomes more conspicuous at extreme ages. Here, we extend our studies by assessing spatial memory 4–6 months old (young), 26 months old (old) and 29–32 months old (senile) Sprague–Dawley female rats as well as the age-related histopathological changes in their dorsal hippocampus. Age changes in spatial memory performance were assessed with a modified version of the Barnes maze test. We employed two probe trials (PT), one and five days after training, respectively, in order to evaluate learning ability as well as short-term and longer-term spatial memory retention. A set of relevant hippocampal cell markers was also quantitated in the animals by means of an unbiased stereological approach. The results revealed that old rats perform better than senile rats in acquisition trials and young rats perform better than both aging groups. However, during short-term PT both aging groups showed a preserved spatial memory while in longer-term PT, spatial memory showed deterioration in both aged groups. Morphological analysis showed a marked decrease (94–97%) in doublecortin neuron number in the dentate gyrus in both aged groups and a reduction in glial fibrillary acidic protein-positive cell number in the stratum radiatum of aging rats. Astroglial process length and branching complexity decreased in the aged rats. We conclude that while target-seeking activity and learning ability decrease in aged females, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of aging rats. PMID:26141841
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O'Reilly, Kally C; Perica, Maria I; Fenton, André A
2016-10-01
Cognitive impairments are amongst the most debilitating deficits of schizophrenia and the best predictor of functional outcome. Schizophrenia is hypothesized to have a neurodevelopmental origin, making animal models of neurodevelopmental insult important for testing predictions that early insults will impair cognitive function. Rats exposed to methylazoxymethanol acetate (MAM) at gestational day 17 display morphological, physiological and behavioral abnormalities relevant to schizophrenia. Here we investigate the cognitive abilities of adult MAM rats. We examined brain activity in MAM rats by histochemically assessing cytochrome oxidase enzyme activity, a metabolic marker of neuronal activity. To assess cognition, we used a hippocampus-dependent two-frame active place avoidance paradigm to examine learning and spatial memory, as well as cognitive control and flexibility using the same environment and evaluating the same set of behaviors. We confirmed that adult MAM rats have altered hippocampal morphology and brain function, and that they are hyperactive in an open field. The latter likely indicates MAM rats have a sensorimotor gating deficit that is common to many animal models used for schizophrenia research. On first inspection, cognitive control seems impaired in MAM rats, indicated by more errors during the two-frame active place avoidance task. Because MAM rats are hyperactive throughout place avoidance training, we considered the possibility that the hyperlocomotion may account for the apparent cognitive deficits. These deficits were reduced on the basis of measures of cognitive performance that account for motor activity differences. However, though other aspects of memory are intact, the ability of MAM rats to express trial-to-trial memory is delayed compared to control rats. These findings suggest that spatial learning and cognitive abilities are largely intact, that the most prominent cognitive deficit is specific to acquiring memory in the MAM neurodevelopmental model, and that hyperactivity can confound assessments of cognition in animal models of mental dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.
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Fernández-Sánchez, Laura; Lax, Pedro; Campello, Laura; Pinilla, Isabel; Cuenca, Nicolás
2015-01-01
Purpose: Retinitis pigmentosa includes a group of progressive retinal degenerative diseases that affect the structure and function of photoreceptors. Secondarily to the loss of photoreceptors, there is a reduction in retinal vascularization, which seems to influence the cellular degenerative process. Retinal macroglial cells, astrocytes, and Müller cells provide support for retinal neurons and are fundamental for maintaining normal retinal function. The aim of this study was to investigate the evolution of macroglial changes during retinal degeneration in P23H rats. Methods: Homozygous P23H line-3 rats aged from P18 to 18 months were used to study the evolution of the disease, and SD rats were used as controls. Immunolabeling with antibodies against GFAP, vimentin, and transducin were used to visualize macroglial cells and cone photoreceptors. Results: In P23H rats, increased GFAP labeling in Müller cells was observed as an early indicator of retinal gliosis. At 4 and 12 months of age, the apical processes of Müller cells in P23H rats clustered in firework-like structures, which were associated with ring-like shaped areas of cone degeneration in the outer nuclear layer. These structures were not observed at 16 months of age. The number of astrocytes was higher in P23H rats than in the SD matched controls at 4 and 12 months of age, supporting the idea of astrocyte proliferation. As the disease progressed, astrocytes exhibited a deteriorated morphology and marked hypertrophy. The increase in the complexity of the astrocytic processes correlated with greater connexin 43 expression and higher density of connexin 43 immunoreactive puncta within the ganglion cell layer (GCL) of P23H vs. SD rat retinas. Conclusions: In the P23H rat model of retinitis pigmentosa, the loss of photoreceptors triggers major changes in the number and morphology of glial cells affecting the inner retina. PMID:26733810
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JEONG, KWANG IL; SUZUKI, HODAKA; NAKAYAMA, HIROYUKI; DOI, KUNIO
2000-01-01
Membranous (M) cells in follicle-associated epithelium (FAE) play an important role in the mucosal immunity through transport of a variety of foreign antigens to the underlying mucosa-associated lymphoid tissue (MALT). We aimed to investigate the ultrastructure of M cells in the FAE covering nasal-associated lymphoid tissue (NALT) both in specific pathogen-free (SPF) rats and in conventional environment-adapted (SPF-CV) rats aged 8–38 wk. In NALT of both SPF and SPF-CV rats, FAE included the nonciliated microvillous cell, which appears to be an analogue of M cell previously described in other MALT. In SPF rats, M cells increased in number only slightly with age, and they maintained morphological uniformity irrespective of age. In SPF-CV rats, M cells selectively increased in number resulting in prominent expansion of FAE surface area in parallel with the duration of maintenance in a conventional environment. In addition, M cells in SPF-CV rats showed heterogeneity in their surface morphology such as the length and number of microvilli and cell surface area and outline. In addition, the FAE was stratified by various subtypes of M cells, which were characterised by several subcellular alterations including the presence of many keratin filaments, homogeneous dark bodies and extensive cytoplasmic interfoliation with wide intercellular spaces filled with amorphous proteinaceous material. These characteristics of M cells in SPF-CV rat were intimately related with a preferential influx of immunocompetent cells into the FAE, which was not seen or was very rare in SPF rats irrespective of age. The results suggest the possibility that NALT may effectively carry out the mucosal immune response against antigenic stimuli of different magnitude through the unique dynamics of M cells which seem to be influenced by the infiltration of immunocompetent cells. PMID:10853966
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Walton, Richard D.; Benson, Alan P.; Hardy, Matthew E. L.; White, Ed; Bernus, Olivier
2013-01-01
Spatial dispersion of repolarization is known to play an important role in arrhythmogenesis. Electrotonic modulation of repolarization by the activation sequence has been observed in some species and tissue preparations, but to varying extents. Our study sought to determine the mechanisms underlying species- and tissue-dependent electrotonic modulation of repolarization in ventricles. Epi-fluorescence optical imaging of whole rat hearts and pig left ventricular wedges were used to assess epicardial spatial activation and repolarization characteristics. Experiments were supported by computer simulations using realistic geometries. Tight coupling between activation times (AT) and action potential duration (APD) were observed in rat experiments but not in pig. Linear correlation analysis found slopes of −1.03 ± 0.59 and −0.26 ± 0.13 for rat and pig, respectively (p < 0.0001). In rat, maximal dispersion of APD was 11.0 ± 3.1 ms but dispersion of repolarization time (RT) was relatively homogeneous (8.2 ± 2.7, p < 0.0001). However, in pig no such difference was observed between the dispersion of APD and RT (17.8 ± 6.1 vs. 17.7 ± 6.5, respectively). Localized elevations of APD (12.9 ± 8.3%) were identified at ventricular insertion sites of rat hearts both in experiments and simulations. Tissue geometry and action potential (AP) morphology contributed significantly to determining influence of electrotonic modulation. Simulations of a rat AP in a pig geometry decreased the slope of AT and APD relationships by 70.6% whereas slopes were increased by 75.0% when implementing a pig AP in a rat geometry. A modified pig AP, shortened to match the rat APD, showed little coupling between AT and APD with greatly reduced slope compared to the rat AP. Electrotonic modulation of repolarization by the activation sequence is especially pronounced in small hearts with murine-like APs. Tissue architecture and AP morphology play an important role in electrotonic modulation of repolarization. PMID:24115934
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Evaluation of imaging biomarkers for identification of single cancer cells in blood
NASA Astrophysics Data System (ADS)
Odaka, Masao; Kim, Hyonchol; Girault, Mathias; Hattori, Akihiro; Terazono, Hideyuki; Matsuura, Kenji; Yasuda, Kenji
2015-06-01
A method of discriminating single cancer cells from whole blood cells based on their morphological visual characteristics (i.e., “imaging biomarker”) was examined. Cells in healthy rat blood, a cancer cell line (MAT-LyLu), and cells in cancer-cell-implanted rat blood were chosen as models, and their bright-field (BF, whole-cell morphology) and fluorescence (FL, nucleus morphology) images were taken by an on-chip multi-imaging flow cytometry system and compared. Eight imaging biomarker indices, i.e., cellular area in a BF image, nucleus area in an FL image, area ratio of a whole cell and its nucleus, distance of the mass center between a whole cell and nucleus, cellular and nucleus perimeter, and perimeter ratios were calculated and analyzed using the BF and FL images taken. Results show that cancer cells can be clearly distinguished from healthy blood cells using correlation diagrams for cellular and nucleus areas as two different categories. Moreover, a portion of cancer cells showed a low nucleus perimeter ratio less than 0.9 because of the irregular nucleus morphologies of cancer cells. These results indicate that the measurements of imaging biomarkers are practically applicable to identifying cancer cells in blood.
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Schwaibold, U; Pillay, N
2003-11-01
We studied the gut morphology of the ice rat Otomys sloggetti robertsi, a non-hibernating murid rodent endemic to the sub-alpine and alpine regions of the southern African Drakensberg and Maluti mountains. The gut structure of O. s. robertsi is well adapted for a high fibre, herbivorous diet, as is the case with other members of its subfamily Otomyinae. Despite the broad similarity in gross gut morphology with mesic- and arid-occurring otomyines, O. s. robertsi has a larger small intestine, caecum, stomach volume and parts of the colon, which we suggest are adaptations for increased energy uptake and/or poor diet quality in alpine environments. However, O. s. robertsi has a smaller larger intestine than other otomyines, perhaps because it occupies a mesic habitat. Seasonal sexual differences occurred, with females increasing dimensions of the stomach, small intestine length, caecum, and large intestine in summer. Sexual asymmetry in gut morphology may be related to increased energy requirements of females during pregnancy and lactation, indicating phenotypic plasticity in response to poor quality vegetation and a shorter growing season in alpine habitats.
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Sarabia-Estrada, Rachel; Ruiz-Valls, Alejandro; Shah, Sagar R; Ahmed, A Karim; Ordonez, Alvaro A; Rodriguez, Fausto J; Guerrero-Cazares, Hugo; Jimenez-Estrada, Ismael; Velarde, Esteban; Tyler, Betty; Li, Yuxin; Phillips, Neil A; Goodwin, C Rory; Petteys, Rory J; Jain, Sanjay K; Gallia, Gary L; Gokaslan, Ziya L; Quinones-Hinojosa, Alfredo; Sciubba, Daniel M
2017-08-01
OBJECTIVE Chordoma is a slow-growing, locally aggressive cancer that is minimally responsive to conventional chemotherapy and radiotherapy and has high local recurrence rates after resection. Currently, there are no rodent models of spinal chordoma. In the present study, the authors sought to develop and characterize an orthotopic model of human chordoma in an immunocompromised rat. METHODS Thirty-four immunocompromised rats were randomly allocated to 4 study groups; 22 of the 34 rats were engrafted in the lumbar spine with human chordoma. The groups were as follows: UCH1 tumor-engrafted (n = 11), JHC7 tumor-engrafted (n = 11), sham surgery (n = 6), and intact control (n = 6) rats. Neurological impairment of rats due to tumor growth was evaluated using open field and locomotion gait analysis; pain response was evaluated using mechanical or thermal paw stimulation. Cone beam CT (CBCT), MRI, and nanoScan PET/CT were performed to evaluate bony changes due to tumor growth. On Day 550, rats were killed and spines were processed for H & E-based histological examination and immunohistochemistry for brachyury, S100β, and cytokeratin. RESULTS The spine tumors displayed typical chordoma morphology, that is, physaliferous cells filled with vacuolated cytoplasm of mucoid matrix. Brachyury immunoreactivity was confirmed by immunostaining, in which samples from tumor-engrafted rats showed a strong nuclear signal. Sclerotic lesions in the vertebral body of rats in the UCH1 and JHC7 groups were observed on CBCT. Tumor growth was confirmed using contrast-enhanced MRI. In UCH1 rats, large tumors were observed growing from the vertebral body. JHC7 chordoma-engrafted rats showed smaller tumors confined to the bone periphery compared with UCH1 chordoma-engrafted rats. Locomotion analysis showed a disruption in the normal gait pattern, with an increase in the step length and duration of the gait in tumor-engrafted rats. The distance traveled and the speed of rats in the open field test was significantly reduced in the UCH1 and JHC7 tumor-engrafted rats compared with controls. Nociceptive response to a mechanical stimulus showed a significant (p < 0.001) increase in the paw withdrawal threshold (mechanical hypalgesia). In contrast, the paw withdrawal response to a thermal stimulus decreased significantly (p < 0.05) in tumor-engrafted rats. CONCLUSIONS The authors developed an orthotopic human chordoma model in rats. Rats were followed for 550 days using imaging techniques, including MRI, CBCT, and nanoScan PET/CT, to evaluate lesion progression and bony integrity. Nociceptive evaluations and locomotion analysis were performed during follow-up. This model reproduces cardinal signs, such as locomotor and sensory deficits, similar to those observed clinically in human patients. To the authors' knowledge, this is the first spine rodent model of human chordoma. Its use and further study will be essential for pathophysiology research and the development of new therapeutic strategies.
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Jansson, Erik Karl Håkan; Clemens, Laura Emily; Riess, Olaf; Nguyen, Huu Phuc
2014-01-01
Huntington disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models.
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Riess, Olaf; Nguyen, Huu Phuc
2014-01-01
Huntington disease (HD) is an inherited neurodegenerative disease characterized by motor, cognitive, psychiatric and metabolic symptoms. Animal models of HD show phenotypes that can be divided into similar categories, with the metabolic phenotype of certain models being characterized by obesity. Although interesting in terms of modeling metabolic symptoms of HD, the obesity phenotype can be problematic as it might confound the results of certain behavioral tests. This concerns the assessment of cognitive function in particular, as tests for such phenotypes are often based on food depriving the animals and having them perform tasks for food rewards. The BACHD rat is a recently established animal model of HD, and in order to ensure that behavioral characterization of these rats is done in a reliable way, a basic understanding of their physiology is needed. Here, we show that BACHD rats are obese and suffer from discrete developmental deficits. When assessing the motivation to lever push for a food reward, BACHD rats were found to be less motivated than wild type rats, although this phenotype was dependent on the food deprivation strategy. Specifically, the phenotype was present when rats of both genotypes were deprived to 85% of their respective free-feeding body weight, but not when deprivation levels were adjusted in order to match the rats' apparent hunger levels. The study emphasizes the importance of considering metabolic abnormalities as a confounding factor when performing behavioral characterization of HD animal models. PMID:25144554
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Oxaliplatin Alters Expression of T1R2 Receptor and Sensitivity to Sweet Taste in Rats.
Ohishi, Akihiro; Nishida, Kentaro; Yamanaka, Yuri; Miyata, Ai; Ikukawa, Akiko; Yabu, Miharu; Miyamoto, Karin; Bansho, Saho; Nagasawa, Kazuki
2016-01-01
As one of the adverse effects of oxaliplatin, a key agent in colon cancer chemotherapy, a taste disorder is a severe issue in a clinical situation because it decreases the quality of life of patients. However, there is little information on the mechanism underlying the oxaliplatin-induced taste disorder. Here, we examined the molecular and behavioral characteristics of the oxaliplatin-induced taste disorder in rats. Oxaliplatin (4-16 mg/kg) was administered to Sprague-Dawley (SD) rats intraperitoneally for 2 d. Expression levels of mRNA and protein of taste receptors in circumvallate papillae (CP) were measured by real-time quantitative polymerase chain reaction (PCR) and immunohistochemistry, respectively. Taste sensitivity was assessed by their behavioral change using a brief-access test. Morphological change of the taste buds in CP was evaluated by hematoxyline-eosin (HE) staining, and the number of taste cells in taste buds was counted by immunohistochemical analysis. Among taste receptors, the expression levels of mRNA and protein of T1R2, a sweet taste receptor subunit, were increased transiently in CP of oxaliplatin-administered rats on day 7. In a brief-access test, the lick ratio was decreased in oxaliplatin-administered rats on day 7 and the alteration was recovered to the control level on day 14. There was no detectable alteration in the morphology of taste buds, number of taste cells or plasma zinc level in oxaliplatin-administered rats. These results suggest that decreased sensitivity to sweet taste in oxaliplatin-administered rats is due, at least in part, to increased expression of T1R2, while these alterations are reversible.
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Neurite outgrowth in human iPSC-derived neurons
Data on morphology of rat and human neurons in cell cultureThis dataset is associated with the following publication:Druwe, I., T. Freudenrich , K. Wallace , T. Shafer , and W. Mundy. Comparison of Human Induced PluripotentStem Cell-Derived Neurons and Rat Primary CorticalNeurons as In Vitro Models of Neurite Outgrowth. Applied In vitro Toxicology. Mary Ann Liebert, Inc., Larchmont, NY, USA, 2(1): 26-36, (2016).
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USDA-ARS?s Scientific Manuscript database
Isoflavones are phytochemical components of soy diets that bind weakly to estrogen receptors (ERs). To study potential estrogen-like actions of soy in the mammary gland during early development, we fed weanling male and female Sprague-Dawley rats a semi-purified diet with casein as the sole protein ...
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Kuevda, E V; Gubareva, E A; Gumenyuk, I S; Sotnichenko, A S; Gilevich, I V; Nakokhov, R Z; Rusinova, T V; Yudina, T G; Red'ko, A N; Alekseenko, S N
2017-03-01
We modified the protocol of obtaining of biological scaffolds of rat lungs based on dynamic recording of specific resistivity of working detergent solution (conductometry) during perfusion decellularization. Termination of sodium deoxycholate exposure after attaining ionic equilibrium plateau did not impair the quality of decellularization and preserved structural matrix components, which was confirmed by morphological analysis and quantitative assay of residual DNA.
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Nassar, Muammar A Y; Eldien, Heba M Saad; Tawab, Hanem S Abdel; Saleem, Tahia H; Omar, Hossam M; Nassar, Ahmed Y; Hussein, Mahmoud Rezk Abdelwahed
2012-10-01
Thermal tissue injury is partly mediated by reactive oxygen metabolites. Oxygen free radicals are contributory to local tissue damage following thermal injury and accordingly an interventional therapy using antioxidants may be beneficial. Copper nicotinate complex can scavenge reactive oxygen species (i.e., has antioxidant activity). To examine time-related morphological and biochemical changes following skin thermal injury and their modulation by copper nicotinate complex. An animal model composed of 80 albino rats was established. Ten rats (nonburn group) served as a control group. Seventy rats (burn group) were anesthetized, given a 10% total body surface area, full-thickness burn. Ten rats (from the postburn group) were sacrificed after 24 h (without treatment, i.e., untreated-burn group). The remaining rats were divided into three subgroups (20 rats, each) and were treated topically either with soft paraffin, moist exposed burn ointment (MEBO, a standard therapeutic treatment for burns), or copper nicotinate complex. Five animals from each subgroup were sacrificed every week over a period of 4 weeks. The morphological and biochemical changes were evaluated and compared among the different groups. High levels of the plasma and skin nitiric oxide (marker of oxidative stress) were observed in the untreated-burn group. These levels were significantly low following the application of copper nicotinate complex. Low levels of plasma and skin superoxide dismutase (marker of oxidative stress) and plasma ceruloplasmin were observed in the untreated-burn group. These levels were significantly high following copper nicotinate complex treatment. The total and differential leukocyte counts were low following the onset of the thermal injury. They gradually returned to normal levels over a 4-week period following the application of MEBO or copper nicotinate complex. Compared to untreated-burn group, postburn-healing changes (resolution of the inflammatory reaction, reepithelization of the epidermis, angiogenesis, deposition of collagen fibers, and recovery of the subcellualr organelles) were significantly accelerated following the application of either MEBO or copper nicotinate complex. Application of copper nicotinate complex was associated with improved healing of the thermal burns of the skin. The underlying molecular changes underlying these effects await further investigations.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Peng, Qiuxian; Department of Biology, Hong Kong Baptist University, Kowloon Tong; Zhang, Qin
Highlights: • AESM is able to prevent the elevation of ALT and AST, and to decreased LDL-C level. • AESM demonstrates the effects of down-regulating blood fat level and protecting liver. • AESM consistent with the efficacy of simvastatin in NAFLD. - Abstract: Objectives: Study the effects of alcohol extract of Sapindus mukorossi Gaertn (AESM) on the metabolism of blood fat, morphology of fenestrated liver sinusoidal endothelial cells (LSEC), and the ultrastructure of liver cells of the rats with non-alcoholic fatty liver disease (NAFLD). Methods: Divide SD rats into control group, model group, simvastatin (7.2 mg/kg) group, and S.mukorossi Gaertnmore » group with high dosage (0.5 g/kg), moderate dosage (0.1 g/kg), and low dosage (0.05 g/kg). After feeding with fat-rich nutrients for 3 weeks and establishing the model of hepatic adipose, conduct intragastric administration and provide the rats with fat-rich nutrients at the same time. At the 43rd day, take blood sample and measure aminotransferase and different indexes of blood fat; take hepatic tissue for pathological section, and observe the hepatic morphological patterns under light microscope; obtain and fix the hepatic tissue after injecting perfusate into the body, and observe the changes of fenestrated LSEC under scanning electron microscope; observe the ultrastructure of liver cells under transmission electron microscope. Results: High-dosage alcohol extracts of S.mukorossi Gaertn can alleviate the AST, ALT, TC, TG, LDL, γ-GT, and ALP level, as well as raise the HDL and APN level in the serum of NAFLD-rat model. In addition, through the observation from light microscope and electron microscopes, the morphology of the hepatic tissue and liver cells as well as the recovery of the fenestrated LSEC in the treatment group has become normal. Conclusions: Alcohol extracts of S.mukorossi Gaertn can regulate the level of blood fat and improve the pathological changes of the hepatic tissues in NAFLD-rat model, which demonstrates the effects of down-regulating fat level and protecting liver.« less
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Guo, Xiangfei; Zhao, Yaning; Li, Jianmin; Liu, Wenqian; Chen, Changxiang
2016-09-01
Objective To investigate the effects of different duration of intermittent hypoxia on the autophagy pathway in the hippocampus and the learning and memory ability after cerebral ischemia in rats. Methods 100 male Wistar rats were randomly divided into sham operation (SO) group, ischemia/reperfusion (I/R) group, intermittent hypoxia for 7 days combined with ischemia/reperfusion (IH7-I/R) group, intermittent hypoxia for 14 days combined with ischemia/reperfusion (IH14-I/R) group, intermittent hypoxia for 21 days combined with ischemia/reperfusion (IH21-I/R) group, n =20 in each group. The rats in IH7-I/R group, IH14-I/R group and IH21-I/R group were respectively subjected to intermittent hypoxia for 7, 14 and 21 days prior to I/R modeling by improved Pulsinelli four-vessel occlusion (4-VO). The morphological changes of nerve cells in the hippocampus of rat brain were detected by HE staining; the levels of mammalian target of rapamycin (mTOR) and beclin 1 mRNA in the hippocampus were determined by quantitative real-time PCR; the distribution of mTOR and beclin 1 in the hippocampus was observed by immunohistochemistry; the learning and memory ability of rats was assessed by the Morris water maze test. Results Compared with the SO group, the never cell morphology was damaged, the number of survival neurons in the hippocampus was reduced, the expressions of mTOR and beclin 1 in the hippocampus were strengthened, and the learning and memory ability declined in the I/R group. Compared with the I/R group, the never cell morphology was damaged seriously, the number of survival neurons in the hippocampus decreased, the expressions of mTOR and beclin 1 in the hippocampus increased, and the learning and memory ability dropped in the intermittent hypoxia groups. What's more, the above changes were dependent on the duration of intermittent hypoxia. Conclusion Intermittent hypoxia aggravates the dysfunction of learning and memory after cerebral ischemia and the damages increase with time passing, which are related to mTOR-beclin 1 activation and increasing neuronal cell death.
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Yang, Zong-Bao; Wang, Chen-Guang; Gong, An; Xie, Yu-feng; Liu, Qiong; Yang, Qing
2013-11-01
To explore relevant material basis of moxibustion for recovering gastric mucosal lesion. METHODL Forty-five SD rats were randomly divided into a normal goup, a model group, an acupoint group and a control group, 15 rats in the model group and 10 rats in the rest three groups. Except the normal group, binding and cold stress method were used to establish gastric mucosa injury model. The suspended moxibustion was applied in the acupoint group and control group at acupoints of the stomach meridian ("Liangmen" (ST 21) and "Zusanli" (ST36) and control acupoints (Laterally 1cm next to the "Liangmen" (ST 21) and Zusanli" (ST36), once a day, consectutively for 12 days. After 12 days, morphology of gastric mucosal was observed under optical microscope; protein fingerprints of gastric mucosa cell in rats were detected by protein fingerprint technology, weak cation chip and weak anion chip. Also mass to charge ratio of differential proteins in groups were compared and analyzed. Compared with the model group, index of gastric mucosal lesion in the acupoint group was reduced and its morphology was obviously improved (P<0.05). Campared with control group, index and morphology of gastric mucosal lesion were significantly improved in the acupoint group (P<0.05). According to test of weak cation chip, there was four marker proteins that had expression differences, indicating moxibustion at acupoints of stomach meridian could inrease expression of three marker protein whose molecular weight was 1354Da, 5692Da and 8432Da (all P<0.05) while reduce expression of marker protein with molecular weight of 3287Da (_<0.05). According to test of weak anion chip, moxibustion at acupoints of stomach meridian could increase expression of three marker proteins whose molecular weight was 2412 Da, 3026Da and 6475 Da (allP<0.05). Moxibustion at acupoints of the stomach meridian could regulate differential expression of gastric mucosa cell-related marker protein in rats with acute gastric ulcer and recover gastric mucosal lesion, it's effect is better than that of the points of laterally 1 cm next to acupoint.
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NASA Astrophysics Data System (ADS)
Clarke, Shanelle; Baumgardt, Shelley; Molthen, Robert
2010-03-01
Microfocal CT was used to image the pulmonary arterial (PA) tree in rodent models of pulmonary hypertension (PH). CT images were used to measure the arterial tree diameter along the main arterial trunk at several hydrostatic intravascular pressures and calculate distensibility. High-resolution planar angiographic imaging was also used to examine distal PA microstructure. Data on pulmonary artery tree morphology improves our understanding of vascular remodeling and response to treatments. Angiotensin II (ATII) has been identified as a mediator of vasoconstriction and proliferative mitotic function. ATII has been shown to promote vascular smooth muscle cell hypertrophy and hyperplasia as well as stimulate synthesis of extracellular matrix proteins. Available ATII is targeted through angiotensin converting enzyme inhibitors (ACEIs), a method that has been used in animal models of PH to attenuate vascular remodeling and decrease pulmonary vascular resistance. In this study, we used rat models of chronic hypoxia to induce PH combined with partial left pulmonary artery occlusion (arterial banding, PLPAO) to evaluate effects of the ACEI, captopril, on pulmonary vascular hemodynamic and morphology. Male Sprague Dawley rats were placed in hypoxia (FiO2 0.1), with one group having underwent PLPAO three days prior to the chronic hypoxia. After the twenty-first day of hypoxia exposure, treatment was started with captopril (20 mg/kg/day) for an additional twenty-one days. At the endpoint, lungs were excised and isolated to examine: pulmonary vascular resistance, ACE activity, pulmonary vessel morphology and biomechanics. Hematocrit and RV/LV+septum ratio was also measured. CT planar images showed less vessel dropout in rats treated with captopril versus the non-treatment lungs. Distensibility data shows no change in rats treated with captopril in both chronic hypoxia (CH) and CH with PLPAO (CH+PLPAO) models. Hemodynamic measurements also show no change in the pulmonary vascular resistance with captopril treatment in both CH and CH+PLPAO.
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Zuckerman, Amitai; Ram, Omri; Ifergane, Gal; Matar, Michael A; Sagi, Ram; Ostfeld, Ishay; Hoffman, Jay R; Kaplan, Zeev; Sadot, Oren; Cohen, Hagit
2017-01-01
The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.
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Gravitational Biology: The Rat Model
NASA Technical Reports Server (NTRS)
1997-01-01
In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Ronco, Ana Maria, E-mail: amronco@inta.cl; Montenegro, Marcela; Castillo, Paula
2011-03-01
Several cardiovascular diseases (CVD) observed in adulthood have been associated with environmental influences during fetal growth. Here, we show that maternal exposure to cadmium, a ubiquitously distributed heavy metal and main component of cigarette smoke is able to induce cardiovascular morpho-functional changes in the offspring at adult age. Heart morphology and vascular reactivity were evaluated in the adult offspring of rats exposed to 30 ppm of cadmium during pregnancy. Echocardiographic examination shows altered heart morphology characterized by a concentric left ventricular hypertrophy. Also, we observed a reduced endothelium-dependent reactivity in isolated aortic rings of adult offspring, while endothelium-independent reactivity remainedmore » unaltered. These effects were associated with an increase of hem-oxygenase 1 (HO-1) expression in the aortas of adult offspring. The expression of HO-1 was higher in females than males, a finding likely related to the sex-dependent expression of the vascular cell adhesion molecule 1 (VCAM-1), which was lower in the adult female. All these long-term consequences were observed along with normal birth weights and absence of detectable levels of cadmium in fetal and adult tissues of the offspring. In placental tissues however, cadmium levels were detected and correlated with increased NF-{kappa}B expression - a transcription factor sensitive to inflammation and oxidative stress - suggesting a placentary mechanism that affect genes related to the development of the cardiovascular system. Our results provide, for the first time, direct experimental evidence supporting that exposure to cadmium during pregnancy reprograms cardiovascular development of the offspring which in turn may conduce to a long term increased risk of CVD.« less
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Ueno, Tatsuya; Yamada, Junko; Nishijima, Haruo; Arai, Akira; Migita, Keisuke; Baba, Masayuki; Ueno, Shinya; Tomiyama, Masahiko
2014-04-01
Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats (a model of Parkinson's disease), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Because the direct pathway of the basal ganglia plays a central role in the development of LID, we quantified the density and size of dendritic spines in intratelencephalic (IT)-type pyramidal neurons in M1 cortex that project to the striatal medium spiny neurons in the direct pathway. The spine density was not different among the four groups. In contrast, spine size became enlarged in the Parkinson's disease and LID rat models. The enlargement was significantly greater in the LID model than in the Parkinson's disease model. This enlargement of the spines suggests that IT-type pyramidal neurons acquire supersensitivity to excitatory stimuli. To confirm this possibility, we monitored miniature excitatory postsynaptic currents (mEPSCs) in the IT-type pyramidal neurons in M1 cortex using whole-cell patch clamp. The amplitude of the mEPSCs was significantly increased in the LID model compared with the control. This indicates that the IT-type pyramidal neurons become hyperexcited in the LID model, paralleling the enlargement of spines. Thus, spine enlargement and the resultant hyperexcitability of IT-type pyramidal neurons in M1 cortex might contribute to the abnormal cortical neuronal plasticity in LID. Copyright © 2013 Elsevier Inc. All rights reserved.
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Cytoarchitectonic analysis of the SDN-POA of the intact and gonadectomized rat.
Bloch, G J; Gorski, R A
1988-09-22
The densely staining group of cells referred to as the sexually dimorphic nucleus of the preoptic area (SDN-POA) is greater in volume in the male than in the female rat. Because we and others have reported absolute volumes that have been consistent within individual studies but that vary considerably, we characterized the SDN-POA by describing its morphology with respect to the cytoarchitectonic divisions of the medial preoptic nucleus (MPN) in intact and gonadectomized rats. We report three major findings: the SDN-POA is heterogeneous and is composed of cells belonging to three distinct cytoarchitectonic divisions; the cytoarchitecture of the MPN and its medial and lateral divisions (MPNm and MPNl, respectively) in male rats appear to be influenced by the hormonal status in adulthood; and a small anteroventral division of the MPN (MPNav) is present in males but virtually absent in females. Specifically, the SDN-POA is located within the MPNm, but consists of subcomponents located within the central division of the MPN (MPNc), the MPNav, and part of the MPNm-exclusive of the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav. The percentage of the total SDN-POA located within the MPNc and MPNav was greater in males, and that in the MPNm-exclusive of the MPNc and MPNav was greater in females, indicating that the SDN-POA has a different cytoarchitectonic composition in the two sexes. Gonadectomy produced no significant differences in SDN-POA volume, but the MPN, MPNl, and MPNm were significantly reduced in gonadectomized versus intact males, suggesting an activational effect of testicular hormones on these structures.
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Camargo, Isabel Cristina Cherici; Leite, Gabriel Adan Araújo; Pinto, Tiago; Ribeiro-Paes, João Tadeu
2014-07-01
The use of anabolic androgenic steroids is often associated with the use of other substances, licit or not, such as nicotine present in the tobacco. The present study investigated for the first time the effects of co-administration of synthetic steroids and nicotine on the ovarian and uterine tissue and fertility of adult female rats. Animals were submitted to treatment groups (n=16/group): nandrolone decanoate (ND; 7.5mg/kg BW/week); testosterone mixture (T; 7.5mg/kg BW/week); nicotine (N; 2.0mg/kg BW/day), and co-administration of ND/N, T/N and ND/T/N. The control group received saline solution daily. The injections were administered subcutaneously for 30 consecutive days. Results demonstrated that all androgenized rats exhibited estral acyclicity and there was suppression of reproductive capacity due to notable ovarian and uterine histological changes. Treatments promoted decrease (p<0.05) in the ovarian weight. Uterine weight increased (p<0.05) in the T and T/N groups, in comparison to control group. ND or T co-administered or not to nicotine promoted intense follicular degeneration, with formation of cysts in the ovaries. High levels of circulating androgens in the ND/T/N group induced the presence of ovarian sex cord-stromal tumors of Sertoli cell pattern. Androgenized females presented endometrial changes characterized by papilliferous or pleated luminal epithelium, oedematous and hemorrhagic stroma and presence of gland cysts. In conclusion, the co-administration of three drugs promoted atypical morphological pattern on the ovaries and uterus of female rats. Copyright © 2014 Elsevier GmbH. All rights reserved.
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Mankouski, Anastasiya; Kantores, Crystal; Wong, Mathew J; Ivanovska, Julijana; Jain, Amish; Benner, Eric J; Mason, Stanley N; Tanswell, A Keith; Auten, Richard L; Jankov, Robert P
2017-02-01
Bronchopulmonary dysplasia (BPD) is a chronic lung injury characterized by impaired alveologenesis that may persist into adulthood. Rat models of BPD using varying degrees of hyperoxia to produce injury either cause early mortality or spontaneously recover following removal of the inciting stimulus, thus limiting clinical relevance. We sought to refine an established rat model induced by exposure to 60% O 2 from birth by following hyperoxia with intermittent hypoxia (IH). Rats exposed from birth to air or 60% O 2 until day 14 were recovered in air with or without IH (FI O 2 = 0.10 for 10 min every 6 h) until day 28 Animals exposed to 60% O 2 and recovered in air had no evidence of abnormal lung morphology on day 28 or at 10-12 wk. In contrast, 60% O 2 -exposed animals recovered in IH had persistently increased mean chord length, more dysmorphic septal crests, and fewer peripheral arteries. Recovery in IH also increased pulmonary vascular resistance, Fulton index, and arterial wall thickness. IH-mediated abnormalities in lung structure (but not pulmonary hypertension) persisted when reexamined at 10-12 wk, accompanied by increased pulmonary vascular reactivity and decreased exercise tolerance. Increased mean chord length secondary to IH was prevented by treatment with a peroxynitrite decomposition catalyst [5,10,15,20-Tetrakis(4-sulfonatophenyl)-21H,23H-porphyrin iron (III) chloride, 30 mg/kg/day, days 14-28], an effect accompanied by fewer inflammatory cells. We conclude that IH during recovery from hyperoxia-induced injury prevents recovery of alveologenesis and leads to changes in lung and pulmonary vascular function lasting into adulthood, thus more closely mimicking contemporary BPD. Copyright © 2017 the American Physiological Society.
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Heatstroke model for desert dry-heat environment and observed organ damage.
ou Zhou, Ren; Liu, Jiang Wei; Zhang, Dong; Zhang, Qiong
2014-06-01
Heatstroke is one of the most common clinical emergencies. Heatstroke that occurred in a dry-heat environment such as desert is usually more seriously effective and often leads to death. However, the report of the pathophysiologic mechanisms about heatstroke in dry-heat environment of desert has not been seen. Our objectives are to establish a rat model of heatstroke of dry-heat environment of desert, to assess the different degrees of damage of organ, and to preliminarily discuss the mechanism of heatstroke in dry-heat environment of desert. The first step, we have established a rat heatstroke model of dry heat environment of desert. The second step, we have accessed changes in morphology and blood indicators of heatstroke rats in dry-heat environment of desert. The heatstroke rats have expressed the changing characteristics of mean arterial pressure, core temperature, and heart rate. The organ damage changed from mild to serious level, specifically in the morphology and blood enzymology parameters such as alanine aminotransferase, aspartate aminotransferase, creatinine, urea, uric acid, creatine kinase-MB, creatine kinase, and blood gas parameters such as base excess extracellular fluid and bicarbonate ions (HCO3-). We have successfully established the rat heatstroke model of dry-heat environment of desert. We have identified heatstroke rats that presented changing characteristics on physiological indicators and varying degrees of organ damage, which are aggravated by the evolution of heatstroke in dry-heat environment of desert. We have preliminarily discussed the mechanism of heatstroke in dry-heat environment of desert. Copyright © 2014 Elsevier Inc. All rights reserved.
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Picut, Catherine A.; Dixon, Darlene; Simons, Michelle L.; Stump, Donald G.; Parker, George A.; Remick, Amera K.
2014-01-01
Histopathologic examination of the immature ovary is a required end point on juvenile toxicity studies and female pubertal and thyroid function assays. To aid in this evaluation and interpretation of the immature ovary, the characteristic histologic features of rat ovary through the developmental periods are described. These histologic features are correlated with published changes in neuroendocrine profiles as the hypothalamic–pituitary–gonadal axis matures. During the neonatal stage (postnatal day [PND] 0–7), ovarian follicle development is independent of pituitary gonadotropins (luteinizing hormone [LH] or follicle-stimulating hormone [FSH]), and follicles remain preantral. Antral development of “atypical” follicles occurs in the early infantile period (PND 8–14) when the ovary becomes responsive to pituitary gonadotropins. In the late infantile period (PND 15–20), the zona pellucida appears, the hilus forms, and antral follicles mature by losing their “atypical” appearance. The juvenile stage (PND 21–32) is the stage when atresia of medullary follicles occurs corresponding to a nadir in FSH levels. In the peripubertal period (PND 33–37), atresia subsides as FSH levels rebound, and LH begins its bimodal surge pattern leading to ovulation. This report will provide pathologists with baseline morphologic and endocrinologic information to aid in identification and interpretation of xenobiotic effects in the ovary of the prepubertal rat. PMID:25107574
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Haba, Daijiro; Minami, Chie; Miyagawa, Miki; Arakawa, Takamitsu; Miki, Akinori
2017-01-01
Due to transection of bilateral sciatic nerves, pressure ulcer-like dermal lesion occurred in the hairy skin covering of the heel skin in almost all rats. In the present study, chronological changes of the rat heel skin after the transection were morphologically and immunohistochemically examined. In the heel skin, redness and swelling began by 3days after the operation, and open wound formed by 17days. At the redness and swelling stage, edema extensively occurred in the dermis. At the thickening stage, the epidermis at the pressed site became transiently thicker, and at the whitening stage, rapidly thinner. At these stages, the epidermis in the skin surrounding the pressed site became gradually thicker. At the yellow scar stage, the skin was covered only by necrotic tissues and horny layer. These layers were scratched during walking and turning, and the yellow scar stage became the open wound stage. Inflammatory reaction began at the thickening stage, and at the yellow scar and open wound stages, necrosis, infiltration of inflammatory cells and dilation of small blood vessels were observed. These morphological features are quite similar to those in the human pressure ulcer. These findings suggest that these dermal injuries could compare the human pressure ulcer for medical treatment and depressurization in future study. Copyright © 2016 Elsevier GmbH. All rights reserved.
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Spontaneous Renal Tumors Suspected of Being Familial in Sprague-Dawley Rats
Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis
2012-01-01
Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan. PMID:23345931
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Spontaneous renal tumors suspected of being familial in sprague-dawley rats.
Kudo, Kayoko; Hoshiya, Toru; Nakazawa, Tomomi; Saito, Tsubasa; Shimoyama, Natsumi; Suzuki, Isamu; Tamura, Kazutoshi; Seely, John Curtis
2012-12-01
Spontaneous renal tubule tumors (RTTs), with a distinctive morphological phenotype, were present in three Sprague-Dawley rats, 1 male and 2 females, out a total of 120 animals of each sex from untreated and placebo control groups in a 2-year carcinogenicity study. One female had one carcinoma, adenoma and hyperplasia, and the other female had five adenomas and many hyperplastic lesions; the male case had one carcinoma. From these cases, a biological continuum of hyperplasia, adenoma and carcinoma could be recognized. The tumors were present in the renal cortex and appeared as solid lobulated growths with occasional central necrosis. The lobules were divided by a small amount of fibrovascular tissue. Occasionally the larger tumors contained a cystic area. Tumor cells appeared distinctive and exhibited variable amounts of eosinophilic/amphophilic and vacuolated cytoplasm. Nuclei were round to oval with a prominent nucleolus. Mitotic figures were uncommon, and no distant metastasis was noted. The tumors were seen as multiple and bilateral lesions in two animals and had no apparent relationship to chronic progressive nephropathy (CPN). Foci of tubule hyperplasia were also noted to contain the same type of cellular morphology. The morphological and biological features of these 3 cases resembled the amphophilic-vacuolar (AV) variant of RTT that has been posited to be of familial origin. This is a report of spontaneous familial renal tumors in Sprague-Dawley rats from Japan.
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Toxicity evaluation of ZnO nanostructures on L929 fibroblast cell line using MTS assay
NASA Astrophysics Data System (ADS)
Bakhori, Siti Khadijah Mohd; Mahmud, Shahrom; Ann, Ling Chuo; Mohamed, Azman Seeni; Saifuddin, Siti Nazmin; Masudi, Sam'an Malik; Mohamad, Dasmawati
2015-04-01
ZnO has wide applications in medical and dentistry apart from being used as optoelectronic devices such as solar cells, photodetectors, sensors and light emitting diodes (LEDs). Therefore, the toxicity evaluation is important to know the toxicity level on normal cell line. The toxicity of two grades ZnO nanostructures, ZnO-4 and ZnO-8 have been carried out using cytotoxicity test of MTS assay on L929 rat fibroblast cell line. Prior to that, ZnO-4 and ZnO-8 were characterized for its morphology, structure and optical properties using FESEM, X-ray diffraction, and Photoluminescence respectively. The two groups revealed difference in morphology and exhibit slightly shifted of near band edge emission of Photoluminescence other than having a similar calculated crystallite size of nanostructures. The viability of cells after 72h were obtained and the statistical significance value was calculated using SPSS v20. The p value is more than 0.05 between untreated and treated cell with ZnO. This insignificant value of p>0.05 can be summarized as a non-toxic level of ZnO-4 and ZnO-8 on the L929 cell line.
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Gold nanoparticles deposited on glass: physicochemical characterization and cytocompatibility
2013-01-01
Properties of gold films sputtered under different conditions onto borosilicate glass substrate were studied. Mean thickness of sputtered gold film was measured by gravimetry, and film contact angle was determined by goniometry. Surface morphology was examined by atomic force microscopy, and electrical sheet resistance was determined by two-point technique. The samples were seeded with rat vascular smooth muscle cells, and their adhesion and proliferation were studied. Gold depositions lead to dramatical changes in the surface morphology and roughness in comparison to pristine substrate. For sputtered gold structures, the rapid decline of the sheet resistance appears on structures deposited for the times above 100 s. The thickness of deposited gold nanoparticles/layer is an increasing function of sputtering time and current. AFM images prove the creation of separated gold islands in the initial deposition phase and a continuous gold coverage for longer deposition times. Gold deposition has a positive effect on the proliferation of vascular smooth muscle cells. Largest number of cells was observed on sample sputtered with gold for 20 s and at the discharge current of 40 mA. This sample exhibits lowest contact angle, low relative roughness, and only mild increase of electrical conductivity. PMID:23705782
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Toxicity evaluation of ZnO nanostructures on L929 fibroblast cell line using MTS assay
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bakhori, Siti Khadijah Mohd; Mahmud, Shahrom; Ann, Ling Chuo
2015-04-24
ZnO has wide applications in medical and dentistry apart from being used as optoelectronic devices such as solar cells, photodetectors, sensors and light emitting diodes (LEDs). Therefore, the toxicity evaluation is important to know the toxicity level on normal cell line. The toxicity of two grades ZnO nanostructures, ZnO-4 and ZnO-8 have been carried out using cytotoxicity test of MTS assay on L929 rat fibroblast cell line. Prior to that, ZnO-4 and ZnO-8 were characterized for its morphology, structure and optical properties using FESEM, X-ray diffraction, and Photoluminescence respectively. The two groups revealed difference in morphology and exhibit slightly shiftedmore » of near band edge emission of Photoluminescence other than having a similar calculated crystallite size of nanostructures. The viability of cells after 72h were obtained and the statistical significance value was calculated using SPSS v20. The p value is more than 0.05 between untreated and treated cell with ZnO. This insignificant value of p>0.05 can be summarized as a non-toxic level of ZnO-4 and ZnO-8 on the L929 cell line.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Miyawaki, Izuru, E-mail: izuru-miyawaki@ds-pharma.co.jp; Tamura, Akitoshi; Matsumoto, Izumi
Clobazam (CLB) is known to increase hepatobiliary thyroxine (T4) clearance in Sprague–Dawley (SD) rats, which results in hypothyroidism followed by thyroid follicular cell hypertrophy. However, the mechanism of the acceleration of T4-clearance has not been fully investigated. In the present study, we tried to clarify the roles of hepatic UDP-glucronosyltransferase (UGT) isoenzymes (UGT1A and UGT2B) and efflux transporter (multidrug resistance–associated protein-2; MRP2) in the CLB-induced acceleration of T4-clearance using two mutant rat strains, UGT1A-deficient mutant (Gunn) and MRP2-deficient mutant (EHBR) rats, especially focusing on thyroid morphology, levels of circulating hormones (T4 and triiodothyronine (T3)) and thyroid-stimulating hormone (TSH), and mRNAmore » or protein expressions of UGTs (Ugt1a1, Ugt1a6, and Ugt2b1/2) and MRP2 (Mrp). CLB induced thyroid morphological changes with increases in TSH in SD and Gunn rats, but not in EHBR rats. T4 was slightly decreased in SD and Gunn rats, and T3 was decreased in Gunn rats, whereas these hormones were maintained in EHBR rats. Hepatic Ugt1a1, Ugt1a6, Ugt2b1/2, and Mrp2 mRNAs were upregulated in SD rats. In Gunn rats, UGT1A mRNAs (Ugt1a1/6) and protein levels were quite low, but UGT2B mRNAs (Ugt2b1/2) and protein were prominently upregulated. In SD and Gunn rats, MRP2 mRNA and protein were upregulated to the same degree. These results suggest that MRP2 is an important contributor in development of the thyroid cellular hypertrophy in CLB-treated rats, and that UGT1A and UGT2B work in concert with MRP2 in the presence of MRP2 function to enable the effective elimination of thyroid hormones. -- Highlights: ► Role of UGT and MRP2 in thyroid pathology was investigated in clobazam-treated rats. ► Clobazam induced thyroid cellular hypertrophy in SD and Gunn rats, but not EHBR rats. ► Hepatic Mrp2 gene and protein were upregulated in SD and Gunn rats, but not EHBR rats. ► Neither serum thyroid hormones (T3/T4) nor thyroid pathology changed in EHBR rats. ► Mrp2 was implied to be a key molecule in clobazam-induced thyroid pathology in rats.« less
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Synchrotron-based XRD from rat bone of different age groups.
Rao, D V; Gigante, G E; Cesareo, R; Brunetti, A; Schiavon, N; Akatsuka, T; Yuasa, T; Takeda, T
2017-05-01
Synchrotron-based XRD spectra from rat bone of different age groups (w, 56 w and 78w), lumber vertebra at early stages of bone formation, Calcium hydroxyapatite (HAp) [Ca 10 (PO 4 ) 6 (OH) 2 ] bone fill with varying composition (60% and 70%) and bone cream (35-48%), has been acquired with 15keV synchrotron X-rays. Experiments were performed at Desy, Hamburg, Germany, utilizing the Resonant and Diffraction beamline (P9), with 15keV X-rays (λ=0.82666 A 0 ). Diffraction data were quantitatively analyzed using the Rietveld refinement approach, which allowed us to characterize the structure of these samples in their early stages. Hydroxyapatite, received considerable attention in medical and materials sciences, since these materials are the hard tissues, such as bone and teeth. Higher bioactivity of these samples gained reasonable interest for biological application and for bone tissue repair in oral surgery and orthopedics. The results obtained from these samples, such as phase data, crystalline size of the phases, as well as the degree of crystallinity, confirm the apatite family crystallizing in a hexagonal system, space group P6 3 /m with the lattice parameters of a=9.4328Å and c=6.8842Å (JCPDS card #09-0432). Synchrotron-based XRD patterns are relatively sharp and well resolved and can be attributed to the hexagonal crystal form of hydroxyapatite. All the samples were examined with scanning electron microscope at an accelerating voltage of 15kV. The presence of large globules of different sizes is observed, in small age groups of the rat bone (8w) and lumber vertebra (LV), as distinguished from, large age groups (56 and 78w) in all samples with different magnification, reflects an amorphous phase without significant traces of crystalline phases. Scanning electron microscopy (SEM) was used to characterize the morphology and crystalline properties of Hap, for all the samples, from 2 to 100μm resolution. Copyright © 2017 Elsevier B.V. All rights reserved.
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Angeloni, Nicholas L.; Bond, Christopher W.; Monsivais, Diana; Tang, Yi; Podlasek, Carol A.
2010-01-01
Introduction Sonic hedgehog (SHH) is an essential regulator of smooth muscle apoptosis in the penis that has significant clinical potential as a therapy to suppress post-prostatectomy apoptosis, an underlying cause of erectile dysfunction (ED). Thus an understanding of how SHH signaling is regulated in the adult penis is essential to move the field of ED research forward and to develop new treatment strategies. We propose that hedgehog-interacting protein (HIP), which has been shown to bind SHH protein and to play a role in SHH regulation during embryogenesis of other organs, is a critical regulator of SHH signaling, penile morphology, and apoptosis induction. Aims We have examined HIP signaling in the penis and cavernous nerve (CN) during postnatal differentiation of the penis, in CN-injured, and a diabetic model of ED. Methods HIP localization/abundance and RNA abundance were examined by immunohistochemical (IHC) analysis and real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in Sprague-Dawley rats between the ages of 7 and 92 days old, in CN-injured Sprague-Dawley rats and in BioBreeding/Worcester diabetic rats. HIP signaling was perturbed in the pelvic ganglia and in the penis and TUNEL assay was performed in the penis. CN tie, lidocaine, and anti-kinesin experiments were performed to examine HIP signaling in the CN and penis. Results In this study we are the first to demonstrate that HIP undergoes anterograde transport to the penis via the CN, that HIP perturbation in the pelvic ganglia or the penis induces apoptosis, and that HIP plays a role in maintaining CN integrity, penile morphology, and SHH abundance. Conclusions These studies are significant because they show HIP involvement in cross-talk (signaling) between the pelvic ganglia and penis, which is integral for maintenance of penile morphology and they suggest a mechanism of how nerves may regulate target organ morphology and function. PMID:19515211
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2018-01-01
The morphology of an animal’s face will have large effects on the sensory information it can acquire. Here we quantify the arrangement of cranial sensory structures of the rat, with special emphasis on the mystacial vibrissae (whiskers). Nearly all mammals have vibrissae, which are generally arranged in rows and columns across the face. The vibrissae serve a wide variety of important behavioral functions, including navigation, climbing, wake following, anemotaxis, and social interactions. To date, however, there are few studies that compare the morphology of vibrissal arrays across species, or that describe the arrangement of the vibrissae relative to other facial sensory structures. The few studies that do exist have exploited the whiskers’ grid-like arrangement to quantify array morphology in terms of row and column identity. However, relying on whisker identity poses a challenge for comparative research because different species have different numbers and arrangements of whiskers. The present work introduces an approach to quantify vibrissal array morphology regardless of the number of rows and columns, and to quantify the array’s location relative to other sensory structures. We use the three-dimensional locations of the whisker basepoints as fundamental parameters to generate equations describing the length, curvature, and orientation of each whisker. Results show that in the rat, whisker length varies exponentially across the array, and that a hard limit on intrinsic curvature constrains the whisker height-to-length ratio. Whiskers are oriented to “fan out” approximately equally in dorsal-ventral and rostral-caudal directions. Quantifying positions of the other sensory structures relative to the whisker basepoints shows remarkable alignment to the somatosensory cortical homunculus, an alignment that would not occur for other choices of coordinate systems (e.g., centered on the midpoint of the eyes). We anticipate that the quantification of facial sensory structures, including the vibrissae, will ultimately enable cross-species comparisons of multi-modal sensing volumes. PMID:29621356
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Ennulat, Daniela; Magid-Slav, Michal; Rehm, Sabine; Tatsuoka, Kay S
2010-08-01
Nonclinical studies provide the opportunity to anchor biochemical with morphologic findings; however, liver injury is often complex and heterogeneous, confounding the ability to relate biochemical changes with specific patterns of injury. The aim of the current study was to compare diagnostic performance of hepatobiliary markers for specific manifestations of drug-induced liver injury in rat using data collected in a recent hepatic toxicogenomics initiative in which rats (n = 3205) were given 182 different treatments for 4 or 14 days. Diagnostic accuracy of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbili), serum bile acids (SBA), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), total cholesterol (Chol), and triglycerides (Trig) was evaluated for specific types of liver histopathology by Receiver Operating Characteristic (ROC) analysis. To assess the relationship between biochemical and morphologic changes in the absence of hepatocellular necrosis, a second ROC analysis was performed on a subset of rats (n = 2504) given treatments (n = 152) that did not cause hepatocellular necrosis. In the initial analysis, ALT, AST, Tbili, and SBA had the greatest diagnostic utility for manifestations of hepatocellular necrosis and biliary injury, with comparable magnitude of area under the ROC curve and serum hepatobiliary marker changes for both. In the absence of hepatocellular necrosis, ALT increases were observed with biochemical or morphologic evidence of cholestasis. In both analyses, diagnostic utility of ALP and GGT for biliary injury was limited; however, ALP had modest diagnostic value for peroxisome proliferation, and ALT, AST, and total Chol had moderate diagnostic utility for phospholipidosis. None of the eight markers evaluated had diagnostic value for manifestations of hypertrophy, cytoplasmic rarefaction, inflammation, or lipidosis.
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Zhou, Zi-Yi; Tang, Yu-Ping; Xiang, Jun; Wua, Pin; Jin, Hui-Ming; Wang, Zhong; Mori, Masao; Cai, Ding-Fang
2010-08-19
To investigate the neuroprotective effects of water-soluble Ganoderma lucidum polysaccharides (GLPS) on cerebral ischemic injury in rats, and to explore the involved mechanisms. Two models [middle cerebral artery occlusion (MCAO) in Sprague-Dawley (SD) rats and oxygen and glucose deprivation (OGD) in primary cultured rat cortical neurons] were employed to mimic ischemia-reperfusion (I/R) damage, in vivo and in vitro, respectively. Cerebral infarct area was measured by tetrazolium staining, and neurological functional deficits were assessed at 24h after I/R. Neuronal apoptosis was studied by Nissl staining and DNA fragmentation assay. Neuronal injury was assessed by morphological examination using phase-contrast microscopy and quantified by measuring the amount of lactate dehydrogenase (LDH) leakage, cell viability was measured by sodium 3'-1- (phenylaminocarbonyl)-3, 4-tetrazolium-bis (4-methoxy-6-nitro) benzene sulfonic acid (XTT) reduction. Neuronal apoptosis was determined by flow cytometry, and electron microscopy was used to study morphological changes of neurons. Caspase-3, -8 and -9 activation and Bcl-2, Bax protein expression were determined by western blot analysis. Oral administration of GLPS (100, 200 and 400mg/kg) significantly reduced cerebral infarct area, attenuated neurological functional deficits, and reduced neuronal apoptosis in ischemic cortex. In OGD model, GLSP (0.1, 1 and 10 microg/ml) effectively reduced neuronal cell death and relieved cell injury. Moreover, GLPS decreased the percentage of apoptotic neurons, relieved neuronal morphological damage, suppressed overexpression of active caspases-3, -8 and -9 and Bax, and inhibited the reduction of Bcl-2 expression. Our findings indicate that GLPS protects against cerebral ischemic injury by inhibiting apoptosis by downregulating caspase-3 activation and modulating the Bcl-2/Bax ratio. (c) 2010 Elsevier Ireland Ltd. All rights reserved.
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Ohguro, Hiroshi; Katsushima, Harumi; Maruyama, Ikuyo; Maeda, Tadao; Yanagihashi, Satsuki; Metoki, Tomomi; Nakazawa, Mitsuru
2002-09-01
The purpose of this study was to investigate the effects of glutamate accumulation in vitreous on retinal structure and function, due to a diet high in sodium glutamate. Three different diet groups were created, consisting of rats fed on a regular diet (diet A), a moderate excess of sodium glutamate diet (diet B) and a large excess of sodium glutamate diet (diet C). After 1, 3 and 6 months of the administration of these diets, amino acids concentrations in vitreous were analyzed. In addition, retinal morphology and function by electroretinogram (ERG) of three different diet groups were studied. Significant accumulation of glutamate in vitreous was observed in rats following addition of sodium glutamate to the diet as compared to levels with a regular diet. In the retinal morphology, thickness of retinal neuronal layers was remarkably thinner in rats fed on sodium glutamate diets than in those on a regular diet. TdT-dUTP terminal nick-end labelling (TUNEL) staining revealed significant accumulation of the positive staining cells within the retinal ganglion cell layers in retinas from diets B and C as compared with that from diet A. Similar to this, immunohistochemistry demonstrated increased expression of glial fibrillary acidic protein (GFAP) within the retinal inner layers from diets B and C as compared with diet A. Functionally, ERG responses were reduced in rats fed on a sodium glutamate diets as compared with those on a regular diet. The present study suggests that a diet with excess sodium glutamate over a period of several years may increase glutamate concentrations in vitreous and may cause retinal cell destruction.
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NASA Astrophysics Data System (ADS)
Molthen, Robert; Wu, Qingping; Baumgardt, Shelley; Kohlhepp, Laura; Shingrani, Rahul; Krenz, Gary
2010-03-01
Pulmonary hypertension (PH) is an incurable condition inevitably resulting in death because of increased right heart workload and eventual failure. PH causes pulmonary vascular remodeling, including muscularization of the arteries, and a reduction in the typically large vascular compliance of the pulmonary circulation. We used a rat model of monocrotaline (MCT) induced PH to evaluated and compared Captopril (an angiotensin converting enzyme inhibitor with antioxidant capacity) and N-acetylcysteine (NAC, a mucolytic with a large antioxidant capacity) as possible treatments. Twenty-eight days after MCT injection, the rats were sacrificed and heart, blood, and lungs were studied to measure indices such as right ventricular hypertrophy (RVH), hematocrit, pulmonary vascular resistance (PVR), vessel morphology and biomechanics. We implemented microfocal X-ray computed tomography to image the pulmonary arterial tree at intravascular pressures of 30, 21, 12, and 6 mmHg and then used automated vessel detection and measurement algorithms to perform morphological analysis and estimate the distensibility of the arterial tree. The vessel detection and measurement algorithms quickly and effectively mapped and measured the vascular trees at each intravascular pressure. Monocrotaline treatment, and the ensuing PH, resulted in a significantly decreased arterial distensibility, increased PVR, and tended to decrease the length of the main pulmonary trunk. In rats with PH induced by monocrotaline, Captopril treatment significantly increased arterial distensibility and decrease PVR. NAC treatment did not result in an improvement, it did not significantly increase distensibility and resulted in further increase in PVR. Interestingly, NAC tended to increase peripheral vascular density. The results suggest that arterial distensibility may be more important than distal collateral pathways in maintaining PVR at normally low values.
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Mu, Shuhua; Wu, Jiajia; Chen, Si; OuYang, Lisi; Lei, Wanlong
2014-01-01
Huntington's disease (HD) is a neurological degenerative disease and quinolinic acid (QA) has been used to establish HD model in animals through the mechanism of excitotoxicity. Yet the specific pathological changes and the underlying mechanisms are not fully elucidated. We aimed to reveal the specific morphological changes of different striatal neurons in the HD model. Sprague-Dawley (SD) rats were subjected to unilaterally intrastriatal injections of QA to mimic the HD model. Behavioral tests, histochemical and immunhistochemical stainings as well as Western blots were applied in the present study. The results showed that QA-treated rats had obvious motor and cognitive impairments when compared with the control group. Immunohistochemical detection showed a great loss of NeuN+ neurons and Darpp32+ projection neurons in the transition zone in the QA group when compared with the control group. The numbers of parvalbumin (Parv)+ and neuropeptide Y (NPY)+ interneurons were both significantly reduced while those of calretinin (Cr)+ and choline acetyltransferase (ChAT)+ were not changed notably in the transition zone in the QA group when compared to the controls. Parv+, NPY+ and ChAT+ interneurons were not significantly increased in fiber density while Cr+ neurons displayed an obvious increase in fiber density in the transition zone in QA-treated rats. The varicosity densities of Parv+, Cr+ and NPY+ interneurons were all raised in the transition zone after QA treatment. In conclusion, the present study revealed that QA induced obvious behavioral changes as well as a general loss of striatal projection neurons and specific morphological changes in different striatal interneurons, which may help further explain the underlying mechanisms and the specific functions of various striatal neurons in the pathological process of HD. PMID:24632560
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Chen, Chun-Han; Chang, Cheng-Chih; Shih, Tsung-Hsien; Aljuffali, Ibrahim A; Yeh, Ta-Sen; Fang, Jia-You
2015-01-01
Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery. PMID:25848259
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Chen, Chun-Han; Chang, Cheng-Chih; Shih, Tsung-Hsien; Aljuffali, Ibrahim A; Yeh, Ta-Sen; Fang, Jia-You
2015-01-01
Roux-en-Y gastric bypass (RYGB) is a popular surgery to reduce the body weight of obese patients. Although food intake is restricted by RYGB, drug absorption is also decreased. The purpose of this study was to develop novel self-nanoemulsifying drug delivery systems (SNEDDS) for enhancing the oral delivery of silymarin, which has poor water solubility. The SNEDDS were characterized by size, zeta potential, droplet number, and morphology. A technique of RYGB was performed in Sprague-Dawley rats. SNEDDS were administered at a silymarin dose of 600 mg/kg in normal and RYGB rats for comparison with silymarin aqueous suspension and polyethylene glycol (PEG) 400 solution. Plasma silibinin, the main active ingredient in silymarin, was chosen for estimating the pharmacokinetic parameters. SNEDDS diluted in simulated gastric fluid exhibited a droplet size of 190 nm with a spherical shape. The nanocarriers promoted silibinin availability via oral ingestion in RYGB rats by 2.5-fold and 1.5-fold compared to the suspension and PEG 400 solution, respectively. A significant double-peak concentration of silibinin was detected for RYGB rats receiving SNEDDS. Fluorescence imaging showed a deeper and broader penetration of Nile red, the fluorescence dye, into the gastrointestinal mucosa from SNEDDS than from PEG 400 solution. Histological examination showed that SNEDDS caused more minor inflammation at the gastrointestinal membrane as compared with that caused by PEG 400 solution, indicating a shielding of direct silymarin contact with the mucosa by the nanodroplets. SNEDDS generally showed low-level or negligible irritation in the gastrointestinal tract. Silymarin-loaded SNEDDS were successfully developed to improve the dissolution, permeability, and oral bioavailability of silymarin. To the best of our knowledge, this is the first investigation reporting the usefulness of SNEDDS for improving drug malabsorption elicited by gastric bypass surgery.
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Hsu, Pei-Yu; Tsai, Ming-Tzu; Wang, Shun-Ping; Chen, Ying-Ju; Wu, Jay; Hsu, Jui-Ting
2016-01-01
Objective This study used microcomputed tomography (micro-CT) to evaluate the effects of ovariectomy on the trabecular bone microarchitecture and cortical bone morphology in the femoral neck and mandible of female rats. Materials and Methods Twelve female Wister rats were divided into two groups: the control and ovariectomized groups. The rats in the ovariectomized group received ovariectomy at 8 weeks of age; all the rats were sacrificed at 20 weeks of age, and their mandibles and femurs were removed and scanned using micro-CT. Four microstructural trabecular bone parameters were measured for the region below the first mandibular molar and the femoral neck region: bone volume fraction (BV/TV), trabecular thickness (TbTh), trabecular separation (TbSp), and trabecular number (TbN). In addition, four cortical bone parameters were measured for the femoral neck region: total cross-sectional area (TtAr), cortical area (CtAr), cortical bone area fraction (CtAr/TtAr), and cortical thickness (CtTh). The CtTh at the masseteric ridge was used to assess the cortical bone morphology in the mandible. The trabecular bone microarchitecture and cortical bone morphology in the femoral necks and mandibles of the control group were compared with those of the ovariectomized group. Furthermore, Spearman’s correlation (rs) was conducted to analyze the correlation between the osteoporosis conditions of the mandible and femoral neck. Results Regarding the trabecular bone microarchitectural parameters, the BV/TV of the trabecular bone microarchitecture in the femoral necks of the control group (61.199±11.288%, median ± interquartile range) was significantly greater than that of the ovariectomized group (40.329±5.153%). Similarly, the BV/TV of the trabecular bone microarchitecture in the mandibles of the control group (51.704±6.253%) was significantly greater than that of the ovariectomized group (38.486±9.111%). Furthermore, the TbSp of the femoral necks in the ovariectomized group (0.185±0.066 mm) was significantly greater than that in the control group (0.130±0.026mm). Similarly, the TbSp of the mandibles in the ovariectomized group (0.322±0.047mm) was significantly greater than that in the control group (0.285±0.041mm). However, the TbTh and TbN trends for the mandibles and femoral necks were inconsistent between the control and ovariectomized groups. Regarding the cortical bone morphology parameters, the TtAr of the femoral necks in the ovariectomized group was significantly smaller than that in the control group. There was no significant difference in the TtAr, CtAr, or CtTh of the femoral necks between the control and ovariectomized groups, and no significant difference in the CtTh of the mandibles between the control and ovariectomized groups. Moreover, the BV/TV and TbSp of the mandibles were highly correlated with those of the femurs (rs = 0.874 and rs = 0.755 for BV/TV and TbSp, respectively). Nevertheless, the TbTh, TbN, and CtTh of the mandibles were not correlated with those of the femoral necks. Conclusion After the rats were ovariectomized, osteoporosis of the trabecular bone microarchitecture occurred in their femurs and mandibles; however, ovariectomy did not influence the cortical bone morphology. In addition, the parametric values of the trabecular bone microarchitecture in the femoral necks were highly correlated with those of the trabecular bone microarchitecture in the mandibles. PMID:27127909
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Szentmihályi, Klára; Fehér, Erzsébet; Vinkler, Péter; Kéry, Agnes; Blázovics, Anna
2004-01-01
A hyperlipidemic rat model was used to examine the therapeutic effect of Sempervivum tectorum plant extract on the metabolic alterations of Al, As, B, Ba, Cd, Hg, Ni, Pb, and Ti in the liver and bile. Hyperlipidemia was produced by lipogenic diet and alcohol and verified by morphological investigation of the liver with the aid of light and an electron microscope. Element concentration in the liver and bile were determined by inductively coupled plasma optical emission spectrometry (ICP-OES). The concentration values in the liver higher than the detection limit (Al, Ba, Ni, Ti) were unambiguous. Significant differences were found for the four groups at p < 0.05 level (ANOVA). A significant difference was observed between Al and B concentration in the bile fluids of the 4 groups (p < 0.05). The excretion of Al and Ti into the bile fluid increased significantly (p < 0.05). Following the administration of S. tectorum extract to rats with hyperlipidemia, the excretion of Al, B and Ba increased, whereas the excretion of Ti decreased significantly (p < 0.05). The favorable action of the extract (protecting the liver in hyperlipidemic rats) was verified by morphological studies, and its detoxicating property was shown by the elimination of Al, Ba, Ni, and Ti from the liver.
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Lee, Seung Hyun; Lee, Byoung Wook; Kim, Seong Who; Choo, Suk Jung
2017-01-01
Decellularization is a proposed method of preparing nonautologous biological arterial vascular scaffolding; however, the fate of the supporting medial elastic fiber, which is important in preserving the vascular structural integrity, is uncertain. The influence of losartan on preserving the medial elastic fiber integrity in decellularized small diameter vascular conduits (SDVC) was investigated. Decellularized infrarenal abdominal aortic allografts were implanted in Sprague-Dawley rats treated either with (study rats, n = 6) or without oral losartan (control rats, n = 6) and graded 8 weeks later according to a remodeling scoring system (1-mild, 2-moderate, 3-severe) which we devised based on the intimal hyperplasia degree, morphologic changes, and elastic fiber fragmentation of the conduits. DAPI immunohistochemistry analysis was performed in 47 (25 decellularization only and 22 losartan treatment) cross-sectional slide specimens. The losartan versus decellularization only SDVC showed a significantly lower medial elastic fragmentation score (1.32 vs. 2.24, P < 0.001), superior medial layer preservation, and relatively more normal appearing intimal cellular morphology. The results suggested rats receiving decellularized SDVCs treated with losartan may yield superior medial layer elastic fiber preservation. © 2016 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.
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Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N
2016-12-01
Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.
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Carvalho, S I C; Bianchetti, L B; Ragassi, C F; Ribeiro, C S C; Reifschneider, F J B; Buso, G S C; Faleiro, F G
2017-07-06
Characterization studies provide essential information for the conservation and use of germplasm in plant breeding programs. In this study, 103 Capsicum frutescens L. accessions from the Active Germplasm Bank of Embrapa Hortaliças, representative of all five Brazilian geographic regions, were characterized based on morphological characteristics and microsatellite (or simple sequence repeat - SSR) molecular markers. Morphological characterization was carried out using 57 descriptors, and molecular characterization was based on 239 alleles from 24 microsatellite loci. From the estimates of genetic distances among accessions, based on molecular characterization, a cluster analysis was carried out, and a dendrogram was established. Correlations between morphological and molecular variables were also estimated. Twelve morphological descriptors were monomorphic for the set of C. frutescens accessions, and those with the highest degree of polymorphism were stem length (14.0 to 62.0 cm), stem diameter (1.0 to 4.2 cm), days to flowering (90 to 129), days to fruiting (100 to 140), fruit weight (0.1 to 1.4 g), fruit length (0.6 to 4.6 cm), and fruit wall thickness (0.25 to 1.5 mm). The polymorphism information content for the SSR loci varied from 0.36 (EPMS 417) to 0.75 (CA49), with an overall mean of 0.57. The correlation value between morphological and molecular characterization data was 0.6604, which was statistically significant. Fourteen accessions were described as belonging to the morphological type tabasco, 85 were described as malagueta, and four were malaguetinha, a morphological type confirmed in this study. The typical morphological pattern of malagueta was described. Six similarity groups were established for C. frutescens based on the dendrogram and are discussed individually. The genetic variability analyzed in the study highlights the importance of characterizing genetic resources available for the development of new C. frutescens cultivars with the potential for various niche markets.
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Hyaluronic acid injections protect patellar tendon from detraining-associated damage.
Frizziero, Antonio; Salamanna, Francesca; Giavaresi, Gianluca; Ferrari, Andrea; Martini, Lucia; Marini, Marina; Veicsteinas, Arsenio; Maffulli, Nicola; Masiero, Stefano; Fini, Milena
2015-09-01
Having previously demonstrated that detraining affects patellar tendon (PT) proteoglycan content and collagen fiber organization, we undertook the present study with two aims: to improve knowledge on the adaptation of PT and its enthesis to detraining from a histological and histomorphometric point of view, and to investigate the hypothesis that repeated peri-patellar injections of hyaluronic acid (HA) on detrained PT may reduce and limit detrained associated-damage. Twenty-four male Sprague-Dawley rats were divided into 3 groups: Untrained (n=6), Trained (n=6) (10 wks-treadmill) and Detrained (n=12). In the detrained rats, the left tendon was untreated while the right tendon received repeated peri-patellar injections of either HA or saline (NaCl). Structure and morphology of PTs (modified Movin score, tear density, collagen type I and III) and enthesis (cell morphology, chondrocyte cluster formation, tidemark integrity, matrix staining and vascularization) were evaluated. The left PT and enthesis of the Detrained groups showed altered structure and morphology with the highest Movin score values, the highest percentage of collagen III and the lowest of collagen I; the lowest score values were observed in the Trained and Detrained-HA groups. Detrained-NaCl PTs showed the highest collagen III and the lowest collagen I values with respect to Detrained-HA PTs. This study strengthens previously published data showing the alteration in tendon and enthesis morphology due to discontinuation of training, and provides new data showing that treatment with HA is effective in the maintenance of the structural properties of PT and enthesis in Detrained rats. Such beneficial effects could play a significant role in the management of conservative and rehabilitation strategies in athletes that change type, intensity and duration of training.
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Jampilek, Josef; Zaruba, Kamil; Oravec, Michal; Kunes, Martin; Babula, Petr; Ulbrich, Pavel; Brezaniova, Ingrid; Opatrilova, Radka; Triska, Jan; Suchy, Pavel
2015-01-01
The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain.
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Zaruba, Kamil; Kunes, Martin; Ulbrich, Pavel; Brezaniova, Ingrid; Triska, Jan; Suchy, Pavel
2015-01-01
The blood-brain barrier prevents the passage of many drugs that target the central nervous system. This paper presents the preparation and characterization of silica-based nanocarriers loaded with piracetam, pentoxifylline, and pyridoxine (drugs from the class of nootropics), which are designed to enhance the permeation of the drugs from the circulatory system through the blood-brain barrier. Their permeation was compared with non-nanoparticle drug substances (bulk materials) by means of an in vivo model of rat brain perfusion. The size and morphology of the nanoparticles were characterized by transmission electron microscopy. The content of the drug substances in silica-based nanocarriers was analysed by elemental analysis and UV spectrometry. Microscopic analysis of visualized silica nanocarriers in the perfused brain tissue was performed. The concentration of the drug substances in the tissue was determined by means of UHPLC-DAD/HRMS LTQ Orbitrap XL. It was found that the drug substances in silica-based nanocarriers permeated through the blood brain barrier to the brain tissue, whereas bulk materials were not detected in the brain. PMID:26075264
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Madgulkar, Ashwini R; Bhalekar, Mangesh R; Kadam, Ashwini A
2018-01-01
Lopinavir is a BCS Class IV drug exhibiting poor bioavailability due to P-gp efflux and limited permeation. The aim of this research was to formulate and characterize microspheres of lopinavir using thiolated xyloglucan (TH-MPs) as carrier to improve its oral bioavailability without co-administration of ritonavir. Thiomeric microspheres were prepared by ionotropic gelation between alginic acid and calcium ions. Interaction studies were performed using Fourier transform infrared spectroscopy (FT-IR). The thiomeric microspheres were characterized for its entrapment efficiency, T 80 , surface morphology, and mucoadhesion employing in vitro wash off test. The microspheres were optimized by 3 2 factorial design. The optimized thiomeric microsphere formulation revealed 93.12% entrapment efficiency, time for 80% drug release (T 80 ) of 358.1 min, and 88% mucoadhesion after 1 h. The permeation of lopinavir from microspheres was enhanced 3.15 times as determined by ex vivo study using everted chick intestine and increased relative bioavailability over 3.22-fold over combination of lopinavir and ritonavir as determined by in vivo study in rat model.
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Morphofunctional analysis of experimental model of esophageal achalasia in rats.
Sabirov, A G; Raginov, I S; Burmistrov, M V; Chelyshev, Y A; Khasanov, R Sh; Moroshek, A A; Grigoriev, P N; Zefirov, A L; Mukhamedyarov, M A
2010-10-01
We carried out a detailed analysis of rat model of esophageal achalasia previously developed by us. Manifest morphological and functional disorders were observed in experimental achalasia: hyperplasia of the squamous epithelium, reduced number of nerve fibers, excessive growth of fibrous connective tissue in the esophageal wall, high contractile activity of the lower esophageal sphincter, and reduced motility of the longitudinal muscle layer. Changes in rat esophagus observed in experimental achalasia largely correlate with those in esophageal achalasia in humans. Hence, our experimental model can be used for the development of new methods of disease treatment.
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Oliveira, Ana Ca; Pereira, Maria Cs; Santana, Luana N da Silva; Fernandes, Rafael M; Teixeira, Francisco B; Oliveira, Gedeão B; Fernandes, Luanna Mp; Fontes-Júnior, Enéas A; Prediger, Rui D; Crespo-López, Maria E; Gomes-Leal, Walace; Lima, Rafael R; Maia, Cristiane do Socorro Ferraz
2015-06-01
There is increasing evidence that heavy ethanol exposure in early life may produce long-lasting neurobehavioral consequences, since brain structural maturation continues until adolescence. It is well established that females are more susceptible to alcohol-induced neurotoxicity and that ethanol consumption is increasing among women, especially during adolescence. In the present study, we investigated whether chronic ethanol exposure during adolescence through early adulthood in female rats may induce hippocampal histological damage and neurobehavioral impairments. Female rats were treated with distilled water or ethanol (6.5 g/kg/day, 22.5% w/v) by gavage from the 35(th)-90(th) day of life. Ethanol-exposed animals displayed reduced exploration of the central area and increased number of fecal boluses in the open field test indicative of anxiogenic responses. Moreover, chronic high ethanol exposure during adolescence induced marked impairments on short-term memory of female rats addressed on social recognition and step-down inhibitory avoidance tasks. These neurobehavioral deficits induced by ethanol exposure during adolescence through early adulthood were accompanied by the reduction of hippocampal formation volume as well as the loss of neurons, astrocytes and microglia cells in the hippocampus. These results indicate that chronic high ethanol exposure during adolescence through early adulthood in female rats induces long-lasting emotional and memory deficits associated with morphological and molecular alterations in the hippocampus. © The Author(s) 2015.
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Sexual differentiation of the adolescent rat brain: A longitudinal voxel-based morphometry study.
Sumiyoshi, Akira; Nonaka, Hiroi; Kawashima, Ryuta
2017-03-06
The sexual differentiation of the rat brain during the adolescent period has been well documented in post-mortem histological studies. However, to further understand the morphological changes occurring in the entire brain, a noninvasive neuroimaging method allowing an unbiased, comprehensive, and longitudinal investigation of brain morphology should be used. In this study, we investigated the sexual differentiation of the rat brain during the adolescent period using longitudinal voxel-based morphometry (VBM) analysis. Male and female Wistar rats (n=12 of each) were scanned in a 7.0-T MRI scanner at five time points from 6 to 10 weeks of age. The T2-weighted MRI images were segmented using the rat brain tissue priors that have been published by our laboratory. At the global level, the results of the VBM analysis showed greater increases in total gray matter volume in the males during the adolescent period, although we did not find significant differences in total white matter volume. At the voxel level, we found significant increases in the regional gray matter volume of the occipital cortex, amygdala, hippocampal formation, and cerebellum. At the regional level, only the occipital cortex in the females exhibited decreases during the adolescent period. These results were, at least in part, consistent with those of previous longitudinal VBM studies in humans, thus providing translational evidence of the sexual differentiation of the developing brain between rodents and humans. Copyright © 2017 Elsevier B.V. All rights reserved.
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Sub-chronic exposure to paraoxon neither induces nor exacerbates diabetes mellitus in Wistar rat.
Nurulain, Syed M; Petroianu, Georg; Shafiullah, Mohamed; Kalász, Huba; Oz, Murat; Saeed, Tariq; Adem, Abdu; Adeghate, Ernest
2013-10-01
There is an increasing belief that organophosphorus compounds (OPCs) impair glucose homeostasis and cause hyperglycemia and diabetes mellitus. The present study was undertaken to investigate the putative diabetogenic effect of sub-lethal and sub-chronic exposure to paraoxon (POX), an extremely hazardous OPC used in pesticides. The effect of paraoxon on streptozotocin-induced diabetic rats was also examined. Each rat was injected with 100 nmol of POX 5 days per week for 6 weeks. Blood glucose levels and red blood cell acetylcholinesterase activity were measured weekly. Biochemical analysis and morphological studies were performed at the end of the experiment. The results revealed that POX neither induces nor exacerbates diabetes mellitus in experimental rats. Liver and kidney/body weight ratios revealed statistically insignificant differences when compared with controls. Biochemical analysis of urine samples showed a small but not significant increase in protein level in all groups. Urine bilirubin was significantly higher in the diabetes + POX group when compared with the control group. The number of blood cells in urine was significantly higher in the POX-treated group compared with the control group. Hyperglycemia was noted in the diabetes and diabetes + POX groups, but neither in the saline control nor in POX-treated normal rats. Electron microscopy of POX-treated pancreas did not show any morphological changes in beta cells. These results suggest that POX does not cause diabetes mellitus at sub-lethal sub-chronic exposure. Copyright © 2012 John Wiley & Sons, Ltd.
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Evidence for Leydig cell dysfunction in rats with seminiferous tubule damage.
Rich, K A; Kerr, J B; de Kretser, D M
1979-02-01
To study the effects of seminiferous tubule damage on Leydig cell function and morphology, rats were treated by fetal irradiation (to induce Sertoli cell-only syndrome, SCO), 3 months administration of hydroxyurea (HU), or chronic feeding of a vitamin A-deficient diet (VAD). Leydig cell function was assessed by the measurement of serum LH and testosterone and the response of serum testosterone to hCG stimulation, while morphology was studied by electron microscopy after perfusion fixation. Serum LH was significantly elevated in each experimental group, while basal serum testosterone was significantly lower only in SCO rats. In all treatment groups, the serum testosterone response to hCG was significantly decreased when measureed as the area under the response curve. Despite a decreased response to hCG, the Leydig cells were larger than normal and showed striking increases in quantities of smooth endoplasmic reticulum, mitochondria and Golgi complex. Leydig cell dysfunction has been demonstrated in animals with varying degrees of seminiferous tubule damage, but paradoxically the cytological features of the Leydig cells were indicative of hypertrophy.
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Peng, Yuanyuan; Liu, Tong; Chen, Yupei; Zou, Dehui; Zhang, Li
2016-03-01
To observe the intervention effect of electroacupuncture (EA) at "Weizhong" (BL 40) on rats with bupivacaine-induced multifidus muscle injury, so as to explore the action mechanism. A total of 72 rats were randomly divided into a control group, a model group, a Weizhong group and a Shenshu group, 18 rats in each group. Each group was again randomly divided into a 4-day subgroup, a 7-day subgroup and a 14-day subgroup, 6 rats in each subgroup. Rats in the model group, Weizhong group and Shenshu group were treated with intramuscular injection of 0.5% bupivacaine (BPVC) to establish the model of multifidus muscle injury. Rats in the Weizhong group and Shenshu group were treated with EA at "Weizhong" (BL 40) and "Shenshu" (BL 23), 20 min per treatment, once a day. Each subgroup was treated for 4 days, 7 days and 14 days respectively. Rats in the control group and model group were treated with immobilization. The morphology and cross sectional area (CSA) changes of multifidus with HE and Masson staining at different time points were observed; the expression of insulin like growth factor 1 (IGF-1) and myogenic differentiation antigen (MyoD) was measured by immunohistochemical method. After the modeling, there were significant morphology changes of multifidus at different time points, which was not fully recovered after 14 days. The morphological observation in the Weizhong group and Shenshu group was superior to that in the model group. At 7th day, the CSA in the Weizhong group was higher than that in the model group (P < 0.05); at 14th day, the CSA in the Weizhong group and Shenshu group was higher than that in the model group (P < 0.01, P < 0.05). At 4th day and 7th day, the expression of IGF-1 in the model group was higher than that in the control group (both P < 0.01); at 4th day, that in the Weizhong group was higher than that in the model group (P < 0.01), and that in the Weizhong group was higher than that in the Shenshu group (P < 0.05), and that in the Shenshu group was as higher than that in the model group (P < 0.05); at 14th day, that in the Shenshu group was higher than that in the model and Weizhong group (P < 0.01). At 4th day, the expression of MyoD in the Weizhong group and Shenshu group was higher than that in the model group (P < 0.01), which was more significant in the Weizhong group (P < 0.01). Electroacupuncture at "Weizhong" (BL 40) and "Shenshu" (BL 23) can both promote the regeneration of multifidus muscle injury. EA at "Weizhong" (BL 40) has a better effect at early phase, which may be related to the up-regulation of IGF-1 and MyoD and the completion of the proliferation of myoblast in advance.
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Chhabra, Priyanka; Tyagi, Priyanka; Bhatnagar, Aseem; Mittal, Gaurav; Kumar, Amit
2016-01-01
Objective: To develop a chitosan-based scaffold and carry out a complete comprehensive study encompassing optimization of exact chitosan strength, product characterization, toxicity evaluation, in vitro validation in cell culture experiments, and finally in vivo efficacy in animal excision wound model. Materials and Methods: Developed chitosan scaffolds (CSs) were optimized for tissue engineering and wound healing efficacy by means of microstructure, toxicity, and biocompatibility evaluation. Results: Scanning electron microscope (SEM) studies revealed that porosity of CS decreased with increase in chitosan concentration. Chemical stability and integrity of scaffolds were confirmed by Fourier transform infrared studies. Highest swelling percentage (SP) of 500% was observed in 2%, while lowest (200%) was observed in 1% CS. Reabsorption and noncytotoxic property of optimized scaffold were established by enzymatic degradation and MTT assay. Enzymatic degradation suggested 20–45% of weight loss (WL) within 14 days of incubation. Cytotoxicity analysis showed that scaffolds were noncytotoxic against normal human dermal fibroblast human dermal fibroblast cell lines. Significant cellular adherence over the scaffold surface with normal cellular morphology was confirmed using SEM analysis. In vivo efficacy evaluation was carried out by means of reduction in wound size on Sprague-Dawley rats. Sprague-Dawley rats treated with optimized scaffold showed ~ 100% wound healing in comparison to ~80% healing in betadine-treated animals within 14 days. Histological examination depicted advance re-epithelization with better organization of collagen bundle in wound area treated with 2% CS in comparison to conventional treatment or no treatment. Conclusion: This study, thus, reveals that 2% CSs were found to have a great potential in wound healing. PMID:28216954
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Suzuki, Hiroki; Moritani, Tatsuru; Morinaga, Tadahiko; Seto, Yoshiki; Sato, Hideyuki; Onoue, Satomi
2017-03-15
The present study aimed to develop an amorphous solid dispersion (ASD) of cyclosporine A (CsA) by a fine droplet drying (FDD) process for improvement in oral absorption of CsA. CsA and hydroxypropyl cellulose-SSL were dissolved in 1,4-dioxane, and the solution was powdered by the FDD process to obtain the ASD formulation of CsA (ASD/CsA). The ASD/CsA was characterized in terms of morphology, particle size distribution, crystallinity, dissolution behavior, physicochemical stability, and pharmacokinetic behavior in rats. The ASD/CsA was obtained in the form of uniform spherical particles, and the span factor was calculated to be ca. 0.4. CsA in the formulation existed in an amorphous state. The ASD/CsA exhibited a higher dissolution behavior of CsA than amorphous CsA, whereas storage of the ASD/CsA under accelerated conditions led to impairment in the dissolution behavior. The constant release of CsA from non-aged ASD/CsA was observed during dissolution testing. After oral administration of CsA samples (10mg-CsA/kg) in rats, the ASD/CsA showed a high and sustained plasma concentration of CsA as evidenced by a 18-fold increase in the oral bioavailability of CsA compared with amorphous CsA. From these findings, the FDD process might be an efficacious option for the ASD formulation of CsA with enhanced biopharmaceutics properties. Copyright © 2017 Elsevier B.V. All rights reserved.
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Role of scanning electron microscopy in identifying drugs used in medical practice.
Fazil Marickar, Y M; Sylaja, N; Koshy, Peter
2009-10-01
Several plant preparations are administered for treatment of stone disease without scientific basis. This paper presents the results of in vitro and animal experimental studies using scanning electron microscopy (SEM) in the identification of the therapeutic properties of trial drugs in medicine. In the first set of the study, urinary crystals namely calcium oxalate monohydrate and calcium oxalate dehydrate were grown in six sets of Hane's tubes in silica gel medium. Trial drugs namely scoparia dulcis Lynn, musa sapiens and dolicos biflorus were incorporated in the gel medium to identify the dopant effect of the trial drugs on the size and extent of crystal column growth. The changes in morphology of crystals were studied using SEM. In the second set, six male Wistar rats each were calculogenised by administering sodium oxalate and ethylene glycol and diabetised using streptozotocin. The SEM changes of calculogenisation were studied. The rats were administered trial drugs before calculogenisation or after. The kidneys of the rats studied under the scanning electron microscope showed changes in tissue morphology and crystal deposition produced by calculogenisation and alterations produced by addition of trial drugs. The trial drugs produced changes in the pattern of crystal growth and in the crystal morphology of both calcium oxalate monohydrate and calcium oxalate dihydrate grown in vitro. Elemental distribution analysis showed that the crystal purity was not altered by the trial drugs. Scoparia dulcis Lynn was found to be the most effective anticalculogenic agent. Musa sapiens and dolicos biflorus were found to have no significant effect in inhibiting crystal growth. The kidneys of rats on calculogenisation showed different grades of crystals in the glomerulus and interstitial tissues, extrusion of the crystals into the tubular lumen, collodisation and tissue inflammatory cell infiltration. Scoparia dulcis Lynn exhibited maximum protector effect against the changes of calculogenisation. Musa sapiens and dolicos biflorus had only minimal effect in preventing crystal deposition, inflammatory cell infiltration and other changes of calculogenisation. SEM was found to be effective in assessing the effect of drugs on crystal growth morphology and tissue histology.
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Paffett, Michael L.; Hesterman, Jacob; Candelaria, Gabriel; Lucas, Selita; Anderson, Tamara; Irwin, Daniel; Hoppin, Jack; Norenberg, Jeffrey; Campen, Matthew J.
2012-01-01
Pulmonary arterial hypertension (PAH) has a complex pathogenesis involving both heart and lungs. Animal models can reflect aspects of the human pathology and provide insights into the development and underlying mechanisms of disease. Because of the variability of most animal models of PAH, serial in vivo measurements of cardiopulmonary function, morphology, and markers of pathology can enhance the value of such studies. Therefore, quantitative in vivo SPECT/CT imaging was performed to assess cardiac function, morphology and cardiac perfusion utilizing 201Thallium (201Tl) in control and monocrotaline-treated rats. In addition, lung and heart apoptosis was examined with 99mTc-Annexin V (99mTc-Annexin) in these cohorts. Following baseline imaging, rats were injected with saline or monocrotaline (50 mg/kg, i.p.) and imaged weekly for 6 weeks. To assess a therapeutic response in an established pulmonary hypertensive state, a cohort of rats received resveratrol in drinking water (3 mg/kg/day) on days 28–42 post-monocrotaline injection to monitor regression of cardiopulmonary apoptosis. PAH in monocrotaline-treated rats was verified by conventional hemodynamic techniques on day 42 (right ventricular systolic pressure (RSVP) = 66.2 mmHg in monocrotaline vs 28.8 mmHg in controls) and in terms of right ventricular hypertrophy (RV/LVS = 0.70 in monocrotaline vs 0.32 in controls). Resveratrol partially reversed both RVSP (41.4 mmHg) and RV/LVS (0.46), as well as lung edema and RV contractility +dP/dtmax. Serial 99mTc-Annexin V imaging showed clear increases in pulmonary and cardiac apoptosis when compared to baseline, which regressed following resveratrol treatment. Monocrotaline induced modest changes in whole-heart perfusion as assessed by 201TI imaging and cardiac morphological changes consistent with septal deviation and enlarged RV. This study demonstrates the utility of functional in vivo SPECT/CT imaging in rodent models of PAH and further confirms the efficacy of resveratrol in reversing established monocrotaline-induced PAH presumably by attenuation of cardiopulmonary apoptosis. PMID:22815866