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Sample records for rat extracardiac tissues

  1. Extracardiac manifestations of bacterial endocarditis.

    PubMed

    Heffner, J E

    1979-08-01

    Bacterial endocarditis is an elusive disease that challenges clinicians' diagnostic capabilities. Because it can present with various combinations of extravalvular signs and symptoms, the underlying primary disease can go unnoticed.A review of the various extracardiac manifestations of bacterial endocarditis suggests three main patterns by which the valvular infection can be obscured. (1) A major clinical event may be so dramatic that subtle evidence of endocarditis is overlooked. The rupture of a mycotic aneurysm may simulate a subarachnoid hemorrhage from a congenital aneurysm. (2) The symptoms of bacterial endocarditis may be constitutional complaints easily attributable to a routine, trivial illness. Symptoms of low-grade fever, myalgias, back pain and anorexia may mimic a viral syndrome. (3) Endocarditis poses a difficult diagnostic dilemma when it generates constellations of findings that are classic for other disorders. Complaints of arthritis and arthralgias accompanied by hematuria and antinuclear antibody may suggest systemic lupus erythematosus; a renal biopsy study showing diffuse proliferative glomerulonephritis may support this diagnosis. The combination of fever, petechiae, altered mental status, thrombocytopenia, azotemia and anemia may promote the diagnosis of thrombotic thrombocytopenic purpura. When the protean guises of bacterial endocarditis create these clinical difficulties, errors in diagnosis occur and appropriate therapy is delayed. Keen awareness of the varied disease presentations will improve success in managing endocarditis by fostering rapid diagnosis and prompt therapy. PMID:516715

  2. Tracheal tissue engineering in rats.

    PubMed

    Jungebluth, Philipp; Haag, Johannes C; Sjöqvist, Sebastian; Gustafsson, Ylva; Beltrán Rodríguez, Antonio; Del Gaudio, Costantino; Bianco, Alessandra; Dehnisch, Ivar; Uhlén, Per; Baiguera, Silvia; Lemon, Greg; Lim, Mei Ling; Macchiarini, Paolo

    2014-09-01

    Tissue-engineered tracheal transplants have been successfully performed clinically. However, before becoming a routine clinical procedure, further preclinical studies are necessary to determine the underlying mechanisms of in situ tissue regeneration. Here we describe a protocol using a tissue engineering strategy and orthotopic transplantation of either natural decellularized donor tracheae or artificial electrospun nanofiber scaffolds into a rat model. The protocol includes details regarding how to assess the scaffolds' biomechanical properties and cell viability before implantation. It is a reliable and reproducible model that can be used to investigate the crucial aspects and pathways of in situ tracheal tissue restoration and regeneration. The model can be established in <6 months, and it may also provide a means to investigate cell-surface interactions, cell differentiation and stem cell fate. PMID:25122525

  3. Adult extracardiac rhabdomyoma of the parapharyngeal space.

    PubMed

    Khan, Aayesha M; Chor, Paula J; Eisenbeis, John F

    2012-09-01

    Adult extracardiac rhabdomyoma (ER) is a rare, slowly growing, benign tumor of skeletal-muscle origin that has a strong predilection for the head and neck. Complete surgical resection has been proposed as the treatment of choice. We describe a case of adult ER that manifested as a nasopharyngeal mass. The diagnosis was made by transnasal endoscopic biopsy, and the patient was managed conservatively. We discuss the current knowledge regarding the clinical presentation, diagnosis, and treatment of adult ER of the parapharyngeal space, and we propose a new concept for treating this tumor nonsurgically in appropriately selected patients. PMID:22996720

  4. Avenanthramide bioavailability and tissue distribution in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Avenanthramides (AVA) are antioxidants found exclusively in oats. The aim of this study was to determine the time course of absorption of AVA into plasma, liver, and other tissues following their oral ingestion. Three fractions of AVA (AVN-A, AVN-B, and AVN-C) were fed to female Sprague-Dawley rat...

  5. Pediatric imaging/doppler ultrasound of the chest: Extracardiac diagnosis

    SciTech Connect

    Huhta, J.C.

    1986-01-01

    In this book the author spells out new diagnostic applications in pediatrics for high resolution cross-sectional ultrasonography, and demonstrates the ways in which Doppler techniques complement the cross-sectional method. This reference presents practical, step-by-step methods for non-invasive ultrasound examination of extra-cardiac anatomy and assessment of vascular blood flow.

  6. Deoxyribonuclease I in mammalian tissues. [Rats

    SciTech Connect

    Lacks, S.A.

    1981-03-25

    Enzymes of the DNase I class, similar to bovine pancreatic DNase I with respect to molecular weight and ionic and pH requirements, were found in various tissues of the rat. Their analysis was facilitated by a method for detection of nucleases in crude extracts after polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and subsequent renaturation of the enzymes. High levels of DNase I were found in digestive tissues, such as the parotid and submaxillary salivary glands and the lining of the small intestine. Appreciable levels were present in the lymph node, kidney, heart, prostate gland, and seminal vesicle. No activity was found in pancreatic extracts. However, under some conditions, tissues rich in proteases gave poor recovery of DNase I. Fourteen other tissues showed little or no DNase I. Inhibition of various DNase I enzymes by rabbit muscle actin was examined both in gels and in solution. Actin inhibited the bovine parotid DNase I as well as the bovine pancreatic enzyme, but actin did not inhibit any of the DNase I enzymes of the rat. This species specificity of actin inhibition makes it unlikely that the very strong association between monomeric actin and bovine DNase I is of general significance for cellular function.

  7. Distribution of prosaposin in rat lymphatic tissues.

    PubMed

    Shimokawa, Tetsuya; Nabeka, Hiroaki; Yamamiya, Kimiko; Wakisaka, Hiroyuki; Takeuchi, Takashi; Kobayashi, Naoto; Matsuda, Seiji

    2013-06-01

    Prosaposin (PSAP) is as a trophic factor and an activator protein for sphingolipid hydrolase in lysosomes. We generated a specific antibody to PSAP and examined the spatiotemporal distribution of PSAP-immunoreactive (PSAP-IR) cells in the lymphatic tissues of Wistar rats. Immunoblots of tissue homogenates separated electrophoretically showed a single band for PSAP in brain but two bands in spleen. PSAP-IR cells were distributed in both the red and white pulp of the spleen, in both the cortex and medulla of the thymus and in mesenteric lymph nodes. Many PSAP-IR cells were found in the dome portion of Peyer's patches and the number of PSAP-IR cells increased with the age of the rat. To identify the PSAP-IR cells, double- and triple-immunostainings were performed with antibodies against PSAP, CD68 and CD1d. The large number of double- and triple-positive cells suggested that antigen-presenting cells contained much PSAP in these lymphatic tissues. Intense expression of PSAP mRNA, examined by in situ hybridisation, was observed in the red pulp and corona of the spleen. In rats, the PSAP gene generates two alternative splicing forms of mRNA: Pro+9 containing a 9-base insertion and Pro+0 without the insertion. We examined the expression patterns of the alternative splicing forms of PSAP mRNA in the spleen. The presence of both types of mRNA (Pro+9 and Pro+0) indicated that the spleen contains various types of prosaposin-producing and/or secreting cells. These findings suggest diverse functions for PSAP in the immune system. PMID:23420452

  8. Extracardiac medical and neuromuscular implications in restrictive cardiomyopathy.

    PubMed

    Stöllberger, Claudia; Finsterer, Josef

    2007-08-01

    Restrictive cardiomyopathy (RCMP) is characterized by restrictive filling and reduced diastolic volume of either or both ventricles with normal or near-normal systolic function and wall thickness. It may occur idiopathically or as a cardiac manifestation of systemic diseases such as scleroderma, amyloidosis, Churg-Strauss syndrome, cystinosis, sarcoidosis, lymphoma, Gaucher's disease, hemochromatosis, Fabry's disease, pseudoxanthoma elasticum, hypereosinophilic syndrome, carcinoid, Noonan's syndrome, reactive arthritis, or Werner's syndrome and various neuromuscular disorders. Whereas in idiopathic RCMP the therapeutic options are only treatment of cardiac congestion, in cases with an underlying disorder, a causal therapy may be available. Patients with RCMP should be investigated as soon as the cardiac diagnosis is established for extracardiac diseases to detect a possibly treatable cause of RCMP before the disease becomes intractable. These investigations include a diligent clinical history and examination, blood tests, and ophthalmologic, otologic, dermatologic, gastroenterologic, nephrologic, hematologic, and neurologic examinations. If extracardiac examinations do not reveal a plausible cause for RCMP, endomyocardial biopsy is indicated. PMID:17680617

  9. Spexin Expression in Normal Rat Tissues

    PubMed Central

    Porzionato, Andrea; Rucinski, Marcin; Macchi, Veronica; Stecco, Carla; Malendowicz, Ludwik K.; De Caro, Raffaele

    2010-01-01

    Spexin is a highly conserved peptide which was recently identified through the bioinformatics approach. Immunohistochemical analysis of its expression has not yet been performed. Thus, in this study, we examined spexin location in a wide range of rat organs by both RT-PCR and IHC. RT-PCR identified spexin mRNA in all tissues examined. Spexin immunoreaction was mainly cytoplasmic. Spexin was immunohistochemically detected, although with different staining intensities, in epithelia and glands of skin and respiratory, digestive, urinary, and reproductive systems. Smooth muscle cells showed weak immunostaining, and connective tissue was negative. In the central nervous system, neuronal groups showed different intensities for reaction product. Immunoreaction was also found in ganglionic cells of both trigeminal and superior cervical ganglia and in photoreceptor, inner nuclear, and ganglionic layers of the retina. In the endocrine system, spexin immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei; adenohypophysis, thyroid, and parathyroid glands; adrenal cortex and medulla (mainly ganglionic cells); Leydig cells; and thecal, luteal, and interstitial cells of the ovary. Because of its widespread expression, spexin is probably involved in many different physiological functions; in particular, location of spexin in neurons and endocrine cells suggests its roles as neurotransmitter/neuromodulator and endocrine factor. (J Histochem Cytochem 58:825–837, 2010) PMID:20530460

  10. Spexin expression in normal rat tissues.

    PubMed

    Porzionato, Andrea; Rucinski, Marcin; Macchi, Veronica; Stecco, Carla; Malendowicz, Ludwik K; De Caro, Raffaele

    2010-09-01

    Spexin is a highly conserved peptide which was recently identified through the bioinformatics approach. Immunohistochemical analysis of its expression has not yet been performed. Thus, in this study, we examined spexin location in a wide range of rat organs by both RT-PCR and IHC. RT-PCR identified spexin mRNA in all tissues examined. Spexin immunoreaction was mainly cytoplasmic. Spexin was immunohistochemically detected, although with different staining intensities, in epithelia and glands of skin and respiratory, digestive, urinary, and reproductive systems. Smooth muscle cells showed weak immunostaining, and connective tissue was negative. In the central nervous system, neuronal groups showed different intensities for reaction product. Immunoreaction was also found in ganglionic cells of both trigeminal and superior cervical ganglia and in photoreceptor, inner nuclear, and ganglionic layers of the retina. In the endocrine system, spexin immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei; adenohypophysis, thyroid, and parathyroid glands; adrenal cortex and medulla (mainly ganglionic cells); Leydig cells; and thecal, luteal, and interstitial cells of the ovary. Because of its widespread expression, spexin is probably involved in many different physiological functions; in particular, location of spexin in neurons and endocrine cells suggests its roles as neurotransmitter/neuromodulator and endocrine factor. PMID:20530460

  11. Extracardiac applications of MR blood pool contrast agent in children.

    PubMed

    Farmakis, Shannon G; Khanna, Geetika

    2014-12-01

    Magnetic resonance (MR) angiography has significantly reduced the need for diagnostic conventional angiography and is preferred over CT angiography in children because of its lack of ionizing radiation. The availability of gadofosveset trisodium (the only clinically approved blood pool MR contrast agent) has led to an increase in applications of MR for vascular imaging and an improvement in diagnostic quality of MR angiography. Gadofosveset is a gadolinium-based contrast agent that binds reversibly to albumin, resulting in increased paramagnetic effect and longer intravascular residence. This allows for high-resolution arterial and venous MR angiography, assessment of flow characteristics of vascular malformations, dynamic vascular imaging, and multi-station imaging with a single low-dose gadolinium contrast injection. The purpose of this pictorial essay is to facilitate understanding of the kinetics and safety profile of gadofosveset trisodium, discuss technical aspects of imaging, and illustrate advantages and extracardiac applications in pediatric body imaging. PMID:25408135

  12. Diffuse Infiltrative Primary Cardiac Lymphoma with Delayed Extracardiac Involvement

    PubMed Central

    Jeoung, Yong; Kim, Ho; Kim, Ji Won; Lee, Jae Joong; Chung, Sang Yoon

    2014-01-01

    Primary cardiac lymphoma (PCL) is an extremely rare and fatal neoplasm of the heart. Traditionally, it is defined as lymphoma involving the heart or pericardium. PCL has a poor prognosis because of the diagnostic difficulty and its location. We present the case of a 48-year-old man who presented with pericardial effusion and diffuse cardiac wall thickening. We first suspected infiltrative heart disease. However, even after performing a biopsy, we could not establish an accurate diagnosis. After 20 months, primary cardiac diffuse large B cell lymphoma (DLBCL) was diagnosed by cervical lymph node biopsy. In this case, after chemotherapy, the DLBCL lesions, including cardiac wall thickening, improved. The treatment outcome suggests that the diagnosis was diffuse infiltrative PCL with delayed extracardiac involvement. PMID:24855605

  13. Extra-cardiac findings in cardiovascular magnetic resonance: what the imaging cardiologist needs to know.

    PubMed

    Rodrigues, Jonathan C L; Lyen, Stephen M; Loughborough, William; Amadu, Antonio Matteo; Baritussio, Anna; Dastidar, Amardeep Ghosh; Manghat, Nathan E; Bucciarelli-Ducci, Chiara

    2016-01-01

    Cardiovascular magnetic resonance (CMR) is an established non-invasive technique to comprehensively assess cardiovascular structure and function in a variety of acquired and inherited cardiac conditions. A significant amount of the neck, thorax and upper abdomen are imaged at the time of routine clinical CMR, particularly in the initial multi-slice axial and coronal images. The discovery of unsuspected disease at the time of imaging has ethical, financial and medico-legal implications. Extra-cardiac findings at the time of CMR are common, can be important and can change clinical management. Certain patient groups undergoing CMR are at particular risk of important extra-cardiac findings as several of the cardiovascular risk factors for atherosclerosis are also risk factors for malignancy. Furthermore, the presence of certain extra-cardiac findings may contribute to the interpretation of the primary cardiac pathology as some cardiac conditions have multi-systemic extra-cardiac involvement. The aim of this review is to give an overview of the type of extra-cardiac findings that may become apparent on CMR, subdivided by anatomical location. We focus on normal variant anatomy that may mimic disease, common incidental extra-cardiac findings and important imaging signs that help distinguish sinister pathology from benign disease. We also aim to provide a framework to the approach and potential further diagnostic work-up of incidental extra-cardiac findings discovered at the time of CMR. However, it is beyond the scope of this review to discuss and determine the clinical significance of extracardiac findings at CMR. PMID:27156861

  14. Incretin attenuates diabetes-induced damage in rat cardiac tissue.

    PubMed

    AbdElmonem Elbassuoni, Eman

    2014-09-01

    Glucagon-like peptide-1 (GLP-1), as a member of the incretin family, has a role in glucose homeostasis, its receptors distributed throughout the body, including the heart. The aim was to investigate cardiac lesions following diabetes induction, and the potential effect of GLP-1 on this type of lesions and the molecular mechanism driving this activity. Adult male rats were classified into: normal, diabetic, 4-week high-dose exenatide-treated diabetic rats, 4-week low-dose exenatide-treated diabetic rats, and 1-week exenatide-treated diabetic rats. The following parameters were measured: in blood: glucose, insulin, lactate dehydrogenase (LDH), total creatine kinase (CK), creatine kinase MB isoenzyme (CK-MB), and CK-MB relative index; in cardiac tissue: lipid peroxide (LPO) and some antioxidant enzymes. The untreated diabetic group displayed significant increases in blood level of glucose, LDH, and CK-MB, and cardiac tissue LPO, and a significant decrease in cardiac tissue antioxidant enzymes. GLP-1 supplementation in diabetic rats definitely decreased the hyperglycemia and abolished the detrimental effects of diabetes on the cardiac tissue. The effect of GLP-1 on blood glucose and on the heart also appeared after a short supplementation period (1 week). It can be concluded that GLP-1 has beneficial effects on diabetes-induced oxidative cardiac tissue damage, most probably via its antioxidant effect directly acting on cardiac tissue and independent of its hypoglycemic effect. PMID:25011640

  15. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-07-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue.

  16. Brain tumor imaging of rat fresh tissue using terahertz spectroscopy

    PubMed Central

    Yamaguchi, Sayuri; Fukushi, Yasuko; Kubota, Oichi; Itsuji, Takeaki; Ouchi, Toshihiko; Yamamoto, Seiji

    2016-01-01

    Tumor imaging by terahertz spectroscopy of fresh tissue without dye is demonstrated using samples from a rat glioma model. The complex refractive index spectrum obtained by a reflection terahertz time-domain spectroscopy system can discriminate between normal and tumor tissues. Both the refractive index and absorption coefficient of tumor tissues are higher than those of normal tissues and can be attributed to the higher cell density and water content of the tumor region. The results of this study indicate that terahertz technology is useful for detecting brain tumor tissue. PMID:27456312

  17. Surface-enhanced Raman scattering of rat tissues.

    PubMed

    Aydin, Omer; Kahraman, Mehmet; Kiliç, Ertuğul; Culha, Mustafa

    2009-06-01

    Surface-enhanced Raman scattering (SERS) is proven to be a powerful tool for investigation of biological structures. In this study, tissues obtained from different rat organs are examined using SERS. The tissue samples are crushed with a pestle after sudden freezing in liquid nitrogen and mixed with a concentrated colloidal silver nanoparticle suspension. The reproducibility of SERS spectra acquired from several tissue samples from different organs is demonstrated. The collected spectra are comparatively evaluated based on the physiological function of the organ from which the tissue is obtained. The spectra from the tissues show significant differences and indicate that they can be used for tissue characterization and differentiation. The identification of the origins of the bands on the spectra is also attempted. This study suggests that SERS can be used to monitor the changes at the molecular level during metabolic changes in an organ or tissue as a result of a disease or another cause. PMID:19531293

  18. Distribution of UDPglucuronosyltransferase in rat tissue.

    PubMed Central

    Chowdhury, J R; Novikoff, P M; Chowdhury, N R; Novikoff, A B

    1985-01-01

    UDPglucuronosyltransferase [UDPglucuronate beta-D-glucuronosyltransferase (acceptor-unspecific), EC 2.4.1.17] is a group of enzymes with distinct but partially overlapping substrate specificity. A rabbit antiserum raised against one purified rat liver UDPglycuronosyltransferase isoform was specific for UDPglucuronosyltransferase and recognized all transferase isoforms by immunodiffusion or immunotransblot analysis. The transferase activity toward all substrates was immunoabsorbed from solubilized rat liver microsomes by IgG purified from the antiserum. The purified IgG was used for immunocytochemical localization of UDP-glucuronosyltransferase in rat liver, jejunum, kidney, and adrenal gland. In the liver, UDPglucuronosyltransferase was present exclusively in hepatocytes and was uniformly distributed within all zones of the hepatic lobule. In the jejunum, the transferase was present exclusively in the epithelial cells and showed a progressive increase in concentration from the crypt to the villar tip. In the kidney, the greatest concentration of the transferase was observed in the epithelial cells of the proximal convoluted tubule. Adrenal medullary cells showed intense immunocytochemical staining; the zona glomerulosa and the zona reticularis of the adrenal cortex were more intensely stained than the zona fasciculata. By light microscopy, UDPglucuronosyltransferase was found in the endoplasmic reticulum and nuclear envelope of all the four organs; this was confirmed in the hepatocyte by electron microscopy. The transferase was not observed in mitochondria, Golgi apparatus, lysosomes, peroxisomes, and plasma membrane, even after 3- to 4-fold induction of various substrate-specific UDPglucuronosyltransferase activities. Images PMID:3921970

  19. 5. cap alpha. -reductase activity in rat adipose tissue

    SciTech Connect

    Zyirek, M.; Flood, C.; Longcope, C.

    1987-11-01

    We measured the 5 ..cap alpha..-reductase activity in isolated cell preparations of rat adipose tissue using the formation of (/sup 3/H) dihydrotestosterone from (/sup 3/H) testosterone as an endpoint. Stromal cells were prepared from the epididymal fat pad, perinephric fat, and subcutaneous fat of male rats and from perinephric fat of female rats. Adipocytes were prepared from the epididymal fat pad and perinephric fat of male rats. Stromal cells from the epididymal fat pad and perinephric fat contained greater 5..cap alpha..-reductase activity than did the adipocytes from these depots. Stromal cells from the epididymal fat pad contained greater activity than those from perinephric and subcutaneous depots. Perinephric stromal cells from female rats were slightly more active than those from male rats. Estradiol (10/sup -8/ M), when added to the medium, caused a 90% decrease in 5..cap alpha..-reductase activity. Aromatase activity was minimal, several orders of magnitude less than 5..cap alpha..-reductase activity in each tissue studied.

  20. Morphological analysis of tissue reaction caused by a new endodontic paste in subcutaneous tissue of rats

    PubMed Central

    Marques, André AF; Sponchiado, Emilio C; Garcia, Lucas FR; Garrido, Angela DB; França, Suzelei C; Lia, Raphael CC

    2011-01-01

    Aim: To assess the biocompatibility of an experimental endodontic paste based on the ethyl acetate fraction of Pothomorphe umbellata + calcium hydroxide, using propylene glycol as vehicle, in connective tissue of rats. Materials and Methods: Fifteen rats had four polyethylene tubes implanted in their backs, with each one containing the experimental paste. The tube side was considered the control group. After 7, 21, and 42 days, animals were euthanized. Results: Intense inflammatory reaction was noticed after 7 days for experimental paste and it was moderate for control group. At 21 days, the inflammatory reaction was moderate for experimental paste and discrete for control group; and at 42 days, it was discrete for experimental paste and control group. Statistical analysis (Dunn's test, P < 0.01) demonstrated significant difference between the fibrous capsule area at 7 and 42 days (P > 0.01) for experimental paste. Conclusions: Experimental endodontic paste presented satisfactory tissue reaction in the connective tissue of rats. PMID:22025840

  1. Wound Hypoxia in Deep Tissue after Incision in the Rats

    PubMed Central

    Kang, Sinyoung; Lee, Dongchul; Theusch, Brett E.; Arpey, Christopher J.; Brennan, Timothy J.

    2013-01-01

    Our previous studies using rat models of incisional pain have demonstrated that tissue lactate levels increase and pH decreases for several days after incision, suggesting the presence of an ischemic-like condition. The purpose of this study was to evaluate the time course and the extent of tissue hypoxia that develops in incised muscle and skin. We directly measured oxygen tension at several time points after incisions of the gastrocnemius muscle, the paraspinal skin, and the plantar hindpaw in anesthetized rats using an oxygen-sensitive microelectrode. In vivo hypoxia of the incised tissues was also evaluated immunohistochemically using a hypoxia marker pimonidazole hydrochloride. To minimized inter-subject variability, unincised contralateral tissues were used as a control. Tissue oxygen tension was decreased in both skeletal muscle and skin compared to control, for several days after incision: when measured directly, oxygen tension decreased immediately and remained low for several days after incisions. Pimonidazole immunostaining revealed hypoxic areas in incised muscle and skin for several days. By postoperative day 10, tissue oxygen tension recovered to that of control tissue. These results support the evidence that a hypoxic condition is present in deep tissue after incisions and that an ischemic-like mechanism may contribute to postoperative pain. PMID:23926943

  2. Insulin is ubiquitous in extrapancreatic tissues of rats and humans.

    PubMed Central

    Rosenzweig, J L; Havrankova, J; Lesniak, M A; Brownstein, M; Roth, J

    1980-01-01

    Insulin has been detected, at levels higher than those in plasma, in a broad range of extrapancreatic tissues in both rats and humans. Rat liver insulin was shown to be indistinguishable from genuine insulin by radioimmunoassay, Sephadex chromatography, bioassay, and antibody neutralization. Liver insulin (like brain insulin) was unchanged in ob/ob mice, in rats treated with streptozotocin, or in fasted rats, despite marked alterations in pancreatic secretion of insulin and in liver content of insulin receptors. Insulin was found in cultured human IM-9 lymphocytes and cultured fibroblasts at concentrations greater than 100 times the levels in the media. IM-9 lymphocyte insulin also was shown to be indistinguishable from genuine insulin, by the same criteria used for liver insulin. The insulin concentration in cultured human cells was unaffected by depletion of insulin from the culture medium or by addition of beef insulin to the medium. The data suggest that a part, if not all, of the extrapancreatic tissue insulin is independent of plasma insulin and may be synthesized by the tissues themselves. PMID:6987656

  3. Percutaneous Transthoracic Computed Tomography-Guided AICD Insertion in a Patient with Extracardiac Fontan Conduit

    SciTech Connect

    Murphy, Darra T. Moynagh, Michael R.; Walsh, Kevin P.; Noelke, Lars; Murray, John G.

    2011-02-15

    Percutaneous pulmonary venous atrial puncture was performed under computed tomography guidance to successfully place an automated implantable cardiac defibrillator into a 26-year-old patient with extracardiac Fontan conduit who had presented with two out-of-hospital cardiac arrests. The procedure avoided the need for lead placement at thoracotomy.

  4. Aminoguanidine cream ameliorates skin tissue microenvironment in diabetic rats

    PubMed Central

    Tian, Ming; Qing, Chun; Niu, Yiwen; Dong, Jiaoyun; Cao, Xiaozan; Song, Fei; Ji, Xiaoyun

    2016-01-01

    Introduction The aim of the study was to explore the effect of aminoguanidine cream on the skin tissue microenvironment in diabetic rats. Material and methods A total of 51 healthy male Sprague Dawley (SD) rats were randomly divided into three groups: the diabetes group (n = 18), the aminoguanidine group (n = 18) and the control group (n = 15). Rats in the diabetes group and aminoguanidine group were injected with 65 mg/kg streptozotocin to induce the diabetes model, and in the control group with citrate buffer. After successful induction of diabetes, the back hair of all rats was stripped by barium sulfide, and the aminoguanidine group was treated with aminoguanidine cream using disinfected cotton swabs twice every day for 40 days, while the diabetes and control groups were treated with the cream matrix. The pathological changes of skin were observed by HE staining, while the content of inflammatory cytokines (TNF-α, IL-8, ICAM and IL-1α) and the antioxidant indexes (T-AOC, GSH-PX, MPO MDA H2O2) were examined using commercial kits. Results After 40 days of treatment, the diabetes group manifested tissue lesions, whereas the aminoguanidine group seemed normal. Compared with the diabetes group, the content of inflammatory cytokines TNF-α, IL-8, ICAM and IL-1α was dramatically lower in the aminoguanidine group. T-AOC in all groups underwent dramatic changes and returned to normal finally. The activities of GSH-PX and MPO and content of H2O2 in the diabetes group were all higher than those in the aminoguanidine group. Conclusions Aminoguanidine may have a good systemic effect on alleviating the pathological changes of skin tissue in diabetic rats, which may be attributed to the regulation of GSH-PX, TNF-α, IL-8, ICAM and IL-1α. PMID:26925135

  5. Association between gravitational force and tissue metabolism in periparturient rats

    NASA Technical Reports Server (NTRS)

    Zakrzewska, E. I.; Maple, R.; Lintault, L.; Wade, C.; Baer, L.; Ronca, A.; Plaut, K.

    2004-01-01

    Recently, interest in mammalian reproduction and offspring survival in altered gravity has been growing. Because successful lactation is critical for mammalian neonate survival, we have been studying the effect of gravity metabolism. We have shown an exponential relationship between glucose metabolic rate in mammary tissue of periparturient rats and an increase in gravity load. In this study we showed that changes in mammary metabolic rate due to gravity force were accompanied by a decrease in glucose metabolism in adipose tissue and by a reduced size of adipocytes. We assume that these changes are likely due to changes in prolactin or leptin levels related to altered gravity load.

  6. BPA uptake in rat tissues after partial hepatectomy

    SciTech Connect

    Slatkin, D.N.; Nawrocky, M.M.; Coderre, J.A.; Fisher, C.D.; Joel, D.D.; Lombardo, D.T.; Micca, P.L.

    1996-12-31

    In boron neutron capture therapy (BNCT), boron given as boronophenylalanine (BPA) accumulates transiently not only in tumors but also in normal tissues. Average boron concentrations in transplanted 9L gliosarcoma tumors of 20 rats were 2.5 to 3.7 times concentrations found in blood. Although boron levels in a variety of tissues were also higher than blood the concentrations were less than the lowest found in the tumor. Further note than although BPA is a structural analogue of phenylalanine (Phe), the pathway of BPA uptake into regenerating liver may not be linked to Phe uptake mechanisms.

  7. Lead Induces Apoptosis and Histone Hyperacetylation in Rat Cardiovascular Tissues

    PubMed Central

    Xu, Li-Hui; Mu, Fang-Fang; Zhao, Jian-Hong; He, Qiang; Cao, Cui-Li; Yang, Hui; Liu, Qi; Liu, Xue-Hui; Sun, Su-Ju

    2015-01-01

    Acute and chronic lead (Pb) exposure might cause hypertension and cardiovascular diseases. The purpose of this study was to evaluate the effects of early acute exposure to Pb on the cellular morphology, apoptosis, and proliferation in rats and to elucidate the early mechanisms involved in the development of Pb-induced hypertension. Very young Sprague-Dawley rats were allowed to drink 1% Pb acetate for 12 and 40 days. Western blot analysis indicated that the expression of proliferating cell nuclear antigen (PCNA) decreased in the tissues of the abdominal and thoracic aortas and increased in the cardiac tissue after 12 and 40 days of Pb exposure, respectively. Bax was upregulated and Bcl-2 was downregulated in vascular and cardiac tissues after 40 days of Pb exposure. In addition, an increase in caspase-3 activity was observed after 40 days of exposure to Pb. In terms of morphology, we found that the internal elastic lamina (IEL) of aorta lost the original curve and the diameter of cardiac cell was enlarged after 40 days. Furthermore, the exposure led to a marked increase in acetylated histone H3 levels in the aortas and cardiac tissue after 12 and 40 days, than that in the control group. These findings indicate that Pb might increase the level of histone acetylation and induce apoptosis in vascular and cardiac tissues. However, the mechanism involved need to be further investigated. PMID:26075388

  8. Toxic effect of acyclovir on testicular tissue in rats

    PubMed Central

    Movahed, Elham; Nejati, Vahid; Sadrkhanlou, Rajabali; Ahmadi, Abbas

    2013-01-01

    Background: Acyclovir (ACV), a synthetic purine nucleoside analogue, is known to be toxic to gonads. Objective: The current study evaluated cytotoxicity of ACV on histopathological changes in testis tissue and serum testosterone and lipid peroxidation concentrations of male rats. Materials and Methods: Animals were divided into five groups. One group served as control and one group served as control sham. In the drug treated groups ACV administered for 15 days. 18 days after the last injection, animals were sacrificed. Histopathological and histomorphometrical analysis of the testis was carried out. Serum levels of testosterone and Lipid Peroxidation and potential fertility of animals was evaluated. Results: Male rats exposed to ACV had significant reduction in serum testosterone concentrations at 16 and 48mg/kg dose-levels (p<0.01). ACV induced histopathological changes in the testis and also increase the mean number of mast cells in peritubular or interstitial tissue in the testis at at 16 and 48mg/kg dose-levels (p<0.01). In addition ACV caused increase of serum level of Lipid Peroxidation at 48mg/kg dose-level (p<0.05). As well ACV decreased potential fertility in male rats. Conclusion: The present results highly support the idea that ACV has adverse effect on the reproductive system in male rat. PMID:24639735

  9. Left ventricular stroke volume in the fetal sheep is limited by extracardiac constraint and arterial pressure.

    PubMed

    Grant, D A; Fauchère, J C; Eede, K J; Tyberg, J V; Walker, A M

    2001-08-15

    1. Extracardiac constraint and sensitivity to arterial pressure may be critical factors that limit the functional reserves of the developing fetal heart in utero. We hypothesise that extracardiac constraint is the predominant factor that limits fetal stroke volume (SV). To test this hypothesis we studied six chronically instrumented fetal sheep to determine the relative roles that extracardiac constraint and arterial pressure play in determining left ventricular (LV) function. 2. Pregnant ewes (128-131 days gestation, term = 147 days) were anaesthetised (5 mg kg(-1) Propofol I.V., then 1.5 % halothane, 50 % O(2), balance N(2)O by inhalation) and instrumented using sterile surgical techniques to record LV end-diastolic pressure (P(lved)), aortic pressure (P(ao)), pericardial pressure (P(per)), and LV SV. 3. After a minimum of 72 h recovery, LV function was assessed by altering fetal blood volume to vary P(lved). Ventricular function curves were generated using two measures of ventricular function, SV and stroke work index (SWI = SV x P(ao)), and two measures of ventricular filling, P(lved) and LV end-diastolic transmural pressure (P(lved,tm) = P(lved) - P(per)). 4. Although decreasing P(lved) from the resting level decreased SV, increasing P(lved) from the resting level did not increase SV because the ventricular function curve plateaued. This plateau was not explained solely by an increase in aortic pressure, as the plateau remained present in the SWI versus P(lved) curve. When extracardiac constraint was accounted for (SV against P(lved,tm)), the plateau was largely eliminated (approximately 80 %). The remaining portion of the plateau (approximately 20 %) was eliminated when both extracardiac constraint and arterial pressure were accounted for (SWI versus P(lved,tm)). 5. Thus, the major limitation upon LV function in the near-term fetus results from extracardiac constraint limiting ventricular filling while, at the same time, a much smaller limitation arises from

  10. Cold ischemia-induced autophagy in rat lung tissue

    PubMed Central

    CHEN, XU; WU, JING-XIANG; YOU, XING-JI; ZHU, HONG-WEI; WEI, JIONG-LIN; XU, MEI-YING

    2015-01-01

    Autophagy is a highly conserved pathway that permits recycling of nutrients within the cell and is rapidly upregulated during starvation or cell stress. Autophagy has been implicated in the pathophysiological process of warm ischemia-reperfusion injury in the rat lung. Cold ischemia (CI) preservation for lung transplantation also exhibits cell stress and nutrient deprivation, however, little is known with regard to the involvement of autophagy in this process. In the present study, CI preservation-induced autophagy and apoptosis was investigated in the lungs of Sprague Dawley rats. Sprague Dawley rat lungs were flushed and preserved at 4°C (i.e. CI) for various durations (0, 3, 6, 12 and 24 h). The levels of autophagy, autophagic cell death and apoptosis were measured at each time point following CI. The results revealed that autophagy was induced by CI preservation, which was initiated at 3 h, peaked at 6 h after CI and declined thereafter. Additionally, a coexistence of autophagic cell death and apoptosis was observed in rat lung tissues following prolonged CI. These findings demonstrate that autophagy is involved in the pathophysiological process of lung CI. Furthermore, autophagic cell death in addition to necrosis and apoptosis occurs following CI in the lung. CI preservation may therefore be a potential mechanism of lung injury during organ preservation prior to lung transplantation. PMID:25435100

  11. Protein turnover in adipose tissue from fasted or diabetic rats

    NASA Technical Reports Server (NTRS)

    Tischler, Marc E.; Ost, Alan H.; Coffman, Julia

    1986-01-01

    Protein synthesis and degradation in vitro were compared in epididymal fat pads from animals deprived of food for 48 h or treated 6 or 12 days prior with streptozotocin to induce diabetes. Although both fasting and diabetes led to depressed (-24 to -57 percent) protein synthesis, the diminution in protein degradation (-63 to -72 percent) was even greater, so that net in vitro protein balance improved dramatically. Insulin failed to inhibit protein degradation in fat pads of these rats as it does for fed animals. Although insulin stimulated protein synthesis in fat pads of fasted and 12 day diabetic rats, the absolute change was much smaller than that seen in the fed state. The inhibition of protein degradation by leucine also seems to be less in fasted animals, probably because leucine catabolism is slower in fasting. These results show that fasting and diabetes may improve protein balance in adipose tissue but diminish the regulatory effects of insulin.

  12. Glutathione peroxidase activity and chemical forms of selenium in tissues of rats given selenite or selenomethionine

    SciTech Connect

    Beilstein, M.A.; Whanger, P.D.

    1988-05-01

    Glutathione peroxidase (GPx) activity and deposition of selenium (Se) were examined in tissues of rats given dietary Se for 7 wk as either selenite or selenomethionine (SeMet) with 75Se radiotracer of the same chemical form. On the basis of Se:75Se ratio, all tissues of the rats fed selenite were equilibrated with the dietary source, but tissues of the SeMet fed animals maintained a ratio of Se:75Se greater than the dietary ratio. Deposition of dietary Se and 75Se was higher in most tissues of rats fed SeMet. Muscle 75Se was the largest single tissue pool of 75Se in both groups accounting for one-third of recovered 75Se in the rats fed selenite, and one-half of recovered 75Se in the rats fed SeMet. Tissue GPx activities were not different between the two dietary groups. The proportion of Se as GPx in tissues was highest in erythrocytes of the rats fed selenite (.81) and lowest in testes and epididymides of the rats fed SeMet (.009). The proportion of Se present in cytosolic GPx was consistently higher in tissues of rats fed selenite. Erythrocytes of the rats fed SeMet had more 75Se associated with hemoglobin, and muscle cytosols of the rats fed selenite had more 75Se associated with the G-protein. The proportion of 75Se as SeMet determined by ion exchange chromatography of tissue hydrolysates was higher in tissues of rats fed SeMet (highest in muscle and hemoglobin, 70%, and lowest in testes, 16%). In contrast, selenocysteine was the predominant form of Se present in tissues of rats given selenite. These results indicate that the form of Se administered will influence the form in the tissues, the percentage of Se with GPx and the body burden of Se.

  13. Albumin extravasation rates in tissues of anesthetized and unanesthetized rats

    SciTech Connect

    Renkin, E.M.; Joyner, W.L.; Gustafson-Sgro, M.; Plopper, G.; Sibley, L.

    1989-05-01

    Bovine serum albumin (BSA) labeled with /sup 131/I was injected intravenously in chronically prepared, unanesthetized rats and into pentobarbital-anesthetized rats that had received 2 ml 5% BSA to help sustain plasma volume. Initial uptake rates (clearances) in skin, skeletal muscles, diaphragm, and heart (left ventricle) were measured over 1 h. BSA labeled with /sup 125/I was injected terminally to correct for intravascular /sup 131/I-BSA. Observed clearances were in the following order in both groups of animals: heart much greater than diaphragm approximately equal to skin greater than resting skeletal muscles. Differences between unanesthetized and anesthetized animals were small and inconsistently directed. Our results suggest that the lower albumin clearances reported in the literature for anesthetized rats are not the result of their immobility or any direct effect of anesthesia on albumin transport in these tissues. The lower transport rates appear to result indirectly from changes produced by anesthesia and/or surgery in controllable parameters such as plasma volume and intravascular protein mass.

  14. Estradiol release kinetics determine tissue response in ovariectomized rats.

    PubMed

    Otto, Christiane; Kantner, Ingrid; Nubbemeyer, Reinhard; Schkoldow, Jenny; Fuchs, Iris; Krahl, Elisabeth; Vonk, Richardus; Schüler, Christiane; Fritzemeier, Karl-Heinrich; Erben, Reinhold G

    2012-04-01

    Estrogen replacement is an effective therapy of postmenopausal symptoms such as hot flushes, bone loss, and vaginal dryness. Undesired estrogen effects are the stimulation of uterine and mammary gland epithelial cell proliferation as well as hepatic estrogenicity. In this study, we examined the influence of different estradiol release kinetics on tissue responsivity in ovariectomized (OVX) rats. Pulsed release kinetics was achieved by ip or sc administration of estradiol dissolved in physiological saline containing 10% ethanol (EtOH/NaCl) whereas continuous release kinetics was achieved by sc injection of estradiol dissolved in benzylbenzoate/ricinus oil (1+4, vol/vol). Initial 3-d experiments in OVX rats showed that pulsed ip estradiol administration had profoundly reduced stimulatory effects on the uterus and the liver compared with continuous release kinetics. On the other hand, both administration forms prevented severe vaginal atrophy. Based on these results, we compared the effects of pulsed (sc in EtOH/NaCl) vs. continuous (sc in benzylbenzoate/ricinus oil) estradiol release kinetics on bone, uterus, mammary gland, and liver in a 4-month study in OVX rats. Ovariectomy-induced bone loss was prevented by both administration regimes. However, pulsed estradiol resulted in lower uterine weight, reduced induction of hepatic gene expression, and reduced mammary epithelial hyperplasia relative to continuous estradiol exposure. We conclude that organ responsivity is influenced by different hormone release kinetics, a fact that might be exploited to reduce undesired estradiol effects in postmenopausal women. PMID:22334713

  15. Distribution of opiate-like substances in rat tissues.

    PubMed

    Neidle, A; Manigault, I; Wajda, I J

    1979-06-01

    Rat tissues were tested for their ability to inhibit the binding of [3H]dihydromorphine or [3H]naloxone to membrane-bound opiate receptors. By this criterion, morphine-like substances were found in lung, heart, liver, and kidney as well as in brain. The relative activity of the extracts, based on initial tissue weight, differed with the radioactive lignand employed. With dihydromorphine, the order was as above. With naloxone, lung was most active, followed by heart, brain, liver, and kidney. The ability of all tissue extracts to inhibit opiate binding was reduced by 100 mM NaC1 and slightly reduced by 1 mM MnC1(2). Gel filtration using Sephadex G-25 indicated that the inhibitory substances were heterogeneous in molecular weight. Only with brain and kidney extracts was there significant activity at the elution volume where enkephalins would be expected. Fractionation using Amberlite XAD-2, a resin which selectively absorbs hydrophobic materials, again indicated that the major protion of activity in all tissue extracts was due to substances other than enkephalins. PMID:223080

  16. Tissue distribution, disposition, and metabolism of cyclosporine in rats

    SciTech Connect

    Wagner, O.; Schreier, E.; Heitz, F.; Maurer, G.

    1987-05-01

    Tissue distribution, disposition, and metabolism of /sup 3/H-cyclosporine were studied in rats after single and repeated oral doses of 10 and 30 mg/kg and after an iv dose of 3 mg/kg. The oral doses of 10 and 30 mg/kg were dissolved in polyethylene glycol 200/ethanol or in olive oil/Labrafil/ethanol. Absorption from both formulations was slow and incomplete, with peak /sup 3/H blood levels at 3-4 hr. Approximately 30% of the radioactive dose was absorbed, which is consistent with oral bioavailability data for cyclosporine. More than 70% of the radioactivity was excreted in feces and up to 15% in urine. Elimination via the bile accounted for 10 and 60% of the oral and iv doses, respectively. Since unchanged cyclosporine predominated in both blood and tissues at early time points, the half-lives of the distribution phases (t 1/2 alpha) of parent drug and of total radioactivity were similar. In blood, kidney, liver, and lymph nodes, t 1/2 alpha of cyclosporine ranged from 6-10 hr. Elimination of radioactivity from the systemic circulation was multiphasic, with a terminal half-life of 20-30 hr. /sup 3/H-Cyclosporine was extensively distributed throughout the body, with highest concentrations in liver, kidney, endocrine glands, and adipose tissue. The concentrations of both total radioactivity and parent drug were greater in tissues than in blood, which is consistent with the high lipid solubility of cyclosporine and some of its metabolites. Skin and adipose tissue were the main storage sites for unchanged cyclosporine. Elimination half-lives were slower for most tissues than for blood and increased with multiple dosing. The amount of unchanged drug was negligible in urine and bile.

  17. Tissue content of mercury in rats given methylmercuric chloride orally: influence of intestinal flora

    SciTech Connect

    Rowland, I.R.; Davies, M.J.; Evans, J.G.

    1980-05-01

    The effect of intestinal flora on the absorption and disposition of mercury in tissues was investigated using conventional rats, and rats treated with antibiotics to eliminate their gut flora. Antibiotic-treated rats given (/sup 203/Hg) -labeled methylmercuric chloride orally had significantly more mercury in their tissues, especially in kidney, brain, lung, blood, and skeletal muscle, and also excreted less mercury in the feces than conventional rats. Furthermore, in the kidneys of the antibiotic-treated rats, the proportion of mercury present as organic mercury was greater than in the kidneys of the conventional rats. The results support the hypothesis that the metabolism of methylmercuric chloride by the gut flora reduces the tissue content of mercury. When rats were administered 10 mg methylmercuric chloride/Kg.day for 6 days, four or five of those given antibiotics developed neurological symptoms of toxicity, whereas only one of five conventional rats given methylmercuric chloride was affected.

  18. Effects of microgravity on rat bone, cartlage and connective tissues

    NASA Technical Reports Server (NTRS)

    Doty, S.

    1990-01-01

    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  19. Somatostatin in rat tissues is depleted by cysteamine administration

    SciTech Connect

    Szabo, S.; Reichlin, S.

    1981-12-01

    Administration of cysteamine (mercaptoethylamine) induces in rats severe perforating duodenal ulcers. Because the ulcerogenic properties of cysteamine are markedly reduced by treatment with somatostatin, we considered the possibility that cysteamine-induced duodenal ulcer might be mediated by depletion of tissue somatostatin, and thereby of its paracrine influences on gastrin and gastric acid secretion. To test this hypothesis, we measured the concentration of immunoreactive somatostatin (IR-somatostatin) in stomach and duodenal mucosa at intervals after administration of a single ulcerogenic dose (30 mg/kg by stomach tube). IR-somatostatin in these tissues fell rapidly to reach a minimum at 4 h (stomach 31%, duodenum 60% of control respectively). IR-somatostatin in hypothalamus and pancreas decreased gradually to a minimum at 7 h. Another duodenal ulcerogen, propionitrile (10 mg/100 g bw, s.c.) which is more toxic than cysteamine, and several stressful procedures including ether anesthesia, restraint and s.c. formalin did not lower stomach or duodenal IR-somatostatin. Gut, pancreas and hypothalamic VIP levels were not influenced by cysteamine. These findings suggest that cysteamine is a relatively specific depletor of tissue somatostatin. Because blood levels of somatostatin fell, and only trivial amounts of the peptide were found in the stomach lumen after cysteamine administration, it appears likely that this agent acts at the cellular level to cause breakdown of preformed somatostatin and/or to acutely reduce its synthesis.

  20. Differential responses of white adipose tissue and brown adipose tissue to caloric restriction in rats.

    PubMed

    Okita, Naoyuki; Hayashida, Yusuke; Kojima, Yumiko; Fukushima, Mayumi; Yuguchi, Keiko; Mikami, Kentaro; Yamauchi, Akiko; Watanabe, Kyoko; Noguchi, Mituru; Nakamura, Megumi; Toda, Toshifusa; Higami, Yoshikazu

    2012-05-01

    Caloric restriction (CR) slows the aging process and extends longevity, but the exact underlying mechanisms remain debatable. It has recently been suggested that the beneficial action of CR may be mediated in part by adipose tissue remodeling. Mammals have two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). In this study, proteome analysis using two-dimensional gel electrophoresis combined with MALDI-TOF MS, and subsequent analyses were performed on both WAT and BAT from 9-month-old male rats fed ad libitum or subjected to CR for 6 months. Our findings suggest that CR activates mitochondrial energy metabolism and fatty acid biosynthesis in WAT. It is likely that in CR animals WAT functions as an energy transducer from glucose to energy-dense lipid. In contrast, in BAT CR either had no effect on, or down-regulated, the mitochondrial electron transport chain, but enhanced fatty acid biosynthesis. This suggests that in CR animals BAT may change its function from an energy consuming system to an energy reservoir system. Based on our findings, we conclude that WAT and BAT cooperate to use energy effectively via a differential response of mitochondrial function to CR. PMID:22414572

  1. Regulation of cholesteryl ester transfer activity in adipose tissue: comparison between hamster and rat species.

    PubMed

    Shen, G X; Angel, A

    1995-07-01

    The present study demonstrates cholesteryl ester transfer activity (CETA) in cultured hamster and rat adipose tissue. Cultured hamster and rat adipose tissue fragments released CETA into the conditioned medium, and this was associated with a reciprocal decrease in adipose tissue CETA. Regional variations in adipose CETA were observed. The levels of CETA released from cultured hamster and rat adipocytes were higher than those from adipose tissue fragments. In hamsters but not in rats, the secretion of CETA from cultured adipose tissue was increased by insulin and inhibited by EDTA in a dose-dependent fashion. Monoclonal antibodies against human cholesteryl ester transfer protein inhibited the CETA secreted from hamster adipose tissue but not that from rat adipose tissue. Fasting for 24 h and a high-cholesterol saturated fat-rich diet increased adipose CETA in hamsters and rats, and this was associated with an elevation of plasma CETA only in hamsters. This supports the view that, in hamsters, adipose CETA has in situ and intravascular functions, whereas in rats the role of adipose CETA is restricted to tissue-specific functions. Hamster cholesteryl ester transfer protein may differ from rat adipose-associated CETA in the structure of the active site and the regulatory mechanism for its secretion. PMID:7631784

  2. Copper deficiency and tissue glutathione concentration in the rat

    SciTech Connect

    Allen, K.G.D.; Arthur, J.R.; Morrice, P.C.; Nicol, F.; Mills, C.F.

    1988-01-01

    Copper deficiency in rats increased renal vein and arterial (heart) plasma GSH concentration by approximately 50%. There was no change in plasma GSSG concentration. Renal vein plasma GSSG/GSH ratio was decreased in copper deficiency, which is consistent with previous reports showing a copper-dependent thiol oxidase activity in the renal basement membrane. No change occurred in arterial plasma GSSG/GSH ratio. Hepatic GSH concentrations were also elevated by 50% in copper deficiency, GSSG concentrations were unaffected, but GSSG/GSH ratio was depressed. Renal and cardiac tissue GSH and GSSG were unaffected by copper deficiency. The decreased SOD activity and GSH-Px activity observed in copper deficiency may contribute to increased hepatic and plasma GSH concentrations.

  3. Optimization of Evans blue quantitation in limited rat tissue samples

    NASA Astrophysics Data System (ADS)

    Wang, Hwai-Lee; Lai, Ted Weita

    2014-10-01

    Evans blue dye (EBD) is an inert tracer that measures plasma volume in human subjects and vascular permeability in animal models. Quantitation of EBD can be difficult when dye concentration in the sample is limited, such as when extravasated dye is measured in the blood-brain barrier (BBB) intact brain. The procedure described here used a very small volume (30 µl) per sample replicate, which enabled high-throughput measurements of the EBD concentration based on a standard 96-well plate reader. First, ethanol ensured a consistent optic path length in each well and substantially enhanced the sensitivity of EBD fluorescence spectroscopy. Second, trichloroacetic acid (TCA) removed false-positive EBD measurements as a result of biological solutes and partially extracted EBD into the supernatant. Moreover, a 1:2 volume ratio of 50% TCA ([TCA final] = 33.3%) optimally extracted EBD from the rat plasma protein-EBD complex in vitro and in vivo, and 1:2 and 1:3 weight-volume ratios of 50% TCA optimally extracted extravasated EBD from the rat brain and liver, respectively, in vivo. This procedure is particularly useful in the detection of EBD extravasation into the BBB-intact brain, but it can also be applied to detect dye extravasation into tissues where vascular permeability is less limiting.

  4. Augmentation of the rat mandible using guided tissue regeneration.

    PubMed

    Kostopoulos, L; Karring, T

    1994-06-01

    The aim of the present study was to investigate whether it is possible to increase the height of the rat mandible at its inferior border using a bioresorbable membrane adapted to create a secluded space for ingrowth of bone tissue. The experiment was carried out in 18 rats. The mandibular ramus was exposed at both sides. A standardized titanium microimplant was then inserted in the naturally existing curvature at the inferior border of the mandible, serving as a fixed reference and space maker. The mandibular border on one side was covered with a polyhydroxybutyrate bioresorbable membrane, and the contralateral side, serving as control, received no membrane before closure of the wound. The membranes were placed in such a way that a space was created in the curvature between the membrane and the inferior border of the mandible. Macerated jaw specimens representing 6 months of healing demonstrated substantial amounts of bone formation in the curvature of the inferior border of the mandible, resulting in a flattening of the inferior border. Negligible amounts of bone formation had occurred in the control sides. Histological analysis demonstrated that, in 4 of 6 experimental specimens, the space created by the membrane was completely filled with new bone after 6 months of healing, but in some specimens soft tissue seemed to have migrated into the space through ruptures of the membrane or because of poor membrane adaptation at its lateral borders, thereby inhibiting bone formation. Only negligible bone formation had occurred at the control sides.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7918912

  5. Lou/C obesity-resistant rat exhibits hyperactivity, hypermetabolism, alterations in white adipose tissue cellularity, and lipid tissue profiles.

    PubMed

    Soulage, Christophe; Zarrouki, Bader; Soares, Anisio Francesco; Lagarde, Michel; Geloen, Alain

    2008-02-01

    Lou/C obesity-resistant rat constitutes an original model to understand the phenomena of overweight and obesity. The aim of the present study was to identify metabolic causes for the outstanding leanness of Lou/C rat. To this end, the metabolic profiles (food intake, energy expenditure, and physical activity) and the cellular characteristics of white adipose tissue (lipogenesis, lipolysis, cellularity, and lipid composition) in 30-wk-old Lou/C rats were compared with age-matched Wistar rats. Lou/C rats exhibited a lower body weight (-45%), reduced adiposity (-80%), increased locomotor activity (+95%), and higher energy expenditure (+11%) than Wistar rats. Epididymal adipose tissue of Lou/C rat was twice lower than that of Wistar rat due to both a reduction in both adipocyte size (-25%) and number (three times). Basal lipolysis and sensitivity to noradrenaline were similar; however, the responsiveness to noradrenaline was lower in adipocytes from Lou/C compared with that from Wistar rats. Lipidomic analysis of plasma, adipose tissue, and liver revealed profound differences in lipid composition between the two strains. Of note, the desaturation indexes (ratio C16:1/C16:0 and C18:1/C18:0) were lower in Lou/C, indicating a blunted activity of delta-9-desaturase such as stearoyl-coenzyme A-desaturase-1. Increased physical activity, increased energy expenditure, and white adipose tissue cellularity are in good agreement with previous observations suggesting that a higher sympathetic tone in Lou/C could contribute to its lifelong leanness. PMID:18006635

  6. Marginal B-6 intake affects protein synthesis in rat tissues

    SciTech Connect

    Sampson, D.A.; Kretsch, M.J.; Young, L.A.; Jansen, G.R.

    1986-03-05

    The role of vitamin B-6 in amino acid metabolism suggests that inadequate B-6 intake may impair protein synthesis. To test this hypothesis, 30 male rats (initially 227 g) were fed AIN76A diets that contained control, marginal or devoid levels of B-6 (5.8, 1.2 or 0.1 mg B-6/kg diet, by analysis) ad libitum for 9 weeks. Protein synthesis rates (PSRs) were measured in liver, kidney and calf muscle using a flooding dose of /sup 3/H-phenylalanine. Marginal and control groups ate and gained weight at similar rates. The marginal diet did not elevate xanthurenic acid (XA) excretion following a tryptophan load. However, marginal B-6 intake did depress liver PSR by 29% (2182 vs 1549 mg/day, P<.05), liver wet weight by 15% (19.0 vs 16.1 g, P<.05) and muscle PSR by 23% (3.0 vs 2.3%/day, P<.10). Unexpectedly, marginal B-6 intake increased PSR in kidney 47% (90 vs 132 mg/day, P<.05). The devoid diet, which increased XA excretion following a tryptophan load by more than 3-fold, depressed PSRs 56% in liver and 31% in muscle. However, the devoid diet decreased food intake by 40% (25.0 vs 15.0 g/day); therefore effects of devoid B-6 intake on PSRs may have been confounded by deficits in protein-energy intake in devoid vs control groups. These data demonstrate that marginal B-6 intake alters protein synthesis in tissues of the rat.

  7. Determinants of renal tissue hypoxia in a rat model of polycystic kidney disease.

    PubMed

    Ow, Connie P C; Abdelkader, Amany; Hilliard, Lucinda M; Phillips, Jacqueline K; Evans, Roger G

    2014-11-15

    Renal tissue oxygen tension (PO2) and its determinants have not been quantified in polycystic kidney disease (PKD). Therefore, we measured kidney tissue PO2 in the Lewis rat model of PKD (LPK) and in Lewis control rats. We also determined the relative contributions of altered renal oxygen delivery and consumption to renal tissue hypoxia in LPK rats. PO2 of the superficial cortex of 11- to 13-wk-old LPK rats, measured by Clark electrode with the rat under anesthesia, was higher within the cysts (32.8 ± 4.0 mmHg) than the superficial cortical parenchyma (18.3 ± 3.5 mmHg). PO2 in the superficial cortical parenchyma of Lewis rats was 2.5-fold greater (46.0 ± 3.1 mmHg) than in LPK rats. At each depth below the cortical surface, tissue PO2 in LPK rats was approximately half that in Lewis rats. Renal blood flow was 60% less in LPK than in Lewis rats, and arterial hemoglobin concentration was 57% less, so renal oxygen delivery was 78% less. Renal venous PO2 was 38% less in LPK than Lewis rats. Sodium reabsorption was 98% less in LPK than Lewis rats, but renal oxygen consumption did not significantly differ between the two groups. Thus, in this model of PKD, kidney tissue is severely hypoxic, at least partly because of deficient renal oxygen delivery. Nevertheless, the observation of similar renal oxygen consumption, despite markedly less sodium reabsorption, in the kidneys of LPK compared with Lewis rats, indicates the presence of inappropriately high oxygen consumption in the polycystic kidney. PMID:25209412

  8. Leptospira in breast tissue and milk of urban Norway rats (Rattus norvegicus).

    PubMed

    DE Oliveira, D; Figueira, C P; Zhan, L; Pertile, A C; Pedra, G G; Gusmão, I M; Wunder, E A; Rodrigues, G; Ramos, E A G; Ko, A I; Childs, J E; Reis, M G; Costa, F

    2016-08-01

    Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. The disease is globally distributed and a major public health concern. The Norway rat (Rattus norvegicus) is the main reservoir of the pathogen in urban slums of developing and developed countries. The potential routes of intra-specific leptospire transmission in rats are largely unknown. Herein, we identified pathogenic Leptospira spp. in breast tissue and milk of naturally infected rats. We examined kidney, breast tissue and milk from 24 lactating rats for the presence of leptospires using immunofluorescence, immunohistochemistry, polymerase chain reaction (PCR) and scanning electronic microscopy. All 24 rats had evidence for Leptospira in the kidneys, indicating chronic carriage. The majority of kidney-positive rats had detectable leptospires in milk (18, 75%) and breast tissue (16, 67%), as evidenced by immunofluorescence assay and immunohistochemistry. Four (17%) milk samples and two (8%) breast tissue samples were positive by quantitative real-time PCR. Scanning electron microscopy confirmed the presence of leptospires in breast tissue. No major pathological changes in breast tissue were found. This study, for the first time, identified leptospires in the milk and breast tissue of wild Norway rats, suggesting the possibility of milk-borne transmission of leptospirosis to neonates. PMID:27019024

  9. Biodistribution of etanercept to tissues and sites of inflammation in arthritic rats.

    PubMed

    Chen, Xi; DuBois, Debra C; Almon, Richard R; Jusko, William J

    2015-06-01

    Many monoclonal antibodies (mAbs) and other protein drugs have targets usually residing within tissues, making tissue concentrations of mAbs relevant to their pharmacologic effects. Therefore, knowledge of tissue distribution kinetics is important to better understand their pharmacokinetics and pharmacodynamics. The tissue distribution of mAbs is affected by many physiologic factors that may be altered in disease status. In the present work, we studied the tissue distribution kinetics of the fusion protein etanercept in inflamed joint tissues and examined the impact of inflammation on the tissue distribution of etanercept. Etanercept concentration profiles in plasma, blister fluid, and different tissues were obtained from healthy and collagen-induced arthritic (CIA) rats by use of a fluorescence quantification method via IRDye800CW labeling. Stepwise minimal and full physiologically based pharmacokinetic (PBPK) approaches were applied to characterize the distribution kinetics of etanercept in tissues in healthy and diseased animals. Etanercept exhibited modest tissue access (tissue/plasma area under the concentration curve [AUC] ratios 0.03-0.15 and estimated tissue reflection coefficients [σ] of 0.6-1.0), but with good penetration into arthritic paws (tissue/plasma AUC ratio 0.23 and σ 0.36). Etanercept exposure in the inflamed paws of CIA rats was approximately 3-fold higher than in normal paws taken from either CIA or healthy rats (tissue/plasma AUC ratios 0.23 versus 0.07 and σ 0.36 versus 0.71). The tissue distribution kinetics of etanercept in arthritic paws were well characterized with PBPK modeling approaches. Etanercept shows good penetration to arthritic paws in CIA rats. Our study indicates that inflammation produced increased tissue distribution of etanercept in CIA rats. PMID:25834031

  10. Extracardiac septum transversum/proepicardial endothelial cells pattern embryonic coronary arterio-venous connections.

    PubMed

    Cano, Elena; Carmona, Rita; Ruiz-Villalba, Adrián; Rojas, Anabel; Chau, You-Ying; Wagner, Kay D; Wagner, Nicole; Hastie, Nicholas D; Muñoz-Chápuli, Ramón; Pérez-Pomares, José M

    2016-01-19

    Recent reports suggest that mammalian embryonic coronary endothelium (CoE) originates from the sinus venosus and ventricular endocardium. However, the contribution of extracardiac cells to CoE is thought to be minor and nonsignificant for coronary formation. Using classic (Wt1(Cre)) and previously undescribed (G2-Gata4(Cre)) transgenic mouse models for the study of coronary vascular development, we show that extracardiac septum transversum/proepicardium (ST/PE)-derived endothelial cells are required for the formation of ventricular coronary arterio-venous vascular connections. Our results indicate that at least 20% of embryonic coronary arterial and capillary endothelial cells derive from the ST/PE compartment. Moreover, we show that conditional deletion of the ST/PE lineage-specific Wilms' tumor suppressor gene (Wt1) in the ST/PE of G2-Gata4(Cre) mice and in the endothelium of Tie2(Cre) mice disrupts embryonic coronary transmural patterning, leading to embryonic death. Taken together, our results demonstrate that ST/PE-derived endothelial cells contribute significantly to and are required for proper coronary vascular morphogenesis. PMID:26739565

  11. Damus-Kaye-Stansel Procedure with Extracardiac Fontan: Successful Recruitment of Previously Ligated Pulmonary Valve.

    PubMed

    Paczkowski, Konrad; Haponiuk, Ireneusz; Chojnicki, Maciej; Jaworski, Radosław

    2016-01-01

    We present a case of a 2.5-year-old-girl with complex congenital heart disease: tricuspid atresia (TA), bulboventricular septal defect (VSD), hypoplastic right ventricle, d-transposition of the great arteries (d-TGA) with aortic outflow from redundant RV. Due to II/III degree atrioventricular block induced after diagnostic cardiac catheterization, an epicardial pacemaker was implanted during the Glenn procedure. Because of severe left ventricle outflow tract obstruction, she was finally referred for extracardiac TCPC (extracardiac Fontan type) with recruitment of PV and Damus-Kaye-Stansel anastomosis. Intraoperatively, the pulmonary trunk stump was opened and a competent pulmonary valve with flaccid leaflets was found. Simple ligation of the pulmonary trunk with a preserved pulmonary valve enabled an effective aorto-pulmonary bridging of systemic outflow tract with the use of natural fully competent ventricle-arterial valves. The relief of single ventricle outflow tract obstruction led to final stabilization of spontaneous sinus rhythm recovery after 2 years of pacemaker stimulation. PMID:27585204

  12. Deamination of newly-formed dopamine in rat renal tissues.

    PubMed Central

    Fernandes, M. H.; Pestana, M.; Soares-da-Silva, P.

    1991-01-01

    1. The present study has examined the formation of dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) in slices of the rat renal cortex and the renal medulla loaded with exogenous L-beta-3,4-dihydroxyphenylalanine (L-DOPA). The effects of pargyline and of two selective inhibitors of monoamine oxidase (MAO) types A and B, respectively Ro 41-1049 and Ro 19-6327, on the deamination of newly-synthesized dopamine in kidney slices incubated with exogenous L-DOPA were also tested. The assay of L-DOPA, dopamine, noradrenaline and DOPAC was performed by means of h.p.l.c. with electrochemical detection. 2. Incubation of renal slices with exogenous L-DOPA resulted in a concentration-dependent accumulation of dopamine and DOPAC; the tissue levels of newly-formed dopamine and DOPAC in slices of the renal medulla were 6-8% of those in cortical slices. 3. Pargyline (0.1 mM) produced a marked decrease (84% reduction) in the formation of DOPAC in kidney slices loaded with 1.0 mM L-DOPA; this effect was accompanied by a 17% increase in the accumulation of dopamine. Similar effects were obtained at higher concentrations of pargyline (0.5 and 1.0 mM). At 5.0 and 10.0 mM pargyline, a marked decrease (46 and 76% reduction) in the accumulation of newly-formed dopamine was observed. 4. The accumulation of dopamine and DOPAC was found to be time-dependent in experiments in which tissues were incubated with 5 and 10 microM L-DOPA for 5, 10, 20 and 30 min. Pargyline (0.1 mM) produced an increase in the accumulation of dopamine at all incubation periods and decreased the formation of DOPAC.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1364853

  13. Metabolism of thyroid hormones by rat thyroid tissue in vitro.

    PubMed

    Green, W L

    1978-09-01

    Rat thyroid lobes or hemilobes have been incubated in Krebs-Ringer phosphate buffer containing labeled T4 and/or T3, and the products were separated by paper chromatography. Labeled T4 was actively degraded; about half of the T4 metabolized was recovered as T3. Labeled T3 was also metabolized, but less rapidly than T4. Other than T3 produced from T4, the major products from both hormones were inorganic iodide and iodoprotein; the latter was presumably a secondary product of iodide organification because its formation was inhibited by hypoxia and methimazole. Feeding the animals a low iodine diet increased their hormone-metabolizing activity. Incubation under nitrogen did not affect the rate of T4 degradation, but partially inhibited T3 degradation. Degradation of both hormones was unchanged in the presence of methimazole and ascorbate, was markedly inhibited by 1 mM propylthiouracil (PTU), and was partially inhibited by azide and cyanide. Thyroid tissues concentrated both hormones, tissue to medium gradients averaging 5.4 for T4 and 20.7 for T3; none of the conditions affecting hormone degradation (incubation under nitrogen or with azide, cyanide, or PTU) significantly altered these gradients. It is concluded that the thyroid can metabolize both of its major hormones by a system distinct from thyroidal peroxidase. Hormone metabolism, therefore, is a potentially important factor in net hormone secretion. In its resistance to hypoxia, methimazole, and ascorbate and its sensitivity to PTU, the thyroid's system for generating T3 from T4 resembles T3-forming systems of liver and kidney. The thyroid, because T3 formation is its dominant pathway for T4 metabolism, may provide a useful model for study of this reaction. PMID:744119

  14. Correlation between light scattering signal and tissue reversibility in rat brain exposed to hypoxia

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Uozumi, Yoichi; Nawashiro, Hiroshi; Ishihara, Miya; Kikuchi, Makoto

    2010-02-01

    Light scattering signal is a potential indicator of tissue viability in brain because cellular and subcellular structural integrity should be associated with cell viability in brain tissue. We previously performed multiwavelength diffuse reflectance measurement for a rat global ischemic brain model and observed a unique triphasic change in light scattering at a certain time after oxygen and glucose deprivation. This triphasic scattering change (TSC) was shown to precede cerebral ATP exhaustion, suggesting that loss of brain tissue viability can be predicted by detecting scattering signal. In the present study, we examined correlation between light scattering signal and tissue reversibility in rat brain in vivo. We performed transcranial diffuse reflectance measurement for rat brain; under spontaneous respiration, hypoxia was induced for the rat by nitrogen gas inhalation and reoxygenation was started at various time points. We observed a TSC, which started at 140 +/- 15 s after starting nitrogen gas inhalation (mean +/- SD, n=8). When reoxygenation was started before the TSC, all rats survived (n=7), while no rats survived when reoxygenation was started after the TSC (n=8). When reoxygenation was started during the TSC, rats survived probabilistically (n=31). Disability of motor function was not observed for the survived rats. These results indicate that TSC can be used as an indicator of loss of tissue reversibility in brains, providing useful information on the critical time zone for treatment to rescue the brain.

  15. Time-resolved spectroscopy of mitochondria, cells, and rat tissues under normal and pathological conditions

    NASA Astrophysics Data System (ADS)

    Beauvoit, Bertrand; Kitai, Toshiyuki; Liu, Hanli; Chance, Britton

    1995-01-01

    In this study, the detailed dependence of the light scattering on the tissue architecture and intracellular composition was investigated. The reduced scattering coefficient ((mu) s') of isolated rat liver mitochondria, isolated liver cells and various rat tissues was measured at 780 nm by using time-resolved spectroscopy and a sample-substitution protocol. In a first part, extrapolations of the in vitro data to the in vivo situation showed that the mitochondrial compartment contributes for 73% of the scattering of the hepatocytes and about 100% of that of the whole liver. Finally, by analyzing different normal rat tissues and tumors, we have shown that the tissue (mu) s' is independent on the cell concentration in the tissue but is roughly proportional to the tissue mitochondrial content.

  16. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

    PubMed

    Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

    2015-06-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than

  17. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover☆

    PubMed Central

    Jugdaohsingh, Ravin; Watson, Abigail I.E.; Pedro, Liliana D.; Powell, Jonathan J.

    2015-01-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially

  18. Detection and severity classification of extracardiac interference in {sup 82}Rb PET myocardial perfusion imaging

    SciTech Connect

    Orton, Elizabeth J. Kemp, Robert A. de; Glenn Wells, R.; Al Harbi, Ibraheem; Klein, Ran; Beanlands, Rob S. B.

    2014-10-15

    Purpose: Myocardial perfusion imaging (MPI) is used for diagnosis and prognosis of coronary artery disease. When MPI studies are performed with positron emission tomography (PET) and the radioactive tracer rubidium-82 chloride ({sup 82}Rb), a small but non-negligible fraction of studies (∼10%) suffer from extracardiac interference: high levels of tracer uptake in structures adjacent to the heart which mask the true cardiac tracer uptake. At present, there are no clinically available options for automated detection or correction of this problem. This work presents an algorithm that detects and classifies the severity of extracardiac interference in {sup 82}Rb PET MPI images and reports the accuracy and failure rate of the method. Methods: A set of 200 {sup 82}Rb PET MPI images were reviewed by a trained nuclear cardiologist and interference severity reported on a four-class scale, from absent to severe. An automated algorithm was developed that compares uptake at the external border of the myocardium to three thresholds, separating the four interference severity classes. A minimum area of interference was required, and the search region was limited to that facing the stomach wall and spleen. Maximizing concordance (Cohen’s Kappa) and minimizing failure rate for the set of 200 clinician-read images were used to find the optimal population-based constants defining search limit and minimum area parameters and the thresholds for the algorithm. Tenfold stratified cross-validation was used to find optimal thresholds and report accuracy measures (sensitivity, specificity, and Kappa). Results: The algorithm was capable of detecting interference with a mean [95% confidence interval] sensitivity/specificity/Kappa of 0.97 [0.94, 1.00]/0.82 [0.66, 0.98]/0.79 [0.65, 0.92], and a failure rate of 1.0% ± 0.2%. The four-class overall Kappa was 0.72 [0.64, 0.81]. Separation of mild versus moderate-or-greater interference was performed with good accuracy (sensitivity

  19. Extracardiac Pulmonary-Systemic Connection via Persistent Levoatriocardinal Vein in Adults.

    PubMed

    Saremi, Farhood; Ho, Siew Yen

    2016-07-01

    The levoatriocardinal vein is a very rare but clinically important intrathoracic venous anomaly that connects the systemic (cardinal) and pulmonary venous channels. We report 4 adults with pulmonary-systemic venous communications that can explain the morphology of the extracardiac interatrial shunting through the persistent levoatriocardinal vein. We discuss the imaging features of the 2 types of such communications: direct connection of the levoatriocardinal vein (1) with the left atrium and (2) with the left superior pulmonary vein in the absence of obstructive left heart disease. Accurate characterization of these diagnostically challenging cases is important because in addition to hemodynamic imbalance they are at risk of paradoxical embolism. Computed tomography and magnetic resonance imaging are noninvasive imaging techniques that should play increasingly important roles in the evaluation of these anomalies. PMID:27174352

  20. Imaging of platelets in right-sided extracardiac conduits in humans

    SciTech Connect

    Agarwal, K.C.; Wahner, H.W.; Dewanjee, M.K.; Fuster, V.; Puga, F.J.; Danielson, G.K.; Chesebro, J.H.; Feldt, R.H.

    1982-04-01

    As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with In-111-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth post-operative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

  1. Imaging of platelets in right-sided extracardiac conduits in humans

    SciTech Connect

    Agarwal, K.C.; Wahner, H.W.; Dewanjee, M.K.; Fuster, V.; Puga, F.J.; Danielson, G.K.; Chesebro, J.H.; Feldt, R.H.

    1982-04-01

    As a connection between the systemic venous ventricle and the pulmonary artery, valved Dacron extracardiac conduits have remarkably influenced the surgical approach to many complex congenital heart defects. Obstruction of the conduit, however, can reduce the long-term effectiveness of this corrective procedure. In addition to stenosis of the porcine valve, formation of thick fibrous neointima plays a major role in the pathogenesis of conduit obstruction. The purpose of this study was to determine whether platelet deposition could be demonstrated in these conduits by external imaging with /sup 111/In-labeled autologous platelets. After injection of labeled platelets either immediately after operation or on the fifth to eighth postoperative day, imaging was performed by standard procedures. Eight of nine patients had platelet accumulation in the conduit, and treatment with aspirin and dipyridamole caused no recognizable change in platelet deposition. This study demonstrates the feasibility of imaging platelet deposition in Dacron conduits and shows that the pattern of deposition varies with time.

  2. Plasma disappearance, urine excretion, and tissue distribution of ribavirin in rats and rhesus monkeys

    SciTech Connect

    Ferrara, E.A.; Oishi, J.S.; Wannemacher, R.W. Jr.; Stephen, E.L.

    1981-06-01

    Ribavirin has been shown to have broad-spectrum antiviral. To study its tissue distribution and disappearance rate, a single dose of 10 mg/kg which contained 10 microCi of (14C)ribavirin was injected intravenously into rhesus monkeys and intramuscularly into monkeys and rats. Except for peak plasma concentrations and the initial phases of the plasma disappearance and urine excretion curves, no significant difference was observed between plasma, tissue, or urine values for intramuscularly or intravenously injected monkeys. Plasma disappearance curves were triphasic; plasma concentrations of ribavirin were similar for both monkeys and rats. Rats excreted ribavirin in the urine more rapidly and to a greater extent (82% excreted in 24 h) than did monkeys (60% excreted in 72 h). In the rat, only 3% of the injected (14C)ribavirin was detected in expired CO2. Therefore, for both species, urine was the major route for the elimination of labeled ribavirin and its metabolites from the body. In monkeys, the amount of parent drug in blood cells increased through 48 h and remained stable for 72 h, whereas in rats, ribavirin decreased at a rate similar to the plasma disappearance curve. Concentrations of ribavirin at 8 h were consistently higher in monkeys than in rats for all tissues except the brain. Thus, these differences in blood cellular components and organ content and in urine excretion suggested that there was greater tissue retention of ribavirin in monkeys than in rats.

  3. Effect of insulin on in vivo glucose utilization in individual tissues of anesthetized lactating rats

    SciTech Connect

    Burnol, A.F.; Ferre, P.; Leturque, A.; Girard, J.

    1987-02-01

    Glucose utilization rate has been measured in skeletal muscles, white adipose tissue, and mammary gland of anesthetized nonlactating and lactating rats. During lactation, basal (1-TH) glucose utilization is decreased by 40% in periovarian white adipose tissue and by 65% in epitrochlearis and extensor digitorum longus but not in soleus muscle. This may be related to the lower blood glucose and plasma insulin concentrations observed during lactation. Basal glucose utilization rate in the mammary gland was, respectively, 18 +/- 2 and 350 +/- 50 g/min in nonlactating and lactating rats. During the euglycemic hyperinsulinemic clamp, a physiological increment in plasma insulin concentration induces a similar increase in glucose utilization rate in skeletal muscles and white adipose tissue in the two groups of rats. Furthermore this low increase in plasma insulin concentration does not alter mammary glucose utilization rate in nonlactating rats but induces the same increase as a maximal insulin concentration in lactating rats. These data show that the active mammary gland is the most insulin-sensitive tissue of the lactating rat that has been tested. The overall increase in insulin sensitivity and responsiveness that has been described in lactating rats can then mainly be attributed to the presence of the active mammary gland. Plasma insulin was determined by radioimmunoassay.

  4. Estrogen deficiency in ovariectomized rats: can resistance training re-establish angiogenesis in visceral adipose tissue?

    PubMed Central

    do Valle Gomes-Gatto, Camila; Duarte, Fernanda Oliveira; Stotzer, Uliana Sbeguen; Rodrigues, Maria Fernanda Cury; de Andrade Perez, Sérgio Eduardo; Selistre-de-Araujo, Heloisa Sobreiro

    2016-01-01

    OBJECTIVE: The purpose of this study was to investigate the effects of resistance training on angiogenesis markers of visceral adipose tissue in ovariectomized rats. METHOD: Adult Sprague-Dawley female rats were divided into four groups (n=6 per group): sham-sedentary, ovariectomized sedentary, sham-resistance training and ovariectomized resistance training. The rats were allowed to climb a 1.1-m vertical ladder with weights attached to their tails and the weights were progressively increased. Sessions were performed three times per week for 10 weeks. Visceral adipose tissue angiogenesis and morphology were analyzed by histology. VEGF-A mRNA and protein levels were analyzed by real-time PCR and ELISA, respectively. RESULTS: Ovariectomy resulted in higher body mass (p=0.0003), adipocyte hypertrophy (p=0.0003), decreased VEGF-A mRNA (p=0.0004) and protein levels (p=0.0009), and decreased micro-vascular density (p=0.0181) in the visceral adipose tissue of the rats. Resistance training for 10 weeks was not able to attenuate the reduced angiogenesis in the visceral adipose tissue of the ovariectomized rats. CONCLUSION: Our findings indicate that the resistance training program used in this study could not ameliorate low angiogenesis in the visceral adipose tissue of ovariectomized rats.

  5. Effects of running training on in vitro brown adipose tissue thermogenesis in rats

    NASA Astrophysics Data System (ADS)

    Nozu, Tsukasa; Kikuchi, Kazue; Ogawa, Koji; Kuroshima, Akihiro

    1992-06-01

    Brown adipose tissue (BAT) is a major site of nonshivering thermogenesis (NST) during cold acclimation for most mammals. Repetitive nonthermal stress such as immobilization has been shown to enhance the capacity of NST as cold acclimation. In the present study, the effects of running training, another type of nonthermal stress, were investigated on in vitro thermogenesis and the cellularity of interscapular BAT in rats. The rats were subjected to treadmill running for 30 min daily at 30 m/min under 8° inclination for 4 5 weeks. In vitro thermogenesis was then measured in minced tissue blocks incubated in a Krebs-Ringer phosphate buffer containing glucose and albumin at 37° C, using a Clark type oxygen electrode. The trained rats showed less body weight gain during the experiment. The weights of BAT and epididymal white adipose tissue were smaller in the trained rats. Noradrenaline- and glucagon-stimulated oxygen consumption were also significantly smaller in the trained rats. The tissue DNA level was greater in the trained rats, but the DNA content per tissue pad did not significantly differ. The results indicate that running training reduces BAT thermogenesis, possibly as an adaptation to conserve energy substrates for physical work.

  6. [Plasma and tissue lipids in rats after a flight on the Kosmos-936 biosatellite].

    PubMed

    Ahlers, J; Tigranian, R A; Praslická, M

    1982-01-01

    The content of triglycerides, total cholesterol, phospholipids and nonesterified fatty acids was measured in plasma and tissues of rats flown for 18.5 days on Cosmos-936 in the weightless and centrifuged state. The weightlessness exposure increased lipid fractions in plasma and tissues, and artificial gravity produced a beneficial effect. PMID:7070041

  7. Enhancement of Sexual Behavior in Female Rats by Neonatal Transplantation of Brain Tissue from Males

    NASA Astrophysics Data System (ADS)

    Arendash, Gary W.; Gorski, Roger A.

    1982-09-01

    Transplantation of preoptic tissue from male rat neonates into the preoptic area of female littermates increased masculine and feminine sexual behavior in the recipients during adulthood. This suggests that functional connections develop between the transplanted neural tissue and the host brain. A new intraparenchymal brain transplantation technique was used to achieve these results.

  8. Changes of gas metabolism, gas homeostasis and tissue respiration in rats during prolonged hypokinesia

    NASA Technical Reports Server (NTRS)

    Popkov, V. L.; Mailyan, E. S.; Galushko, Y. S.; Kovalenko, Y. A.; Zaytseva, Y. I.; Nitochkina, I. A.; Stulova, L. V.; Ryazhskiy, A. F.

    1979-01-01

    The oxygen uptake and tissue gas homeostasis of restrained albinic rats remained relatively constant during a 60 day experiment. The gas metabolism in some tissues changed, and O2 consumption increased in the liver and decreased in the myocardium. Capacity for physical work was reduced by five times. Hypokinesia for 60 days resulted in a delay in the animals growth.

  9. Follicle Development of Xenotransplanted Sheep Ovarian Tissue into Male and Female Immunodeficient Rats

    PubMed Central

    Tahaei, Leila Sadat; Eimani, Hussein; Hajmusa, Ghazaleh; Fathi, Rouhollah; Rezazadeh Valojerdi, Mojtaba; Shahverdi, Abdolhossein; Eftekhari-Yazdi, Poopak

    2015-01-01

    Background This study aimed to assess follicle survival after xenotransplantation of sheep ovarian tissue into male and female immunodeficient rats. We evaluated the effects of gonadotropin treatment on follicular development in the transplanted tissue. Materials and Methods In this experimental study, sheep ovarian cortical strips were transplanted into the neck back muscles of 8 male and 8 female immunodeficient, castrated rats. Fourteen days after surgery, each rat was treated with human menopausal gonadotropin (hMG) for 9 weeks. One day after the last injection, ovarian tissues were removed and fixed for histology assessment. Histology analyses were performed before and after grafting. Estradiol (E2) levels were measured before and after gonadectomy, and at the end of the experiment. The control group consisted of 7 male and 7 female noncastrated/non-grafted rats and the sham group comprised 7 male and 7 female castrated/ non-grafted rats for comparison of serum E2 concentrations. Results The percentage of primordial follicles decreased after transplantation in male (25.97%) and female (24.14%) rats compared to the control group (ovarian tissue nongrafted; 37.51%). Preantral follicles increased in the male (19.5%) and female (19.49%) transplanted rats compared to the control group (11.4%). Differences in antral follicles between male (0.06 ± 0.0%) and female (0.06 ± 0.0%) rats were not noticeable compared to control (1.25 ± 0.0%) rats. We observed a significantly higher percent of mean E2 secretion in grafted males compared to grafted females (P˂0.05). Conclusion Despite significant differences in E2 secretion between xenografted male and female rats, we observed no statistical differences in terms of follicular development. PMID:26644859

  10. Tissue, cellular, and subcellular distribution of /sup 241/Pu in the rat testes

    SciTech Connect

    Miller, S.C.; Bowman, B.M.

    1983-05-01

    The distribution and localization of /sup 241/Pu in rat testes were determined by quantitative autoradiography. Rats were given intravenous injection of /sup 241/Pu citrate and tissues were collected 1 week later. The tissue distribution of /sup 241/Pu was determined by light microscope autoradiography. Significant concentrations of /sup 241/Pu were observed in the interstitial tissue but not in seminiferous tubules. The cellular distribution and subcellular localization of /sup 241/Pu were determined by electron microscope autoradiography. Within the interstitial tissue, /sup 241/Pu was concentrated in microphages. There was no preferential localization of /sup 241/Pu in any other interstitial tissue components. Within interstitial tissue macrophages, /sup 241/Pu was concentrated in the lysosomal system of the cell. Other organellar compartments of the cell did not preferentially incorporate /sup 241/Pu. The association of /sup 241/Pu with the macrophage lysosomal system may explain the long retention times of Pu in testes as observed in experimental studies.

  11. Implanted depleted uranium fragments cause soft tissue sarcomas in the muscles of rats.

    PubMed Central

    Hahn, Fletcher F; Guilmette, Raymond A; Hoover, Mark D

    2002-01-01

    In this study, we determined the carcinogenicity of depleted uranium (DU) metal fragments containing 0.75% titanium in muscle tissues of rats. The results have important implications for the medical management of Gulf War veterans who were wounded with DU fragments and who retain fragments in their soft tissues. We compared the tissue reactions in rats to the carcinogenicity of a tantalum metal (Ta), as a negative foreign-body control, and to a colloidal suspension of radioactive thorium dioxide ((232)Th), Thorotrast, as a positive radioactive control. DU was surgically implanted in the thigh muscles of male Wistar rats as four squares (2.5 x 2.5 x 1.5 mm or 5.0 x 5.0 x 1.5 mm) or four pellets (2.0 x 1.0 mm diameter) per rat. Ta was similarly implanted as four squares (5.0 x 5.0 x 1.1 mm) per rat. Thorotrast was injected at two sites in the thigh muscles of each rat. Control rats had only a surgical implantation procedure. Each treatment group included 50 rats. A connective tissue capsule formed around the metal implants, but not around the Thorotrast. Radiographs demonstrated corrosion of the DU implants shortly after implantation. At later times, rarifactions in the radiographic profiles correlated with proliferative tissue responses. After lifetime observation, the incidence of soft tissue sarcomas increased significantly around the 5.0 x 5.0 mm squares of DU and the positive control, Thorotrast. A slightly increased incidence occurred in rats implanted with the 2.5 x 2.5 mm DU squares and with 5.0 x 5.0 mm squares of Ta. No tumors were seen in rats with 2.0 x 1.0 mm diameter DU pellets or in the surgical controls. These results indicate that DU fragments of sufficient size cause localized proliferative reactions and soft tissue sarcomas that can be detected with radiography in the muscles of rats. PMID:11781165

  12. Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats.

    PubMed

    Tinkov, Alexey A; Popova, Elizaveta V; Polyakova, Valentina S; Kwan, Olga V; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p<0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity. PMID:25194956

  13. Identification of intracellular peptides in rat adipose tissue: Insights into insulin resistance.

    PubMed

    Berti, Denise A; Russo, Lilian C; Castro, Leandro M; Cruz, Lilian; Gozzo, Fábio C; Heimann, Joel C; Lima, Fabio B; Oliveira, Ariclécio C; Andreotti, Sandra; Prada, Patrícia O; Heimann, Andrea S; Ferro, Emer S

    2012-08-01

    Intracellular peptides generated by the proteasome and oligopeptidases have been suggested to function in signal transduction and to improve insulin resistance in mice fed a high-caloric diet. The aim of this study was to identify specific intracellular peptides in the adipose tissue of Wistar rats that could be associated with the physiological and therapeutic control of glucose uptake. Using semiquantitative mass spectrometry and LC/MS/MS analyses, we identified ten peptides in the epididymal adipose tissue of the Wistar rats; three of these peptides were present at increased levels in rats that were fed a high-caloric Western diet (WD) compared with rats fed a control diet (CD). The results of affinity chromatography suggested that in the cytoplasm of epididymal adipose tissue from either WD or CD rats, distinctive proteins bind to these peptides. However, despite the observed increase in the WD animals, the evaluated peptides increased insulin-stimulated glucose uptake in 3T3-L1 adipocytes treated with palmitate. Thus, intracellular peptides from the adipose tissue of Wistar rats can bind to specific proteins and facilitate insulin-induced glucose uptake in 3T3-L1 adipocytes. PMID:22740317

  14. Pharmacokinetics of warfarin in rats: role of serum protein binding and tissue distribution

    SciTech Connect

    Cheung, W.K.

    1985-01-01

    The purpose of this study was to explore the role of serum protein binding and tissue distribution in the non-linear pharmacokinetics of warfarin in rats. The first phase of the research was an attempt to elucidate the causes of intersubject differences in serum protein binding of warfarin in rats. It was found that the distribution of S-warfarin between blood and liver, kidneys, muscle, or fatty tissue was non-linear. Based on the tissue distribution data obtained, a physiologically-based pharmacokinetic model was developed to describe the time course of S-warfarin concentrations in the serum and tissues of rats. The proposed model was able to display the dose-dependent pharmacokinetics of warfarin in rats. Namely a lower clearance and a smaller apparent volume of distribution with increasing dose, which appear to be due to the presence of capacity-limited, high-affinity binding sites for warfarin in various tissues. To determine if the binding of warfarin to the high-affinity binding sites in the liver of rats is reversible, concentrations of S-warfarin in the liver and serum of rats were monitored for a very long time after an intravenous injection of a 1 mg/kg dose. In another study in rats, non-radioactive warfarin was found to be able to displace tissue-bound C/sup 14/-warfarin which was administered about 200 hours before the i.v. injection of the non-radioactive warfarin, showing that the binding of warfarin to the high-affinity binding sites in the body is persistent and reversible.

  15. Endothelin-1 receptors in rat tissues: characterization by bosentan, ambrisentan and CI-1020.

    PubMed

    Yokoyama, Yoshinari; Osano, Ayaka; Hayashi, Hideki; Itoh, Kunihiko; Okura, Takashi; Deguchi, Yoshiharu; Ito, Yoshihiko; Yamada, Shizuo

    2014-01-01

    The present study aimed to characterize comparatively endothelin-1 (ET-1) receptors in rat tissues by radioligand binding assay using [(125)I]ET-1 and to examine receptor binding after oral administration of bosentan. Significant amount of specific [(125)I]ET-1 binding was detected in the lung, heart, kidney, bladder and cerebral cortex of rats. ET-1, bosentan, ambrisentan, and CI-1020 inhibited specific [(125)I]ET-1 binding in these tissues in a concentration-dependent manner. The Hill coefficients of each agent in the rat lung and cerebral cortex and those of bosentan and ET-1 in the heart, kidney and bladder were close to unity, while the Hill coefficients of ambrisentan and CI-1020 in the heart, kidney and bladder were less than one. The nonlinear least squares regression analysis revealed the presence of high- and low-affinity ET-1 receptor sites in these tissues for ambrisentan and CI-1020. Oral administration of bosentan caused a dose-dependent decrease in specific [(125)I]ET-1 binding in the rat lung, kidney and bladder, suggesting significant binding of the tissue ET-1 receptors in vivo. In conclusion, it has been shown that a significant amount of pharmacologically relevant ET-1 receptors may exist in rat tissues and that ET-1 receptor antagonists such as bosentan at pharmacological doses may exert some pharmacological effects by binding these ET-1 receptors. PMID:24583865

  16. Effect of 3-methylcholanthrene-induced increases in ascorbic acid levels on tissue. beta. -glucuronidase activity in rats

    SciTech Connect

    Calabrese, E.J.; Barrett, T.J.; Leonard, D.A.; Horton, H.M.; Kenyon, E.M.

    1988-01-01

    The interrelationship between tissue ascorbic acid levels and tissue ..beta..-glucuronidase activity was examined in rats injected with 3-methylcholanthrene, an agent which induces ascorbic acid synthesis in rats. Six Fisher 344 rats were dosed intraperitoneally (IP) with 30 mg/kg of 3-methylcholanthrene. Ascorbic acid levels and ..beta..-glucuronidase (..beta..-G) activity were determined for lung, liver and kidney tissues. In a follow-up study, rats were dosed for three consecutive days with 3-methylcholanthrene. Controls in both groups were dosed IP with Emulphor (EL-620). Animals were sacrificed one week after the final dosage and lung, liver and kidney tissues were examined.

  17. Changes in the dielectric properties of rat tissue as a function of age at microwave frequencies

    NASA Astrophysics Data System (ADS)

    Peyman, A.; Rezazadeh, A. A.; Gabriel, C.

    2001-06-01

    The dielectric properties of ten rat tissues at six different ages were measured at 37 °C in the frequency range of 130 MHz to 10 GHz using an open-ended coaxial probe and a computer controlled network analyser. The results show a general decrease of the dielectric properties with age. The trend is more apparent for brain, skull and skin tissues and less noticeable for abdominal tissues. The variation in the dielectric properties with age is due to the changes in the water content and the organic composition of tissues. The percentage decrease in the dielectric properties of certain tissues in the 30 to 70 day old rats at cellular phone frequencies have been tabulated. These data provide an important input in the provision of rigorous dosimetry in lifetime-exposure animal experiments. The results provide some insight into possible differences in the assessment of exposure for children and adults.

  18. [Plasma and tissue lipids in rats after a flight on the Kosmos-1129 biosatellite].

    PubMed

    Ahlers, J; Tigranian, R A; D'jatelinka, J; Smajda, B; Toropila, M

    1982-01-01

    Concentrations of triglycerides, total cholesterol, lipid phosphorus and nonesterified fatty acids were measured in blood plasma, liver, thymus, bone marrow and adipose tissues of rats flown for 18.5 days onboard the biosatellite Cosmos-1129. This exposure was accompanied by increases in lipomobilization, content of total cholesterol and lipid phosphorus in plasma, and triglycerides in the thymus and bone marrow. The postflight exposure to repeated stresses demonstrated changes in the lipid content in all animal groups, especially in flight rats. PMID:7070042

  19. Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats

    PubMed Central

    Sjöqvist, Sebastian; Jungebluth, Philipp; Ling Lim, Mei; Haag, Johannes C.; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Angel Burguillos, Miguel; Del Gaudio, Costantino; Rodríguez, Antonio Beltrán; Sotnichenko, Alexander; Kublickiene, Karolina; Ullman, Henrik; Kielstein, Heike; Damberg, Peter; Bianco, Alessandra; Heuchel, Rainer; Zhao, Ying; Ribatti, Domenico; Ibarra, Cristián; Joseph, Bertrand; Taylor, Doris A.; Macchiarini, Paolo

    2014-01-01

    A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi. PMID:24736316

  20. Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

    PubMed Central

    Santos, Carlos F.; Morandini, Ana C.; Dionísio, Thiago J.; Faria, Flávio A.; Lima, Marta C.; Figueiredo, Caio M.; Colombini-Ishikiriama, Bella L.; Sipert, Carla R.; Maciel, Rubens P.; Akashi, Ana P.; Souza, Gabriela P.; Garlet, Gustavo P.; Rodini, Camila O.; Amaral, Sandra L.; Becari, Christiane; Salgado, Maria C.; Oliveira, Eduardo B.; Matus, Isaac; Didier, Daniela N.; Greene, Andrew S.

    2015-01-01

    The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats. PMID:26244896

  1. Chinese green tea consumption reduces oxidative stress, inflammation and tissues damage in smoke exposed rats

    PubMed Central

    Al-Awaida, Wajdy; Akash, Muhanad; Aburubaiha, Zaid; Talib, Wamidh H.; Shehadeh, Hayel

    2014-01-01

    Objective(s): One cause of cigarette smoking is oxidative stress that may alter the cellular antioxidant defense system, induce apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. It has been shown that Chinese green tea (CGT) (Lung Chen Tea) has higher antioxidant property than black tea. In this paper, we will explore the preventive effect of CGT on cigarette smoke-induced oxidative damage, apoptosis and tissues inflammation in albino rat model. Materials and Methods: Albino rats were randomly divided into four groups, i.e. sham air (SA), cigarette smoke (CS), CGT 2% plus SA or plus CS. The exposure to smoking was carried out as a single daily dose (1 cigarette/rat) for a period of 90 days using an electronically controlled smoking machine. Sham control albino rats were exposed to air instead of cigarette smoke. Tissues were collected 24 hr after last CS exposure for histology and all enzyme assays. Apoptosis was evidenced by the fragmentation of DNA using TUNEL assay. Results: Long-term administration of cigarette smoke altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and damage in liver, lung, and kidney. All these pathophysiological and biochemical events were significantly improved when the cigarette smoke-exposed albino rats were given CGT infusion as a drink instead of water. Conclusion: Exposure of albino rat model to cigarette smoke caused oxidative stress, altered the cellular antioxidant defense system, induced apoptosis in lung tissue, inflammation and tissues damage, which could be prevented by supplementation of CGT. PMID:25729541

  2. Insulin receptor content in tissues of normal and diabetic rats measured by radioimmunoassay.

    PubMed

    Pezzino, V; Costantino, A; Russo, P; Gullo, D; Papa, V

    1996-10-01

    Insulin receptor (IR) content in different tissues has been quantitatively evaluated by means of steady state binding studies with radiolabeled insulin. The information provided by this approach, however, does not give a direct measurement of the receptor protein. Rather, it depends on the binding function of the IR, evaluated on the basis of curvilinear plots derived by Scatchard analysis of the experimental data. In the present report we employed a sensitive and specific radioimmunoassay (RIA) that allows a direct measurement of IR in solubilized cells or tissues. By this method we studied: a) IR distribution in several tissues of the rat, the animal model most frequently used in studies of insulin action; b) IR regulation in streptozotocin-treated, diabetic insulin deficient rats. Tissues from male Wistar rats (11 controls and 6 streptozotocin-treated diabetic animals) were homogenized, solubilized with Triton X-100 in the presence of protease inhibitors and stored at -80 C. IR content in the solubilized material was then measured by RIA. IR were detectable in all 11 tissues tested. Liver, kidney and brain neocortex had the highest IR content. (24.7 +/- 1.0, 20.5 +/- 1.1, 25.9 +/- 1.6 ng/mg protein, m +/- SE, respectively). As expected, circulating insulin levels were lower in diabetic rats than in control rats. In diabetic, insulin deficient rats, liver, kidney and skeletal muscle contained more IR than in control rats (p = 0.001; p = 0.018; p = 0.003, respectively), whereas IR content in neocortex was similar in the two groups. The IR RIA may represent a useful tool for the study of IR regulation and patho-physiology. Our data provide a comparative direct measurement of IR distribution in a variety of rat tissues. IR content in diabetic rats is increased in typical target organs for insulin action, as a consequence of up-regulation due to the reduced insulin levels. This is not the case for metabolically insulin-dependent tissues, like brain. PMID:8957742

  3. Pharmacokinetic study of arctigenin in rat plasma and organ tissue by RP-HPLC method.

    PubMed

    He, Fan; Dou, De-Qiang; Hou, Qiang; Sun, Yu; Kang, Ting-Guo

    2013-01-01

    A high-performance liquid chromatography (HPLC) technique was developed for the determination of arctigenin in plasma and various organs of rats after the oral administration of 30, 50 and 70 mgkg(-1) of arctigenin to the Sprague-Dawley rats. Results showed that the validated HPLC method was simple, fast, reproducible and suitable to the determination of arctigenin in rat plasma and organ tissue and one-compartmental model with zero-order absorption process can well describe the changes of arctigenin concentration in the plasma. The concentration of compound was highest in the spleen, less in the liver and the least in the lung. PMID:22404522

  4. Tissue Distribution and Associated Toxicological Effects of Decabrominated Diphenyl Ether in Subchronically Exposed Male Rats

    PubMed Central

    Wang, Fuxin; Wang, Jianshe; Hu, Guocheng; Luo, Xiaojun; Mai, Bixian; Dai, Jiayin

    2011-01-01

    Concerns about decabrominated diphenyl ether (BDE-209) have arisen recently due to its increasing concentrations in the environment. We investigated the tissue concentration, distribution, and the debromination of BDE-209 after oral exposure, using rats as a model. Three groups of male rats were administrated by oral gavage with corn oil containing 0, 10, or 50 mg/kg bw/day of BDE-209 over 90 days. After exposure, BDE-209 and its metabolites levels in the liver, kidney, and adipose of the rats were measured. The mRNA expression levels of cytochrome P450 (CYP) enzymes in liver, serum thyroid hormone levels, and open-field tests were also measured. BDE-209 and several octa- and nona-BDE congeners were detected in the tissues of the dosed rats, indicating that BDE-209 was bioavailable and biotransformative in male rats. BDE-209 and its debrominated congeners had no mRNA level effect on selective genes from the CYP family in the liver or on the spontaneous behavior of adult male rats. Conversely, the level of thyroid hormone, total triiodothyronine (T3) in rats from the dosed treatments increased significantly compared to the control group. PMID:23724291

  5. Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120.

    PubMed

    Velenosi, Thomas J; Hennop, Anzel; Feere, David A; Tieu, Alvin; Kucey, Andrew S; Kyriacou, Polydoros; McCuaig, Laura E; Nevison, Stephanie E; Kerr, Michael A; Urquhart, Bradley L

    2016-01-01

    Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD. PMID:26932318

  6. Untargeted plasma and tissue metabolomics in rats with chronic kidney disease given AST-120

    PubMed Central

    Velenosi, Thomas J.; Hennop, Anzel; Feere, David A.; Tieu, Alvin; Kucey, Andrew S.; Kyriacou, Polydoros; McCuaig, Laura E.; Nevison, Stephanie E.; Kerr, Michael A.; Urquhart, Bradley L.

    2016-01-01

    Chronic kidney disease (CKD) results in the accumulation of metabolic waste products that are normally cleared by the kidney, known as uremia. Many of these waste products are from bacteria metabolites in the gut. Accumulation of uremic toxins in plasma and tissue, as well as the gut-plasma-tissue metabolic axis are important for understanding pathophysiological mechanisms of comorbidities in CKD. In this study, an untargeted metabolomics approach was used to determine uremic toxin accumulation in plasma, liver, heart and kidney tissue in rats with adenine-induced CKD. Rats with CKD were also given AST-120, a spherical carbon adsorbent, to assess metabolic changes in plasma and tissues with the removal of gut-derived uremic toxins. AST-120 decreased >55% of metabolites that were increased in plasma, liver and heart tissue of rats with CKD. CKD was primarily defined by 8 gut-derived uremic toxins, which were significantly increased in plasma and all tissues. These metabolites were derived from aromatic amino acids and soy protein including: indoxyl sulfate, p-cresyl sulfate, hippuric acid, phenyl sulfate, pyrocatechol sulfate, 4-ethylphenyl sulfate, p-cresol glucuronide and equol 7-glucuronide. Our results highlight the importance of diet and gut-derived metabolites in the accumulation of uremic toxins and define the gut-plasma-tissue metabolic axis in CKD. PMID:26932318

  7. Distribution of bisphenol A into tissues of adult, neonatal, and fetal Sprague-Dawley rats

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Vanlandingham, Michelle; Brown, Ronald P.; Fisher, Jeffrey W.

    2011-09-15

    Bisphenol A (BPA) is an important industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA metabolites in urine of > 90% of Americans aged 6-60 suggests ubiquitous and frequent exposure in the range of 0.02-0.2 {mu}g/kg bw/d (25th-95th percentiles). The current study used LC/MS/MS to measure placental transfer and concentrations of aglycone (receptor-active) and conjugated (inactive) BPA in tissues from Sprague-Dawley rats administered deuterated BPA (100 {mu}g/kg bw) by oral and IV routes. In adult female rat tissues, the tissue/serum concentration ratios for aglycone BPA ranged from 0.7 in liver to 5 in adipose tissue, reflecting differences in tissue perfusion, composition, and metabolic capacity. Following IV administration to dams, placental transfer was observed for aglycone BPA into fetuses at several gestational days (GD), with fetal/maternal serum ratios of 2.7 at GD 12, 1.2 at GD 16, and 0.4 at GD 20; the corresponding ratios for conjugated BPA were 0.43, 0.65, and 3.7. These ratios were within the ranges observed in adult tissues and were not indicative of preferential accumulation of aglycone BPA or hydrolysis of conjugates in fetal tissue in vivo. Concentrations of aglycone BPA in GD 20 fetal brain were higher than in liver or serum. Oral administration of the same dose did not produce measurable levels of aglycone BPA in fetal tissues. Amniotic fluid consistently contained levels of BPA at or below those in maternal serum. Concentrations of aglycone BPA in tissues of neonatal rats decreased with age in a manner consistent with the corresponding circulating levels. Phase II metabolism of BPA increased with fetal age such that near-term fetus was similar to early post-natal rats. These results show that concentrations of aglycone BPA in fetal tissues are similar to those in other maternal and neonatal tissues and that maternal Phase II metabolism, especially following oral

  8. Experimental and numerical study on the mechanical behavior of rat brain tissue.

    PubMed

    Karimi, A; Navidbakhsh, M; Yousefi, H; Haghi, A Motevalli; Sadati, Sja

    2014-02-01

    Brain tissue is a very soft tissue in which the mechanical properties depend on the loading direction. While few studies have characterized these biomechanical properties, it is worth knowing that accurate characterization of the mechanical properties of brain tissue at different loading directions is a key asset for neuronavigation and surgery simulation through haptic devices. In this study, the hyperelastic mechanical properties of rat brain tissue were measured experimentally and computationally. Prepared cylindrical samples were excised from the parietal lobes of rats' brains and experimentally tested by a tensile testing machine. The effects of loading direction on the mechanical properties of brain tissue were measured by applying load on both longitudinal and circumferential directions. The general prediction ability of the proposed hyperelastic model was verified using finite element (FE) simulations of brain tissue tension experiments. The uniaxial experimental results compared well with those predicted by the FE models. The results revealed the influence of loading direction on the mechanical properties of brain tissue. The Ogden hyperelastic material model was suitably represented by the non-linear behavior of the brain tissue, which can be used in future biomechanical simulations. The hyperelastic properties of brain tissue provided here have interest to the medical research community as there are several applications where accurate characterization of these properties are crucial for an accurate outcome, such as neurosurgery, robotic surgery, haptic device design or car manufacturing to evaluate possible trauma due to an impact. PMID:24519528

  9. Evaluation of the biocompatibility of resin-based root canal sealers in rat periapical tissue.

    PubMed

    Mutoh, Noriko; Satoh, Takenori; Watabe, Hirotaka; Tani-Ishii, Nobuyuki

    2013-01-01

    We evaluated the biocompatibility of resin-based root canal sealers (RCSs) in the periapical tissues of rats. Wistar rats underwent tooth replantation for reproducing the response of periapical tissue with RCSs. The resin-based Epipany SE, AH Plus Jet, the eugenol-based sealer (Canals) and a control group were employed. The upper right first molar was extracted and applied with RCSs on apices, and then the tooth was repositioned. Histological evaluation demonstrated that mild inflammation occurred in the periapical tissue with Epiphany and AH Plus Jet sealers on day 7, whereas Canals induced severe-to-moderate inflammation. The statistical analyses demonstrated that the significant differences were observed between Canals and the other groups on day 7 regarding inflammatory response. On day 14, the lesions induced by all sealers were healed and replaced predominantly by fibrous connective tissue. Our results suggest that Epiphany SE and AH Plus Jet are good biocompatible materials. PMID:23719002

  10. Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study

    PubMed Central

    Tennstedt, C; Chaoui, R; Korner, H; Dietel, M

    1999-01-01

    OBJECTIVE—To analyse the spectrum of congenital heart malformations, the frequency of extracardiac malformations, and the proportion of chromosome aberrations among fetuses sent for necropsy.
MATERIAL—Necropsies were performed on 815 fetuses—448 induced abortions (55%), 220 spontaneous abortions (27%), and 147 stillbirths (18%)—during a seven year period (1991-97) in the department of pathology of the Charité Medical Centre in Berlin. A congenital heart defect was identified in 129 cases (16%). For all 129 fetuses, karyotyping and an ultrasound examination had been performed.
RESULTS—Congenital heart defects were present in 22% of induced abortions (99 cases), 9% of spontaneous abortions (20 cases), and 7% of stillbirths (10 cases). The heart malformations were classified into 13 categories. A fetus with more than one defect was included only in the category of the most serious defect. The malformations in order of frequency were: ventricular septal defect (VSD) (28%), atrioventricular septal defect (AVSD) (16%), hypoplastic left heart (HLH) (16%), double outlet right ventricle (DORV) (12%), coarctation of the aorta (CoA) (6%), transposition of the great arteries (TGA) (4%), aortic valve stenosis (AoVS) (4%), tetralogy of Fallot (TOF) (3%), truncus arteriosus communis (TAC) (3%), pulmonary valve stenosis/pulmonary valve atresia (PaVS/PaVA) (3%), tricuspid atresia (TA) (3%), single ventricle (SV) (1.5%), and atrial septal defect (ASD) (0.5%). The most common congenital heart defects were VSD, AVSD, HLH, and DORV, which made up 72% of all the cases. In 11 cases the heart defect was isolated (no other cardiovascular or extracardiac malformations present), 85 cases (66%) were associated with additional cardiac malformations, 85 cases (66%) were associated with extracardiac malformations, and chromosome anomalies were detected in 43 cases (33%).
CONCLUSIONS—Fetal congenital heart malformations are common. These defects are often

  11. Interaction between heat acclimation and exogenous insulin in brown adipose tissue of rats

    NASA Astrophysics Data System (ADS)

    Ohno, H.; Yamashita, H.; Sato, N.; Habara, Y.; Gasa, S.; Nagasawa, J.; Sato, Y.; Ishikawa, M.; Segawa, M.; Yamamoto, M.

    1992-09-01

    Seventy-one male Wistar strain rats (7 weeks old) were kept at 5, 25, or 34° C, respectively, for 2 weeks with or without insulin administration. Insulin (Novo Lente MC) was given subcutaneously in a dose of 3.62 nmol/125 µl saline per 100 g body weight. An apparent effect of insulin treatment was noted only in heat-exposed rats, resulting in a remarkable gain in inter-scapular brown adipose tissue (BAT) mass of heat-acclimated, insulin-treated rats in terms of weight or weight per unit body weight. The BAT from heat-acclimated, insulin-treated rats had significantly higher levels of protein, DNA, RNA, and triglyceride than BAT from heat-acclimated, saline-treated rats. Therefore, it seems likely that the growth of BAT in heat-acclimated, insulin-treated rats was mostly due to the anabolic effects of insulin. The uncoupling protein mRNA was, however, present in BAT of heat-acclimated, insulin-treated rats at rather a depressed level, explaining a corresponding decrease in cold tolerance. On the other hand, the expression of insulin receptor mRNA was attenuated in BAT of rats from all the insulin-treated groups, possibly due to the down-regulation of insulin. Thus, there appeared to be some linkage among BAT, heat acclimation, and insulin.

  12. Extracardiac anomalies in the heterotaxy syndromes with focus on anomalies of midline-associated structures.

    PubMed

    Ticho, B S; Goldstein, A M; Van Praagh, R

    2000-03-15

    The extracardiac defects in patients with heterotaxy have not been examined as extensively as cardiac defects. We found a high incidence of midline-associated defects in 160 autopsied cases of heterotaxy (asplenia, polysplenia, or single right-sided spleen). Fifty-two percent of patients with left-sided polysplenia had a midline-associated defect, as did 45% of those with asplenia. Most common were musculoskeletal or genitourinary anomalies, as well as cleft palate. Fused adrenal glands and anal stenosis or atresia occurred exclusively among patients with asplenia. A midline anomaly was twice as likely to be detected on complete autopsy than from clinical findings alone. Linkage studies should take into account that affected subjects may have isolated subclinical midline defects. The high incidence of midline-associated defects supports the theory that the midline plays a critical role in establishing left-right asymmetry in the body. Comparison of these defects with mouse models of laterality defects suggests that mutations that disrupt the transforming growth factor beta pathway may result in heterotaxy. PMID:12000048

  13. Brown adipose tissue thermogenesis contributes to emotional hyperthermia in a resident rat suddenly confronted with an intruder rat

    PubMed Central

    Mohammed, Mazher; Ootsuka, Youichirou

    2014-01-01

    Body temperature increases when individuals experience salient, emotionally significant events. There is controversy concerning the contribution of nonshivering thermogenesis in brown adipose tissue (BAT) to emotional hyperthermia. In the present study we compared BAT, core body, and brain temperature, and tail blood flow, simultaneously measured, to determine whether BAT thermogenesis contributes to emotional hyperthermia in a resident Sprague-Dawley rat when an intruder rat, either freely-moving or confined to a small cage, is suddenly introduced into the cage of the resident rat for 30 min. Introduction of the intruder rat promptly increased BAT, body, and brain temperatures in the resident rat. For the caged intruder these temperature increases were 1.4 ± 0.2, 0.8 ± 0.1, 1.0 ± 0.1°C, respectively, with the increase in BAT temperature being significantly greater (P < 0.01) than the increases in body and brain. The initial 5-min slope of the BAT temperature record (0.18 ± 0.02°C/min) was significantly greater (P < 0.01) than the corresponding value for body (0.10 ± 0.01°C/min) and brain (0.09 ± 0.02°C/min). Tail artery pulse amplitude fell acutely when the intruder rat was introduced, possibly contributing to the increases in body and brain temperature. Prior blockade of β3 adrenoceptors (SR59230A 10 mg/kg ip) significantly reduced the amplitude of each temperature increase. Intruder-evoked increases in BAT temperature were similar in resident rats maintained at 11°C for 3 days. In the caged intruder situation there is no bodily contact between the rats, so the stimulus is psychological rather than physical. Our study thus demonstrates that BAT thermogenesis contributes to increases in body and brain temperature occurring during emotional hyperthermia. PMID:24452545

  14. In vivo effects of T-2 mycotoxin on synthesis of proteins and DNA in rat tissues

    SciTech Connect

    Thompson, W.L.; Wannemacher, R.W. Jr. )

    1990-09-15

    Rats were given an ip injection of T-2 mycotoxin (T-2), the T-2 metabolite, T-2 tetraol (tetraol), or cycloheximide. Serum, liver, heart, kidney, spleen, muscle, and intestine were collected at 3, 6, and 9 hr postinjection after a 2-hr pulse at each time with (14C)leucine and (3H)thymidine. Protein and DNA synthesis levels in rats were determined by dual-label counting of the acid-precipitable fraction of tissue homogenates. Rats given a lethal dose of T-2, tetraol, or cycloheximide died between 14 and 20 hr. Maximum inhibition of protein synthesis at the earliest time period was observed in additional rats given the same lethal dose of the three treatments and continued for the duration of the study (9 hr). With sublethal doses of T-2 or tetraol, the same early decrease in protein synthesis was observed but, in most of the tissues, recovery was seen with time. In the T-2-treated rats. DNA synthesis in the six tissues studied was also suppressed, although to a lesser degree. With sublethal doses, complete recovery of DNA synthesis took place in four of the six tissues by 9 hr after toxin exposure. The appearance of newly translated serum proteins did not occur in the animals treated with T-2 mycotoxin or cycloheximide, as evidenced by total and PCA-soluble serum levels of labeled leucine. An increase in tissue-pool levels of free leucine and thymidine in response to T-2 mycotoxin was also noted. T-2 mycotoxin, its metabolite, T-2 tetraol, and cycloheximide cause a rapid inhibition of protein and DNA synthesis in all tissue types studied. These results are compared with the responses seen in in vitro studies.

  15. Re-assessment of chronic radio-induced tissue damage in a rat hindlimb model

    PubMed Central

    PHULPIN, BÉRENGÈRE; DOLIVET, GILLES; MARIE, PIERRE-YVES; POUSSIER, SYLVAIN; GALLET, PATRICE; LEROUX, AGNÈS; GRAFF, PIERRE; GROUBACH, FREDERIQUE; BRAVETTI, PIERRE; MERLIN, JEAN-LOUIS; TRAN, NGUYEN

    2010-01-01

    Radiotherapy is successfully used to treat neoplastic lesions, but may adversely affect normal tissues within the irradiated volume. However, additional clinical and para-clinical data are required for a comprehensive understanding of the pathogenesis of this damage. We assessed a rat model using clinical records and medical imaging to gain a better understanding of irradiation-induced tissue damage. The hindlimbs of the rats in this model were irradiated with a single dose of 30 or 50 Gy. Sequential analysis was based on observation records of stage and planar scintigraphy. Additional radiography, radiohistology and histology studies were performed to detect histological alterations. All animals developed acute and late effects, with an increased severity after a dose of 50 Gy. The bone uptake of 99mTc-HDP was significantly decreased in a dose- and time-dependent manner. Histologically, significant tissue damage was observed. After the 50 Gy irradiation, the animals developed lesions characteristic of osteoradionecrosis (ORN). Radiographic and histological studies provided evidence of lytic bone lesions. Our rat model developed tissue damage characteristic of radiation injury after a single 30 Gy irradiation and tissue degeneration similar to that which occurs during human ORN after a 50 Gy irradiation. The development of this animal model is an essential step in exploring the pathogenesis of irradiation-induced tissue damage, and may be used to test the efficacy of new treatments. PMID:22993575

  16. Biokinetics of radiolabeled monoclonal antibodies in heterotransplanted nude rats: Evaluation of corrected specific tissue uptake

    SciTech Connect

    Ingvar, C.; Norrgren, K.; Strand, S.E.; Brodin, T.; Joensson, P.E.S.; Sjoegren, H.O. )

    1989-07-01

    A tumor model is presented to study the biokinetics and localization of radiolabeled monoclonal antibodies (MAb) in the nude rat (Rowett RNu/RNu) heterotransplanted with human melanoma metastases. The nude rat is larger, less sensitive, and lives longer than the nude mouse. It is, therefore, well suited for in vivo studies of tumor localization with radiolabeled monoclonal antibodies. The tumor-to-host weight ratio was closer to the human situation for the nude rat than for the mouse, and quantitative imaging could be performed with a parallel hole collimator. We followed the antibody biokinetics for as long as 8 days, with repeated blood sampling and imaging. Specific uptake of MAb was higher in tumor tissue than in all other tissues except blood. Initial high uptake was also recorded in the bone marrow. The lymph glands showed a slow uptake of specific and control antibody. A simple in vitro correction procedure is described to calculate the corrected specific tissue uptake (STUcorr) that takes the blood activity into account. Thus it was shown that 80% of the tissue uptake in the dissected liver at 30 hr was due to labeled antibodies circulating in the blood. The specific tissue uptake ratio of antibodies 96.5 and OKT3 (nonspecific control) was unity for all other organs except for tumor tissue, where the ratio was greater than two and even higher when correction for blood content of labeled antibody was made.

  17. Metformin Ameliorates Podocyte Damage by Restoring Renal Tissue Podocalyxin Expression in Type 2 Diabetic Rats

    PubMed Central

    Zhai, Limin; Gu, Junfei; Yang, Di; Wang, Wei; Ye, Shandong

    2015-01-01

    Podocalyxin (PCX) is a signature molecule of the glomerular podocyte and of maintaining integrity of filtration function of glomerulus. The aim of this study was to observe the effect of different doses of metformin on renal tissue PCX expression in type 2 diabetic rats and clarify its protection on glomerular podocytes. Type 2 diabetic Sprague-Dawley (SD) rats in which diabetes was induced by high-fat diet/streptozotocin (HFD-STZ) were treated with different doses of metformin (150, 300, and 500 mg/kg per day, resp.) for 8 weeks. Various biochemical parameters, kidney histopathology, and renal tissue PCX expression levels were examined. In type 2 diabetic rats, severe hyperglycemia and hyperlipidemia were developed. Urinary albumin and PCX were markedly increased. Diabetes induced significant alterations in renal glomerular structure. In addition, protein and mRNA expression of renal tissue PCX were highly decreased. However, treatment of rats with different doses of metformin restored all these changes to a varying degree. These results suggested that metformin can ameliorate glomerular podocyte damage in type 2 diabetic rats, which may be partly associated with its role in restoring PCX expression and inhibiting urinary excretion of PCX with dose dependence. PMID:26075281

  18. Conversion of dietary phylloquinone to tissue menaquinone-4 in rats is not dependent on gut bacteria.

    PubMed

    Davidson, R T; Foley, A L; Engelke, J A; Suttie, J W

    1998-02-01

    The ability of male rats to accumulate menaquinone-4 (MK-4) in tissues when fed a vitamin K-deficient diet supplemented with intraperitoneal phylloquinone (K) as the sole source of vitamin K for 14 d was assessed. In both conventionally housed controls and gnotobiotic rats, supplementation with the equivalent of 1500 microg vitamin K/kg diet increased (P < 0.001) tissue MK-4 concentrations above those of controls fed a vitamin K-deficient diet. MK-4 concentrations were approximately 5 ng/g (11 pmol/g) in liver, 14 ng/g in heart, 17 ng/g in kidney, 50 ng/g in brain and 250 ng/g in mandibular salivary glands of gnotobiotic rats. MK-4 concentrations in conventionally housed rats were higher than in gnotobiotic rats in heart (P < 0.01), brain (P < 0.01) and kidney (P < 0.05) but lower in salivary gland (P < 0.05). Cultures of a kidney-derived cell line (293) converted K to the expoxide of MK-4 in a manner that was dependent on both time of incubation and concentration of vitamin K in the media. A liver-derived cell line (H-35) was less active in carrying out this conversion. These data offer conclusive proof that the tissue-specific formation of MK-4 from K is a metabolic transformation that does not require bacterial transformation to menadione as an intermediate in the process. PMID:9446847

  19. Tissue fluid shift, forelimb loading, and tail tension in tail-suspended rats

    NASA Technical Reports Server (NTRS)

    Hargens, A. R.; Steskal, J.; Johansson, C.; Tipton, C. M.

    1984-01-01

    The tail suspension model (head-down tilt) simulates hypogravity in terms of musculoskeletal loss in the rat. However, little is known of tissue fluid shifts and body weight distribution in this model. Tissue fluid pressures were measured by wick catheters in 12 Munich-Wistar rats before, during, and after 48 hrs of tail suspension (about 30 deg head-down tilt). Subcutaneous tissue fluid pressure in the neck increased from -2.2 + or - 0.4 (normal horizontal position) to +4.0 + or - 1.5 cm H2O during tail suspension, indicating a cephalic fluid shift and significant edema during head-down tilt. In a separate study, six rats were suspended at 30-70 deg, and forelimb load and tail tension were measured by a balance and force transducer, respectively. Approximately 50 percent of body weight (BW) was loaded on forelimbs at a head-down tilt angle of 30 deg and forelimb load declined linearly to 10 percent BW at 70 deg. Furthermore, tail tension increased from 50 percent BW at 30 deg to 85 percent BW at 70 deg. These results indicate that less than normal loads are applied to forelimbs of rats suspended at angles of less than 30 deg and that the tail bears an increasing proportion of the rat's body weight at head-down tilt angles of less than 30 deg.

  20. Biopersistence of silver nanoparticles in tissues from Sprague–Dawley rats

    PubMed Central

    2013-01-01

    Silver nanoparticles are known to be distributed in many tissues after oral or inhalation exposure. Thus, understanding the tissue clearance of such distributed nanoparticles is very important to understand the behavior of silver nanoparticles in vivo. For risk assessment purposes, easy clearance indicates a lower overall cumulative toxicity. Accordingly, to investigate the clearance of tissue silver concentrations following oral silver nanoparticle exposure, Sprague–Dawley rats were assigned to 3 groups: control, low dose (100 mg/kg body weight), and high dose (500 mg/kg body weight), and exposed to two different sizes of silver nanoparticles (average diameter 10 and 25 nm) over 28 days. Thereafter, the rats were allowed to recover for 4 months. Regardless of the silver nanoparticle size, the silver content in most tissues gradually decreased during the 4-month recovery period, indicating tissue clearance of the accumulated silver. The exceptions were the silver concentrations in the brain and testes, which did not clear well, even after the 4-month recovery period, indicating an obstruction in transporting the accumulated silver out of these tissues. Therefore, the results showed that the size of the silver nanoparticles did not affect their tissue distribution. Furthermore, biological barriers, such as the blood–brain barrier and blood-testis barrier, seemed to play an important role in the silver clearance from these tissues. PMID:24059869

  1. Extraction and Quantification of Carbon Nanotubes in Biological Matrices with Application to Rat Lung Tissue

    PubMed Central

    Doudrick, Kyle; Corson, Nancy; Oberdörster, Günter; Elder, Alison; Herckes, Pierre; Halden, Rolf U.; Westerhoff, Paul

    2013-01-01

    Extraction of carbon nanotubes (CNTs) from biological matrices such as rat lung tissue is integral to developing a quantification method for evaluating the environmental and human health exposure and toxicity of CNTs. The ability of various chemical treatment methods, including Solvable (2.5% sodium hydroxide/surfactant mixture), ammonium hydroxide, nitric acid, sulfuric acid, hydrochloric acid, hydrofluoric acid, hydrogen peroxide, and proteinase K, to extract CNTs from rat lung tissue was evaluated. CNTs were quantified using programmed thermal analysis (PTA). Two CNTs were used to represent the lower (500°C) and upper (800°C) PTA limit of CNT thermal stability. The recovery efficiency of each of the eight chemical reagents evaluated was found to depend on the ability to (1) minimize oxidation of CNTs, (2) remove interfering background carbon from the rat lung tissue, and (3) separate the solid-phase CNTs from the liquid-phase dissolved tissue via centrifugation. A two-step extraction method using Solvable and proteinase K emerged as the optimal approach, enabling a recovery of 98 ± 15% of a 2.9 ± 0.19 µg CNT loading that was spiked into whole rat lungs. Due to its high yield and applicability to low organ burdens of nanomaterials, this extraction method is particularly well suited for in vivo studies to quantify clearance rates and retained CNTs in lungs and other organs. PMID:23992048

  2. LONG-TERM ACCUMULATION OF HEXACHLOROBENZENE IN ADIPOSE TISSUE OF PARENT AND FILIAL RATS

    EPA Science Inventory

    The concentrations of hexachlorobenzene (HCB) in adipose tissue were similar for FO and Flb generations in rats fed 20 ppm HCB until 45 weeks of age. Nulliparous females receiving treatment equivalent to the HCB-treated FO generation rapidly accumulated HCB in their fat and, by 1...

  3. Vibration Training Triggers Brown Adipocyte Relative Protein Expression in Rat White Adipose Tissue

    PubMed Central

    Sun, Chao; Zeng, Ruixia; Cao, Ge; Song, Zhibang; Zhang, Yibo; Liu, Chang

    2015-01-01

    Recently, vibration training is considered as a novel strategy of weight loss; however, its mechanisms are still unclear. In this study, normal or high-fat diet-induced rats were trained by whole body vibration for 8 weeks. We observed that the body weight and fat metabolism index, blood glucose, triglyceride, cholesterol, and free fatty acid in obesity rats decreased significantly compared with nonvibration group (n = 6). Although intrascapular BAT weight did not change significantly, vibration enhanced ATP reduction and increased protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 in BAT. Interestingly, the adipocytes in retroperitoneal white adipose tissue (WAT) became smaller due to vibration exercise and had higher protein level of the key molecule of brown adipose tissue (BAT), PGC-1α, and UCP1 and inflammatory relative proteins, IL-6 and TNFα. Simultaneously, ATP content and PPARγ protein level in WAT became less in rats compared with nonvibration group. The results indicated that vibration training changed lipid metabolism in rats and promoted brown fat-like change in white adipose tissues through triggering BAT associated gene expression, inflammatory reflect, and reducing energy reserve. PMID:26125027

  4. Pixe analysis of trace elements in tissues of rats treated with anticonvulsants

    NASA Astrophysics Data System (ADS)

    Hurd, R. W.; Van Rinsvelt, H. A.; Kinyua, A. M.; O'Neill, M. P.; Wilder, B. J.; Houdayer, A.; Hinrichsen, P. F.

    1987-04-01

    Several lines of evidence implicate metals in epilepsy. Anticonvulsant drugs are noted to alter levels of metals in humans and animals. PIXE analysis was used to investigate effects of three anticonvulsant drugs on tissue and brain cortex trace elements. The content of zinc and copper was increased in liver and spleen of rats treated with anticonvulsants while selenium was decreased in cortex.

  5. Changes in gas exchange, tissue respiration and glycolysis in rats during hypokinesia

    NASA Technical Reports Server (NTRS)

    Zorya, L. V.

    1980-01-01

    The results of an experiment which studied changes in oxygen balance under conditions of hypokinesia in rats is presented. The effect of the stress during hypokinesia is expressed most clearly in the changes of general gas exchange, and in the intensity of liver and myocardial tissue respiration.

  6. Changes in enzyme activities in tissues of rats exposed to hypoxia (Short Communication)

    PubMed Central

    Cryer, Anthony; Bartley, Walter

    1973-01-01

    Rats were exposed to various degrees of hypoxia and enzyme activities in their tissues were determined. In general, oxidative metabolism was not increased in response to hypoxia, nor was anaerobic metabolism. Physiological and anatomical changes were concluded to be more important than changes in cellular enzyme activities in the overall adaptation to acute hypoxia. PMID:4357712

  7. Citrulline synthesis in rat tissues and liver content of carbamoyl phosphate and ornithine

    PubMed Central

    Raijman, Luisa

    1974-01-01

    Rat liver ornithine carbamoyltransferase appears to be located exclusively in the mitochondria; the activity that is found in the soluble fraction is indistinguishable from mitochondrial ornithine carbamoyltransferase by simple kinetic criteria, and seems to result from breakage of mitochondria during homogenization. Of several rat tissues studied, only the liver and the mucosa of small intestine contain significant amounts of ornithine carbamoyltransferase; the activity in intestinal mucosa is less than one thousandth of that in liver. Qualitatively, this distribution coincides with that of carbamoyl phosphate synthetase I and its cofactor, acetylglutamate. The rat liver contents of carbamoyl phosphate and ornithine were 0.1 and 0.15μmol/g wet wt. of tissue respectively. On the basis of these values, it is proposed that in vivo the ornithine carbamoyltransferase activity of liver may be much lower than its maximal activity in vitro might suggest. PMID:4822731

  8. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    PubMed

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group). PMID:24254959

  9. The effect of artificial gravity on plasma and tissue lipids in rats: The Cosmos 936 experiment

    NASA Astrophysics Data System (ADS)

    Ahlers, I.; Praslička, M.; Tigranyan, R. A.

    Plasma and tissue lipids in male SPF Wistar rats flown for 18.5 days aboard the Cosmos 936 biosatellite were analyzed. One group of rats was subjected to artificial gravity by use of a centrifuge during the flight. An experiment simulating known space flight factors other than weightlessness was done on Earth. An increase of total cholesterol in plasma, of nonesterified fatty acids in plasma and brown adipose tissue, of triacylglycerols in plasma, liver, thymus and bone marrow was noted several hours after biosatellite landing. Smaller changes were observed in the terrestrial control experiment. With the exception of triacylglycerol accumulation in bone marrow, these increases disappeared 25 days after biosatellite landing. Exposing the rats aboard the biosatellite to artificial gravity was beneficial in the sense that such exposure inhibited the phospholipid and triacylglycerol increase in plasma and inhibited the increase of triacylglycerol in liver and especially in bone marrow.

  10. Perfusion assessment in rat spinal cord tissue using photoplethysmography and laser Doppler flux measurements

    NASA Astrophysics Data System (ADS)

    Phillips, Justin P.; Cibert-Goton, Vincent; Langford, Richard M.; Shortland, Peter J.

    2013-03-01

    Animal models are widely used to investigate the pathological mechanisms of spinal cord injury (SCI), most commonly in rats. It is well known that compromised blood flow caused by mechanical disruption of the vasculature can produce irreversible damage and cell death in hypoperfused tissue regions and spinal cord tissue is particularly susceptible to such damage. A fiberoptic photoplethysmography (PPG) probe and instrumentation system were used to investigate the practical considerations of making measurements from rat spinal cord and to assess its suitability for use in SCI models. Experiments to assess the regional perfusion of exposed spinal cord in anesthetized adult rats using both PPG and laser Doppler flowmetry (LDF) were performed. It was found that signals could be obtained reliably from all subjects, although considerable intersite and intersubject variability was seen in the PPG signal amplitude compared to LDF. We present results from 30 measurements in five subjects, the two methods are compared, and practical application to SCI animal models is discussed.

  11. Iron supplementation at high altitudes induces inflammation and oxidative injury to lung tissues in rats

    SciTech Connect

    Salama, Samir A.; Omar, Hany A.; Maghrabi, Ibrahim A.; AlSaeed, Mohammed S.; EL-Tarras, Adel E.

    2014-01-01

    Exposure to high altitudes is associated with hypoxia and increased vulnerability to oxidative stress. Polycythemia (increased number of circulating erythrocytes) develops to compensate the high altitude associated hypoxia. Iron supplementation is, thus, recommended to meet the demand for the physiological polycythemia. Iron is a major player in redox reactions and may exacerbate the high altitudes-associated oxidative stress. The aim of this study was to explore the potential iron-induced oxidative lung tissue injury in rats at high altitudes (6000 ft above the sea level). Iron supplementation (2 mg elemental iron/kg, once daily for 15 days) induced histopathological changes to lung tissues that include severe congestion, dilatation of the blood vessels, emphysema in the air alveoli, and peribronchial inflammatory cell infiltration. The levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), lipid peroxidation product and protein carbonyl content in lung tissues were significantly elevated. Moreover, the levels of reduced glutathione and total antioxidant capacity were significantly reduced. Co-administration of trolox, a water soluble vitamin E analog (25 mg/kg, once daily for the last 7 days of iron supplementation), alleviated the lung histological impairments, significantly decreased the pro-inflammatory cytokines, and restored the oxidative stress markers. Together, our findings indicate that iron supplementation at high altitudes induces lung tissue injury in rats. This injury could be mediated through excessive production of reactive oxygen species and induction of inflammatory responses. The study highlights the tissue injury induced by iron supplementation at high altitudes and suggests the co-administration of antioxidants such as trolox as protective measures. - Highlights: • Iron supplementation at high altitudes induced lung histological changes in rats. • Iron induced oxidative stress in lung tissues of rats at high altitudes. • Iron

  12. Tissue distribution of concentrative and equilibrative nucleoside transporters in male and female rats and mice.

    PubMed

    Lu, Hong; Chen, Chuan; Klaassen, Curtis

    2004-12-01

    Concentrative nucleoside transporters (Cnts) and equilibrative nucleoside transporters (Ents) have essential physiological functions and are important in disposition of anticancer and antiviral nucleoside analogs. Information on tissue distribution of Cnts and Ents in rodents is sparse. Thus, the present study aimed to determine the distribution of Cnt1-3 and Ent1-3 transcripts in 19 tissues of Sprague-Dawley rats and C57BL/6 mice of both genders. These six transcripts were quantified using the branched DNA signal amplification assay. Cnt1 transcripts were highest in small intestine, followed by kidney and testes, with similar expression in both species. Cnt2 mRNA was expressed highest in the small intestine of both rats and mice, intermediate in liver of rats but not in mice, and lower in thymus and spleen of both species. Cnt3 mRNA has marked species differences, with the highest expression in lung of rats but uterus of mice. Ent1 mRNA was most highly expressed in testes and lung of both species. Ent1 mRNA was highly expressed in liver and pituitary of mice, but not in rats. Ent2 mRNA was highly expressed in testes and brain of both species. Ent3 mRNA was highest in kidney, followed by testes, in both species. Significant gender differences were observed in kidney (mouse) and heart (rat). These studies demonstrate that in general, tissue distribution of Cnt and Ent is similar in rats and mice. However, a few important species and gender differences do exist, which could be responsible for related differences in efficacy and toxicity of substrates for these transporters. PMID:15371301

  13. Fatty acid composition of brown adipose tissue in genetically heat-tolerant FOK rats

    NASA Astrophysics Data System (ADS)

    Ohno, T.; Furuyama, F.; Kuroshima, A.

    The phospholipid fatty acid composition of brown adipose tissue (BAT) was examined in inbred heat-tolerant FOK rats and compared with that in conventional Wistar rats not previously exposed to heat. The FOK rats showed higher unsaturation states, as indicated by higher levels of polyunsaturated fatty acids and a higher unsaturation index and polyunsaturated fatty acids/saturated fatty acids ratio. This higher level of unsaturation was characterized by the higher amount of polyunsaturated fatty acids such as linoleic acid, arachidonic acid and docosahexaenoic acid. It may be concluded that the increased docosahexaenoic acid level in BAT phospholipids brings about the hyperplasia of BAT, causing an enhancement of its in vivo thermogernic activity as well as the systemic non-shivering thermogenesis observed in heat-tolerant FOK rats.

  14. Effect of chemical form of selenium on tissue glutathione peroxidase activity in developing rats

    NASA Technical Reports Server (NTRS)

    Lane, Helen W.; Strength, Ralph; Johnson, Janet; White, Marguerite T.

    1991-01-01

    The hypothesis that the stage of development of rats may affect the availability of various forms of selenium for the activity of glutathione peroxidase (GSHPx) in the rat was experimentally investigated. One experiment evaluated the availability of selenium as selenite or selenomethionine for GSPHx activity during three developmental states in rats: fetus and 7-day old and 14-day old nursing pups. In all tissues studied, GSHPx activity was highest in the 14-day-old pups whose dams were in the selenomethionine group. Rat pups given intraperitoneal selenite had higher liver and kidney GSHPx activity than pups given the same amount of selenium as intraperitoneal selenomethionine. In a second experiment, all dams were fed the same basal diet and pups were weaned to diets containing one of two levels of selenium and one of three forms of selenium (selenite, selenomethionine, or selenocystine). The results also supported the hypothesis these dietary forms of selenium are differentially available for GSHPx activity.

  15. Hydrolysis kinetics of propylene glycol monomethyl ether acetate in rats in vivo and in rat and human tissues in vitro.

    PubMed

    Domoradzki, J Y; Brzak, K A; Thornton, C M

    2003-09-01

    The kinetic equivalency of propylene glycol monomethyl ether (PGME), derived from propylene glycol monomethyl ether acetate (PGMEA), as well as the parent compound (PGME) following intravenous administration to Fischer 344 rats was evaluated. In addition, in vitro hydrolysis rates of PGMEA in blood and liver tissue from rats and humans were determined. The blood kinetics were determined following iv administration to rats of PGME and PGMEA of low [10 and 14.7 mg/kg body weight (bw)] or high (100 and 147 mg/kg) equimolar dosages of PGME and PGMEA, respectively. The blood time courses of PGME elimination for both dosages of both compounds were identical. Half-lives of PGMEA elimination following iv administration of 14.7 or 147 mg PGMEA/kg bw were calculated to be 1.6 and 2.3 min, respectively. Rat and human in vitro hydrolysis rates of PGMEA were determined by incubation of 5 or 50 microg PGMEA/ml in whole blood or liver homogenate. The rate of loss of PGMEA was more rapid in rat blood than in human blood, with hydrolysis half-lives of 36 and 34 min in human blood and 16 and 15 min in rat blood for the 5 and 50 microg/ml concentrations of PGMEA, respectively. In contrast the rate of loss of PGMEA in human and rat liver homogenate incubations was similar, 27-30 min and 34 min, respectively. These data demonstrate the rapid hydrolysis of PGMEA in vivo to its parent glycol ether, PGME and that, once hydrolyzed, the kinetics for PGME derived from PGMEA are identical to that for PGME. This study supports the use of the toxicological database on PGME as a surrogate for PGMEA. PMID:12857936

  16. State of the mineral component of rat bone tissue during hypokinesia and the recovery period

    NASA Technical Reports Server (NTRS)

    Volozhin, A. I.; Stupakov, G. P.; Pavlova, M. N.; Muradov, I. S.

    1980-01-01

    Experiments were conducted on young growing rats. Hypokinesia lasting from 20 to 200 days caused retarded gain in weight and volume of the femur and delayed development of the cortical layer of the diaphysis. In contrast, the density of the cortical layer of the femoral diaphysis increased due to elevation of the mineral saturation of the bone tissue microstructures. Incorporation of Ca into the bone tissue in hypokinesia had a tendency to reduce. Partial normalization of the bone tissue mineral component occurred during a 20 day recovery period following hypokinesia.

  17. The influence of lithium on calcium and magnesium homeostasis in serum and tissues of rats.

    PubMed

    Kiełczykowska, Małgorzata; Pasternak, Kazimierz; Musik, Irena

    2003-01-01

    Lithium is used in medicine. However, its administration can have negative side effects, disturb the water-electrolyte equilibrium and affect the level of essential elements. For these reasons the influence of oral lithium intoxication at the dose of 150 mg Li dm(-3) on magnesium and calcium levels in serum and tissues of rats was investigated. The concentration of Mg and Ca in serum increased throughout the experiment. The concentration of magnesium in tissues decreased after three weeks in liver, kidney, brain and femoral muscle. The trend of the changes of calcium tissue concentration was opposite to the one observed in the case of magnesium. PMID:15323205

  18. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    SciTech Connect

    Lanza-Jacoby, S.; Tabares, A. )

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  19. Effect of garlic (Allium sativum L.) extract on tissue lead level in rats.

    PubMed

    Senapati, S K; Dey, S; Dwivedi, S K; Swarup, D

    2001-08-01

    The prophylactic efficacy of garlic (Allium sativum L.) extract to reduce tissue lead (Pb) concentration was evaluated experimentally in rats. Thirty female rats were divided into five groups, keeping group A as a healthy control. Rats of groups B, C, D and E received lead acetate orally at the rate of 5 mg per kg body weight daily for 6 weeks. The garlic extract was tried in three doses, viz. 100 (low), 200 (medium) and 400 mg (high) per kg body weight orally and given simultaneously with lead salt to the rats of group C, D and E, respectively. Mean blood lead concentrations in lead-exposed rats ranged between 0.13+/-0.02 and 0.96+/-0.06 microg/ml, whereas in garlic-treated rats, the range was between 0.16+/-0.01 and 0.80+/-0.05; 0.13+/-0.01 and 0.71+/-0.06 and 0.14+/-0.01 and 0.60+/-0.05 microg per ml in low, medium and high dose groups, respectively. The mean lead concentration in liver, kidneys, brain and bone of lead exposed rats was 2.943+/-0.206, 4.780+/-0.609, 1.019+/-0.100 and 44.075+/-2.60 microg per ml, respectively. Concomitant use of garlic extract at the three different doses was found to reduce lead concentration considerably indicating the potential therapeutic activity of garlic against lead. PMID:11448543

  20. Determinants of rat albumin promoter tissue specificity analyzed by an improved transient expression system.

    PubMed Central

    Heard, J M; Herbomel, P; Ott, M O; Mottura-Rollier, A; Weiss, M; Yaniv, M

    1987-01-01

    The 150-base-pairs region located upstream of the transcriptional start site of the rat albumin gene contains all of the critical sequences necessary for this gene's tissue-specific expression in rat hepatoma cells. In transient expression assays using an improved CAT system or direct mRNA analysis we were able to detect a faithful transcription from the albumin promoter in albumin-negative dedifferentiated H5 hepatoma cells which was 250-fold weaker than in differentiated H4II hepatoma cells producing albumin. This strong tissue specificity could be completely overcome through the cis action of a non-tissue-specific enhancer. Two upstream regions from nucleotides -151 to -119 and from -118 to -94, were required for efficient transcription in H4II cells. Each region contained a sequence motif highly conserved among different species. The effect of the -151/-119 region was strictly tissue specific, while the -118/-94 region was also involved in the low level of transcription observed in H5 cells. Finally, sequences between the CCAAT box and the TATA box also contributed to the overall tissue specificity of rat albumin gene transcription. Images PMID:3475566

  1. Tissue distribution of amiodarone and desethylamiodarone in rats after multiple intraperitoneal administration of various amiodarone dosages.

    PubMed

    Plomp, T A; Wiersinga, W M; Maes, R A

    1985-01-01

    Tissue distribution of amiodarone (Cordarone) and desethylamiodarone in the rat was studied after repeated intraperitoneal administration of the drug. Tissue and serum concentrations of amiodarone and desethylamiodarone were determined by high-performance liquid chromatography. The levels of amiodarone and desethylamiodarone in serum and tissues obtained after repeated intraperitoneal application of doses varying from 25 mg to 200 mg/kg show that the accumulation of amiodarone and desethylamiodarone in the rat is dose-dependent and both drugs are preferentially distributed in decreasing order in adipose tissue, lung, liver, kidney and thyroid gland. The penetration of the drug and its metabolite into brain was poor and with all the applied dosages brain levels were considerably lower than the corresponding serum levels. Desethylamiodarone serum and tissue concentrations were substantially lower than the corresponding amiodarone concentrations and varied from 1 to 48% (mean 15%) depending on the dosage used and the kind of tissue. The amiodarone tissue/serum concentration ratios were exceptionally high in adipose tissue (1,000-4,000) and moderate to high in the other tissues except brain (5-90), and indicate an extensive distribution of the drug with fat as a reservoir with a large storage capacity. The levels of amiodarone and desethylamiodarone, obtained with 50 mg/kg and 100 mg/kg dosages, showed in function of time clearly an increase in serum and tissues. The observed amiodarone tissue/serum ratios in function of time revealed no further significant increase (p less than or equal to 0.05) after 3 injections over a 6-day period, indicating the attainment of "steady-state".(ABSTRACT TRUNCATED AT 250 WORDS) PMID:4039141

  2. Characterization and tissue distribution of conjugated metabolites of pyrene in the rat

    PubMed Central

    SAENGTIENCHAI, Aksorn; IKENAKA, Yoshinori; DARWISH, Wageh Sobhy; NAKAYAMA, Shouta M.M.; MIZUKAWA, Hazuki; ISHIZUKA, Mayumi

    2015-01-01

    Pyrene (PY) is a polycyclic aromatic hydrocarbon (PAH) that is often used as a biomarker for human and wildlife exposure to PAHs. As the metabolites of PAHs, similar to their parent compounds, pose public health risks, it is necessary to study their characteristics and tissue-specific distribution. The present study was performed to experimentally characterize PY metabolites and analyze the tissue-specific distribution of the conjugated metabolites after oral administration of PY to rats. PY metabolites, such as pyrenediol-disulfate (PYdiol-diS), pyrenediol-sulfate (PYdiol-S), pyrene-1-sufate (PYOS), pyrene-1-glucuronide (PYOG) and 1-hydroxypyrene (PYOH), were detected in rat urine. Although glucuronide conjugate was the predominant metabolite, the metabolite composition varied among tissues. Interestingly, the proportion of PYOH was high in the large intestine. Furthermore, PYOH was the only PY metabolite detected in feces. PMID:26028020

  3. Immunohistochemical distribution of leptin in kidney tissues of melatonin treated diabetic rats.

    PubMed

    Elis Yildiz, S; Deprem, T; Karadag Sari, E; Bingol, S A; Koral Tasci, S; Aslan, S; Nur, G; Sozmen, M

    2015-05-01

    We examined using immunohistochemistry the distribution of leptin in kidney tissues of melatonin treated, streptozotocin (STZ) diabetic rats. The animals were divided into five groups: control, sham, melatonin-treated, diabetic and melatonin-treated diabetic. Kidney sections were prepared and stained with hematoxylin and eosin, and Crossman's triple staining for histological examination. The immunohistochemical localization of leptin in the kidney tissue was determined using the streptavidin-biotin-peroxidase method. We determined that on days 7 and 14, the leptin immunoreactivity of the diabetic and melatonin-treated diabetic groups was weaker than for the other groups. Weak immunoreactivity was found in the proximal and distal tubules of the kidney in the diabetic and melatonin-treated diabetic groups on days 7 and 14, and strong immunoreactivity was found in the control, sham and melatonin groups. Melatonin application had no significant effect on leptin production in the kidney tissues of diabetic rats. PMID:25539049

  4. Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats

    PubMed Central

    Lim, Chae Jeong; Lee, So Yeong; Ryu, Pan Dong

    2015-01-01

    The primo-vascular system (PVS) is a novel network identified in various animal tissues. However, the PVS in subcutaneous tissue has not been well identified. Here, we examined the putative PVS on the surface of abdominal subcutaneous tissue in rats. Hemacolor staining revealed dark blue threadlike structures consisting of nodes and vessels, which were frequently observed bundled with blood vessels. The structure was filled with various immune cells including mast cells and WBCs. In the structure, there were inner spaces (20–60 µm) with low cellularity. Electron microscopy revealed a bundle structure and typical cytology common with the well-established organ surface PVS, which were different from those of the lymphatic vessel. Among several subcutaneous (sc) PVS tissues identified on the rat abdominal space, the most outstanding was the scPVS aligned along the ventral midline. The distribution pattern of nodes and vessels in the scPVS closely resembled that of the conception vessel meridian and its acupoints. In conclusion, our results newly revealed that the PVS is present in the abdominal subcutaneous tissue layer and indicate that the scPVS tissues are closely correlated with acupuncture meridians. Our findings will help to characterize the PVS in the other superficial tissues and its physiological roles. PMID:26379751

  5. Identification of Primo-Vascular System in Abdominal Subcutaneous Tissue Layer of Rats.

    PubMed

    Lim, Chae Jeong; Lee, So Yeong; Ryu, Pan Dong

    2015-01-01

    The primo-vascular system (PVS) is a novel network identified in various animal tissues. However, the PVS in subcutaneous tissue has not been well identified. Here, we examined the putative PVS on the surface of abdominal subcutaneous tissue in rats. Hemacolor staining revealed dark blue threadlike structures consisting of nodes and vessels, which were frequently observed bundled with blood vessels. The structure was filled with various immune cells including mast cells and WBCs. In the structure, there were inner spaces (20-60 µm) with low cellularity. Electron microscopy revealed a bundle structure and typical cytology common with the well-established organ surface PVS, which were different from those of the lymphatic vessel. Among several subcutaneous (sc) PVS tissues identified on the rat abdominal space, the most outstanding was the scPVS aligned along the ventral midline. The distribution pattern of nodes and vessels in the scPVS closely resembled that of the conception vessel meridian and its acupoints. In conclusion, our results newly revealed that the PVS is present in the abdominal subcutaneous tissue layer and indicate that the scPVS tissues are closely correlated with acupuncture meridians. Our findings will help to characterize the PVS in the other superficial tissues and its physiological roles. PMID:26379751

  6. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability. PMID:17652829

  7. Effect of Hypothyroidism and Hyperthyroidism on Tissue Thyroid Hormone Concentrations in Rat

    PubMed Central

    Donzelli, Riccardo; Colligiani, Daria; Kusmic, Claudia; Sabatini, Martina; Lorenzini, Leonardo; Accorroni, Alice; Nannipieri, Monica; Saba, Alessandro; Iervasi, Giorgio; Zucchi, Riccardo

    2016-01-01

    Background and Objective The present study was aimed at determining the effects of experimental hypothyroidism and hyperthyroidism on tissue thyroid hormones by a mass spectrometry-based technique. Methods Rats were subjected to propylthiouracil treatment or administration of exogenous triiodothyronine (T3) or thyroxine (T4). Tissue T3 and T4 were measured by liquid chromatography tandem mass spectrometry in the heart, liver, kidney, visceral and subcutaneous adipose tissue, and brain. Results Baseline tissue T3 and T4 concentrations ranged from 0.2 to 20 pmol ∙ g-1 and from 3 to 125 pmol ∙ g-1, respectively, with the highest values in the liver and kidney, and the lowest values in the adipose tissue. The T3/T4 ratio (expressed as a percentage) was in the 7-20% range in all tissues except the brain, where it averaged 75%. In hypothyroidism, tissue T3 was more severely reduced than serum free T3, averaging 1-6% of the baseline versus 30% of the baseline. The extent of tissue T3 reduction, expressed as percentage of the baseline, was not homogeneous (p < 0.001), with liver = kidney > brain > heart > adipose tissue. The tissue T3/T4 ratio significantly increased in all organs except the kidney, averaging 330% in the brain and 50-90% in the other tissues. By contrast, exogenous T3 and T4 administration produced similar increases in serum free T3 and in tissue T3, and the relative changes were not significantly different between different tissues. Conclusions While the response to increased thyroid hormones availability was similar in all tissues, decreased thyroid hormone availability induced compensatory responses, leading to a significant mismatch between changes in serum and in specific tissues. PMID:27099836

  8. Rare DNA copy number variants in cardiovascular malformations with extracardiac abnormalities

    PubMed Central

    Lalani, Seema R; Shaw, Chad; Wang, Xueqing; Patel, Ankita; Patterson, Lance W; Kolodziejska, Katarzyna; Szafranski, Przemyslaw; Ou, Zhishuo; Tian, Qi; Kang, Sung-Hae L; Jinnah, Amina; Ali, Sophia; Malik, Aamir; Hixson, Patricia; Potocki, Lorraine; Lupski, James R; Stankiewicz, Pawel; Bacino, Carlos A; Dawson, Brian; Beaudet, Arthur L; Boricha, Fatima M; Whittaker, Runako; Li, Chumei; Ware, Stephanie M; Cheung, Sau Wai; Penny, Daniel J; Jefferies, John Lynn; Belmont, John W

    2013-01-01

    Clinically significant cardiovascular malformations (CVMs) occur in 5–8 per 1000 live births. Recurrent copy number variations (CNVs) are among the known causes of syndromic CVMs, accounting for an important fraction of cases. We hypothesized that many additional rare CNVs also cause CVMs and can be detected in patients with CVMs plus extracardiac anomalies (ECAs). Through a genome-wide survey of 203 subjects with CVMs and ECAs, we identified 55 CNVs >50 kb in length that were not present in children without known cardiovascular defects (n=872). Sixteen unique CNVs overlapping these variants were found in an independent CVM plus ECA cohort (n=511), which were not observed in 2011 controls. The study identified 12/16 (75%) novel loci including non-recurrent de novo 16q24.3 loss (4/714) and de novo 2q31.3q32.1 loss encompassing PPP1R1C and PDE1A (2/714). The study also narrowed critical intervals in three well-recognized genomic disorders of CVM, such as the cat-eye syndrome region on 22q11.1, 8p23.1 loss encompassing GATA4 and SOX7 and 17p13.3-p13.2 loss. An analysis of protein-interaction databases shows that the rare inherited and de novo CNVs detected in the combined cohort are enriched for genes encoding proteins that are direct or indirect partners of proteins known to be required for normal cardiac development. Our findings implicate rare variants such as 16q24.3 loss and 2q31.3-q32.1 loss, and delineate regions within previously reported structural variants known to cause CVMs. PMID:22929023

  9. Impact of Extracardiac Findings during Cardiac MR on Patient Management and Outcome

    PubMed Central

    Dunet, Vincent; Barras, Heloise; Boulanger, Xavier; Monney, Pierre; Qanadli, Salah D.; Meuli, Reto; Schwitter, Juerg; Beigelman-Aubry, Catherine

    2015-01-01

    Background Cardiac magnetic resonance (CMR) is increasingly used to assess heart diseases. Relevant non-cardiac diseases may also be incidentally found on CMR images. The aim of this study was to determine the prevalence and nature of incidental extra-cardiac findings (IEF) and their clinical impact in non-selected patients referred for CMR. Material/Methods MR images of 762 consecutive patients (515 men, age: 56±18 years) referred for CMR were prospectively interpreted by 2 radiologists blinded for any previous imaging study. IEFs were classified as major when requiring treatment, follow-up, or further investigation. Clinical follow-up was performed by checking hospital information records and by calling referring physicians. The 2 endpoints were: 1) non-cardiac death and new treatment related to major IEFs, and 2) hospitalization related to major IEFs during follow-up. Results Major IEFs were proven in 129 patients (18.6% of the study population), 14% of those being unknown before CMR. During 15±6 month follow-up, treatment of confirmed major IEFs was initiated in 1.4%, and no non-cardiac deaths occurred. Hospitalization occurred in 8 patients (1.0% of the study population) with confirmed major IEFs and none occurred in the remaining 110 patients with unconfirmed/unexplored major IEFs (p<0.001). Conclusions Screening for major IEFs in a population referred for routine CMR changed management in 1.4% of patients. Major IEFs unknown before CMR but without further exploration, however, carried a favorable prognosis over a follow-up period of 15 months. PMID:25943552

  10. Effect of choline magnesium trisalicylate on prostacyclin production by isolated vascular tissue of the rat.

    PubMed

    Levy, J V

    1983-01-15

    Choline Magnesium Trisalicylate (Trilisate), in therapeutic concentrations of 5, 10, 15 and 30 mg/100 ml, did not significantly affect production of prostacyclin-like (PGI2) substance by rat aortic tissue in vitro. The ED50 for inhibition of aorta PGI2-like substance production by Trilisate was 1,200 mg/100 ml. This is approximately 40 times the maximum therapeutic blood concentration achieved in humans. Choline or Magnesium salicylate produced slight but insignificant inhibition of PGI2-like substance production by rat aortic tissue in vitro. The ED50 for ibuprofen (Motrin) for inhibition of PGI2-like production of rat aortic rings was 0.65-0.92 mg/100 ml. Injection of Choline Magnesium Trisalicylate into rats (124, 250, 500 mg/kg I.P.) did not affect the normal production of PGI2-like substance of aortic tissue obtained one hour after in vivo treatment. These results suggest this anti-inflammatory salicylate does not adversely affect PGI2-like production by blood vessels, in concentrations associated with therapeutic effects in man. PMID:6342204

  11. Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

    NASA Astrophysics Data System (ADS)

    Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

    2010-04-01

    This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

  12. Pref-1 and adipokine expression in adipose tissues of GK and Zucker rats.

    PubMed

    Barbu, Andreea; Hedlund, Gabriella Persdotter; Lind, Jenny; Carlsson, Carina

    2009-02-27

    In view of the central role of preadipocyte factor-1, adiponectin and leptin in white adipose tissue function, the aim of the present study was to analyze the mRNA expression of these proteins and of the inflammatory markers interleukin-6 and tumor necrosis factor-alpha in visceral and subcutaneous fat pads of rats with different metabolic disorders. We demonstrated highly divergent expression of preadipocyte factor-1, upregulated expression of adiponectin, interleukin-6 and TNF-alpha mRNA in adipose tissues of the diabetic Goto Kakizaki rat compared to the obese Zucker rat. This was correlated to an increased number of large adipocytes and serum levels of adiponectin. Furthermore, in all four strains studied (as above plus Wistar Furth and Zucker Lean), significant heterogeneity was evident in adipokine expression within specific adipose tissues previously defined as belonging to the visceral or subcutaneous fat depots. These results suggest that significantly increased levels of inflammation and redistribution of adipocyte size are mechanisms contributing to the development of type 2 diabetes in the GK rat. PMID:19084046

  13. Tissue Reaction to Different Types of Calcium Hydroxide Paste in Rat.

    PubMed

    Zarei, Mina; Javidi, Maryam; Gharechahi, Maryam; Kateb, Moaied; Zare, Reza; Kelagari, Ziba Shirkhani

    2016-01-01

    The purpose of this study was to compare the biocompatibility of two types of calcium hydroxide paste in subcutaneous tissue in rat. Twenty-two Wistar rats were divided into 4 experimental (n=5 each) and one control (n=2) group. A polyethylene tube filled with either Dentsply or Sure-Paste was implanted in each rat in the experimental groups, while an empty polyethylene tube was used in the control group. After 15 or 60 days, the animals were sacrificed and histopathological examination carried out. Tissue reaction was assessed by inflammatory cell infiltration using a 4-point scoring system, ranging from 0 to 3. Data were analyzed with the Kruskal-Wallis, Wilcoxon, and McNemar tests. Both types of paste induced an inflammatory response at each time point, although the intensity varied. A significant reduction in the number of inflammatory cells was observed at 60 days. Dentsply appeared to induce a more marked inflammatory response at both time points, although the difference was not significant. These results suggest that both types of paste are biocompatible with subcutaneous tissue in rat. PMID:27320294

  14. 3,5-Diiodo-L-thyronine activates brown adipose tissue thermogenesis in hypothyroid rats.

    PubMed

    Lombardi, Assunta; Senese, Rosalba; De Matteis, Rita; Busiello, Rosa Anna; Cioffi, Federica; Goglia, Fernando; Lanni, Antonia

    2015-01-01

    3,5-Diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis. PMID:25658324

  15. 3,5-Diiodo-L-Thyronine Activates Brown Adipose Tissue Thermogenesis in Hypothyroid Rats

    PubMed Central

    Lombardi, Assunta; Senese, Rosalba; De Matteis, Rita; Busiello, Rosa Anna; Cioffi, Federica; Goglia, Fernando; Lanni, Antonia

    2015-01-01

    3,5-diiodo-l-thyronine (T2), a thyroid hormone derivative, is capable of increasing energy expenditure, as well as preventing high fat diet-induced overweight and related metabolic dysfunction. Most studies to date on T2 have been carried out on liver and skeletal muscle. Considering the role of brown adipose tissue (BAT) in energy and metabolic homeostasis, we explored whether T2 could activate BAT thermogenesis. Using euthyroid, hypothyroid, and T2-treated hypothyroid rats (all maintained at thermoneutrality) in morphological and functional studies, we found that hypothyroidism suppresses the maximal oxidative capacity of BAT and thermogenesis, as revealed by reduced mitochondrial content and respiration, enlarged cells and lipid droplets, and increased number of unilocular cells within the tissue. In vivo administration of T2 to hypothyroid rats activated BAT thermogenesis and increased the sympathetic innervation and vascularization of tissue. Likewise, T2 increased BAT oxidative capacity in vitro when added to BAT homogenates from hypothyroid rats. In vivo administration of T2 to hypothyroid rats enhanced mitochondrial respiration. Moreover, UCP1 seems to be a molecular determinant underlying the effect of T2 on mitochondrial thermogenesis. In fact, inhibition of mitochondrial respiration by GDP and its reactivation by fatty acids were greater in mitochondria from T2-treated hypothyroid rats than untreated hypothyroid rats. In vivo administration of T2 led to an increase in PGC-1α protein levels in nuclei (transient) and mitochondria (longer lasting), suggesting a coordinate effect of T2 in these organelles that ultimately promotes net activation of mitochondrial biogenesis and BAT thermogenesis. The effect of T2 on PGC-1α is similar to that elicited by triiodothyronine. As a whole, the data reported here indicate T2 is a thyroid hormone derivative able to activate BAT thermogenesis. PMID:25658324

  16. Regulation of Mammary and Adipose Tissue Lipoprotein Lipase and Blood Triacylglycerol in Rats during Late Pregnancy

    PubMed Central

    Spooner, Peter M.; Garrison, Mary M.; Scow, Robert O.

    1977-01-01

    The effects of several prostaglandins on lipoprotein lipase activity of mammary gland and adipose tissue and serum triacylglycerol were studied during late pregnancy in rats. Prostaglandins were injected twice daily for 2 days before and once on the day of analysis. In rats pregnant 20 days, prostaglandin F2α (PGF2α) increased the activity of lipoprotein lipase in mammary gland fourfold, reduced the activity in adipose tissue about 60%, and decreased serum concentration of triacylglycerol 50%. PGF2α also reduced serum concentration of progesterone 90% and increased that of prolactin fivefold, but had no effect on serum concentrations of either immuno-reactive insulin or 17β-estradiol. Injections of 13,14-dihydro-15-keto PGF2α, a metabolite of PGF2α, had similar effects in rats pregnant 20 days, whereas prostaglandins E1 and E2 did not. In rats pregnant 16 days, PGF2α did not affect lipoprotein lipase activity in the tissues or the concentration of triacylglycerol and prolactin in serum, although it decreased serum progesterone 80%. 2-Br-α-ergocryptine prevented the increase in serum prolactin in response to PGF2α, but did not alter the effect of PGF2α on lipoprotein lipase activity or serum triacylglycerol. Progesterone completely blocked the effects of PGF2α on lipoprotein lipase activity and serum triacylglycerol and prolactin concentrations. These findings indicate that the changes in lipoprotein lipase activity and serum triacylglycerol in PGF2α-treated rats are probably related to the inhibitory action of PGF2α on progesterone secretion. They also suggest that endogenous F prostaglandins may play a role in the regulation of lipoprotein lipase activity in mammary gland and adipose tissue near parturition. PMID:893673

  17. Nutritional and exercise interventions variably affect estrogen receptor expression in the adipose tissue of male rats.

    PubMed

    Metz, Lore; Gerbaix, Maude; Masgrau, Aurélie; Guillet, Christelle; Walrand, Stéphane; Boisseau, Nathalie; Boirie, Yves; Courteix, Daniel

    2016-03-01

    Energy-dense food consumption and lack of physical activity are implicated in the development of the current obesity epidemic. The role of estrogen in adiposity and fuel partitioning is mediated mainly though the estrogen receptor α (ERα) isoform. We hypothesized that nutritional adaptation and exercise training, either individually or combined, could impact ERα expression in adipose tissue relative to glucose tolerance. Seventy-two Wistar rats were submitted to a high-fat, high-sucrose (HF-HS) diet for 16weeks. The first phase of our study was to investigate the effect of an HF-HS diet on whole-body glucose tolerance, as well as on body composition and ERα expression in different adipose tissues. Second, we investigated the effect of switching to a well-balanced diet, with or without exercise training for 8 weeks, on those same parameters. After the first part of this study, HF-HS-fed rats were fatter (8%) than control rats. Despite a decrease in glucose tolerance, ERα expression in adipose tissues was not significantly altered by an HF-HS diet. The return to a well-balanced diet significantly increased ERα expression in perirenal and epididymal adipose tissue, but there was no effect of diet or exercise training on whole-body glucose tolerance. The present findings suggest that diet is a powerful modulator of ERα expression in adipose tissue, as nutritional modulation after an HF-HS diet strongly affects ERα expression, particularly in perirenal and epididymal adipose tissue. However, ERα expression in adipose tissue does not appear to be associated with whole-body glucose tolerance. PMID:26923515

  18. Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

    PubMed

    Frigolet, María E; Torres, Nimbe; Tovar, Armando R

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities. PMID:21736766

  19. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

    PubMed Central

    Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

    2007-01-01

    Background Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα) values showed overexpression (198%). Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID:17725831

  20. Biocompatibility of a calcium hydroxide-propolis experimental paste in rat subcutaneous tissue.

    PubMed

    Mori, Graziela Garrido; Rodrigues, Sindineia da Silva; Shibayama, Sheila Tieko; Pomini, Marcelo; do Amaral, Cristhiane Olivia Ferreira

    2014-01-01

    Intracanal medications are fundamental for disinfection of the root canal system and participate in periapical repair, so their biocompatibility is of utmost importance to avoid tissue damage. This study evaluated the biocompatibility of a experimental paste of calcium hydroxide and propolis in the subcutaneous tissue of rats. The study was conducted on 15 male Wistar rats. Two incisions were made on the dorsal region of each animal for introduction of 4 tubes: one tube was empty; one contained zinc oxide-eugenol cement, and the two other tubes were filled with experimental paste. After 7, 14 and 30 days, the animals were euthanized and the specimens were subjected to histotechnical preparation. The hematoxylin and eosin-stained histological sections were analyzed by light microscopy. Scores were established according to the inflammatory process and statistically compared by the Tukey test (α = 5%). The analysis of histological sections showed non-significant or mild inflammatory reaction in the connective tissue in contact with the empty tubes in all study periods while the contact of subcutaneous tissue with zinc oxide-eugenol elicited moderate or severe inflammation similarly without significant difference among the study periods. The connective tissue was moderately inflamed at 7 days when contacting the experimental paste, but the inflammatory process was non-significant or mild at 14 and 30 days. The experimental paste was biocompatible with the tissues after 14 days of subcutaneous implantation. PMID:25140713

  1. Release of Zn from maternal tissues in pregnant rats deficient in Zn or Zn and Ca

    SciTech Connect

    Hurley, L.S.; Masters, D.G.; Lonnerdal, B.; Keen, C.L.

    1986-03-05

    Earlier studies have shown that diets that increase tissue catabolism reduce the teratogenic effects of Zn deficiency. The hypothesis that Zn may be released from body tissues when the metabolic state is altered was further tested. Nonpregnant Sprague Dawley females were injected with Zn-65; after equilibration, the two major pools of Zn, bone and muscle, had different specific activities (SA), muscle being much higher. Females were mated and fed diets adequate in Zn and Ca (C) or deficient in Zn (ZnD) or deficient in both Zn and Ca (ZnCaD). Calculations using weight loss in ZnD and ZnCaD rats, Zn content of maternal bone and muscle, and total fetal Zn at term indicated that in ZnCaD rats a relatively small amount of Zn from bone early in pregnancy was sufficient to prevent abnormal organogenesis, but most fetal Zn came from breakdown of maternal muscle in the last 3 days of pregnancy. Isotope data supported this conclusion. SA of Zn in ZnD fetuses was equal and high, indicating that most Zn came from the same maternal tissue. High muscle SA prior to mating, and increased SA in tibia and liver during pregnancy suggest that muscle provided Zn for other maternal tissues as well as fetuses. In contrast, SA in C fetuses was less than 30% of that of the D groups, consistent with the earlier hypothesis that most fetal Zn in C rats is accrued directly from the diet.

  2. Absorption, tissue distribution, and excretion of tritium-labeled ivermectin in cattle, sheep, and rat

    SciTech Connect

    Chiu, Shuething Lee; Green, M.L.; Baylis, F.P.; Eline, D.; Rosegay, A.; Meriwether, H.; Jacob, T.A. )

    1990-11-01

    Tritium-labeled ivermectin was studied in cattle, sheep, and rat for absorption, tissue residue distribution, and excretion at doses of 0.3 mg/kg of body weight. The drug was absorbed by various dosing routes. By intraruminal and subcutaneous dosing routes, highest tissue residues were present in fat and liver of cattle, with half-lives of 6-8 and 4-5 days, respectively. Shorter half-lives (1-2 days) were observed in sheep and rat. The tissue residue distribution pattern was essentially the same for all species studied and similar in male and female rats. With doses of tritium-labeled avermectin B{sub 1a} ranging from 0.06 to 7.5 mg/kg of body weight, plasma and tissue residue concentrations increased proportionally with the dose. When ivermectin was administered by various routes (ip, sc, iv, oral, and intraruminal), blood residue levels converged to 20-50 ppb 4 h after dosing and then depleted at similar rate regardless of the dosing route. Ivermectin was excreted primarily in the feces, with only less than 2% of the doses being eliminated in the urine in all three species studied.

  3. Determination of ecliptasaponin A in rat plasma and tissues by liquid chromatography-tandem mass spectrometry.

    PubMed

    Zhao, Jing; Liu, Erwei; Han, Lifeng; Wang, Linlin; Zhang, Yi; Wang, Tao; Fang, Shiming; Gao, Xiumei

    2016-06-01

    A sensitive, rapid and specific high-performance liquid chromatography tandem mass spectrometry method (HPLC-MS/MS) was developed to determine ecliptasaponin A in rat plasma and tissues after oral administration. Ginsenoside Rg1 was used as the internal standard (IS). The plasma and tissues samples were prepared by liquid-liquid extraction with ethyl acetate and separated on an Eclipse Plus C18 column (2.1 mm × 150 mm, 5 µm) at a flow rate of 0.4 mL/min using acetonitrile and water (containing 0.05% acetic acid) as the mobile phase. The tandem mass detection was carried out with eletrospray ionization in negative mode. Quantification was performed by using multiple reaction monitoring (MRM), which monitored the fragmentation of m/z 633.4→587.2 for ecliptasaponin A and m/z 859.4→637.4 for the IS. The calibration curves obtained were linear in different matrices, and the lower limit of quantification (LLOQ) achieved was 0.5 ng/mL both for rat plasma and tissues. The intra- and inter-day precisions were below 15%. This method was successfully applied to pharmacokinetic study of ecliptasaponin A in rat plasma and tissues after oral administration. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26378987

  4. Effect of combined recompression and air, oxygen, or heliox breathing on air bubbles in rat tissues.

    PubMed

    Hyldegaard, O; Kerem, D; Melamed, Y

    2001-05-01

    The fate of bubbles formed in tissues during the ascent from a real or simulated air dive and subjected to therapeutic recompression has only been indirectly inferred from theoretical modeling and clinical observations. We visually followed the resolution of micro air bubbles injected into adipose tissue, spinal white matter, muscle, and tendon of anesthetized rats recompressed to and held at 284 kPa while rats breathed air, oxygen, heliox 80:20, or heliox 50:50. The rats underwent a prolonged hyperbaric air exposure before bubble injection and recompression. In all tissues, bubbles disappeared faster during breathing of oxygen or heliox mixtures than during air breathing. In some of the experiments, oxygen breathing caused a transient growth of the bubbles. In spinal white matter, heliox 50:50 or oxygen breathing resulted in significantly faster bubble resolution than did heliox 80:20 breathing. In conclusion, air bubbles in lipid and aqueous tissues shrink and disappear faster during recompression during breathing of heliox mixtures or oxygen compared with air breathing. The clinical implication of these findings might be that heliox 50:50 is the mixture of choice for the treatment of decompression sickness. PMID:11299250

  5. Tissue distribution, metabolism, and clearance of the convulsant trimethylolpropane phosphate in rats.

    PubMed

    Rossi, J; Jung, A E; Ritchie, G D; Lindsey, J W; Nordholm, A F

    1998-11-01

    The distribution, metabolism, and clearance of trimethylolpropane phosphate (TMPP), a potent, bicyclophosphate, gamma-aminobutyric acid-ergic convulsant, were studied in male Fischer-344 rats. Intraperitoneal administration of TMPP was compared with oral gavage with respect to rates of absorption, distribution, and clearance. Distribution of TMPP to major body tissues was evaluated for the first 24 hr after administration or, in the case of regional brain distribution, immediately after the first TMPP-induced clinical seizure. Samples purified from the urine, feces, and bile of rats exposed to TMPP, as well as from rat liver microsomes incubated with TMPP in vitro, were analyzed for possible phase I and phase II metabolism, using HPLC. The disposition and clearance of TMPP in the blood and major body tissues were measured. TMPP was found to be well distributed to highly vascularized tissue compartments, with little retention >24 hr after administration. TMPP was eliminated through the urine and feces as the parent compound, with no evidence of phase I or phase II metabolism. TMPP was rapidly cleared from the blood during the first 30 min after exposure, with slower clearance of >87% of the drug during the following 8-hr period and >99.5% clearance by 100 hr after injection. Repeated daily exposure to TMPP for up to 5 successive days resulted in no measurable accumulation in the brain or other major tissue compartments. Possible mechanisms for TMPP-induced, short- and long-term, neurobehavioral modulation are discussed. PMID:9806946

  6. Cardiac and vascular responses of isolated rat tissues treated with diterpenes from Sinularia flexibilis (coelenterata: octocorallia).

    PubMed

    Aceret, T L; Brown, L; Miller, J; Coll, J C; Sammarco, P W

    1996-10-01

    The marine environment is a rich source of compounds with cardiovascular activity. This study characterizes the cardiac and vascular responses in isolated rat tissues of flexibilide, dihydroflexibilide and sinulariolide, three diterpenes isolated from the soft coral Sinularia flexibilis. On rat left ventricular papillary muscles, dihydroflexibilide and flexibilide showed similar potencies (-log EC50 = 4.69 +/- 0.05 and 4.66 +/- 0.06, respectively); the maximal response to dihydroflexibilide of 1.4 +/- 0.2 mN was 35 +/- 7% that of calcium chloride in the same muscles. All diterpenes relaxed rat thoracic aortic rings precontracted with KC1 (100 mM) with similar potencies (flexibilide, -log EC50 = 4.17 +/- 0.06). Flexibilide was further characterized and shown to increase force in isolated rat left atria by 0.8 +/- 0.5 mN at 1 x 10(-4) M, to increase rate of contraction in isolated rat right atria by 18 +/- 5 beta/min at 3 x 10(-5) M and to completely relax endothelium-denuded rat thoracic aortic rings (-log EC50 = 4.14 +/- 0.05). Toxicity as indicated by the occurrence of ectopic beats was not observed with the diterpenes at concentrations which produced complete relaxation of blood vessels, maximal positive inotropic activity and minor positive chronotropic responses. Thus, these compounds may be useful lead compounds in the search for improved treatment of cardiovascular disease, especially heart failure. PMID:8931257

  7. Restricted passage of insulin across capillary endothelium in perfused rat adipose tissue

    SciTech Connect

    Chernick, S.S.; Gardiner, R.J.; Scow, R.O. )

    1987-11-01

    Passage of insulin across capillary endothelium was monitored in perfused rat parametrial adipose tissue by the effect of intra-arterially infused insulin on oxidation of (U-{sup 14}C)glucose to CO{sub 2}. Glucose oxidation was constant at 34 nmol C {center dot} g{sup {minus}1} {center dot} min{sup {minus}1} for 90 min in tissues perfused with 0 or 50 {mu}U/ml. The rate of oxidation was doubled in 90 min at 100 {mu}U/ml and maximal in 40 min at 200 {mu}U/ml and in 20-30 min at 500 {mu}U/ml. The slow decline in oxidation rate when insulin infusion was stopped suggested that insulin was sequestered in the tissue. Although half-maximal response to insulin occurred in perfused tissues at 100 {mu}U/ml, it occurred at 8 {mu}U/ml in incubated adipocytes and at 30 {mu}U/ml in incubated tissue. In addition, the time required for maximal response to insulin was longer in perfused adipose tissue than in incubated cells and tissues. The data indicate that the transfer of insulin from blood to parenchymal cells in perfused tissue was restricted. The minimal amount of insulin needed for a response by adipocytes in perfused tissue was estimated at be <1% of that in blood. The findings are consistent with the concept that insulin is transferred across capillary endothelium by a receptor-mediated process.

  8. Differential tissue regulation of insulin-like growth factor binding proteins in experimental diabetes mellitus in the rat.

    PubMed

    Gelato, M C; Alexander, D; Marsh, K

    1992-12-01

    The expression and regulation of IGF-I is tissue-specific in diabetes mellitus in the rat. These studies were designed to examine if similar tissue specificity exists for IGF-BPs in the diabetic milieu. Diabetes mellitus was induced by a single i.p. injection of STZ (100 mg/kg body weight). Rats were treated with either vehicle--insulin, vanadate, or phlorizin for 7-14 days. Tissues were analyzed for IGF-BPs by ligand blotting and by affinity cross-linking and immunoprecipitation. In liver tissue from nondiabetic control rats, multiple forms of IGF-BPs were noted, ranging from 48,000 to 25,000 M(r). In diabetic rat liver tissue, the 25,000-M(r) form was unchanged, whereas the higher M(r) forms (48,000-42,000 M(r)) were decreased, and the 30,000-M(r) form was increased. Insulin therapy of diabetic rats decreased all forms to below control levels. In the kidney tissue of control rats, faint IGF-BP bands were seen at 30,000 and 25,000 M(r). In diabetic rat kidney tissue, the 30,000-M(r) form again was increased (as in liver) and restored to control levels with insulin therapy. In contrast, only a 30,000-M(r) band was seen in control pituitary tissue, which was slightly increased in the diabetic rats and also was decreased below control levels by insulin. In hypothalamus and cerebral cortex tissue, bands at 30,000 and 25,000 M(r) were noted, and neither was altered by diabetes or insulin treatment. Treatment of diabetic rats with vanadate and phlorizin resulted in comparable blood glucose levels, which were only slightly higher than those achieved with insulin therapy.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1280236

  9. Zinc deficiency decreases the activity of calmodulin regulated cyclic nucleotide phosphodiesterases in vivo in selected rat tissues.

    PubMed

    Law, J S; McBride, S A; Graham, S; Nelson, N R; Slotnick, B M; Henkin, R I

    1988-08-01

    The effect of zinc deficiency on calmodulin function was investigated by assessing the in vivo activity of two calmodulin regulated enzymes, adenosine 3',5'-monophosphate (c-AMP) and guanosine 3',5'-monophosphate (c-GMP) phosphodiesterase (PDE) in several rat tissues. Enzymatic activities in brain, heart, and testis of rats fed a zinc deficient diet were compared with activities in these tissues from pair fed, zinc supplemented rats. In testis, a tissue in which zinc concentration decreased with zinc deficient diet, enzyme activities were significantly decreased over those in rats who were pair fed zinc supplemented diets. In brain and heart, tissues in which zinc concentrations did not change with either diet, enzymatic activities between the groups were not different. These results indicate that zinc deficiency influences the activity of calmodulin-regulated phosphodiesterases in vivo supporting the hypothesis that zinc plays a role in calmodulin function in vivo in zinc sensitive tissues. PMID:2484550

  10. Characteristics of submucosal lymphoid tissue located in the proximal colon of the rat.

    PubMed Central

    Crouse, D A; Perry, G A; Murphy, B O; Sharp, J G

    1989-01-01

    In this study we have examined the morphology and steroid sensitivity of proximal colonic lymphoid tissue in the Fisher 344 rat. A time course study was conducted in which groups of animals were injected subcutaneously with hydrocortisone sodium succinate (125 mg/kg body weight) and killed on Days 0-4. Thymus, jejunal and ileal Peyer's patches and proximal colonic lymphoid tissue were excised, weighed and processed for histological analysis. The results showed that the maximum cytoreductive effects of the hydrocortisone were evident on Day 2. Thymus and proximal colonic lymphoid tissue weight decreased to 5 and 18% of the control values respectively, before returning towards control values over the next two days. In contrast, jejunal and ileal Peyer's patch weights were unaltered. A dose response experiment was conducted using the same endpoints. Rats were injected subcutaneously with hydrocortisone at 60, 120, 200 and 300 mg/kg body weight and killed on Day 2. The results of this experiment showed that the proximal colonic lymphoid tissue, like thymus, responded with a dose-dependent loss of tissue weight. The spleen and Peyer's patches showed only a slight weight decrease compared to the control. These data showed that the response of proximal colonic lymphoid tissue to steroids was more similar to that of thymus, a primary lymphoid tissue, than to other secondary lymphoid tissues. Finally, grafts of fetal proximal colon under the kidney capsule of syngeneic adults supported the development of this lymphoid aggregate in the absence of luminal antigenic stimulation. These results suggest that the development and functional contribution of proximal colonic lymphoid tissue to the immune system warrants a more detailed examination. Images Fig. 2 Fig. 3 Fig. 5 Fig. 6 PMID:2808123

  11. Effect of Gymnema montanum Leaves on Serum and Tissue Lipids in Alloxan Diabetic Rats

    PubMed Central

    Latha, M.; Ramkumar, K. M.; Pari, L.; Baskar, C.; Bai, V. Narmatha

    2003-01-01

    The effect of Gymnema montanum leaves on alloxaninduced hyperlipidemia was studied in male Wistar rats. Ethanolic extract of G. montanum leaves was administered orally and different doses of the extract on blood glucose, serum and tissue lipids, hexokinase, glucose-6-phosphatase, thiobarbituric acid–reactive substances (TBARS), hydroperoxides, and glutathione in alloxan-induced diabetic rats were studied. G. montanum leaf extract (GLEt) at doses of 50, 100, 200 mg/kg body weight for 3 weeks suppressed the elevated blood glucose and lipid levels in diabetic rats. GLEt at 200 mg/kg body weight was found to be comparable to glibenclamide, a reference drug. These data indicate that G. montanum represents an effective antihyperglycemic and antihyperlipidemic adjunct for the treatment of diabetes and a potential source of discovery of new orally active agent for future therapy. PMID:15061646

  12. [Carbohydrate and nitrogenous metabolism condition in the rat tissue under experimental rhabdomyolysis].

    PubMed

    Kaliman, P A; Okhrimenko, S M

    2012-01-01

    Some effects of glycerol injection on indices of the condition of the thiol-disulfide system as well as carbohydrate and nitrogen metabolism in rats in vivo were studied. A decrease was revealed in levels of non-protein SH-groups in the liver, kidney and heart, as well as of protein SH-groups in the kidney and heart of rats following glycerol injection. That might be connected with SH-group oxidation under the excessive arrival of free haem into tissues under rhabdomyolysis. A decrease in glycogen and increase in tyrosine aminotransferase activity in the liver were observed. Activation of nitrogenous metabolism following glycerol injection is indicated by the increase of aminotransferase activity in organs, and concentration of blood urea. High concentration of creatinine in the rat serum can reflect malfiltration in kidneys. PMID:22679761

  13. Normalization of periodontal tissues in osteopetrotic mib mutant rats, treated with CSF-1

    NASA Technical Reports Server (NTRS)

    Wojtowicz, A.; Yamauchi, M.; Sotowski, R.; Ostrowski, K.

    1998-01-01

    The osteopetrotic mib mutation in rats causes defects in the skeletal bone tissue in young animals. These defects, i.e. slow bone remodelling, changes in both crystallinity and mineral content, are transient and undergo normalization, even without any treatment in 6-wk-old animals. Treatment with CSF-1 (colony stimulating factor-1) accelerates the normalization process in skeletal bones. The periodontal tissues around the apices of incisors show abnormalities caused by the slow remodelling process of the mandible bone tissue, the deficiency of osteoclasts and their abnormal morphology, as well as the disorganization of periodontal ligament fibres. In contrast to the skeletal tissues, these abnormalities would not undergo spontaneous normalization. Under treatment with colony stimulating factor 1 (CSF-1), the primitive bone trabeculae of mandible are resorbed and the normalization of the number of osteoclasts and their cytology occurs. The organization of the periodontal ligament fibres is partially restored, resembling the histological structure of the normal one.

  14. Specific accumulation of cholesterol-rich liposomes in the inflammatory tissue of rats with adjuvant arthritis.

    PubMed Central

    Love, W G; Amos, N; Kellaway, I W; Williams, B D

    1990-01-01

    High performance liquid chromatography has shown that after intravenous injection cholesterol-poor liposomes (100 nm) are unstable and their phospholipid is redistributed. Under identical conditions cholesterol-rich liposomes remain structurally intact within the circulation. When injected intravenously cholesterol-rich liposomes accumulate within the inflamed paws of rats with adjuvant induced arthritis to the same extent as cholesterol-poor liposomes. Uptake in inflamed tissue of three cholesterol-rich liposome preparations was always significantly greater than the uptake noted in normal tissue. The degree of accumulation in inflamed tissue was found to depend on the size of the liposome, with the greatest uptake, 7% of the injected dose, achieved by the smallest vesicle (100 nm). These results indicate that intact liposomes accumulate at inflamed joint tissue sites. Therefore the passive targeting of anti-inflammatory drugs encapsulated within these liposomes could be contemplated. PMID:2396866

  15. Lipogenesis in liver, lung and adipose tissue of rats fed with oleoylanilide.

    PubMed Central

    Casals, C; Garcia-Barreno, P; Municio, A M

    1983-01-01

    Oleoylanilide was administered orally to groups of rats according to different patterns. Subcellular fractionation of liver, lung and adipose tissue was then carried out in order to study the main enzyme activities involved in the lipogenesis. The observed findings indicate that adipose tissue and lung are the main target organs for the anilide, adipose tissue being involved in a general decrease of the enzyme activities, whereas transacylation reaction exhibits the most marked depletion of all the enzyme activities in the lung. The enzyme activities in liver were not markedly affected by this oral administration, although some data support the existence of a latent liver toxicity. These data suggest that oleoylanilide has the capacity to alter lipid metabolism of lung and adipose tissue to a considerable extent, whereas no major effect was produced in the liver. This different organ response could be related to the lymphatic gland via absorption of the substance. PMID:6882376

  16. Tissue somatostatin levels in three models of genetic obesity in rats.

    PubMed

    Voyles, N R; Bhathena, S J; Kennedy, B; Wilkins, S D; Michaelis, O E; Zalenski, C M; Timmers, K I; Recant, L

    1987-05-01

    A potential role for somatostatin (SRIF) in the pathogenesis of the hyperinsulinemia of obese rats was considered. SRIF like immunoreactivity (ng/mg protein) was therefore measured in hot 2 N acetic acid extracts of pancreas, stomach, pituitary, and hypothalamus in tissues obtained from three models of genetic obesity in rats. These models included the obese and lean controls of LA/N-cp, SHR/N-cp, and Zucker rats. To assess the effects of diet on SRIF levels, mixed diets were provided ad lib which contained a carbohydrate as either sucrose or starch. Some groups were fed chow diets. No significant dietary effects on tissue levels of SRIF were obtained. However, two of the three models (Zucker and SHR/N-cp) showed phenotypic effects on SRIF levels in pancreas; namely, obese rats showed a significantly greater concentration of SRIF (P less than 0.0005 and less than 0.0002, respectively) than did the lean littermates. These findings were confirmed by measurement of total pancreas SRIF content. Gastric levels were significantly altered only in the obese Zucker rats (P less than 0.005) where obese tissues had lower concentrations than those of lean animals. However similar directional changes in pancreas and stomach were observed in all models. It is concluded that the hyperinsulinemia of the obese animals studied is not due to absolute deficiency in pancreatic SRIF content. It is postulated however that decreased pancreatic SRIF secretion (paracrine or otherwise) relative to pancreatic insulin content could still play a role. PMID:2883660

  17. Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue

    NASA Astrophysics Data System (ADS)

    Yamashita, Hitoshi; Yamamoto, Mikio; Sato, Yuzo; Izawa, Tetsuya; Komabayashi, Takao; Saito, Daizo; Ohno, Hideki

    1993-03-01

    The effect was investigated of endurance training on the expression of uncoupling protein (UCP) mRNA in brown adipose tissue (BAT) of rats. The exercised rats were trained on a rodent treadmill for 5 days per week and a total of 9 weeks. After the training programme, a marked decrease in BAT mass was found in terms of weight or weight per unit body weight; there was a corresponding decrease in DNA content and a downward trend in RNA and glycogen levels. The UCP mRNA was present at a markedly decreased level in BAT of trained animals. In consideration of the reduced levels of mRNAs for hormone-sensitive lipase and acylCoA synthetase, the brown adipose tissue investigated appeared to be in a relatively atrophied and thermogenically quiescent state.

  18. Quantification of phenylethylamine and p-tyramine in rat tissues using a new radioenzymatic assay

    SciTech Connect

    Hamburger, S.A.; Henry, D.P.

    1986-03-05

    Phenylethylamine (PEA) and p-tyramine (p-tym) are biologically active aralkylamines that are found in a number of mammalian tissues, including brain and plasma. The investigation of the biological role of these substances has been hampered by the lack of accessible assay methodology. They have developed a new radioenzymatic assay using barley root tyramine N-methyltransferase and tritiated S-adenosylmethionine. The products formed by the reaction are isolated by TLC. The assay sensitivity was 2.1 and 1.0 pg/tube for PEA and p-tym, respectively. The concentration of PEA and p-tym was determined simultaneously in tissues from Sprague-Dawley rats (280 gm). Plasma PEA and p-tym were 478 +/- 66 and 309 +/- 69 pg/ml, respectively. They conclude that this new procedure is applicable to all tissues examined in that all tissues contain both PEA and p-tym and that these amines are heterogeneously distributed in rat tissues.

  19. Azodicarbonamide: methods for the analysis in tissues of rats and inhalation disposition.

    PubMed

    Bechtold, W E; Medinsky, M A; Cheng, Y S; Hobbs, C H

    1989-09-01

    1. A method has been developed for measuring azodicarbonamide (ADA) and its metabolite biurea in tissues of rat. The method is based on the reaction of ADA with triphenylphosphine; the derivative so formed was isolated and quantified using reversed-phase h.p.l.c. Quantification was by u.v. detection with 14C-ADA as internal standard. Biurea was measured by oxidation to ADA, followed by treatment as described above. 2. When biurea was added to tissues at 100-400 micrograms, recoveries of 92-125% were observed. In contrast, recoveries of ADA added to tissues were generally much less than 100% and could not be reliably determined. The inability to quantify ADA added to tissues was ascribed to its rapid and facile reduction by tissue sulphydryl groups. 3. When rats were exposed to ADA aerosol concentrations of 200, 100, 50 and 0 mg/m3 for 13 weeks by inhalation, a non-linear dose-dependent accumulation of biurea was observed in lungs. No ADA was detected in lungs. Neither biurea nor ADA could be detected in kidneys. PMID:2815834

  20. Structural characterization of rat ventricular tissue exposed to the smoke of two types of waterpipe

    PubMed Central

    Al-Awaida, Wajdy; Najjar, Hossam; Shraideh, Ziad

    2015-01-01

    Objective(s): this study focused on the effect of waterpipe smoke exposure toxicity on the structure of albino rat’s ventricular tissue and their recovery. Materials and Methods: Albino rats were divided into three groups: control, flavored, and unflavored. The control group was exposed to normal air while the flavored and unflavored groups were exposed to waterpipe smoke for a period of 90 days. Each group was followed by a period of 90 days of fresh air exposure. Following each period, the ventricular tissue was removed for biochemical and histopathological studies. Results: The ventricular tissues of waterpipe exposed rats showed some degree of separation between cardiac muscle fibers, infiltration of lymphocytes, and congestion of blood vessel. Also, thin cross sections of ventricular cells revealed pleomorphic mitochondria with partially disrupted cristae, partial disruption of the myofibrils, and deposited toxic materials. The unflavored waterpipe has more deleterious effects on heart ventricular tissues than the flavored one. Waterpipe smoke didn’t induce apoptosis in the ventricular tissue. We also found very high levels of plasma thiocyanate after exposure to smoke in the flavored and unflavored groups, while the control group showed no increase. After the recovery period, those tissues showed partial recovery. Conclusion: Waterpipe smoke induces structural changes in the heart ventricle tissues, causing a negative impact on the capacity of the cardiac muscle for pumping blood and may lead to heart attack due to accumulation of free radicals and tissue inflammation. Cessation of smoking is important in returning most of these changes to their normal structure. PMID:26730327

  1. Effects of hydrogen-rich water on aging periodontal tissues in rats.

    PubMed

    Tomofuji, Takaaki; Kawabata, Yuya; Kasuyama, Kenta; Endo, Yasumasa; Yoneda, Toshiki; Yamane, Mayu; Azuma, Tetsuji; Ekuni, Daisuke; Morita, Manabu

    2014-01-01

    Oxidative damage is involved in age-related inflammatory reactions. The anti-oxidative effects of hydrogen-rich water suppress oxidative damage, which may aid in inhibiting age-related inflammatory reactions. We investigated the effects of drinking hydrogen-rich water on aging periodontal tissues in healthy rats. Four-month-old male Fischer 344 rats (n = 12) were divided into two groups: the experimental group (hydrogen-rich water treatment) and the control group (distilled water treatment). The rats consumed hydrogen-rich water or distilled water until 16 months of age. The experimental group exhibited lower periodontal oxidative damage at 16 months of age than the control group. Although protein expression of interleukin-1β did not differ, gene expression of Nod-like receptor protein 3 inflammasomes was activated in periodontal tissues from the experimental group as compared with the control group. Drinking hydrogen-rich water is proposed to have anti-aging effects on periodontal oxidative damage, but not on inflammatory reactions in healthy rats. PMID:24985521

  2. Magnetic Resonance Imaging of Soft Tissue Infection with Iron Oxide Labeled Granulocytes in a Rat Model

    PubMed Central

    Wedekind, Dirk; Meier, Martin; Bleich, André; Glage, Silke; Hedrich, Hans-Juergen; Kutschka, Ingo; Haverich, Axel

    2012-01-01

    Object We sought to detect an acute soft tissue infection in rats by magnetic resonance imaging (MRI) using granulocytes, previously labeled with superparamagnetic particles of iron oxide (SPIO). Materials and Methods Parasternal infection was induced by subcutaneous inoculation of Staphylococcus aureus suspension in rats. Granulocytes isolated from isogenic donor rats were labeled with SPIO. Infected rats were imaged by MRI before, 6 and 12 hours after intravenous injection of SPIO-labeled or unlabeled granulocytes. MR findings were correlated with histological analysis by Prussian blue staining and with re-isolated SPIO-labeled granulocytes from the infectious area by magnetic cell separation. Results Susceptibility effects were present in infected sites on post-contrast T2*-weighted MR images in all animals of the experimental group. Regions of decreased signal intensity (SI) in MRI were detected at 6 hours after granulocyte administration and were more pronounced at 12 hours. SPIO-labeled granulocytes were identified by Prussian blue staining in the infected tissue and could be successfully re-isolated from the infected area by magnetic cell separation. Conclusion The application of SPIO-labeled granulocytes in MRI offers new perspectives in diagnostic specificity and sensitifity to detect early infectious processes. PMID:23236524

  3. Mass spectrometric profiling of lipids in intestinal tissue from rats fed cereals processed for medical conditions.

    PubMed

    Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

    2016-06-01

    Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used for lipid profiling of intestine tissue sections from rats fed specially processed cereals and rats fed ordinary feed as a control. This cereal is known to increase the activity of antisecretory factor in plasma and the exact mechanism for the activation process at the cellular level is unclear. ToF-SIMS has been used to track food induced changes in lipid content in intestinal tissue sections to gain insight into the possible mechanisms involved. Data from 20 intestine sections belonging to four different rats from each group of control and specially processed cereals-fed rats were obtained using the stage scan macroraster with a lateral resolution of 5 μm. Data were subsequently subjected to orthogonal partial least squares discriminant analysis. The data clearly show that changes of certain lipids are induced by the specially processed cereal feed. Scores plots show a well-defined separation between the two groups. The corresponding loading plots reveal that the groups separate mainly due to changes of vitamin E, phosphocholine, and phosphosphingolipid fragments, and that for the c18:2 fatty acid. The observed changes in lipids might give insight into the working mechanisms of antisecretory factor in the body, and this has been successfully used to understand the working mechanism of specially processed cereal-induced antisecretory factor activation in intestine. PMID:26753787

  4. Gene Expression Profiling in Lung Tissues from Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Lam, Chiu-Wing; Zalesak, Selina M.; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Scully, Robert R.; Williams, Kyle; Wu, Honglu; James, John T.

    2014-01-01

    The Moon's surface is covered by a layer of fine, reactive dust. Lunar dust contain about 1-2% of very fine dust (< 3 micron), that is respirable. The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues from rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m(exp 3) of lunar dust. Five rats per group were euthanized 1 day, and 3 months after the last inhalation exposure. The total RNAs were isolated from lung tissues after being lavaged. The Agilent Rat GE v3 microarray was used to profile global gene expression (44K). The genes with significant expression changes are identified and the gene expression data were further analyzed using various statistical tools.

  5. Massage-induced morphological changes of dense connective tissue in rat's tendon.

    PubMed

    Kassolik, Krzysztof; Andrzejewski, Waldemar; Dziegiel, Piotr; Jelen, Michal; Fulawka, Lukasz; Brzozowski, Marcin; Kurpas, Donata; Gworys, Bohdan; Podhorska-Okolow, Marzenna

    2013-01-01

    The aim of the experiment was to determine if possible changes in connective tissue induced by massage could have a positive effect justifing the use of massage in all post-traumatic connective tissue conditions, e.g. tendon injuries. The investigations were performed in a group of 18 Buffalo rats. The rats were divided into two groups (experimental and control). To standardize the massage procedure, it was performed with an algometer probe of 0.5 cm2 with constant pressure force of 1 kG (9,81 N). To analyse the number and diameter of collagen fibrils, two electron micrographs were performed for each rat of the collected segments of tendons of rat tail lateral extensor muscle. After image digitalization and calibration, the measurements were carried out using iTEM 5.0 software. The number of fibrils, their diameter and area were measured in a cross-sectional area. An increase of the number of collagen fibrils was observed in the tendons of massaged animals compared to the control group. Our study demonstrated that massage may cause a beneficial effect on metabolic activity of tendon's fibroblasts and, in consequence, may be applied for more effective use of massage for the prevention of tendon injury as well as after the injury has occurred. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 103-106). PMID:23690224

  6. Direct Comparison of Rat- and Human-Derived Ganglionic Eminence Tissue Grafts on Motor Function.

    PubMed

    Lelos, Mariah J; Roberton, Victoria H; Vinh, Ngoc-Nga; Harrison, Carl; Eriksen, Peter; Torres, Eduardo M; Clinch, Susanne P; Rosser, Anne E; Dunnett, Stephen B

    2016-01-01

    Huntington's disease (HD) is a debilitating, genetically inherited neurodegenerative disorder that results in early loss of medium spiny neurons from the striatum and subsequent degeneration of cortical and other subcortical brain regions. Behavioral changes manifest as a range of motor, cognitive, and neuropsychiatric impairments. It has been established that replacement of the degenerated medium spiny neurons with rat-derived fetal whole ganglionic eminence (rWGE) tissue can alleviate motor and cognitive deficits in preclinical rodent models of HD. However, clinical application of this cell replacement therapy requires the use of human-derived (hWGE), not rWGE, tissue. Despite this, little is currently known about the functional efficacy of hWGE. The aim of this study was to directly compare the ability of the gold standard rWGE grafts, against the clinically relevant hWGE grafts, on a range of behavioral tests of motor function. Lister hooded rats either remained as unoperated controls or received unilateral excitotoxic lesions of the lateral neostriatum. Subsets of lesioned rats then received transplants of either rWGE or hWGE primary fetal tissue into the lateral striatum. All rats were tested postlesion and postgraft on the following tests of motor function: staircase test, apomorphine-induced rotation, cylinder test, adjusting steps test, and vibrissae-evoked touch test. At 21 weeks postgraft, brain tissue was taken for histological analysis. The results revealed comparable improvements in apomorphine-induced rotational bias and the vibrissae test, despite larger graft volumes in the hWGE cohort. hWGE grafts, but not rWGE grafts, stabilized behavioral performance on the adjusting steps test. These results have implications for clinical application of cell replacement therapies, as well as providing a foundation for the development of stem cell-derived cell therapy products. PMID:26727032

  7. Determination of trimebutine maleate in rat plasma and tissues by using capillary zone electrophoresis.

    PubMed

    Li, F; Yu, L

    2001-06-01

    A simple and rapid capillary zone electrophoresis method was developed for the determination of trimebutine maleate in rat plasma and tissues. Rat plasma and tissue homogenates were mixed with acetonitrile containing internal standard, ephedrine hydrochloride, and then centrifuged. The supernatant was dried under a stream of nitrogen, and the residue was reconstituted in methanol-water (1:1). The electrophoresis was performed in uncoated capillary with 30 mmol/L phosphate buffer of pH 6.0 as the separation electrolyte. The applied voltage was 10 kV and the UV detection was set at 214 nm. The peak height ratio vs concentration in plasma or homogenates was linear over the range of 5-500 ng/mL and the limit of quantitation was 5 ng/mL. The intra- and inter-day precision was RSD < 14% and <15%. The accuracy was relative error (RE) within +/- 14%. This method was applied to studying the pharmacokinetics and tissue distribution after a single dose of trimebutine maleate was administrated to the rats. The T(max), AUC, C(max) and t(1/2) were 30 min, 7.8 x 10(2) (ng/mL) min, 39 ng/mL and 1.7 x 10(2) min. The drug distribution was found in a decreasing order of liver, kidney, spleen, lung and heart. PMID:11438965

  8. Tissue Reaction and Biocompatibility of Implanted Mineral Trioxide Aggregate with Silver Nanoparticles in a Rat Model

    PubMed Central

    Zand, Vahid; Lotfi, Mehrdad; Aghbali, Amirala; Mesgariabbasi, Mehran; Janani, Maryam; Mokhtari, Hadi; Tehranchi, Pardis; Pakdel, Seyyed Mahdi Vahid

    2016-01-01

    Introduction: Biocompatibility and antimicrobial activity of endodontic materials are of utmost importance. Considering the extensive applications of mineral trioxide aggregate (MTA) in dentistry and antimicrobial properties of silver nanoparticles, this study aimed to evaluate the subcutaneous inflammatory reaction of rat connective tissues to white MTA with and without nanosilver (NS) particles. Methods and Materials: Polyethylene tubes (1.1×8 mm) containing experimental materials (MTA and MTA+NS and empty control tubes) were implanted in subcutaneous tissues of seventy-five male rats. Animals were divided into five groups (n=15) according to the time of evaluation: group 1; after 7 days, group 2; after 15 days, group 3; after 30 days, group 4; after 60 days and group 5; after 90 days. The inflammatory reaction was graded and data was analyzed using the Kruskal-Wallis and Mann-Whitney U tests. Statistical significance was defined at 0.05. Results: Comparison of cumulative inflammatory reaction at all intervals revealed that the mean grade of inflammatory reaction to MTA, MTA+NS and control samples were 3, 2 and 2, respectively. According to the Mann-Whitney analysis there were no significant differences between MTA+NS and MTA (P=0.42). Conclusion: Incorporation of 1% nanosilver to MTA does not affect the inflammatory reaction of subcutaneous tissue in rat models. PMID:26843871

  9. Effect of fructose on insulin action in adipose tissue of Wistar rats

    SciTech Connect

    Akintilo, A.; Pointer, R.H.; Blakely, S.R.

    1986-05-01

    The present study was conducted to examine the effects of dietary fructose, with and without insulin stimulation, on glucose oxidation to carbon dioxide and on fatty acid synthesis in epididymal adipose tissue of rats. Two groups of male weanling Wistar rats were fed ad libitum 54% (W/W) carbohydrate diets containing 27% cornstarch plus either 27% D-fructose (FRU) or 27% D-glucose (GLU) for eleven weeks. Each diet also contained 16% fat and 20% protein. Neither body weights nor epididymal adipose tissue weights were significantly different between groups. Insulin action was assessed by incubating adipose tissue in Krebs-Ringer bicarbonate buffer (pH 7.4) containing 90 ..mu..moles (U-/sup 14/C)-D-glucose with and without insulin (1 mU/ml) for 1 hour, trapping the /sup 14/CO/sub 2/ on filter paper, and extracting the /sup 14/C-lipid with Dole's mixture. Means +/- SEM with identical superscripts are not different at the P < .05 level. These results indicate that FRU feeding stimulated glucose oxidation at a rate higher than that of GLU feeding and comparable to that stimulated by insulin. However, lipogenesis was lower in FRU fed than either in GLU fed rats or with insulin stimulation. FRU feeding does not alter the action of insulin on glucose oxidation or lipogenesis.

  10. Weight loss and brown adipose tissue reduction in rat model of sleep apnea

    PubMed Central

    Martinez, Denis; Vasconcellos, Luiz FT; de Oliveira, Patricia G; Konrad, Signorá P

    2008-01-01

    Background - Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats. Methods Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. Results Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054). Conclusion Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT. PMID:18671859

  11. The effect of microgravity on tissue structure and function of rat testis.

    PubMed

    Ding, Ye; Tang, Jin; Zou, Jun; She, Ruiping; Wang, Yinghua; Yue, Zhuo; Tian, Jijing; Xia, Kangkang; Yin, Jun; Wang, Desheng

    2011-12-01

    To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis. PMID:22042268

  12. Antioxidant effects of proanthocyanidin from grape seed on hepatic tissue injury in diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abedi, Hassan Ali

    2014-01-01

    Objective(s): Diabetes plays an important role in the induction of the liver injury. Grape seed proanthocyanidin (GSP) have a wide range of medicinal properties against oxidative stress. In this study we evaluated antioxidant effects of GSP on liver in streptozotocin-induced diabetic rats. Materials and Methods: Thirty male Sprague–Dawley rats were divided into three groups: control, untreated diabetic and diabetic rats treated with GSP. Diabetes was induced in rats by intraperitoneal injection of streptozotocin (50 mg/kg). GSP were administered via oral gavage (200 mg/kg) for 4 weeks. Results: GSP produced significant hepatoprotective effects by decreasing activities of serum aminotransferases and alkaline phosphatase, and decreasing liver malondialdehyde and bilirubin (P<0.05) levels. It increased liver superoxide dismutase, catalase and glutathione peroxidase activities and albumin level (P<0.05). Administration of GSP significantly ameliorated structural changes induced in liver of diabetic rats. Conclusion: GSP have protective effects against hepatic tissue injury due to antioxidant properties. PMID:25140209

  13. Characterisation of the metabolome of ocular tissues and post-mortem changes in the rat retina.

    PubMed

    Tan, Shi Z; Mullard, Graham; Hollywood, Katherine A; Dunn, Warwick B; Bishop, Paul N

    2016-08-01

    Time-dependent post-mortem biochemical changes have been demonstrated in donor cornea and vitreous, but there have been no published studies to date that objectively measure post-mortem changes in the retinal metabolome over time. The aim of the study was firstly, to investigate post-mortem, time-dependent changes in the rat retinal metabolome and secondly, to compare the metabolite composition of healthy rat ocular tissues. To study post-mortem changes in the rat retinal metabolome, globes were enucleated and stored at 4 °C and sampled at 0, 2, 4, 8, 24 and 48 h post-mortem. To study the metabolite composition of rat ocular tissues, eyes were dissected immediately after culling to isolate the cornea, lens, vitreous and retina, prior to storing at -80 °C. Tissue extracts were subjected to Gas Chromatograph Mass Spectrometry (GC-MS) and Ultra High Performance Liquid Chromatography Mass Spectrometry (UHPLC-MS). Generally, the metabolic composition of the retina was stable for 8 h post-mortem when eyes were stored at 4 °C, but showed increasing changes thereafter. However, some more rapid changes were observed such as increases in TCA cycle metabolites after 2 h post-mortem, whereas some metabolites such as fatty acids only showed decreases in concentration from 24 h. A total of 42 metabolites were identified across the ocular tissues by GC-MS (MSI level 1) and 2782 metabolites were annotated by UHPLC-MS (MSI level 2) according to MSI reporting standards. Many of the metabolites detected were common to all of the tissues but some metabolites showed partitioning between different ocular structures with 655, 297, 93 and 13 metabolites being uniquely detected in the retina, lens, cornea and vitreous respectively. Only a small percentage (1.6%) of metabolites found in the vitreous were only detected in the retina and not other tissues. In conclusion, mass spectrometry-based techniques have been used for the first time to compare the metabolic composition of

  14. Global Gene Expression Profiling in Lung Tissues of Rat Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Yeshitla, Samrawit A.; Lam, Chiu-Wing; Kidane, Yared H.; Feiveson, Alan H.; Ploutz-Snyder, Robert; Wu, Honglu; James, John T.; Meyers, Valerie E.; Zhang, Ye

    2014-01-01

    The Moon's surface is covered by a layer of fine, potential reactive dust. Lunar dust contain about 1-2% respirable very fine dust (less than 3 micrometers). The habitable area of any lunar landing vehicle and outpost would inevitably be contaminated with lunar dust that could pose a health risk. The purpose of the study is to analyze the dynamics of global gene expression changes in lung tissues of rats exposed to lunar dust particles. F344 rats were exposed for 4 weeks (6h/d; 5d/wk) in nose-only inhalation chambers to concentrations of 0 (control air), 2.1, 6.8, 21, and 61 mg/m3 of lunar dust. Animals were euthanized at 1 day and 13 weeks after the last inhalation exposure. After being lavaged, lung tissue from each animal was collected and total RNA was isolated. Four samples of each dose group were analyzed using Agilent Rat GE v3 microarray to profile global gene expression of 44K transcripts. After background subtraction, normalization, and log transformation, t tests were used to compare the mean expression levels of each exposed group to the control group. Correction for multiple testing was made using the method of Benjamini, Krieger, and Yekuteli (1) to control the false discovery rate. Genes with significant changes of at least 1.75 fold were identified as genes of interest. Both low and high doses of lunar dust caused dramatic, dose-dependent global gene expression changes in the lung tissues. However, the responses of lung tissue to low dose lunar dust are distinguished from those of high doses, especially those associated with 61mg/m3 dust exposure. The data were further integrated into the Ingenuity system to analyze the gene ontology (GO), pathway distribution and putative upstream regulators and gene targets. Multiple pathways, functions, and upstream regulators have been identified in response to lunar dust induced damage in the lung tissue.

  15. Pharmacokinetics in rats and tissue distribution in mouse of berberrubine by UPLC-MS/MS.

    PubMed

    Wang, Xianqin; Wang, Shuanghu; Ma, Jianshe; Ye, Tao; Lu, Mengrou; Fan, Miao; Deng, Mingjie; Hu, Lufeng; Gao, Zhimou

    2015-11-10

    Berberrubine is an isoquinoline alkaloid isolated from Berberis vulgaris L, and it is readily derived from berberine. In this study, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of berberrubine in rat plasma and mouse tissue has been developed. Magnoflorine was employed as an internal standard (IS), and liquid-liquid extraction by ethyl acetate was used for sample preparation. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1mm×100mm, 1.7μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 322.0→307.0 for berberrubine and m/z 342.8→298.2 for IS. Calibration plots were linear in the range of 2-2000ng/mL for berberrubine in rat plasma and mouse tissue. Mean recoveries of berberrubine in rat plasma ranged from 79.6% to 84.8%. Intra-day and inter-day precision were less than 11%. The accuracy ranged from 93.6% to 106.8%. The method has also been successfully applied in pharmacokinetics and tissue distribution study of berberrubine. The absolute bioavailability of berberrubine was determined to be 31.6%. The results also show that berberrubine is rapidly absorbed and widely distributed in various tissues. The level of berberrubine in liver is highest, and followed by kidney, spleen and heart. Furthermore, the concentration of berberrubine in various tissues could also be predicted by a BP-ANN model. PMID:26279368

  16. Tissue distribution study of columbianadin and its active metabolite columbianetin in rats.

    PubMed

    Zhang, You-Bo; Yang, Xiu-Wei

    2016-02-01

    Columbianadin, one of the main bioactive constituents of the roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan, has been found to possess obvious pharmacological effects in previous studies. In this study, a valid and sensitive reverse-phase high-performance liquid chromatography (RP-HPLC) method was established and validated for the determination of columbianadin (CBN) and its active metabolite columbianetin (CBT) in rat tissue samples. Sample separation was performed on an RP-HPLC column using a mobile phase of MeOH-H2 O (75:25, v/v) at a flow rate of 1.0 mL/min. The UV absorbance of the samples was measured at the wavelength 325 nm. The calibration curves for CBN were linear over the ranges of 0.5-20 µg/g for brain, testes and muscle, 1.0-10.0 µg/g for stomach and intestine, and 0.2-20.0 µg/g for heart, liver, spleen, lung and kidney. The calibration curves for CBT were linear over the ranges of 0.5-25 µg/g for stomach and intestine, and 0.1-10.0 µg/g for heart, liver, spleen, lung and kidney. The analysis method was successfully applied to a tissue distribution study of CBN and CBT after intravenous administration of CBN to rats. The results of this study indicated that CBN could be detected in all of the selected tissues after i.v. administration. CBN was distributed to rat tissues rapidly and could be metabolized to CBT in most detected tissues. Of the detected tissues, heart had the highest uptake of CBN, which suggested that heart might be one of the main target tissues of CBN. Concentrations of CBT were obviously higher in the digestive system than in other assayed tissues. The information provided by this research is very useful for gaining knowledge of the capacities of CBN and CBT to access different tissues. PMID:26115176

  17. Mechanotransduction in rat myometrium: coordination of contractions of electrically and chemically isolated tissues.

    PubMed

    Young, Roger C; Goloman, Gabriela

    2011-01-01

    The generally accepted mechanism for global uterine coordination is propagation of electrical activity. Mechanotransduction mechanisms were briefly considered as a secondary mechanism 40 years ago, but scant data have appeared. Here, we provide evidence that tissue strips are capable of functionally interacting solely by mechanical mechanisms. We mechanically linked, in series, 2 rat myometrial strips of similar size. Strips were placed in separate baths to ensure they were electrically and chemically isolated. A force transducer was used to measure force production. We precisely determined when each tissue contracted by simultaneously measuring each strip's electrical activity using contact electrodes. We observed both in-phase and out-of-phase contraction patterns from the tissues. To determine whether modulation of the electrical properties of the tissue is involved in the mechanotransduction mechanism, we briefly stretched single tissue strips during alternate contractions. This technique provided a control contraction for each test contraction. The duration of the contraction that was stretched measured longer than the control in 33 of 35 pairs (P = .0001, Wilcoxon signed-rank test for paired data). Interestingly, briefly slackening the tissue also prolonged the force-producing phase of that contraction (39 of 42 pairs; P = .0006). Because our data show that mechanotransduction mechanisms coordinate tissue-level contractions, we speculate that mechanotransduction mechanisms may contribute to organ-level coordination of contractions. PMID:20713968

  18. Tissue distribution and physiologically based pharmacokinetics of antisense phosphorothioate oligonucleotide ISIS 1082 in rat.

    PubMed

    Peng, B; Andrews, J; Nestorov, I; Brennan, B; Nicklin, P; Rowland, M

    2001-02-01

    The aim of this study was to develop a whole body physiologically based model of the pharmacokinetics (PBPK) of the phosphorothioate oligonucleotide (PS-ODN) ISIS 1082 in vivo. Rats were administered an intravenous (i.v.) bolus dose of ISIS 1082 (10 mg/kg plus 3H tracer), and arterial blood and tissues were taken at specific times up to 72 hours. Radioactivity was measured in all samples. The parent compound was determined specifically in blood and tissues at 90 minutes and in liver and kidney also at 24 hours, using capillary gel electrophoresis (CGE). A whole body PBPK model was fitted to the combined blood and tissue radioactivity data using nonlinear regression analysis. CGE analysis indicated that the predominant species in plasma and all tissues is ISIS 1082, together with some n-1 and n-2 metabolites. Total radioactivity primarily reflects these species. The whole body model successfully described temporal events in all tissues. However, to adequately model the experimental data, all tissues had to be partitioned into vascular and extravascular spaces to accommodate the relatively slow distribution of ISIS 1082 out of blood because of a permeability rate limitation. ISIS 1082 distributes extensively into tissues, but the relative affinity varies enormously, being highest for kidney and liver and lowest for muscle and brain. A whole body PBPK model with a permeability rate limited tissue distribution was developed that adequately described events in both blood and tissue for an oligonucleotide. This model has the potential not only to characterize the events in individual tissues throughout the body for such compounds but also to scale across animal species, including human. PMID:11258618

  19. Increased in vivo glucose utilization in 30-day-old obese Zucker rat: Role of white adipose tissue

    SciTech Connect

    Krief, S.; Bazin, R.; Dupuy, F.; Lavau, M. )

    1988-03-01

    In vivo whole-body glucose utilization and uptake in multiple individual tissues were investigated in conscious 30-day-old Zucker rats, which when obese are hyperphagic, hyperinsulinemic, and normoglycemic. Whole-body glucose metabolism (assessed by (3-{sup 3}H)glucose) was 40% higher in obese (fa/fa) than in lean (Fa/fa) rats, suggesting that obese rats were quite responsive to their hyperinsulinemia. In obese compared with lean rats, tissue glucose uptake was increased by 15, 12, and 6 times in dorsal, inguinal, perigonadal white depots, respectively; multiplied by 2.5 in brown adipose tissue; increased by 50% in skin from inguinal region but not in that from cranial, thoracic, or dorsal area; and increased twofold in diaphragm but similar in heart in proximal intestine, and in total muscular mass of limbs. The data establish that in young obese rats the hypertrophied white adipose tissue was a major glucose-utilizing tissue whose capacity for glucose disposal compared with that of half the muscular mass. Adipose tissue could therefore play an important role in the homeostasis of glucose in obese rats in the face of their increased carbohydrate intake.

  20. Human periodontal ligament cell sheets can regenerate periodontal ligament tissue in an athymic rat model.

    PubMed

    Hasegawa, Masateru; Yamato, Masayuki; Kikuchi, Akihiko; Okano, Teruo; Ishikawa, Isao

    2005-01-01

    Conventional periodontal regeneration methods remain insufficient to attain complete and reliable clinical regeneration of periodontal tissues. We have developed a new method of cell transplantation using cell sheet engineering and have applied it to this problem. The purpose of this study was to investigate the characteristics of human periodontal ligament (HPDL) cell sheets retrieved from culture on unique temperature-responsive culture dishes, and to examine whether these cell sheets can regenerate periodontal tissues. The HPDL cell sheets were examined histologically and biochemically, and also were transplanted into a mesial dehiscence model in athymic rats. HPDL cells were harvested from culture dishes as a contiguous cell sheet with abundant extracellular matrix and retained intact integrins that are susceptible to trypsin-EDTA treatment. In the animal study, periodontal ligament-like tissues that include an acellular cementum-like layer and fibrils anchoring into this layer were identified in all the athymic rats transplanted with HPDL cell sheets. This fibril anchoring highly resembles native periodontal ligament fibers; such regeneration was not observed in nontransplanted controls. These results suggest that this technique, based on the concept of cell sheet engineering, can be useful for periodontal tissue regeneration. PMID:15869425

  1. Fluorescence spectroscopy and cryoimaging of rat lung tissue mitochondrial redox state

    NASA Astrophysics Data System (ADS)

    Sepehr, R.; Audi, S.; Staniszewski, K.; Maleki, S.; Ranji, M.

    2011-07-01

    The objective of this study was to demonstrate the utility of optical cryoimaging and fluorometry to evaluate tissue redox state of the mitochondrial metabolic coenzymes NADH (Nicotinamide Adenine Dinucleotide) and FAD (Flavin Adenine Dinucleotide) in intact rat lungs. The ratio (NADH/FAD), referred to as mitochondrial redox ratio (RR), is a measure of the lung tissue mitochondrial redox state. Isolated rat lungs were connected to a ventilation-perfused system. Surface NADH and FAD fluorescence signals were acquired before and after lung perfusion in the absence (control perfusate) or presence of potassium cyanide (KCN, complex IV inhibitor) to reduce the mitochondrial respiratory chain (state 5 respiration). Another group of lungs were perfused with control perfusate or KCN-containing perfusate as above, after which the lungs were deflated and frozen rapidly for subsequent 3D cryoimaging. Results demonstrate that lung treatment with KCN increased lung surface NADH signal by 22%, decreased FAD signal by 8%, and as result increased RR by 31% as compared to control perfusate (baseline) values. Cryoimaging results also show that KCN increased mean lung tissue NADH signal by 37%, decreased mean FAD signal by 4%, and increased mean RR by 47%. These results demonstrate the utility of these optical techniques to evaluate the effect of pulmonary oxidative stress on tissue mitochondrial redox state in intact lungs.

  2. Connective Tissue Reaction to White and Gray MTA Mixed With Distilled Water or Chlorhexidine in Rats

    PubMed Central

    Yavari, Hamid Reza; Shahi, Shahriar; Rahimi, Saeed; Shakouie, Sahar; Roshangar, Leila; Mesgari Abassi, Mehran; Sattari Khavas, Sahar

    2009-01-01

    INTRODUCTION: The purpose of this study was to compare the histocompatibility of white (WMTA) and gray (GMTA) mineral trioxide aggregate mixed with 0.12% chlorhexidine (CHX) and distilled water (DW) in subcutaneous connective tissues of rats. MATERIALS AND METHODS: The freshly mixed WMTA and GMTA with CHX or DW were inserted in polyethylene tubes and implanted into dorsal subcutaneous connective tissue of 50 Wistar Albino rats; tissue biopsies were collected and were then examined histologically 7, 15, 30, 60 and 90 days after the implantation procedure. The histology results were scored from 1-4; score 4 was considered as the worst finding. Data were analyzed using one-way ANOVA tests. RESULTS: All experimented materials were tolerated well by the connective tissues after 90-day evaluation, except for the WMTA/CHX group that had significantly more mean inflammatory scores (P<0.001). There was a statistically significant difference in the mean inflammation grades between experimental groups in each interval (P<0.001). After 90 days, GMTA/CHX group had the lowest inflammatory score. CONCLUSION: Although adding CHX to WMTA produces significantly higher inflammatory response, it seems a suitable substitute for DW in combination with GMTA. Further research is necessary to recommend this mixture for clinical use. PMID:23864873

  3. Survival of cultured plant cells grafted into the subcutaneous tissue of rats (preliminary report).

    PubMed

    Lozoya, X; Madrazo, I; Guizar, G; Villarreal, M L; Grijalva, I; Salgado, H; Boijseauneau, E; Ibarra, A; Arias-Castro, C; Rodríguez-Mendiola, M A

    1995-01-01

    To evaluate the survival of plant tissue in an animal environment, cultured calli from a Mexican medicinal plant (Mimosa tenuiflora Poir.) were transplanted under sterile conditions into the subcutaneous tissue of rats. Microscopic studies of grafted areas were carried out at the 30th, 60th and 120th days after transplantation. Histological evidence of plant graft survival was found in specimens of all groups. during the first month of subcutaneous grafting a moderate inflammatory reaction around the callus was observed characterized by the presence of polymorphonuclear cells and some macrophages and the formation of a fibrous capsule. Nevertheless, the plant grafts remained viable and a decrease of the inflammatory reaction around the callus was observed in the specimens during the following months. In the fourth month specimens the formation of blood vessels inside the grafted plant tissue was observed. Once removed from rats, plant tissues showed high viability according to the fluorescein test. These calli were then transferred to the original in vitro medium showing growth capacity during the following weeks. These results demonstrate, for the first time, that cultivated cells of higher plants survive in an animal environment, suggesting the possibility to utilize pharmacologically active plant transplants in animals, a technique proposed here as inter-regni transplants. Further studies are required to explore this new field of research that opens numerous questions about plant-animal cellular interaction. PMID:7711454

  4. Investigation of endocrine and immunological response in fat tissue to hyperbaric oxygen administration in rats.

    PubMed

    Şen, H; Erbağ, G; Ovali, M A; Öztopuz, R Ö; Uzun, M

    2016-01-01

    Though HBO treatment is becoming more common, the mechanism of action is not fully known. The positive effects of HBO administration on the inflammatory response is thought to be a possible basic mechanism. As a result, we aimed to research whether endocrine and immunological response of fat tissue changes in rats given HBO treatment model. This research was carried out on Wistar albino rats, they were treated with hyperbaric oxygen therapy. Their fatty tissue were taken from the abdomen, gene expression of the cytokines and adipokines were analyzed with Real time PCR method. When the gene expression of hormones and cytokines by fat tissue was examined, the leptin, visfatin, TNF-α, IL-1β and IL-10 levels in the HBO treatment group were statistically significantly increased compared to the control group (p=0.0313, p=0.0156, p=0.0156, p=0.0156, p=0.0313). In conclusion, in our study we identified that HBO administration affected the endochrinological functions of fat tissue. PMID:27188864

  5. A histopathological study of the role of periodontal ligament tissue in root resorption in the rat.

    PubMed

    Shiraishi, C; Hara, Y; Abe, Y; Ukai, T; Kato, I

    2001-02-01

    Whether periodontal ligament (PDL) tissue is capable of inducing root resorption was examined. The distal root of the rat molar was sectioned at the furcation and the PDL tissue removed from the root (non-PDL group, n=40). The distal root with the PDL intact was also prepared (PDL-intact group, n=40). The roots were transplanted into the dorsal skin of the rat. On the 1st, 3rd, 5th, 7th, 10th, 14th, 21st or 28th day after transplantation, the roots were removed together with surrounding dorsal subcutaneous tissue and were fixed, demineralized and embedded in paraffin. Serial sections from each block were stained with haematoxylin and eosin or by the tartrate-resistant acid phosphatase (TRAP) method to observe root-resorbing cell formation. Cyclo-oxygenase-2 (COX2) was also detected immunohistologically to examine prostaglandin E(2) production. On the 7th day after transplantation, multinucleated root-resorbing cells with TRAP were observed in the PDL-intact group. The number of TRAP-positive cells peaked on the 10th day after transplantation. COX2-positive cells were observed in PDL during the early experimental stages. No root resorption was seen in the non-PDL group. These results suggest that PDL tissue is involved in the formation of root-resorbing cells and root resorption. PMID:11163317

  6. Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats.

    PubMed

    Wen, Shi; Li, Zhishui; Feng, Jianghua; Bai, Jianxi; Lin, Xianchao; Huang, Heguang

    2016-06-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC. PMID:27019331

  7. Effect of cadmium intoxication on collagen and elastin content in tissues of the rat

    SciTech Connect

    Kucharz, E.J.

    1988-02-01

    Cadmium produces a variety of pathological effects in various organs in experimental animals or in accidentally intoxicated humans. The mechanism of these phenomena has been the subject of numerous investigations. Many of the observed toxic effects are thought to be the results of secondary deficiencies in such essential trace elements as zinc, copper and iron. Metabolism of the fibrous components of connective tissue, i.e. collagen and elastin, requires the presence of so me trace elements. It is also believed that elastin biosynthesis depends on the presence of some trace metals. Copper deficiency produces significant decrease in elastic tissue resistance, caused by diminished cross-link formation. Experimental studies showed that cadmium treatment of rats produced an increase in the urinary excretion of collagen catabolites. It was also shown that cadmium intoxication influenced bone structure and fetal growth. These two effects on connective tissue were probably accompanied by disturbances in collagen metabolism. Moreover, it is known that fungal collagenase activity was affected by cadmium. In the present paper a decrease in collagen and elastin content, and impaired extracellular maturation of the collagen fibers in some tissues of rats intoxicated with cadmium were described.

  8. Subacute toxic effects of zinc on various tissues and organs of rats.

    PubMed

    Piao, Fengyuan; Yokoyama, Kazuhito; Ma, Ning; Yamauchi, Toru

    2003-11-01

    In order to expand our knowledge of zinc toxicity and to assess further the toxicities of zinc systematically, we observed the toxic effects of zinc on the functions of various tissues and organs in rats. The rats were randomly divided into four groups (14 in each group), viz. one normal control group (received saline), two zinc groups (Znlow: 4 mg/kg of zinc acetate; Znhigh: 8 mg/kg of zinc acetate), and one cyclophosphamide group (50 mg/kg, as positive control of micronucleated polychromatic erythrocytes (MPCEs)). Saline and zinc acetate were administered intraperitoneally to the rats once every 2 days, seven times in total. Cyclophosphamide was given intraperitoneally to the rats once. The concentration of blood zinc was determined and accumulation of zinc was not observed in the experimental groups. The frequencies of basophilic stippled erythrocyte (BSE) and MPCEs in the Znhigh group were significantly higher than those in the control group (P<0.05). The levels of serum glutamic oxalacetic transaminase (GOT) and serum triiodothyronine (T3) in the Znhigh groups decreased significantly, compared with the control group (P<0.01 or 0.05). Moreover, we also observed that the level of serum cortisol, another adrenal corticoid hormone in rats, was increased by zinc acetate in a dose-dependent manner. According to the literature and our findings, exposure to zinc, especially at higher doses, may produce toxic effects on various tissues and organs including the hematopoietic system, cytogenetics, biochemistry and endocrine system function. Therefore, it is suggested that zinc should be used carefully, especially by high risk groups such as children and pregnant women despite its use as a food additive or in self-medication. At the same time, it is necessary to investigate and research further these toxicities of zinc with long-term administration of low dosage. PMID:12962971

  9. Protective effects of different antioxidants against cadmium induced oxidative damage in rat testis and prostate tissues.

    PubMed

    Jahan, Sarwat; Zahra, Asia; Irum, Umaira; Iftikhar, Natasha; Ullah, Hizb

    2014-08-01

    The present study was performed to determine the effects of different antioxidants on testicular histopathology and oxidative damage induced by cadmium (Cd) in rat testis and prostate. Twenty five rats were equally divided into five groups (n = 5/group). The control group was injected subcutaneously with saline while the Cd alone treated group received a subcutaneous injection of 0.2 mg/kg CdCl(2). Other groups were treated with sulphoraphane (25 µg/rat), vitamin E (75 mg/kg), and Ficus Religiosa plant extract (100 mg/kg) orally along with subcutaneous injections of 0.2 mg/kg CdCl(2) for fifteen days. Oxidative damage in the testicular and prostate tissues were assessed by the estimation of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and glutathione reductase (GSR) activity. Lipid peroxidation (TBARS), protein estimation, and histomorphology were also assessed. Cadmium exposure caused a significant decrease in antioxidant enzymes like CAT, POD, SOD, GSR, protein concentrations, and a marked increase in TBARS activity in rat testis and prostate. Histological examination of adult male rat testes showed a disruption in the arrangement of seminiferous tubules along with a reduction in the number of germ cells, Leydig cells, tunica albuginea thickness, diameter of seminiferous tubules, and height of germinal epithelium. Co-treatment with vitamin E, sulphoraphane, and Ficus religiosa were found to be effective in reversing Cd induced toxicity, representing potential therapeutic options to protect the reproductive tissues from the detrimental effects of Cd toxicity. PMID:24758558

  10. Ameliorative effect of vanadium on oxidative stress in stomach tissue of diabetic rats.

    PubMed

    Yilmaz-Ozden, Tugba; Kurt-Sirin, Ozlem; Tunali, Sevim; Akev, Nuriye; Can, Ayse; Yanardag, Refiye

    2014-05-01

    Between their broad spectrum of action, vanadium compounds are shown to have insulin mimetic/enhancing effects. Increasing evidence in experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of diabetes and on the onset of diabetic complications. Thus, preventive therapy can alleviate the possible side effects of the disease. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the stomach tissue of diabetic rats. Male Swiss albino rats were randomly divided into 4 groups: control; control+vanadyl sulfate; diabetic; diabetic+vanadyl sulfate. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ; 65 mg/kg body weight). Vanadyl sulfate (100 mg/kg body weight) was given daily by gavage for 60 days. At the last day of the experiment, stomach tissues were taken and homogenized to make a 10% (w/v) homogenate. Catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), myeloperoxidase (MPO), carbonic anhydrase (CA), glucose-6-phosphate dehydrogenase (G6PD) and lactate dehydrogenase (LDH) activities were determined in the stomach tissue. CAT, SOD, GR, GPx, GST, CA, G6PD and LDH activities were increased in diabetic rats when compared to normal rats. Vanadium treatment significantly reduced the elevated activities of GR, GPx, GST compared with the diabetic group whereas the decreases in CAT, SOD, CA, G6PD and LDH activities were insignificant. No significant change was seen for MPO activity between the groups. It was concluded that vanadium could be used for its ameliorative effect against oxidative stress in diabetes. PMID:24856383

  11. Characterization of a local renin-angiotensin system in rat gingival tissue

    PubMed Central

    Santos, C.F.; Akashi, A.E.; Dionísio, T.J.; Sipert, C.R.; Didier, D.N.; Greene, A.S.; Oliveira, S.H.P.; Pereira, H.J.; Becari, C.; Oliveira, E.B.; Salgado, M.C.O.

    2009-01-01

    Background Systemic renin-angiotensin system (RAS) promotes plasmatic production of angiotensin (Ang) II, which acts through interaction with specific receptors. There is growing evidence that local systems in various tissues and organs are capable of generating angiotensins independently of circulating RAS. The aims of this work were to: 1) study the expression and localization of RAS components in rat gingival tissue and 2) evaluate the in vitro production of Ang II and other peptides catalyzed by rat gingival tissue homogenates incubated with different Ang II precursors. Methods Reverse transcription-polymerase chain reaction (RT-PCR) assessed mRNA expression. Immunohistochemical (IHC) analysis aimed to detect and localize renin. Standardized fluorimetric method with tripeptide Hippuryl-Histidyl-Leucine (Hip-His-Leu) was used to measure tissue ACE activity, while high performance liquid chromatography (HLPC) showed products formed after incubation of tissue homogenates with Ang I or tetradecapeptide renin substrate (TDP). Results mRNA for renin, angiotensinogen, ACE and Ang II receptors (AT1a, AT1b and AT2) was detected in gingival tissue; cultured gingival fibroblasts expressed renin, angiotensinogen and AT1a receptor. Renin was present in the vascular endothelium and intensely expressed in the epithelial basal layer of periodontally affected gingival tissue. ACE activity was detected (4.95±0.89 nmol His-Leu/g.min). When Ang I was used as substrate, Ang 1-9 (0.576±0.128 nmol/mg.min), Ang II (0.066±0.008 nmol/mg.min) and Ang 1-7 (0.111±0.017 nmol/mg.min) were formed, whereas these same peptides (0.139±0.031; 0.206±0.046 and 0.039±0.007 nmol/mg.min, respectively) and Ang I (0.973±0.139 nmol/mg.min) were formed when TDP was the substrate. Conclusion Results presented here clearly show existence of a local RAS in rat gingival tissue, which is capable of generating Ang II and other vasoactive peptides in vitro. PMID:19228099

  12. Distribution of phospholipase C isozymes in various rat tissues and cultured cells

    SciTech Connect

    Suh, P.G.; Ryu, S.H.; Choi, W.C.; Lee, K.Y.; Rhee, S.G.

    1987-05-01

    Monoclonal antibodies prepared against PLC-I or PLC-II enzyme did not cross-react with the other. Using a pair of antibodies which recognizes 2 different antigenic sites on the same molecule, radioimmunoassays were developed for the quantitation of PLC-I and PLC-II in homogenates of various tissues and cultured cells, prepared by homogenization in a 2 M KCl buffer. The contents of PLC enzymes were measured in 19 rat tissues, in human platelets and in 17 cultured cells. Results indicate that the concentration of PLC-I and PLC-II is very high in brain, PLC-I is localized mainly in brain and partly in seminal vesicles, PLC-II is found in most tissues and cells. PLC-I is highly localized even in brain: 5 different neuroblastoma did not contain PLC-I while 2 glioma and 1 astrocytoma contained significant amounts.

  13. Terahertz spectroscopy and detection of brain tumor in rat fresh-tissue samples

    NASA Astrophysics Data System (ADS)

    Yamaguchi, S.; Fukushi, Y.; Kubota, O.; Itsuji, T.; Yamamoto, S.; Ouchi, T.

    2015-03-01

    Terahertz (THz) spectroscopy and imaging of biomedical samples is expected to be an important application of THz analysis techniques. Identification and localization of tumor tissue, imaging of biological samples, and analysis of DNA by THz spectroscopy have been reported. THz time-domain spectroscopy (TDS) is useful for obtaining the refractive index over a broad frequency range. However, THz-TDS spectra of fresh tissue samples are sensitive to procedures such as sample preparation, and a standardized measurement protocol is required. Therefore, in this work, we establish a protocol for measurements of THz spectra of fresh tissue and demonstrate reliable detection of rat brain tumor tissue. We use a reflection THz-TDS system to measure the refractive index spectra of the samples mounted on a quartz plate. The tissue samples were measured immediately after sectioning to avoid sample denaturalization during storage. Special care was taken in THz data processing to eliminate parasitic reflections and reduce noise. The error level in our refractive index measurements was as low as 0.02 in the frequency range 0.8-1.5 THz. With increasing frequency, the refractive index in the tumor and normal regions monotonically decreased, similarly to water, and it was 0.02 higher in the tumor regions. The spectral data suggest that the tumor regions have higher water content. Hematoxylin-eosin stained images showed that increased cell density was also responsible for the observed spectral features. A set of samples from 10 rats showed consistent results. Our results suggest that reliable tumor detection in fresh tissue without pretreatment is possible with THz spectroscopy measurements. THz spectroscopy has the potential to become a real-time in vivo diagnostic method.

  14. Immunohistochemical localization and activity of glutathione transferase zeta (GSTZ1-1) in rat tissues.

    PubMed

    Lantum, Hoffman B M; Baggs, Raymond B; Krenitsky, Daria M; Board, Philip G; Anders, M W

    2002-06-01

    Glutathione transferase zeta (GSTZ1-1) catalyzes the biotransformation of a range of alpha-haloacids, including dichloroacetic acid (DCA), and the penultimate step in the tyrosine degradation pathway. DCA is a rodent carcinogen and a common drinking water contaminant. DCA also causes multiorgan toxicity in rodents and dogs. The objective of this study was to determine the expression and activities of GSTZ1-1 in rat tissues with maleylacetone and chlorofluoroacetic acid as substrates. GSTZ1-1 protein was detected in most tissues by immunoblot analysis after immunoprecipitation of GSTZ1-1 and by immunohistochemical analysis; intense staining was observed in the liver, testis, and prostate; moderate staining was observed in the brain, heart, pancreatic islets, adrenal medulla, and the epithelial lining of the gastrointestinal tract, airways, and bladder; and sparse staining was observed in the renal juxtaglomerular regions, skeletal muscle, and peripheral nerve tissue. These patterns of expression corresponded to GSTZ1-1 activities in the different tissues with maleylacetone and chlorofluoroacetic acid as substrates. Specific activities ranged from 258 +/- 17 (liver) to 1.1 +/- 0.4 (muscle) nmol/min/mg of protein with maleylacetone as substrate and from 4.6 +/- 0.89 (liver) to 0.09 +/- 0.01 (kidney) nmol/min/mg of protein with chlorofluoroacetic acid as substrate. Rats given DCA had reduced amounts of immunoreactive GSTZ1-1 protein and activities of GSTZ1-1 in most tissues, especially in the liver. These findings indicate that the DCA-induced inactivation of GSTZ1-1 in different tissues may result in multiorgan disorders that may be associated with perturbed tyrosine metabolism. PMID:12019185

  15. Effect of Diet and Cold Exposure on Norepinephrine Turnover in Brown Adipose Tissue of the Rat

    PubMed Central

    Young, James B.; Saville, Elizabeth; Rothwell, Nancy J.; Stock, Michael J.; Landsberg, Lewis

    1982-01-01

    Brown adipose tissue (BAT) is an important site of adaptive changes in thermogenesis in the rat. The sympathetic nervous system, which richly supplies BAT, is thought to play an important role in the regulation of BAT thermogenesis because catecholamines stimulate and beta adrenergic blocking agents inhibit oxygen consumption in this tissue. The present studies were carried out to assess directly sympathetic activity in BAT in response to cold exposure and to changes in dietary intake, both of which alter heat production in the rat. Sympathetic activity was determined from the rate of norepinephrine (NE) turnover in interscapular brown adipose tissue (IBAT) after preliminary experiments validated the use of NE turnover techniques in IBAT. Acute exposure to 4°C increased NE turnover in IBAT 4- to 12-fold compared with ambient temperature controls, depending upon the interval over which the turnover measurement was made, while in the heart NE turnover doubled in response to the same cold stimulus. In animals exposed to cold continuously for 10 d before study, NE turnover measurements in IBAT and in the heart were elevated comparably to those obtained during acute exposure. Alterations in feeding were also associated with changes in NE turnover in IBAT. Fasting for 2 d decreased NE turnover in IBAT (-35% from 29.2±4.2 ng NE/h to 18.9±5.9) and in heart (-52%). In animals fed a “cafeteria” diet, a model of voluntary overfeeding in the rat, NE turnover was increased in both IBAT (+108% from 24.8±4.5 ng NE/h to 51.7±6.8) and heart (+66%). Because ganglionic blockade exerted a greater effect on NE turnover in IBAT in cafeteria-fed rats than in controls, the increase in NE turnover in IBAT with this overfeeding regimen reflects enhanced central sympathetic outflow. Thus NE turnover techniques can be satisfactorily applied to the assessment of sympathetic nervous system activity in IBAT. The experiments reported here demonstrate changes in sympathetic activity in

  16. Dietary Iron Concentration May Influence Aging Process by Altering Oxidative Stress in Tissues of Adult Rats

    PubMed Central

    Arruda, Lorena Fernandes; Arruda, Sandra Fernandes; Campos, Natália Aboudib; de Valencia, Fernando Fortes; Siqueira, Egle Machado de Almeida

    2013-01-01

    Iron is an essential element. However, in its free form, iron participates in redox-reactions, leading to the production of free radicals that increase oxidative stress and the risk of damaging processes. Living organisms have an efficient mechanism that regulates iron absorption according to their iron content to protect against oxidative damage. The effects of restricted and enriched-iron diets on oxidative stress and aging biomarkers were investigated. Adult Wistar rats were fed diets containing 10, 35 or 350 mg/kg iron (adult restricted-iron, adult control-iron and adult enriched-iron groups, respectively) for 78 days. Rats aged two months were included as a young control group. Young control group showed higher hemoglobin and hematocrit values, lower levels of iron and lower levels of MDA or carbonyl in the major studied tissues than the adult control group. Restricted-iron diet reduced iron concentrations in skeletal muscle and oxidative damage in the majority of tissues and also increased weight loss. Enriched-iron diet increased hematocrit values, serum iron, gamma-glutamyl transferase, iron concentrations and oxidative stress in the majority of tissues. As expected, young rats showed higher mRNA levels of heart and hepatic L-Ferritin (Ftl) and kidneys SMP30 as well as lower mRNA levels of hepatic Hamp and interleukin-1 beta (Il1b) and also lower levels of liver protein ferritin. Restricted-iron adult rats showed an increase in heart Ftl mRNA and the enriched-iron adult rats showed an increase in liver nuclear factor erythroid derived 2 like 2 (Nfe2l2) and Il1b mRNAs and in gut divalent metal transporter-1 mRNA (Slc11a2) relative to the control adult group. These results suggest that iron supplementation in adult rats may accelerate aging process by increasing oxidative stress while iron restriction may retards it. However, iron restriction may also impair other physiological processes that are not associated with aging. PMID:23593390

  17. Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

    PubMed Central

    Chen, Jiann-Hwa; Kuo, Hsing-Chun; Lee, Kam-Fai; Tsai, Tung-Hu

    2015-01-01

    Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury

  18. Localization of cholesterol in rat cerebellum with imaging TOF-SIMS. Effect of tissue preparation

    NASA Astrophysics Data System (ADS)

    Nygren, Håkan; Börner, Katrin; Malmberg, Per; Hagenhoff, Birgit

    2006-07-01

    Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was utilized to address the issue of cholesterol localization in rat cerebellum, a subject not previously investigated. Rat cerebellum was prepared by three different procedures: (1) fixation in formaldehyde, freeze-protection by sucrose, freezing in liquid nitrogen and sectioning by cryoultramicrotomy and drying at room temperature or (2) freezing in liquid nitrogen, cryostat sectioning at -40 °C and drying at room temperature or (3) high-pressure freezing, freeze-fracturing and freeze-drying. The samples were analyzed in an imaging TOF-SIMS instrument equipped with a Bi 1-7+-source. The cholesterol signal ( m/ z 369 and 385), showed high intensity in the glial cells in white matter and lower intensity in Purkinje cells and in nuclei of granular layer cells. Specimen treated by procedure 1 showed some signs of diffusion of cholesterol in the tissue. Specimen treated by procedure 2 showed freeze-damage of the cells. Specimen treated by procedure 3 showed distinct localization of cholesterol in well preserved tissue. Thus, high-pressure freezing and freeze-fracturing was used for further characterization of the distribution of cholesterol in rat cerebellum.

  19. Markers of protein oxidation by hydroxyl radical and reactive nitrogen species in tissues of aging rats.

    PubMed

    Leeuwenburgh, C; Hansen, P; Shaish, A; Holloszy, J O; Heinecke, J W

    1998-02-01

    Many lines of evidence implicate oxidative damage in aging. Possible pathways include reactions that modify aromatic amino acid residues on proteins. o-Tyrosine is a stable marker for oxidation of protein-bound phenylalanine by hydroxyl radical, whereas 3-nitrotyrosine is a marker for oxidation of protein-bound tyrosine by reactive nitrogen species. To test the hypothesis that proteins damaged by hydroxyl radical and reactive nitrogen accumulate with aging, we used isotope dilution gas chromatography-mass spectrometry to measure levels of o-tyrosine and 3-nitrotyrosine in heart, skeletal muscle, and liver from young adult (9 mo) and old (24 mo) female Long-Evans/Wistar hybrid rats. We also measured these markers in young adult and old rats that received antioxidant supplements (alpha-tocopherol, beta-carotene, butylated hydroxytoluene, and ascorbic acid) from the age of 5 mo. We found that aging did not significantly increase levels of protein-bound o-tyrosine or 3-nitrotyrosine in any of the tissues. Antioxidant supplementation had no effect on the levels of protein-bound o-tyrosine and 3-nitrotyrosine in either young or old animals. These observations indicate that the o-tyrosine and 3-nitrotyrosine do not increase significantly in heart, skeletal muscle, and liver in old rats, suggesting that proteins damaged by hydroxyl radical and reactive nitrogen species do not accumulate in these tissues with advancing age. PMID:9486304

  20. Influence of co-administered danshensu on pharmacokinetic fate and tissue distribution of paeonol in rats.

    PubMed

    Li, Hua; Wang, Siwang; Zhang, Bangle; Xie, Yanhua; Wang, Jianbo; Yang, Qian; Cao, Wei; Hu, Jing; Duan, Linrui

    2012-01-01

    Cortex Moutan (root bark of Paeonia suffruticosa Andrew) and Radix Salviae miltiorrhizae (root and rhizome of Salvia miltiorrhiza Bunge) are two herbs widely used in traditional Chinese medicine (TCM) to treat cerebrovascular and cardiovascular diseases. In clinical practice, these two herbs are prescribed together. Studies on the pharmacokinetic interaction between the active constituents of these two herbs (paeonol and danshensu, respectively) can provide substantial foundation for understanding its mechanism and empirical evidence to support the clinical practice. A simple and sensitive high-performance liquid chromatographic (HPLC) method coupled with ultraviolet detector was developed for determination of paeonol in plasma and different tissues (heart, liver, spleen, lung, kidney, and brain) of male Sprague-Dawley rats. When co-administering danshensu, the peak plasma concentration of paeonol was decreased (p < 0.01), the mean residence time (MRT) was prolonged (p < 0.001), the volume of distribution (Vd/F) was increased (p < 0.001), and the concentrations of paeonol in heart, brain, and lung were dramatically increased (p < 0.01 or p < 0.001), compared with these values for rats administered paeonol alone. The results showed that the co-administration of danshensu could alter pharmacokinetic fate and tissue distribution of paeonol in rats, especially in heart and brain, providing substantial foundation for the investigation of the impact of danshensu on paeonol in clinical applications. PMID:21986818

  1. Epiphany root canal sealer prepared with resinous solvent is irritating to rat subcutaneous tissues

    PubMed Central

    Daleffe, Élcio; Vieira-Ozório, José E.; Sousa-Neto, Manoel D

    2012-01-01

    Objective: This study assessed the biocompatibility of the Epiphany endodontic sealer prepared with resinous solvent of Epiphany system (Thinning resin) in rat subcutaneous tissues. Study Design: Polyethylene tubes were filled with the sealer and 4 groups were established: GI, Epiphany prepared with 1 drop of resinous solvent (RS); GII, Epiphany prepared with 1 drop of RS and photoactivated; GIII, Epiphany associated with self-etch primer and prepared with 1 drop of RS; GIV, Epiphany associated with self-etch primer, prepared with 1 drop of RS and photoactivated. The filled tubes were implanted into 4 different regions of the dorsum of 20 adult male rats. Results: After 7, 14 and 21 days, all groups presented a moderate to severe chronic inflammation, necrosis and foreign-body giant cells. At 42 days, although the intensity of chronic inflammatory reaction decreased, the other features still were observed. Conclusion: The Epiphany sealer prepared with the RS was irritating to rat subcutaneous tissues. Key words:Biocompatibility, Epiphany, methacrylate resin sealer, resinous solvent, root canal sealer. PMID:22322512

  2. Sensitive assay of GTP cyclohydrolase I activity in rat and human tissues using radioimmunoassay of neopterin

    SciTech Connect

    Sawada, M.; Horikoshi, T.; Masada, M.; Akino, M.; Sugimoto, T.; Matsuura, S.; Nagatsu, T.

    1986-04-01

    A highly sensitive and simple assay for the activity of GTP cyclohydrolase I (EC 3.5.4.16) was established using a newly developed radioimmunoassay. D-erythro-7,8-Dihydroneopterin triphosphate formed from GTP by GTP cyclohydrolase I was oxidized by iodine and dephosphorylated by alkaline phosphatase to D-erythro-neopterin, and quantified by a radioimmunoassay for D-erythro-neopterin. This method was highly sensitive and required only 0.2 mg of rat liver tissues for the measurement of the activity. It was reproducible and can be applied for the simultaneous assay of many samples. The activity of GTP cyclohydrolase I was measured in several rat tissues. For example, the enzyme activity in rat striatum (n = 5) was 13.7 +/- 1.5 pmol/mg protein per hour (mean +/- SE), and agreed well with those obtained by high-performance liquid chromatography with fluorescence detection. The activity in the autopsy human brains (caudate nucleus) was measured by this new method for the first time. The activity in the caudate nucleus from parkinsonian patients (n = 6) was 0.82 +/- 0.56 pmol/mg protein per hour which was significantly lower than the control value, 4.22 +/- 0.43 pmol/mg protein per hour (n = 10).

  3. Effect of chronic ethanol consumption on fatty acid profile of heart tissue in rats.

    PubMed

    Gómez-Tubío, A; Carreras, O; Tavares, E; Delgado, M J

    1999-03-01

    The effect of chronic ethanol ingestion on fatty acid composition and lipid content of heart tissue in rats, and whether this effect depends on age, was studied. Rats were maintained on a 30% ethanol solution in drinking water for 3 and 5 months. Control animals were given water. Phospholipid concentration was unchanged in the ethanol-fed groups, compared with control groups, whereas total cholesterol content was increased at 5 months of treatment. An increase in stearic acid, palmitoleic acid, and 22:5n6 were observed at 3 months of ethanol ingestion. When ethanol was administered for 5 months, polyunsaturated fatty acids series n3 were decreased with respect to control. The effect of age on the profile of fatty acids of heart showed an increase of monounsaturated fatty acids and a decrease of long-chain polyunsaturated fatty acids in both control and ethanol-fed rats. The effect of ethanol ingestion on fatty acid composition of heart tissue is not very pronounced, but the small changes observed could contribute to the development of functional and electrophysiological features of alcoholic heart disease. PMID:10195810

  4. Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Xue, Bai; Nie, Jing; Wang, Xi; DuBois, Debra C; Jusko, William J; Almon, Richard R

    2015-01-01

    Development and progression of type 2 diabetes is a complex interaction between genetics and environmental influences. High dietary fat is one environmental factor that is conducive to the development of insulin-resistant diabetes. In the present report, we compare the responses of lean poly-genic, diabetic Goto-Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat diet from weaning to 20 weeks of age. This comparison included a wide array of physiological measurements along with gene expression profiling of abdominal adipose tissue using Affymetrix gene array chips. Animals of both strains fed a high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for this comparison. The microarray analysis revealed that the two strains developed different adaptations to increased dietary fat. WKY rats decrease fatty acid synthesis and lipogenic processes whereas GK rats increase lipid elimination. However, on both diets the major differences between the two strains remained essentially the same. Specifically relative to the WKY strain, the GK strain showed lipoatrophy, chronic inflammation, and insulin resistance. PMID:26309393

  5. Adipose tissue-derived stem cell therapy in rat cryopreserved ovarian grafts.

    PubMed

    Damous, Luciana Lamarão; Nakamuta, Juliana Sanajotti; de Carvalho, Ana Elisa Teófilo Saturi; Soares-Jr, José Maria; de Jesus Simões, Manuel; Krieger, José Eduardo; Baracat, Edmund C

    2015-01-01

    The preliminary results of ovarian transplantation in clinical practice are encouraging. However, the follicular depletion caused by ischemic injury is a main concern and is directly related to short-term graft survival. Cell therapy with adipose tissue-derived stem cells (ASCs) could be an alternative to induce early angiogenesis in the graft. This study aimed to evaluate ASCs therapy in rat cryopreserved ovarian grafts. A single dose of rat ASC (rASCs) or vehicle was injected into the bilateral cryopreserved ovaries of twelve adult female rats immediately after an autologous transplant. Daily vaginal smears were performed for estrous cycle evaluation until euthanasia on postoperative day 30. Follicle viability, graft morphology and apoptosis were assessed. No differences were found with respect to estrous cycle resumption and follicle viability (P>0.05). However, compared with the vehicle-treated grafts, the morphology of the ASCs-treated grafts was impaired, with diffuse atrophy and increased apoptosis (P<0.05). ASCs direct injected in the stroma of rat cryopreserved ovarian grafts impaired its morphology although may not interfere with the functional resumption on short-term. Further investigations are necessary to evaluated whether it could compromise their viability in the long-term. PMID:25889829

  6. Tissue inhibitor of metalloproteinase-1 and -2 RNA expression in rat and human liver fibrosis.

    PubMed Central

    Herbst, H.; Wege, T.; Milani, S.; Pellegrini, G.; Orzechowski, H. D.; Bechstein, W. O.; Neuhaus, P.; Gressner, A. M.; Schuppan, D.

    1997-01-01

    The remodeling of extracellular matrix during chronic liver disease may partially be attributed to altered activity of matrix metalloproteinases and their tissue inhibitors (TIMPs). Expression of TIMP-1 and -2 was studied by in situ hybridization combined with immunohistochemistry in rat (acute and chronic carbon tetrachloride intoxication and secondary biliary fibrosis) and human livers and on isolated rat hepatic stellate cells. TIMP-1 and -2 transcripts appeared in rat livers within 1 to 3 hours after intoxication, pointing to a role in the protection against accidental activation of matrix metalloproteinases, and were present at high levels in all fibrotic rat and human livers predominantly in stellate cells. TIMP-2 RNA distribution largely matched with previously reported patterns of matrix metalloproteinase-2 (72-kd gelatinase) expression, suggesting generation of a TIMP-2/matrix metalloproteinase-2 complex (large inhibitor of metalloproteinases). Isolated stellate cells expressed TIMP-1 and -2 RNA. Addition of transforming growth factor-beta 1 enhanced TIMP-1 and matrix metalloproteinase-2 RNA levels in vitro, whereas TIMP-2-specific signals were reduced, likely to result in a stoichiometric excess of matrix-metalloproteinase-2 over TIMP-2. In the context of previous demonstrations of transforming growth factor-beta 1 and matrix metalloproteinase-2 in vivo, these patterns suggest an intrahepatic environment permitting only limited matrix degradation, ultimately resulting in redistribution of extracellular matrix with relative accumulation of collagen type 1. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:9137090

  7. Monitoring the process of tissue healing of rat skin in vivo after laser irradiation based on optical coherence tomography

    NASA Astrophysics Data System (ADS)

    He, Youwu; Wu, Shulian; Li, Zhifang; Cai, Shoudong; Li, Hui

    2010-11-01

    It is imperative to evaluate the tissue wound healing response after laser irradiation so as to develop effective devices for this clinical indication, and evaluate the thermal damage degree to take appropriate treatment. In our research, we prepare 6 white rat (approximately 2 months old, weight :28+/-2g). Each rat was injected intraperitoneally a single dose of 2% pentobarbital sodium. After the rat was anesthetized, the two side of the rats' back were denuded and antisepsised a standardized. An Er:YAG laser (2940nm, 2.5J/cm2, single spot, 4 times) was irradiated on rat skin in vivo, and the skin which before irradiated and the process of renovating scathe that irradiated after Er:YAG laser were observed by an Optical coherence tomography (OCT). The tissue recovery is about a twelve -day period. The results indicate that the scattering coefficient of post- tissue has changed distinctly. The and flexibility fiber is the chief component of rat dermis and the collagen is the main scattering material. The normal tissue has a large scattering coefficient, after laser irradiated, the collagen became concreting and putrescence and caused the structure change. It became more uniform density distribution, which results in a reduced scattering coefficient. In a word, OCT can noninvasively monitor changes in collagen structure and the recover process in thermal damage through monitor the tissue scattering coefficient.

  8. Effect of quercetin against lindane induced alterations in the serum and hepatic tissue lipids in wistar rats

    PubMed Central

    Padma, Viswanadha Vijaya; Lalitha, Gurusamy; Shirony, Nicholson Puthanveedu; Baskaran, Rathinasamy

    2012-01-01

    Objective To assess the effect of quercetin (flavonoid) against lindane induced alterations in lipid profile of wistar rats. Methods Rats were administered orally with lindane (100 mg/kg body weight) and quercetin (10 mg/kg body weight) for 30 days. After the end of treatment period lipid profile was estimated in serum and tissue. Results Elevated levels of serum cholesterol, triglycerides, low density lipoprotein (LDL), very Low Density Lipoprotein (VLDL) and tissue triglycerides, cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats. Conclusions Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids. The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane. PMID:23569870

  9. Novel alternative splice variants of rat phosphodiesterase 7B showing unique tissue-specific expression and phosphorylation.

    PubMed Central

    Sasaki, Takashi; Kotera, Jun; Omori, Kenji

    2002-01-01

    cDNA species coding for novel variants of cyclic-AMP-specific phosphodiesterases (PDEs), namely the PDE7B family, were isolated from rats and characterized. Rat PDE7B1 (RNPDE7B1) was composed of 446 amino acid residues. Rat PDE7B2 (RNPDE7B2) and PDE7B3 (RNPDE7B3), which possessed unique N-terminal sequences, consisted of 359 and 459 residues respectively. Northern hybridization analysis showed that rat PDE7B transcripts were particularly abundant in the striatum and testis. PCR analyses revealed that rat PDE7B2 transcripts were restricted to the testis and that low levels of PDE7B3 transcripts were expressed in the heart, lung and skeletal muscle. In situ hybridization analysis demonstrated that rat PDE7B transcripts were expressed in striatal neurons and spermatocytes. In spermatocytes, rat PDE7B transcripts were expressed in a stage-specific manner during spermatogenesis. The K(m) values of recombinant rat PDE7B1, PDE7B2 and PDE7B3 for cAMP were 0.05, 0.07 and 0.05 microM respectively. Each rat PDE7B variant was the most sensitive to 3-isobutyl-1-methylxanthine (IC(50) 1.5-2.1 microM). Two phosphorylation sites for cAMP-dependent protein kinase (PKA) were found in rat PDE7B1 and PDE7B3, whereas rat PDE7B2 possessed one site. PKA-dependent phosphorylation was observed in C-terminal phosphorylation sites of three rat PDE7B variants, in addition to unique N-terminal regions of rat PDE7B1 and PDE7B3. Unique tissue distribution and PKA-dependent phosphorylation of PDE7B variants suggested that each variant has a specific role for cellular functions via cAMP signalling in various tissues. PMID:11772393

  10. Comparison of tissue metal concentrations in Zucker lean, Zucker obese, and Zucker diabetic fatty rats and the effects of chromium supplementation on tissue metal concentrations.

    PubMed

    Staniek, Halina; Rhodes, Nicholas R; Di Bona, Kristin R; Deng, Ge; Love, Sharifa T; Pledger, Leigh Ann; Blount, Jeremy; Gomberg, Emmalea; Grappe, Frances; Cernosek, Chelsea; Peoples, Brittany; Rasco, Jane F; Krejpcio, Zbigniew; Vincent, John B

    2013-03-01

    Diabetes results in several metabolic changes, including alterations in the transport, distribution, excretion, and accumulation of metals. While changes have been examined in several rat models of insulin resistance and diabetes, the metal ion concentrations in the tissues of Zucker lean, Zucker obese (an insulin resistance and early stage diabetes model), and Zucker diabetic fatty (ZDF, a type 2 diabetes model) have not previously been examined in detail. The concentration of Cu, Zn, Fe, Mg, and Ca were examined in the liver, kidney, heart and spleen, and Cr concentration in the liver and kidney of these rats were examined. Zucker obese rats have a reduction in the concentration of Cu, Zn, Fe, Mg in the liver compared to ZDF and/or lean Zucker rats, presumably as a result of the increased fat content of the liver of the obese rats. ZDF rats have increased concentrations of kidney Cu compared to the lean rats, while kidney Ca concentrations are increased in the Zucker obese rats. Spleen Fe concentrations are decreased in Zucker obese rats compared to the lean rats. No effects on metal concentrations in the heart were observed between the lean, obese, and ZDF rats, and no effects on Cr concentrations were identified. Cr(III) complexes have previously been shown to have beneficial effects on the signs of insulin resistance in Zucker obese and ZDF rats. The effects of daily gavage administration of chromium picolinate ([Cr(pic)(3)]) (1 mg Cr/kg body mass), CrCl(3) (1 mg Cr/kg body mass), and Cr3 ([Cr(3)O(propionate)(6)(H(2)O)(3)](+)) (33 μg and 1 mg Cr/kg body mass) on metal concentrations in these tissues were examined. Treatment with CrCl(3) and Cr3, but not [Cr(pic)(3)], at 1 mg Cr/kg resulted in a statistically significant accumulation of Cr in the kidney of lean and obese but not ZDF rats but resulted in lowering the elevated levels of kidney Cu in ZDF rats, suggesting a beneficial effect on this symptom of type 2 diabetes. PMID:23250541

  11. Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth)

    PubMed Central

    Fossey, Stacey; Vahle, John; Long, Philip; Schelling, Scott; Ernst, Heinrich; Boyce, Rogely Waite; Jolette, Jacquelin; Bolon, Brad; Bendele, Alison; Rinke, Matthias; Healy, Laura; High, Wanda; Roth, Daniel Robert; Boyle, Michael; Leininger, Joel

    2016-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the skeletal tissues and teeth of laboratory rats and mice, with color photomicrographs illustrating examples of many common lesions. The standardized nomenclature presented in this document is also available on the internet (http://www.goreni.org/). Sources of material were databases from government, academic and industrial laboratories throughout the world. PMID:27621538

  12. Nonproliferative and Proliferative Lesions of the Rat and Mouse Skeletal Tissues (Bones, Joints, and Teeth).

    PubMed

    Fossey, Stacey; Vahle, John; Long, Philip; Schelling, Scott; Ernst, Heinrich; Boyce, Rogely Waite; Jolette, Jacquelin; Bolon, Brad; Bendele, Alison; Rinke, Matthias; Healy, Laura; High, Wanda; Roth, Daniel Robert; Boyle, Michael; Leininger, Joel

    2016-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Project (www.toxpath.org/inhand.asp) is an initiative of the Societies of Toxicological Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP) and North America (STP) to develop an internationally accepted nomenclature for proliferative and nonproliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature for classifying microscopic lesions observed in the skeletal tissues and teeth of laboratory rats and mice, with color photomicrographs illustrating examples of many common lesions. The standardized nomenclature presented in this document is also available on the internet (http://www.goreni.org/). Sources of material were databases from government, academic and industrial laboratories throughout the world. PMID:27621538

  13. Destruction of Tissue, Cells and Organelles in Type 1 Diabetic Rats Presented at Macromolecular Resolution

    PubMed Central

    Ravelli, Raimond B. G.; Kalicharan, Ruby D.; Avramut, M. Cristina; Sjollema, Klaas A.; Pronk, Joachim W.; Dijk, Freark; Koster, Abraham J.; Visser, Jeroen T. J.; Faas, Frank G. A.; Giepmans, Ben N. G.

    2013-01-01

    Finding alternatives for insulin therapy and making advances in etiology of type 1 diabetes benefits from a full structural and functional insight into Islets of Langerhans. Electron microscopy (EM) can visualize Islet morphology at the highest possible resolution, however, conventional EM only provides biased snapshots and lacks context. We developed and employed large scale EM and compiled a resource of complete cross sections of rat Islets during immuno-destruction to provide unbiased structural insight of thousands of cells at macromolecular resolution. The resource includes six datasets, totalling 25.000 micrographs, annotated for cellular and ultrastructural changes during autoimmune diabetes. Granulocytes are attracted to the endocrine tissue, followed by extravasation of a pleiotrophy of leukocytes. Subcellullar changes in beta cells include endoplasmic reticulum stress, insulin degranulation and glycogen accumulation. Rare findings include erythrocyte extravasation and nuclear actin-like fibers. While we focus on a rat model of autoimmune diabetes, our approach is general applicable. PMID:23652855

  14. An opioid system in connective tissue: a study of achilles tendon in the rat.

    PubMed

    Ackermann, P W; Spetea, M; Nylander, I; Ploj, K; Ahmed, M; Kreicbergs, A

    2001-11-01

    The occurrence of endogenous opioids and their receptors in rat achilles tendon was analyzed by immunohistochemistry (IHC), radioimmunoassay (RIA), and in vitro binding assays. The investigation focused on four enkephalins, dynorphin B, and nociceptin/orphanin FQ. Nerve fibers immunoreactive to all enkephalins (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Gly-Lys, Met-enkephalin-Arg-Phe) were consistently found in the loose connective tissue and the paratenon, whereas dynorphin B and nociceptin/orphanin FQ could not be detected. The majority of enkephalin-positive nerve fibers exhibited varicosities predominantly seen in blood vessel walls. Measurable levels of Met-enkephalin-Arg-Phe and nociceptin/orphanin FQ were found in tendon tissue using RIA, whereas dynorphin B could not be detected. In addition to the endogenous opioids identified, delta-opioid receptors on nerve fibers were also detected by IHC. Binding assays to characterize the opioid binding sites showed that they were specific and saturable for [3H]-naloxone (Kd 7.01 +/- 0.98 nM; Bmax 23.52 +/- 2.23 fmol/mg protein). Our study demonstrates the occurrence of an opioid system in rat achilles tendon, which may be assumed to be present also in other connective tissues of the locomotor apparatus. This system may prove to be a useful target for pharmacological therapy in painful and inflammatory conditions by new drugs acting selectively in the periphery. PMID:11668192

  15. [Characteristics of brain tissue damage in kaolin-induced infantile rat hydrocephalus].

    PubMed

    Okuyama, T; Hashi, K; Okada, T; Sasaki, S

    1986-01-01

    Experimental hydrocephalus was induced by an intracisternal injection of 4% or 40% kaolin suspension in 2 days old Wistar rats. They were examined histologically and microangiographically 2 weeks after the injection of kaolin. Hydrocephalic rats were classified into 2 groups, severe hydrocephalic group A and mild hydrocephalic group B. In group A, a marked enlargement of the entire ventricular system with a thinning of the cerebral mantle was observed. On the other hand, the dilatation of the fourth ventricle was more pronounced compared with the other ventricles in group B. In group A, a spongy appearance of brain tissue was observed in the periventricular white matter accompanied with an intracerebral cavity. In these edematous areas, the lack of carbon black perfusion was apparent indicating an occurrence of microcirculatory disturbances. These microcirculatory disturbances and mechanical compression to the cerebral parenchyma may produce defective brain tissue (intracerebral cavity formation). The ependymal cell walls and subependymal glial cell layers were well preserved in spite of the damaged periventricular white matter. In group A, kaolin was present in the fourth ventricle and Sylvian aqueduct. Subependymal gliosis containing macrophages and newly produced blood vessels were observed in the region between the periventricular brain tissue and kaolin granules. These findings indicate that kaolin may produce changes in the ependymal cell and cerebral parenchyma as well as fibrosis and meningitis in the subarachnoid space. PMID:3964487

  16. Tissue distribution of residual antimony in rats treated with multiple doses of meglumine antimoniate

    PubMed Central

    Coelho, Deise Riba; Miranda, Elaine Silva; Saint’Pierre, Tatiana Dillenburg; Paumgartten, Francisco José Roma

    2014-01-01

    Meglumine antimoniate (MA) and sodium stibogluconate are pentavalent antimony (SbV) drugs used since the mid-1940s. Notwithstanding the fact that they are first-choice drugs for the treatment of leishmaniases, there are gaps in our knowledge of their toxicological profile, mode of action and kinetics. Little is known about the distribution of antimony in tissues after SbV administration. In this study, we evaluated the Sb content of tissues from male rats 24 h and three weeks after a 21-day course of treatment with MA (300 mg SbV/kg body wt/d, subcutaneous). Sb concentrations in the blood and organs were determined by inductively coupled plasma-mass spectrometry. In rats, as with in humans, the Sb blood levels after MA dosing can be described by a two-compartment model with a fast (t1/2 = 0.6 h) and a slow (t1/2 >> 24 h) elimination phase. The spleen was the organ that accumulated the highest amount of Sb, while bone and thyroid ranked second in descending order of tissues according to Sb levels (spleen >> bone, thyroid, kidneys > liver, epididymis, lungs, adrenals > prostate > thymus, pancreas, heart, small intestines > skeletal muscle, testes, stomach > brain). The pathophysiological consequences of Sb accumulation in the thyroid and Sb speciation in the liver, thyroid, spleen and bone warrant further studies. PMID:25075781

  17. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder.

    PubMed

    Kim, Aram; Yu, Hwan Yeul; Heo, Jinbeom; Song, Miho; Shin, Jung-Hyun; Lim, Jisun; Yoon, Soo-Jung; Kim, YongHwan; Lee, Seungun; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 10(6)) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy. PMID:27481042

  18. Age-related changes of dental pulp tissue after experimental tooth movement in rats.

    PubMed

    Von Böhl, Martina; Ren, Yijin; Kuijpers-Jagtman, Anne M; Fudalej, Piotr S; Maltha, Jaap C

    2016-01-01

    It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals. PMID:26855867

  19. Age-related changes of dental pulp tissue after experimental tooth movement in rats

    PubMed Central

    Von Böhl, Martina; Ren, Yijin; Kuijpers-Jagtman, Anne M.; Maltha, Jaap C.

    2016-01-01

    It is generally accepted that the effect of orthodontic tooth movement on the dental pulp in adolescents is reversible and that it has no long-lasting effect on pulpal physiology. However, it is not clear yet if the same conclusion is also valid for adult subjects. Thus, in two groups of rats, aged 6 and 40 weeks respectively, 3 molars at one side of the maxilla were moved together in a mesial direction with a standardized orthodontic appliance delivering a force of 10 cN. The contralateral side served as a control. Parasagittal histological sections were prepared after tooth movement for 1, 2, 4, 8, and 12 weeks. The pulp tissue was characterized for the different groups, with special emphasis on cell density, inflammatory cells, vascularity, and odontoblasts. Dimensions of dentin and the pulpal horns was determined and related with the duration of orthodontic force application and age ware evaluated. We found that neither in young nor in adult rats, force application led to long-lasting or irreversible changes in pulpal tissues. Dimensional variables showed significant age-related changes. In conclusion, orthodontic tooth movement per se has no long-lasting or irreversible effect on pulpal tissues, neither in the young nor in the adult animals. PMID:26855867

  20. Mesenchymal stem cells protect against the tissue fibrosis of ketamine-induced cystitis in rat bladder

    PubMed Central

    Kim, Aram; Yu, Hwan Yeul; Heo, Jinbeom; Song, Miho; Shin, Jung-Hyun; Lim, Jisun; Yoon, Soo-Jung; Kim, YongHwan; Lee, Seungun; Kim, Seong Who; Oh, Wonil; Choi, Soo Jin; Shin, Dong-Myung; Choo, Myung-Soo

    2016-01-01

    Abuse of the hallucinogenic drug ketamine promotes the development of lower urinary tract symptoms that resemble interstitial cystitis. The pathophysiology of ketamine-induced cystitis (KC) is largely unknown and effective therapies are lacking. Here, using a KC rat model, we show the therapeutic effects of human umbilical cord-blood (UCB)-derived mesenchymal stem cells (MSCs). Daily injection of ketamine to Sprague-Dawley rats for 2-weeks resulted in defective bladder function, indicated by irregular voiding frequency, increased maximum contraction pressure, and decreased intercontraction intervals and bladder capacity. KC bladders were characterized by severe mast-cell infiltration, tissue fibrosis, apoptosis, upregulation of transforming growth factor-β signaling related genes, and phosphorylation of Smad2 and Smad3 proteins. A single administration of MSCs (1 × 106) into bladder tissue not only significantly ameliorated the aforementioned bladder voiding parameters, but also reversed the characteristic histological and gene-expression alterations of KC bladder. Treatment with the antifibrotic compound N-acetylcysteine also alleviated the symptoms and pathological characteristics of KC bladder, indicating that the antifibrotic capacity of MSC therapy underlies its benefits. Thus, this study for the first-time shows that MSC therapy might help to cure KC by protecting against tissue fibrosis in a KC animal model and provides a foundation for clinical trials of MSC therapy. PMID:27481042

  1. Effects of isomers of apomorphines on dopamine receptors in striatal and limbic tissue of rat brain

    SciTech Connect

    Kula, N.S.; Baldessarini, R.J.; Bromley, S.; Neumeyer, J.L.

    1985-09-16

    The optical isomers of apomorphine (APO) and N-propylnorapomorphine (NPA) were interacted with three biochemical indices of dopamine (Da) receptors in extrapyramidal and limbic preparations of rat brain tissues. There were consistent isomeric preferences for the R(-) configuration of both DA analogs in stimulation adenylate cyclase (D-1 sites) and in competing for high affinity binding of /sup 3/H-spiroperidol (D-2 sites) and of /sup 3/H-ADTN (DA agonist binding sites) in striatal tissue, with lesser isomeric differences in the limbic tissue. The S(+) apomorphines did not inhibit stimulation of adenylate cyclase by DA. The tendency for greater activity of higher apparent affinity of R(-) apomorphines in striatum may reflect the evidently greater abundance of receptor sites in that region. There were only small regional differences in interactions of the apomorphine isomers with all three receptor sites, except for a strong preference of (-)NPA for striatal D-2 sites. These results do not parallel our recent observations indicating potent and selective antidopaminergic actions of S(+) apomorphines in the rat limbic system. They suggest caution in assuming close parallels between current biochemical functional, especially behavioral, methods of evaluating dopamine receptors of mammalian brain.

  2. Gingival tissue healing following Er:YAG laser ablation compared to electrosurgery in rats.

    PubMed

    Sawabe, Masanori; Aoki, Akira; Komaki, Motohiro; Iwasaki, Kengo; Ogita, Mayumi; Izumi, Yuichi

    2015-02-01

    The erbium-doped yttrium aluminum garnet (Er:YAG) laser is currently used for periodontal soft tissue management with favorable outcomes. However, the process of wound healing after Er:YAG laser (ErL) treatment has not been fully elucidated yet. The aim of this study was to investigate the gingival tissue healing after ErL ablation in comparison with that after electrosurgery (ElS). Gingival defects were created in 28 rats by ablation with ErL irradiation or ElS. The chronological changes in wound healing were evaluated using histological, histometrical, and immunohistochemical analyses. The ErL-ablated gingival tissue revealed much less thermal damage, compared to the ElS. In the ElS sites, the postoperative tissue destruction continued due to thermal damage, while in the ErL sites, tissue degradation was limited and the defects were re-epithelialized early. Heat shock protein (Hsp) 72/73 expression was detected abundantly remote from the wound in the ElS, whereas it was slightly observed in close proximity to the wound in the ErL sites. Hsp47 expression was observed in the entire connective tissue early in the wound healing and was found limited in the wound area later. This phenomenon proceeded faster in the ErL sites than in the ElS sites. Expression of proliferating cell nuclear antigen (PCNA) persisted in the epithelial tissue for a longer period in the ElS than that in the ErL. The ErL results in faster and more favorable gingival wound healing compared to the ElS, suggesting that the ErL is a safe and suitable tool for periodontal soft tissue management. PMID:24241972

  3. Renal handling of cadmium in perfused rat kidney and effects on renal function and tissue composition.

    PubMed

    Diamond, G L; Cohen, J J; Weinstein, S L

    1986-11-01

    Isolated rat kidneys perfused with a Krebs-Ringer bicarbonate (KRB) solution containing 1 microM CdCl2 plus 6% substrate-free albumin (SFA) and a mixture of substrates accumulated substantially less cadmium in tissue than kidneys perfused with 1 microM CdCl2 in a protein-free KRB solution containing the same substrates: 11 vs. 205 nmol Cd/g dry wt. Decreasing the glomerular filtration rate (GFR) by occluding the ureters of kidneys perfused in the absence of albumin did not change the rate of net tissue uptake of cadmium (Cd), suggesting that the kidney can extract Cd from the peritubular capillary fluid and that net uptake of Cd is not dependent on the reabsorption of filtered Cd. The tissue accumulation of large quantities of Cd (1.8 mumol Cd/g dry wt), which established levels of non-metallothionein-bound Cd exceeding 1 mumol Cd/g dry wt, caused no changes in either GFR, perfusion flow rate, fractional reabsorption of Na+, fractional reabsorption of K+, fractional reabsorption of glucose, or free-water clearance. However, discrete changes in renal tissue K+ content were observed. Exposure to 1 microM CdCl2 resulted in a net loss of renal tissue K+ in rat kidneys perfused with substrate-enriched KRB containing 6% albumin. Exposure to 0.8 microM or 7 microM CdCl2 completely prevented K+ loss from kidneys perfused with a substrate-enriched, protein-free KRB solution. PMID:3777178

  4. Tissue distribution of sup 3 H-nicotine in rats after bolus or constant injection

    SciTech Connect

    Chowdhury, P.; Pasley, J.N.; Rayford, P.L. )

    1989-01-01

    Two groups of rats, (N = 7), were fasted for 24 hrs prior to the study. On the day of the experiment, the animals were anesthetized and infused with either 5 ml nicotine solution (200 {mu}g/L) in saline containing 5 {mu}c {sup 3}H-nicotine, (sp. activity 50-80 mCi/mol) for 90 minutes or injected as a bolus with 0.5 ml of the same nicotine (200 {mu}g/L) solution. The animals were sacrificed 60 minutes after the injection or after the infusion was stopped. Blood and tissue samples were counted by liquid scintillation counting. Percent distribution of {sup 3}H-nicotine per gm of tissue was calculated from the total radioactivity recovered in individual tissues over the total activity injected into the rat and the values were compared using student's t test. Results: Distribution of {sup 3}H-nicotine was found highest in kidney (45-49%) among all tissues examined and was not different between routes of administration. Significantly higher retention of {sup 3}H-nicotine was found with continuous infusion in esophagus, fundus, antrum, spleen, cecum, pancreas, testes, heart and muscle when {sup 3}H-nicotine retentions were compared with bolus injection. In contrast, the distribution of {sup 3}H-nicotine in adrenal gland, was significantly lower in continuous infusion group. Distribution in blood was 6 fold higher in continuous infusion (7.26%) compared to bolus (1.11%) injection. The distribution {sup 3}H-nicotine in other tissues were not different by either routes of injection.

  5. Identification of some volatile endogenous constituents in rat brain tissue and the effects of lithium carbonate and chloral hydrate.

    PubMed

    Politzer, I R; McDonald, L K; Laseter, J L

    1976-11-01

    Nine endogenous volatile compounds were found in rat brain tissue, and were identified by mass spectrometry as chloroform, a 5-C-aldehyde, dimethyl disulphide, 2,5-dimethyl tetrahydrofuran, a 8-C-alkane, xylene, 2-heptanone, heptaldehyde and 2-n-pentylfuran. Using gas chromatographic and gas chromatographic mass spectrometric techniques, it was established that lithium carbonate did not induce the production of detectable amounts of any new volatile compounds in brain tissue. However, after administration of chloral hydrate, trichloroethanol, a compound not normally present in rat brain tissue, was found to be present. PMID:996360

  6. Tolerance to low temperatures of domestic and sylvatic Trichinella spp. in rat muscle tissue.

    PubMed

    Malakauskas, Alvydas; Kapel, Christian M O

    2003-08-01

    The present study was designed to investigate the tolerance to low temperatures of 9 Trichinella isolates in rat muscle tissue. Nine groups of 24 rats were infected with encapsulated Trichinella spiralis, Trichinella nativa, Trichinella britovi, Trichinella murrelli, Trichinella T6, Trichinella nelsoni, and 3 nonencapsulated Trichinella pseudospiralis strains. Six rats from each of the groups were necropsied at 5, 10, 20, and 40 wk postinfection (wpi). Muscle tissues containing Trichinella larvae were exposed to temperatures of -18, -5, and 5 C for 1 or 4 wk, and afterward the reproductive capacity index (RCI) in mice was determined for the 9 individual Trichinella isolates. Only T. nativa muscle larvae were infective after freezing at a temperature of -18 C. At 5 wpi all encapsulated isolates, except for the tropical species T. nelsoni, remained infective after exposure to a temperature of -5 C for both 1 and 4 wk, whereas nonencapsulated T. pseudospiralis survived only 1 wk of exposure. All Trichinella spp. remained infective after exposure to a temperature of 5 C. Muscle larvae for all investigated species remained infective as long as they persisted in live rats during the experiment. Analysis of variance showed a significant effect of age on the temperature tolerance of encapsulated T. spiralis and nonencapsulated T. pseudospiralis. In addition, significant interaction between age of muscle larvae and length of exposure was found. In general Trichinella muscle larvae of medium age (10 and 20 wpi) tolerated freezing better than early and late stages of infection (5 and 40 wpi). This is the first study to demonstrate such a relationship between age of infection and temperature tolerance of Trichinella spp. muscle larvae. PMID:14533685

  7. The cytotoxic evaluation of mineral trioxide aggregate and bioaggregate in the subcutaneous connective tissue of rats

    PubMed Central

    Acar, Gözde; Yalcin, Yagmur; Dindar, Seckin; Sancakli, Hande; Erdemir, Ugur

    2013-01-01

    Objectives: The purpose of this study was to evaluate and compare the cytotoxic effects of ProRoot MTA and DiaRoot BA, a bioceramic nanoparticulate cement, on subcutaneous rat tissue. Study Design: Fifty Sprouge Dawley rats were used in this study. Polyethylene tubes filled with ProRoot MTA and DiaRoot BioAggregate, along with a control group of empty, were implanted into dorsal connective tissue of rats for 7, 15, 30, 60, and 90 days. After estimated time intervals the rats were sacrificed. The specimens were fixed, stained with hematoxylin and eosin, and then evaluated under a light microscope for inflammatory reactions and mineralization. Results: All groups evoked a severe to moderate chronic inflammatory reaction at 7 and 15 days, which decreased with time. Both the MTA and BioAggregate groups showed similar inflammatory reactions, except at 90 days when MTA showed statistically significant greater inflammation (p>0.05). The MTA group showed foreign body reaction at all times. Compared to BioAggregate, MTA showed significantly more foreign body reaction at 60 and 90 days (p<0.0001). After 30 days foreign body reaction of BioAggregate decreased significantly. Both MTA and BioAggregate groups showed similar necrosis at 7 and 15 days (p=0.094 and p=0.186 respectively). No necrosis was observed after 15 days. Similarly there was no fibrosis after 30 days for both MTA and BioAggregate groups (p>0.05). Conclusions: Since DiaRoot BioAggregate showed significantly better results than MTA, we can conclude that it is more biocompatible. However, further studies are required to confirm this result. Key words:Biocompatibility, mineral trioxide aggregate, bioAggregate. PMID:23722144

  8. Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

    NASA Astrophysics Data System (ADS)

    Sato, Yoshinori; Yokoyama, Atsuro; Nodasaka, Yoshinobu; Kohgo, Takao; Motomiya, Kenichi; Matsumoto, Hiroaki; Nakazawa, Eiko; Numata, Tomoko; Zhang, Minfang; Yudasaka, Masako; Hara, Hideyuki; Araki, Rikita; Tsukamoto, Osamu; Saito, Hiroaki; Kamino, Takeo; Watari, Fumio; Tohji, Kazuyuki

    2013-08-01

    Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials.

  9. Self-organization of rat cardiac cells into contractile 3-D cardiac tissue.

    PubMed

    Baar, Keith; Birla, Ravi; Boluyt, Marvin O; Borschel, Gregory H; Arruda, Ellen M; Dennis, Robert G

    2005-02-01

    The mammalian heart is not known to regenerate following injury. Therefore, there is great interest in developing viable tissue-based models for cardiac assist. Recent years have brought numerous advances in the development of scaffold-based models of cardiac tissue, but a self-organizing model has yet to be described. Here, we report the development of an in vitro cardiac tissue without scaffolding materials in the contractile region. Using an optimal concentration of the adhesion molecule laminin, a confluent layer of neonatal rat cardiomyogenic cells can be induced to self-organize into a cylindrical construct, resembling a papillary muscle, which we have termed a cardioid. Like endogenous heart tissue, cardioids contract spontaneously and can be electrically paced between 1 and 5 Hz indefinitely without fatigue. These engineered cardiac tissues also show an increased rate of spontaneous contraction (chronotropy), increased rate of relaxation (lusitropy), and increased force production (inotropy) in response to epinephrine. Cardioids have a developmental protein phenotype that expresses both alpha- and beta-tropomyosin, very low levels of SERCA2a, and very little of the mature isoform of cardiac troponin T. PMID:15574489

  10. The Neuroprotective Effect of Cornus mas on Brain Tissue of Wistar Rats

    PubMed Central

    Francik, Renata; Kryczyk, Jadwiga; Krośniak, Mirosław; Berköz, Mehmet; Sanocka, Ilona; Francik, Sławomir

    2014-01-01

    Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. Flavonoid derivatives as nonenzymatic antioxidants are important in the pathophysiology of many diseases including neurological disorders (e.g., Alzheimer's disease) or heart disease. In this study, we examined the effect of an addition of freeze-dried fruit of cornelian cherry on three types of diets: control diet, fructose diet, and diet enriched in fats (high-fat diet). This effect was studied by determining the following antioxidant parameters in both brain tissue and plasma in rats: catalase, ferric reducing ability of plasma, paraoxonase, protein carbonyl groups, and free thiol groups. Results indicate that both fructose diet and high-fat diet affect the antioxidant capacity of the organism. Furthermore, an addition of cornelian cherry resulted in increased activity of catalase in brain tissue, while in plasma it caused the opposite effect. In turn, with regard to paraoxonase activity in both brain tissue and plasma, it had a stimulating effect. Adding cornelian cherry to the tested diets increased the activity of PON in both tested tissues. Moreover, protective effect of fruits of this plant was observed in the process of oxidation of proteins by decreasing levels of protein carbonyl groups and thiol groups in brain tissue as well as in plasma. PMID:25401157

  11. Adipose tissue depot specific differences of PLIN protein content in endurance trained rats.

    PubMed

    Ramos, Sofhia V; Turnbull, Patrick C; MacPherson, Rebecca E K

    2016-01-01

    Adipose tissue is classified as either white (WAT) or brown (BAT) and differs not only by anatomical location but also in function. WAT is the main source of stored energy and releases fatty acids in times of energy demand, whereas BAT plays a role in regulating non-shivering thermogenesis and oxidizes fatty acids released from the lipid droplet. The PLIN family of proteins has recently emerged as being integral in the regulation of fatty acid storage and release in adipose tissue. Previous work has demonstrated that PLIN protein content varies among adipose tissue depots, however an examination of endurance training-induced depot specific changes in PLIN protein expression has yet to be done. Male Sprague-dawley rats (n = 10) underwent 8-weeks of progressive treadmill training (18-25 m/min for 30-60 min at 10% incline) or remained sedentary as control. Following training, under isoflurane induced anesthesia epidydmal (eWAT), inguinal subcutaneous (iWAT) and intrascapular brown adipose tissue (BAT) was excised, and plasma was collected. Endurance training resulted in an increase in BAT PLIN5 and iWAT PLIN3 content, while there was no difference in PLIN protein content in endurance trained eWAT. Interestingly, endurance training resulted in a robust increase in ATGL and CGI-58 in eWAT alone. Together these results suggest the potential of a depot specific function of PLIN3 and PLIN5 in adipose tissue in response to endurance training. PMID:27386161

  12. Quantitative Tissue Oxygen Measurement in Multiple Organs Using 19F MRI in a Rat Model

    PubMed Central

    Liu, Siyuan; Shah, Sameer J.; Wilmes, Lisa J.; Feiner, John; Kodibagkar, Vikram D.; Wendland, Michael F.; Mason, Ralph P.; Hylton, Nola; Hopf, Harriet W.; Rollins, Mark D.

    2011-01-01

    Measurement of individual organ tissue oxygen levels can provide information to help evaluate and optimize medical interventions in many areas including wound healing, resuscitation strategies, and cancer therapeutics. Echo planar 19F MRI has previously focused on tumor oxygen measurement at low oxygen levels (pO2) < 30 mmHg. It uses the linear relationship between spin-lattice relaxation rate (R1) of hexafluorobenzene (HFB) and pO2. The feasibility of this technique for a wider range of pO2 values and individual organ tissue pO2 measurement was investigated in a rat model. Spin-lattice relaxation times (T1=1/R1) of HFB were measured using 19F saturation recovery echo planar imaging (EPI). Initial in vitro studies validated the linear relationship between R1 and pO2 from 0 mmHg to 760 mmHg oxygen partial pressure at 25°C, 37°C, and 41°C at 7 Tesla for HFB. In vivo experiments measured rat tissue oxygen (ptO2) levels of brain, kidney, liver, gut, muscle and skin during inhalation of both 30% and 100% oxygen. All organ ptO2 values significantly increased with hyperoxia (p<0.001). This study demonstrates that 19F MRI of HFB offers a feasible tool to measure regional ptO2 in vivo, and that hyperoxia significantly increases ptO2 of multiple organs in a rat model. PMID:21688315

  13. Do adipose tissue-derived mesenchymal stem cells ameliorate Parkinson's disease in rat model?

    PubMed

    Ahmed, Hh; Salem, Am; Atta, Hm; Ghazy, Ma; Aglan, Ha

    2014-12-01

    Parkinson's disease (PD) is a common neurodegenerative disorder in middle-aged and elderly people. This study aimed to elucidate the role of mesenchymal stem cells (MSCs) in management of PD in ovariectomized rat model. MSCs were excised from adipose tissue of both the omentum and the inguinal fat pad of male rats, grown, and propagated in culture; then characterized morphologically; and by the detection of surface markers gene expression. In this study, 40 ovariectomized animals were classified into 5 groups; group 1 was ovariectomized control, groups 2 to 5 were subcutaneously administered with rotenone for 14 days after 1 month of ovariectomy for induction of PD. Group 2 was left untreated; groups 3, 4, and 5 were treated with Sinemet(®), Cerebrolysin(®), and a single dose of adipose tissue-derived MSCs (ADMSCs), respectively. Y-chromosome gene (sry) was assessed by polymerase chain reaction (PCR) in brain tissue of the female rats. Serum transforming growth factor β (TGF-β), monocyte chemoattractant protein 1 (MCP-1), and brain-derived neurotrophic factor (BDNF) levels were assayed using enzyme-linked immunosorbent assay technique. Brain dopamine level was assayed fluorometrically, while brain tyrosine hydroxylase (TH) gene expression was detected by semiquantitative real-time PCR. The PD group showed significant increase in serum TGF-β and MCP-1 levels associated with significant decrease in serum BDNF, brain dopamine, and brain TH gene expression levels. In contrast, all treatments produce significant decrease in serum TGF-β and MCP-1 levels in concomitant with significant increase in serum BDNF, brain dopamine, and brain TH gene expression levels. In conclusion, the observed improvements in the studied biomarkers due to ADMSCs infusion might be attributed to their immunomodulatory, anti-inflammatory, and neurotrophic effects. PMID:24567299

  14. Arsenic-induced biochemical and genotoxic effects and distribution in tissues of Sprague-Dawley rats.

    PubMed

    Patlolla, Anita K; Todorov, Todor I; Tchounwou, Paul B; van der Voet, Gijsbert; Centeno, Jose A

    2012-11-01

    Arsenic (As) is a well documented human carcinogen. However, its mechanisms of toxic action and carcinogenic potential in animals have not been conclusive. In this research, we investigated the biochemical and genotoxic effects of As and studied its distribution in selected tissues of Sprague-Dawley rats. Four groups of six male rats, each weighing approximately 60 ± 2 g, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15, 20 mg/kg bw of arsenic trioxide. A control group was also made of 6 animals injected with distilled water. Following anaesthetization, blood was collected and enzyme analysis was performed by spectrophotometry following standard protocols. At the end of experimentation, the animals were sacrificed, and the lung, liver, brain and kidney were collected 24 h after the fifth day treatment. Chromosome and micronuclei preparation was obtained from bone marrow cells. Arsenic exposure significantly increased (p<0.05) the activities of plasma alanine aminotransferase-glutamate pyruvate transaminase (ALT/GPT), and aspartate aminotransferase-glutamate oxaloacetate transaminase (AST/GOT), as well as the number of structural chromosomal aberrations (SCA) and frequency of micronuclei (MN) in the bone marrow cells. In contrast, the mitotic index in these cells was significantly reduced (p<0.05). These findings indicate that aminotransferases are candidate biomarkers for arsenic-induced hepatotoxicity. Our results also demonstrate that As has a strong genotoxic potential, as measured by the bone marrow SCA and MN tests in Sprague-Dawley rats. Total arsenic concentrations in tissues were measured by inductively coupled plasma mass spectrometry (ICP-MS). A dynamic reaction cell (DRC) with hydrogen gas was used to eliminate the ArCl interference at mass 75, in the measurement of total As. Total As doses in tissues tended to correlate with specific exposure levels. PMID:23175155

  15. Stress response of bovine artery and rat brain tissue due to combined translational shear and fixed unconfined compression

    NASA Astrophysics Data System (ADS)

    Leahy, Lauren

    During trauma resulting from impacts and blast waves, sinusoidal waves permeate the brain and cranial arterial tissue, both non-homogeneous biological tissues with high fluid contents. The experimental shear stress response to sinusoidal translational shear deformation at 1 Hz and 25% strain amplitude and either 0% or 33% compression is compared for rat brain tissue and bovine aortic tissue. Both tissues exhibit Mullins effect in shear. Harmonic wavelet decomposition, a novel application to the mechanical response of these tissues, shows significant 1 Hz and 3 Hz components. The 3 Hz component magnitude in brain tissue, which is much larger than in aortic tissue, may correlate to interstitial fluid induced drag forces that decrease on subsequent cycles perhaps because of damage resulting in easier fluid movement. The fluid may cause the quasiperiodic, viscoelastic behavior of brain tissue. The mechanical response differences under impact may cause shear damage between arterial and brain connections.

  16. Tissue distribution and elimination after oral and intravenous administration of different titanium dioxide nanoparticles in rats

    PubMed Central

    2014-01-01

    Objective The aim of this study was to obtain kinetic data that can be used in human risk assessment of titanium dioxide nanomaterials. Methods Tissue distribution and blood kinetics of various titanium dioxide nanoparticles (NM-100, NM-101, NM-102, NM-103, and NM-104), which differ with respect to primary particle size, crystalline form and hydrophobicity, were investigated in rats up to 90 days post-exposure after oral and intravenous administration of a single or five repeated doses. Results For the oral study, liver, spleen and mesenteric lymph nodes were selected as target tissues for titanium (Ti) analysis. Ti-levels in liver and spleen were above the detection limit only in some rats. Titanium could be detected at low levels in mesenteric lymph nodes. These results indicate that some minor absorption occurs in the gastrointestinal tract, but to a very limited extent. Both after single and repeated intravenous (IV) exposure, titanium rapidly distributed from the systemic circulation to all tissues evaluated (i.e. liver, spleen, kidney, lung, heart, brain, thymus, reproductive organs). Liver was identified as the main target tissue, followed by spleen and lung. Total recovery (expressed as % of nominal dose) for all four tested nanomaterials measured 24 h after single or repeated exposure ranged from 64-95% or 59-108% for male or female animals, respectively. During the 90 days post-exposure period, some decrease in Ti-levels was observed (mainly for NM-100 and NM-102) with a maximum relative decrease of 26%. This was also confirmed by the results of the kinetic analysis which revealed that for each of the investigated tissues the half-lifes were considerable (range 28–650 days, depending on the TiO2-particle and tissue investigated). Minor differences in kinetic profile were observed between the various particles, though these could not be clearly related to differences in primary particle size or hydrophobicity. Some indications were observed for an

  17. Chronic ingestion of Mn/sub 3/O/sub 4/ by young rats: tissue accumulation, distribution, and depletion

    SciTech Connect

    Rehnberg, G.L.; Hein, J.F.; Carter, S.D.; Linko, R.S.; Laskey, J.W.

    1981-02-01

    Mn accumulation, distribution, and disappearance were evaluated in selected tissues of preweanling rats dosed daily with particulate Mn/sub 3/O/sub 4/ for 12 or 27 d postpartum. Significant findings include a high rate of Mn absorption and localization in tissues, especially the cerebrum, hypothalamus, and pituitary. In these tissues, the return of Mn concentrations to control levels was much slower when Mn dosing was continued beyond 18-20 d postpartum.

  18. Gene Expression Profiling of Lung Tissue of Rats Exposed to Lunar Dust Particles

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Feiveson, Alan H.; Lam, Chiu-Wing; Kidane, Yared H.; Ploutz-Snyder Robert; Yeshitla, Samrawit; Zalesak, Selina M.; Scully, Robert R.; Wu, Honglu; James, John T.

    2014-01-01

    The purpose of the study is to analyze the dynamics of global gene expression changes in the lung tissue of rats exposed to lunar dust particles. Multiple pathways and transcription factors were identified using the Ingenuity Pathway Analysis tool, showing the potential networks of these signaling regulations involved in lunar dust-induced prolonged proflammatory response and toxicity. The data presented in this study, for the first time, explores the molecular mechanisms of lunar dust induced toxicity. This work contributes not only to the risk assessment for future space exploration, but also to the understanding of the dust-induced toxicity to humans on earth.

  19. Tissue distribution and urinary excretion of dimethylated arsenic and its metabolites in dimethylarsinic acid- or arsenate-treated rats

    SciTech Connect

    Adair, Blakely M.; Moore, Tanya; Conklin, Sean D.; Creed, John T.; Wolf, Douglas C.; Thomas, David J. . E-mail: thomas.david@epa.gov

    2007-07-15

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethylated and trimethylated arsenicals; urines were analyzed for these arsenicals and their thiolated derivatives. In dimethylarsinic acid-treated rats, highest concentrations of dimethylated arsenic were found in blood. In lung, liver, and kidney, concentrations of dimethylated arsenic exceeded those of trimethylated species; in urinary bladder and urine, trimethylated arsenic predominated. Dimethylthioarsinic acid and trimethylarsine sulfide were present in urine of dimethylarsinic acid-treated rats. Concentrations of dimethylated arsenicals were similar in most tissues of dimethylarsinic acid- and arsenate-treated rats, including urinary bladder which is the target for dimethylarsinic acid-induced carcinogenesis in the rat. Mean concentration of dimethylated arsenic was significantly higher (P < 0.05) in urine of dimethylarsinic acid-treated rats than in arsenate-treated rats, suggesting a difference between treatment groups in the flux of dimethylated arsenic through urinary bladder. Concentrations of trimethylated arsenic concentrations were consistently higher in dimethylarsinic acid-treated rats than in arsenate-treated rats; these differences were significant (P < 0.05) in liver, urinary bladder, and urine. Concentrations of dimethylthioarsinic acid and trimethylarsine sulfide were higher in urine from dimethylarsinic acid-treated rats than from arsenate-treated rats. Dimethylarsinic acid is extensively metabolized in the rat, yielding significant concentrations of trimethylated species and of thiolated derivatives. One or more of these metabolites could be the species causing alterations of cellular function that lead to tumors in the urinary bladder.

  20. Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

    NASA Astrophysics Data System (ADS)

    Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

    2015-02-01

    Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

  1. Characterization of the pseudocapsule of soft-tissue sarcomas. An experimental study in rats

    SciTech Connect

    Gitelis, S.; Thomas, R.; Templeton, A.; Schajowicz, F. )

    1989-09-01

    The effect of preoperative radiation therapy on the pseudocapsule of experimental rat soft-tissue sarcomas has not been histologically evaluated in a controlled study. The irradiated animal showed marked thickening of the capsular structure surrounding the sarcoma. Everywhere morphologically distinct from the tumor, there was no evidence of tumor invasion into or through this capsular structure. The membrane was consistently thicker and more hyalinized than in the control animals. The nonirradiated animals showed a minimal pseudocapsular structure with a characteristic tumor penetration. Irradiation produced distinct histologic changes in the pseudocapsule. Although assumed on the basis of clinical observations alone, irradiation-induced pseudocapsule has not previously been demonstrated in an experimental model of soft-tissue sarcoma.

  2. [Medichronal lowers blood ethanol and acetaldehyde and restores the concentration of catecholamines in rat tissues].

    PubMed

    Bozhko HKZh; Boĭko, T P; Kostiukovs'ka, L S

    1995-01-01

    Variation of ethanol and acetaldehyde concentrations in blood, catecholamines in hypothalamus, brain stem and hemispheres, heart and adrenal glands, serotonin in the same structures of the brain, thin intestine and blood in rats was studied. Isolated action of medichronal during 10 days against the background of prolonged administration of moderate doses of ethanol significantly lowered ethanol and acetaldehyde concentration in the animal blood. Medichronal increased the level of noradrenaline, lowered under the conditions of ethanol intoxication in the hypothalamus, and increased adrenalina level in the heart; noradrenaline level in adrenal glands is restored. The amount of serotonin in the blood and tissues increased under the conditions of ethanol intoxication did not vary under the action of medichronal. The obtained results indicate to pronounced detoxication influence of medichronal. One of the mechanisms of its action is normalizing the catecholamine changes caused by the ethanol intoxication in tissues. PMID:8592777

  3. Pharmacokinetics and tissue distribution study of Isovitexin in rats by HPLC-MS/MS.

    PubMed

    Li, Yaxin; Zhang, Yanqing; Yang, Tan; Li, Hui; Guo, Jiang; Zhao, Qiqing; Xie, Junbo

    2015-06-01

    A sensitive and credible high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established and validated for the determination of isovitexin in rat plasma and various tissues (including heart, liver, lung, kidney, stomach, intestine, muscle, brain and cerebellum). The samples were prepared with methanol by liquid-liquid extraction, and puerarin was used as the internal standard. The chromatographic separation was carried out on an Agilent Poroshell 120 EC-C18 column (4.6mm×50mm, 2.7μm) with a mobile phase consisting of acetonitrile and 0.1% formic acid (21:79, v/v). The MS analysis was performed by multiple reaction monitoring (MRM) with electronic spray ionization source (ESI(-)) for quantitative response of isovitexin (431.0→311.0) and puerarin (415.1→295.0). The linearity of isovitexin in all the biosamples was good, with correlation coefficients greater than 0.9912 within the corresponding concentration range. The intra- and inter-day precisions in plasma and various tissues were less than 11.80%, and the accuracy (RE %) ranged from -4.89% to 4.78%. The extraction recoveries were in the range of 72.70%-90.81%. The present method was successfully applied to pharmacokinetics and tissue distribution of isovitexin in rats after tail vein injection with 2.0mg/kg of the compound. The pharmacokinetic parameters were demonstrated as followed: the half-life (t1/2) was 1.05±0.325h, the apparent volume of mean residual time (MRT) was 1.229±0.429h, and the area under the curve (AUC) was 11.39±5.05μg/mL/h. The results of tissue distribution showed that the main tissue depots for isovitexin in rats were kidney, intestine and liver. The results provided a meaningful insight for the further pharmacological investigation of isovitexin. PMID:25902051

  4. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus.

    PubMed

    Jugé, Lauriane; Pong, Alice C; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  5. Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

    PubMed Central

    Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

    2016-01-01

    Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P < 0.001, for both), an alteration of the corpus callosum and periventricular white matter microstructure (CC+PVWM) and rearrangement of the cortical gray matter microstructure (P < 0.001, for both), while compression without gross microstructural alteration was evident in the caudate-putamen and ventral internal capsule (P < 0.001, for both). During hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P < 0.001), while a decrease in space was observed for the ventral internal capsule (P < 0.001). For the cortical gray matter, an increase in extracellular tissue water was significantly associated with a decrease in tissue stiffness (P = 0.001). To conclude, this study characterizes the temporal changes in tissue microstructure, water content and stiffness in different brain regions and their association with ventricular enlargement. In summary, whilst diffusion changes were larger and statistically significant for majority of the brain regions studied

  6. Gamma-Glutamyl Cysteine Attenuates Tissue Damage and Enhances Tissue Regeneration in a rat Model of Lead-Induced Nephrotoxicity.

    PubMed

    Salama, Samir A; Arab, Hany H; Maghrabi, Ibrahim A; Hassan, Memy H; AlSaeed, Mohammed S

    2016-09-01

    Lead is a biohazardous metal that is commonly involved in human illness including renal injury. Although it is a non-redox reactive metal, lead-induced renal injury is largely based on oxidative stress. The current work aimed at exploring the possible protective effect of γ-glutamyl cysteine (γGC) against lead-induced renal injury. Rats were allocated to normal and γGC control groups, lead-treated group, and lead and γGC-treated group. γGC alleviated lead-induced renal injury as evidenced by attenuation of histopathological aberration, amelioration of oxidative injury as demonstrated by significant reduction in lipid and protein oxidation, elevation of total antioxidant capacity, and glutathione level. The activity of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) was significantly elevated. γGC significantly decreased levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β and the activity of the apoptotic marker caspase-3. In addition, γGC reduced kidney lead content, enhanced weight gain, and improved renal function as demonstrated by reduced serum levels of urea and creatinine. Importantly, γGC upregulated proliferating cell nuclear antigen (PCNA) expression, denoting enhanced renal regenerative capacity. Together, our findings highlight evidence for alleviating effects of γGC against lead-induced renal injury that is potentially mediated through diminution of oxidative tissue injury, reduction of inflammatory response, attenuation of apoptosis, and enhancement of renal regenerative capacity. PMID:26767370

  7. Altered adipose tissue metabolism in offspring of dietary obese rat dams.

    PubMed

    Benkalfat, Nassira Batoul; Merzouk, Hafida; Bouanane, Samira; Merzouk, Sid-Ahmed; Bellenger, Jérôme; Gresti, Joseph; Tessier, Christian; Narce, Michel

    2011-07-01

    To investigate further the mechanisms of developmental programming, we analysed the effects of maternal overnutrition and of postnatal high-fat feeding on adipose tissue metabolism in the offspring. Postnatal changes in serum adiponectin, leptin and TAG [triacylglycerol (triglyceride)] levels, adipose tissue TAGs, fatty acids and enzyme activities were determined in offspring of cafeteria-diet-fed dams during gestation and lactation, weaned on to standard chow or on to cafeteria diet. Obese rats showed higher adiposity (+35% to 85%) as well as a significant increase in serum glucose, insulin, leptin, adiponectin and TAG levels (P<0.01) and adipose tissue LPL (lipoprotein lipase) and GPDH (glycerol-3-phosphate dehydrogenase) activities (P<0.01), compared with control pups at weaning (day 21) and at adulthood (day 90). Adipose HSL (hormone-sensitive lipase) activity was increased only at day 90 (P<0.05), and FAS (fatty acid synthase) activity remained unchanged. The proportions of SFAs (saturated fatty acids) and MUFAs (mono-unsaturated fatty acids) and the Δ(9)-desaturation index were significantly increased (P<0.05), whereas PUFAs (polyunsaturated fatty acids) were decreased (P<0.01) in serum and adipose TAGs of obese pups compared with controls. The cafeteria diet at weaning induced more severe abnormalities in obese rats. In conclusion, maternal overnutrition induced permanent changes in adipose tissue metabolism of the offspring. These pre-existing alterations in offspring were worsened under a high-fat diet from weaning to adulthood. Consequently, adipose adipokines and enzymes could provide a potential therapeutic target, and new investigations in this field could constitute strategies to improve the impact of early-life overnutrition. PMID:21288203

  8. Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress.

    PubMed

    Sepehr, Reyhaneh; Staniszewski, Kevin; Maleki, Sepideh; Jacobs, Elizabeth R; Audi, Said; Ranji, Mahsa

    2012-04-01

    Ventilation with enhanced fractions of O(2) (hyperoxia) is a common and necessary treatment for hypoxemia in patients with lung failure, but prolonged exposure to hyperoxia causes lung injury. Ischemia-reperfusion (IR) injury of lung tissue is common in lung transplant or crush injury to the chest. These conditions are associated with apoptosis and decreased survival of lung tissue. The objective of this work is to use cryoimaging to evaluate the effect of exposure to hyperoxia and IR injury on lung tissue mitochondrial redox state in rats. The autofluorescent mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are electron carriers in ATP generation. These intrinsic fluorophores were imaged for rat lungs using low-temperature fluorescence imaging (cryoimaging). Perfused lungs from four groups of rats were studied: normoxia (control), control perfused with an mitochondrial complex IV inhibitor (potassium cyanide, KCN), rats exposed to hyperoxia (85% O(2)) for seven days, and from rats subjected to lung IR in vivo 24 hours prior to study. Each lung was sectioned sequentially in the transverse direction, and the images were used to reconstruct a three-dimensional (3-D) rendering. In KCN perfused lungs the respiratory chain was more reduced, whereas hyperoxic and IR lung tissue have a more oxidized respiratory chain than control lung tissue, consistent with previously measured mitochondrial dysfunction in both hyperoxic and IR lungs. PMID:22559688

  9. Optical imaging of tissue mitochondrial redox state in intact rat lungs in two models of pulmonary oxidative stress

    NASA Astrophysics Data System (ADS)

    Sepehr, Reyhaneh; Staniszewski, Kevin; Maleki, Sepideh; Jacobs, Elizabeth R.; Audi, Said; Ranji, Mahsa

    2012-04-01

    Ventilation with enhanced fractions of O2 (hyperoxia) is a common and necessary treatment for hypoxemia in patients with lung failure, but prolonged exposure to hyperoxia causes lung injury. Ischemia-reperfusion (IR) injury of lung tissue is common in lung transplant or crush injury to the chest. These conditions are associated with apoptosis and decreased survival of lung tissue. The objective of this work is to use cryoimaging to evaluate the effect of exposure to hyperoxia and IR injury on lung tissue mitochondrial redox state in rats. The autofluorescent mitochondrial metabolic coenzymes nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) are electron carriers in ATP generation. These intrinsic fluorophores were imaged for rat lungs using low-temperature fluorescence imaging (cryoimaging). Perfused lungs from four groups of rats were studied: normoxia (control), control perfused with an mitochondrial complex IV inhibitor (potassium cyanide, KCN), rats exposed to hyperoxia (85% O2) for seven days, and from rats subjected to lung IR in vivo 24 hours prior to study. Each lung was sectioned sequentially in the transverse direction, and the images were used to reconstruct a three-dimensional (3-D) rendering. In KCN perfused lungs the respiratory chain was more reduced, whereas hyperoxic and IR lung tissue have a more oxidized respiratory chain than control lung tissue, consistent with previously measured mitochondrial dysfunction in both hyperoxic and IR lungs.

  10. Differential inhibitory effects of methylmalonic acid on respiratory chain complex activities in rat tissues.

    PubMed

    Pettenuzzo, Leticia F; Ferreira, Gustavo da C; Schmidt, Anna Laura; Dutra-Filho, Carlos S; Wyse, Angela T S; Wajner, Moacir

    2006-02-01

    Methylmalonic acidemia is an inherited metabolic disorder biochemically characterized by tissue accumulation of methylmalonic acid (MMA) and clinically by progressive neurological deterioration and kidney failure, whose pathophysiology is so far poorly established. Previous studies have shown that MMA inhibits complex II of the respiratory chain in rat cerebral cortex, although no inhibition of complexes I-V was found in bovine heart. Therefore, in the present study we investigated the in vitro effect of 2.5mM MMA on the activity of complexes I-III, II, II-III and IV in striatum, hippocampus, heart, liver and kidney homogenates from young rats. We observed that MMA caused a significant inhibition of complex II activity in striatum and hippocampus (15-20%) at low concentrations of succinate in the medium, but not in the peripheral tissues. We also verified that the inhibitory property of MMA only occurred after exposing brain homogenates for at least 10 min with the acid, suggesting that this inhibition was mediated by indirect mechanisms. Simultaneous preincubation with the nitric oxide synthase inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME) and catalase (CAT) plus superoxide dismutase (SOD) did not prevent MMA-induced inhibition of complex II, suggesting that common reactive oxygen (superoxide, hydrogen peroxide and hydroxyl radical) and nitric (nitric oxide) species were not involved in this effect. In addition, complex II-III (20-35%) was also inhibited by MMA in all tissues tested, and complex I-III only in the kidney (53%) and liver (38%). In contrast, complex IV activity was not changed by MMA in all tissues studied. These results indicate that MMA differentially affects the activity of the respiratory chain pending on the tissues studied, being striatum and hippocampus more vulnerable to its effect. In case our in vitro data are confirmed in vivo in tissues from methylmalonic acidemic patients, it is feasible that that the present findings may be

  11. Preventive effects of garlic (Allium sativum) on oxidative stress and histopathology of cardiac tissue in streptozotocin-induced diabetic rats.

    PubMed

    Naderi, R; Mohaddes, G; Mohammadi, M; Alihemmati, A; Badalzadeh, R; Ghaznavi, R; Ghyasi, R; Mohammadi, Sh

    2015-12-01

    Since some complications of diabetes mellitus may be caused or exacerbated by an oxidative stress, the protective effects of garlic (Allium sativum) were investigated in the blood and heart of streptozotocin-induced diabetic rats. Twenty-eight male Wistar rats were randomly divided into four groups: control, garlic, diabetic, and diabetic+garlic. Diabetes was induced by intraperitoneal (i.p.) injection of streptozotocin (50 mg/kg) in male rats. Rats were fed with raw fresh garlic homogenate (250 mg/kg) six days a week by gavage for a period of 6 weeks. At the end of the 6th week blood samples and heart tissues were collected and used for determination of glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and histological evaluation. Induction of diabetes increased MDA levels in blood and homogenates of heart. In diabetic rats treated with garlic, MDA levels decreased in blood and heart homogenates. Treatment of diabetic rats with garlic increased SOD, GPX and CAT in blood and heart homogenates. Histopathological finding of the myocardial tissue confirmed a protective role for garlic in diabetic rats. Thus, the present study reveals that garlic may effectively modulate antioxidants status in the blood and heart of streptozotocin induced-diabetic rats. PMID:26690030

  12. Application of Coenzyme Q10 for Accelerating Soft Tissue Wound Healing after Tooth Extraction in Rats

    PubMed Central

    Yoneda, Toshiki; Tomofuji, Takaaki; Kawabata, Yuya; Ekuni, Daisuke; Azuma, Tetsuji; Kataoka, Kota; Kunitomo, Muneyoshi; Morita, Manabu

    2014-01-01

    Accelerating wound healing after tooth extraction is beneficial in dental treatment. Application of antioxidants, such as reduced coenzyme Q10 (rCoQ10), may promote wound healing after tooth extraction. In this study, we examined the effects of topical application of rCoQ10 on wound healing after tooth extraction in rats. After maxillary first molars were extracted, male Fischer 344 rats (8 weeks old) (n = 27) received topical application of ointment containing 5% rCoQ10 (experimental group) or control ointment (control group) to the sockets for 3 or 8 days (n = 6–7/group). At 3 days after extraction, the experimental group showed higher collagen density and lower numbers of polymorphonuclear leukocytes in the upper part of socket, as compared to the control group (p < 0.05). Gene expression of interleukin-1β, tumor necrosis factor-α and nuclear factor-κB were also lower in the experimental group than in the control group (p < 0.05). At 8 days after tooth extraction, there were no significant differences in collagen density, number of polymorphonuclear leukocytes and bone fill between the groups. Our results suggest that topical application of rCoQ10 promotes wound healing in the soft tissue of the alveolar socket, but that rCoQ10 has a limited effect on bone remodeling in rats. PMID:25514392

  13. Morphometric effects of different energy densities of diode laser on adipose tissue in rats

    NASA Astrophysics Data System (ADS)

    Senhorinho, Halina C.; Bichinho, Gerson L.; Nohama, Percy; Gariba, Munir A.

    2008-02-01

    The aim of this study consisted in evaluating the influence of low power laser on the morfometry of white adipose cells in rats. The sample consisted of 20 adult female rats, from Wistar strain, randomized in four groups. All groups were submitted to tricotomy of the dorsal thoracic area and the first three groups were exposed to a InGaAlP laser (660 nm wavelength) with fluencies of 2, 8 and 16 J/cm2 for groups L1, L2 and L3, respectively. L4 was the control. The groups were submitted to the protocols three times a week, for three weeks. The irradiated tissue was excised and submitted to histological treatment by HE for optical microscopy and the Kruskal-Wallis test was used for the statistical analysis. The average morphometry, in number of pixels, was: 3741 +/- 704, 3762 +/-947, 3737 +/-1076 and 4619 +/-781 for L1, L2, L3 and L4, respectively. There was no significant difference among groups L1 to L3 for the variable tested. From these results, it can be concluded that the application of low power laser - under the conditions proposed and for the fluency values chosen - influence the morphometry of white adipose cells in rats in the same manner, producing similar results.

  14. Increased lipid peroxidation in tissues of nickel chloride-treated rats

    SciTech Connect

    Sunderman, F.W. Jr.; Marzouk, A.; Hopfer, S.M.; Zaharia, O.; Reid, M.C.

    1985-01-01

    Parenteral administration of nickel chloride (NiCl/sub 2/) to rats enhanced lipid peroxidation in liver, kidney, and lung as measured by the thiobarbituric acid reaction for malondialdehyde (MDA) and related chromogens in fresh tissue homogenates. After sc injection of NiCl/sub 2/ (0.75 mmol per kg body wt), MDA concentrations in liver and kidney became significantly increased by nine h and reached peak values at 48 h. For example, in nine rats killed 48 h after the NiCl/sub 2/ injection, hepatic MDA concentrations averaged 2.5 +/- 1.0 ..mu.. mol per g dry wt (P < 0.001 versus 0.5 +/- 0.3 ..mu.. mol per g in 30 controls). Dose-effect relationships for lipid peroxidation in liver and kidney were observed with NiCl/sub 2/ dosages ranging from 0.12 to 0.75 mmol per kg, sc. Intrarenal administration of a carcinogenic nickel compound, nickel subsulfide (Ni/sub 3/S/sub 2/, 0.36 mmol per kg body wt), did not affect MDA concentrations in the injected kidneys of rats killed one to 20 days post-injection. The results of this study implicate lipid peroxidation as a molecular mechanism for cell injury in acute NiCl/sub 2/ poisoning, but they do not furnish any evidence that lipid peroxidation is involved in the initiation of nickel carcinogenesis. 46 references, 4 tables.

  15. Ethanol-induced hypothermia and thermogenesis of brown adipose tissue in the rat.

    PubMed

    Huttunen, P; Sämpi, M; Myllylä, R

    1998-05-01

    The effects of two ethanol doses (2 and 3 g/kg) on colonic temperature and levels of norepinephrine (NE) and uncoupling protein (UCP) mRNA in the interscapular brown adipose tissue (IBAT) were examined in rats exposed to 20 degrees C or 4 degrees C for 2 h. The controls received 0.9% NaCl solution. Ethanol produced a significant hypothermic effect versus saline at both temperature conditions. The dose at 3 g/kg reduced colonic temperature more in the cold than at room temperature (p < 0.01), whereas the ambient temperature did not affect the decrease in rats that received ethanol 2 g/kg. At room temperature ethanol did not significantly change the levels of NE or UCP mRNA, whereas after cold exposure (4 degrees C) NE levels in the ethanol-treated rats were significantly lower than in the controls (p < 0.001). Ethanol did not prevent a cold-induced increase in the UCP mRNA levels, although it reduced an increase. The magnitude of the reduction in increase was dependent on the dose, being significant at the dose of 3 g/kg (p < 0.05). The results show that the ethanol-induced drop in body temperature is not necessarily related to IBAT thermogenesis, as indicated by the levels of NE and UCP mRNA. PMID:9590517

  16. Protection of normal tissue against late radiation injury by WR-2721. [/sup 60/Co; rats

    SciTech Connect

    Utley, J.F.; Quinn, C.A.; White, F.C.; Seaver, N.A.; Bloor, C.M.

    1981-02-01

    The ability of WR-2721 to protect against late radiation damage has been studied in skin, muscle, and vascular tissues of rats. Animals treated with and without WR-2721 received irradiation to the left hind limb; representative groups were killed at intervals ranging from 72 h to 6 months. Comparison of all drug-treated and non-drug-treated animals showed significant protection (P = less than or equal to 0.05). The time pattern of injury in non-drug-treated rats was biphasic, with significant damage occurring at 72 h and 1 week, returning to normal between 1 and 3 months, but showing significant late damage at 6 months (P = less than or equal to 0.001). Again, this injury pattern did not appear in WR-2721-treated rats. Thus the ability of WR-2721 to protect against acute and chronic radiation injury in vessels, skin, and muscle indicates that an increased therapeutic gain can be expected when this drug is used in clinical radiation therapy.

  17. Inhalation uptake of low level elemental mercury vapor and its tissue distribution in rats

    SciTech Connect

    Oberski, S.P.; Fang, S.C.

    1980-07-01

    Elemental mercury vapor is the major component of mercury found in the atmosphere. Furthermore, if usage of coal is increased to meet the energy demand, then atmospheric levels of mercury are expected to rise. Current atmospheric concentrations of mercury vapor over select urban areas of the United States range from 0.5 to 50 ng m/sup -3/ with a mean of 7 ng m/sup -3/. Mercury concentration in brain tissue following inhalation of elemental mercury is significantly higher than those from intravenous injection or oral administration of either organic or ionic mercurials. Although elemental mercury is rapidly oxidized in the blood to the less diffusable mercuric ion, the transient occurrence of elemental mercury in the blood stream and the increased levels detected in the central nervous system are likely a result of its rapid diffusion into target tissues. This study reports the inhalation uptake and consequent tissue distribution of radioactive elemental mercury vapor in rats over a concentration range of 15 to 916 ng m/sup -3/, with particular emphasis on measurement below 50 ng m/sup -3/, in an effort to determine if the tissue distribution of mercury after a low level exposure is similar to those reported using higher concentrations.

  18. Quantitative analysis of the tissue response to chronically implanted microwire electrodes in rat cortex.

    PubMed

    Winslow, Brent D; Tresco, Patrick A

    2010-03-01

    Several hypotheses have been proposed to explain how the brain tissue reaction to single unit recording electrodes influences biocompatibility including progressive changes in the spatial distribution of reactive astrocytes, and the loss of neurons over the indwelling period. To examine these hypotheses, the spatial distribution of biomarkers associated with the foreign body response to insulated microwires placed in rat cerebral cortex was analyzed 2, 4, and 12 weeks after implantation using quantitative methods. We observed a stereotypical tissue response that was similar in some aspects to that previously reported for penetrating planar silicon microelectrode arrays with some specific differences including an overall lower degree of cortical tissue reactivity. While we found no evidence that reactive gliosis increases over time or that neuronal loss is progressive, we did find evidence of persistent inflammation and enhanced BBB permeability at the electrode brain tissue interface that extended over the 3 month indwelling period and that exhibited more animal to animal variability at 3 months than at 2 and 4 weeks. PMID:19963267

  19. Pharmacokinetics and tissue distribution of spinosin after intravenous administration in rats.

    PubMed

    Li, Yu-Juan; Dai, Yue-Han; Yu, Ye-Ling; Li, Yan; Deng, Yu-Lin

    2007-08-01

    Spinosin is the major effective single constituent in the traditional Chinese herb Semen Ziziphi Spinosae, which is used for sedation and hypnosis. For the further use of spinosin in treating insomnia, the pharmacokinetics and tissue distribution of spinosin after intravenous administration to rats was investigated. An HPLC method with an ODS column (250 mm x 4.6 mm, i.d.) and a mobile phase of acetonitrile-water-acetic acid (23:77:1) was used for the determination of spinosin in the plasma and tissues of rats. Vanillin was used as an internal standard, and spinosin was detected at 334 nm. The calibration curve of spinosin in plasma showed good linearity over the concentration range of 1-300 microg/ml, and the quantitation of limit of plasma was 1 microg/ml. The linear range of concentrations of spinosin in the heart, spleen, stomach, lung, testis, brain, and intestine was 0.1-40 microg/ml and the quantitation limit was 0.1 microg/ml. The linear range of concentrations of spinosin in the liver and kidney was 1-150 microg/ml, and the quantitation limit was 1 microg/ml. The correlation coefficients of all calibration curves were between 0.9939 and 0.9980. The intra and interrun precision for all samples was less than < or =11.0%. The time-concentration curve of spinosin after the intravenous administration of a single dose of 20 mg/kg to rats corresponded to the two-compartment model. The main pharmacokinetic parameters T(0.5alpha), T(0.5beta), CLs, AUC(0-T), and V(c) were 6.66 min, 51.5 min, 1.42 l.min(-1), 2.83 mg.min.ml(-1), and 14.0 l.kg(-1), respectively. At 20 min, a concentration peak occurred in liver and brain tissues. The highest level of spinosin occurred in the liver, followed by the spleen and kidney. The lowest level of spinosin appeared in the testis, followed by the brain. Spinosin was not detected in smooth and skeletal muscle. After intravenous administration, the drug was distributed extensively and transferred quickly in rats in vivo. PMID

  20. Expression of Serotonin Receptors in the Colonic Tissue of Chronic Diarrhea Rats

    PubMed Central

    Zhu, Tong; Qiu, Juanjuan; Wan, Jiajia; Wang, Fengyun; Tang, Xudong; Guo, Huishu

    2016-01-01

    Background/Aims: This study aimed to investigate the difference among the expression of serotonin receptors (5-HT3, 5-HT4, and 5-HT7 receptors) in colonic tissue of chronic diarrhea rats. Materials and Methods: A rat model of chronic diarrhea was established by lactose diet. The expression of 5-HT3, 5-HT4, and 5-HT7 receptors in the colonic tissue was detected using immunohistochemistry, real-time PCR and Western blotting techniques. Results: There is no significant difference on the protein expression of 5-HT3 receptor between the normal group and the chronic diarrhea model group. The mRNA expression of 5-HT3 receptor in the chronic diarrhea model group was significantly lower than that in the normal group (n = 10; P < 0.01). The protein and mRNA expression of 5-HT4 receptor in the chronic diarrhea model group were significantly higher than those in the normal group (n = 10; P < 0.05, P < 0.01). On the contrary, the protein and mRNA expressions of 5-HT7 receptor in the chronic diarrhea model group were significantly decreased compared with the normal group (n = 10; P < 0.01, P < 0.01). Conclusions: The results suggested the receptors of 5-HT4 and 5-HT7 may be involved in inducing diarrhea by lactose diet. PMID:27184643

  1. 65zinc uptake from blood into brain and other tissues in the rat

    SciTech Connect

    Pullen, R.G.; Franklin, P.A.; Hall, G.H. )

    1990-10-01

    Zinc is essential for normal growth, development and brain function although little is known about brain zinc homeostasis. Therefore, in this investigation we have studied 65Zn uptake from blood into brain and other tissues and have measured the blood-brain barrier permeability to 65Zn in the anaesthetized rat in vivo. Adult male Wistar rats within the weight range 500-600 g were used. 65ZnCl2 and (125I)albumin, the latter serving as a vascular marker, were injected in a bolus of normal saline I.V. Sequential arterial blood samples were taken during experiments that lasted between 5 min and 5 hr. At termination, samples from the liver, spleen, pancreas, lung, heart, muscle, kidney, bone, testis, ileum, blood cells, csf, and whole brain were taken and analysed for radio-isotope activity. Data have been analysed by Graphical Analysis which suggests 65Zn uptake from blood by all tissues sampled was unidirectional during this experimental period except brain, where at circulation times less than 30 min, 65Zn fluxes were bidirectional. In addition to the blood space, the brain appears to contain a rapidly exchanging compartment(s) for 65Zn of about 4 ml/100g which is not csf.

  2. An activity in rat tissues that modifies nitrotyrosine-containing proteins

    PubMed Central

    Kamisaki, Yoshinori; Wada, Kouichirou; Bian, Ka; Balabanli, Barbaros; Davis, Karen; Martin, Emil; Behbod, Fariba; Lee, Yu-Chen; Murad, Ferid

    1998-01-01

    Homogenates from rat spleen and lung could modify nitrotyrosine-containing BSA. With incubation, nitrotyrosine-containing BSA lost its epitope to a monoclonal antibody that selectively recognized nitrotyrosine-containing proteins. In the presence of protease inhibitors, the loss of the nitrotyrosine epitope occurred without protein degradation and hydrolysis. This activity was found in supernatant but not particulate fractions of spleen homogenates. The factor was heat labile, was sensitive to trypsin treatment, and was retained after passage through a membrane with a 10-kDa retention. The activity was time- and protein-concentration dependent. The activity increased about 2-fold in spleen extracts with endotoxin (bacterial lipopolysaccharide) treatment of animals, suggesting that the activity is inducible or regulatable. Other nitrotyrosine-containing proteins also served as substrates, while free nitrotyrosine and some endogenous nitrotyrosine-containing proteins in tissue extracts were poor substrates. Although the product and possible cofactors for this reaction have not yet been identified, this activity may be a “nitrotyrosine denitrase” that reverses protein nitration and, thus, decreases peroxynitrite toxicity. This activity was not observed in homogenates from rat liver or kidney, suggesting that there may also be some tissue specificity for the apparent denitrase activity. PMID:9751709

  3. Effects of dietary apple polyphenol on adipose tissues weights in Wistar rats.

    PubMed

    Nakazato, Koichi; Song, Hongsun; Waga, Toshiaki

    2006-07-01

    In this study, we investigated whether dietary apple polyphenol (APP) had an effect on adipose weights.Twenty-four Wistar male rats (10 weeks of age) were assigned to three groups: (1) the 5%APP group (diet containing 5% APP, N=8); (2) the 0.5%APP group (diet containing 0.5% APP, N=8); and (3) the control group (N=8) so that average weights of the groups were the same. After a three-week experimental period, adipose tissue weights were measured. Pathological and plasma characteristics were also examined. Retroperitoneal and epididymal adipose tissue weights in the 5%APP group were significantly lower than those of the control (P<0.05). Pathological examination showed that form-like cells were observed only in the control group, suggesting the existence of proliferating pre-adipocytes only in the control group. Lipid-related plasma profiles showed no statistical differences. Dietary polyphenol did not induce any anorectic effects as reported in studies concerning tea polyphenol. We conclude that dietary APP has an anti-adipogenic effect in Wistar rats without any anorectic phenomenon. PMID:16880686

  4. Variations in Lead Isotopic Abundances in Sprague-Dawley Rat Tissues: Possible Reason of Formation

    PubMed Central

    Liu, Duojian; Wu, Jing; Ouyang, Li; Wang, Jingyu

    2014-01-01

    It has been reported in previous research that the lead isotopic composition of blood, urine and feces samples statistically differed from the given lead sources in Sprague-Dawley (SD) rats. However, the reason for this phenomenon is still unclear. An animal experiment was performed to investigate the lead isotope fractionation in diverse biological samples (i.e., lungs, liver, kidneys, bone) and to explore the possible reasons. SD rats were intratracheally instilled with lead acetate at the concentrations of 0, 0.02, 0.2, and 2 mg/kg body weight. Biological samples were collected for lead isotope analysis using an inductively coupled plasma mass spectrometry (ICP-MS). Significant differences are observed in lead isotope abundances among the diverse biological samples. The lead isotope abundances (206Pb, 207Pb and 208Pb) in diverse biological samples show different degrees and directions of departure from the given lead source. The results suggest that differences in enrichment or depletion capacity for each lead isotope in the various tissues might lead to the variation in lead isotopic abundances in tissues. Moreover, a nonlinear relationship between the blood lead level and the lead isotope abundances in liver and bone is observed. When the whole-blood level is higher than 50 ng/mL, the lead isotopic compositions of biological samples tend to be the same. Thus, the data support the speculation of a fractionation functional threshold. PMID:24587048

  5. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth.

    PubMed

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  6. Extracellular Vesicles from Metastatic Rat Prostate Tumors Prime the Normal Prostate Tissue to Facilitate Tumor Growth

    PubMed Central

    Halin Bergström, Sofia; Hägglöf, Christina; Thysell, Elin; Bergh, Anders; Wikström, Pernilla; Lundholm, Marie

    2016-01-01

    Accumulating data indicates that tumor-derived extracellular vesicles (EVs) are responsible for tumor-promoting effects. However, if tumor EVs also prepare the tumor-bearing organ for subsequent tumor growth, and if this effect is different in low and high malignant tumors is not thoroughly explored. Here we used orthotopic rat Dunning R-3327 prostate tumors to compare the role of EVs from fast growing and metastatic MatLyLu (MLL) tumors with EVs from more indolent and non-metastatic Dunning G (G) tumors. Prostate tissue pre-conditioned with MLL-EVs in vivo facilitated G tumor establishment compared to G-EVs. MLL-EVs increased prostate epithelial proliferation and macrophage infiltration into the prostate compared to G-EVs. Both types of EVs increased macrophage endocytosis and the mRNA expression of genes associated with M2 polarization in vitro, with MLL-EVs giving the most pronounced effects. MLL-EVs also altered the mRNA expression of growth factors and cytokines in primary rat prostate fibroblasts compared to G-EVs, suggesting fibroblast activation. Our findings propose that EVs from metastatic tumors have the ability to prime the prostate tissue and enhance tumor growth to a higher extent than EVs from non-metastatic tumors. Identifying these differences could lead to novel therapeutic targets and potential prognostic markers for prostate cancer. PMID:27550147

  7. In vitro differentiation of rat spermatogonia into round spermatids in tissue culture

    PubMed Central

    Reda, A.; Hou, M.; Winton, T.R.; Chapin, R.E.; Söder, O.; Stukenborg, J.-B.

    2016-01-01

    STUDY QUESTION Do the organ culture conditions, previously defined for in vitro murine male germ cell differentiation, also result in differentiation of rat spermatogonia into post-meiotic germ cells exhibiting specific markers for haploid germ cells? SUMMARY ANSWER We demonstrated the differentiation of rat spermatogonia into post-meiotic cells in vitro, with emphasis on exhibiting, protein markers described for round spermatids. WHAT IS KNOWN ALREADY Full spermatogenesis in vitro from immature germ cells using an organ culture technique in mice was first reported 5 years ago. However, no studies reporting the differentiation of rat spermatogonia into post-meiotic germ cells exhibiting the characteristic protein expression profile or into functional sperm have been reported. STUDY DESIGN, SAMPLES/MATERIALS, METHODS Organ culture of testicular fragments of 5 days postpartum (dpp) neonatal rats was performed for up to 52 days. Evaluation of microscopic morphology, testosterone levels, mRNA and protein expression as measured by RT-qPCR and immunostaining were conducted to monitor germ cell differentiation in vitro. Potential effects of melatonin, Glutamax® medium, retinoic acid and the presence of epidydimal fat tissue on the spermatogenic process were evaluated. A minimum of three biological replicates were performed for all experiments presented in this study. One-way ANOVA, ANOVA on ranks and student's t-test were applied to perform the statistical analysis. MAIN RESULTS AND THE ROLE OF CHANCE Male germ cells, present in testicular tissue pieces grown from 5 dpp rats, exhibited positive protein expression for Acrosin and Crem (cAMP (cyclic adenosine mono phosphate) response element modulator) after 52 days of culture in vitro. Intra-testicular testosterone production could be observed after 3 days of culture, while when epididymal fat tissue was added, spontaneous contractility of cultured seminiferous tubules could be observed after 21 days. However, no

  8. TISSUE 65ZINC TRANSLOCATION IN A RAT MODEL OF CHRONIC ALDOSTERONISM

    PubMed Central

    Selektor, Yelena; Parker, Robert B.; Sun, Yao; Zhao, Wenyuan; Bhattacharya, Syamal K.; Weber, Karl T.

    2009-01-01

    Zinc, an essential micronutrient, is involved in wound healing. The hypozincemia seen with chronic aldosteronism is associated with enhanced fecal and urinary excretory Zn losses while its tissue distribution is less certain. Herein, we monitored tissue 65Zn distribution in uninephrectomized rats at wks 1 and 4 of aldosterone/salt treatment (ALDOST). Plasma and tissue total radionucleotide uptake was determined by calculating its mean radioactivity at 1, 4, 8, 24, and 48 h after intravenous 65Zn administration and where respective area under the concentration-time curves (AUC) were determined by the linear trapezoidal rule and expressed as a tissue:plasma AUC ratio. Tissues examined included: injured heart and kidney in response to ALDOST and incised skin; noninjured liver, skeletal muscle, and spleen, sites of stress-linked Zn uptake; and bone, a major storage and release site when Zn homeostasis is threatened. Compared to age-/gender-matched controls, with wk 1 and 4 ALDOST we found: reduced plasma 65Zn; an accumulation of 65Zn in heart and kidneys, where a well-known vasculopathy involves intramural vessels, and in incised skin at wk 1; an organ-specific increase in tissue 65Zn in liver, in keeping with upregulated metallothionein expression, skeletal muscle, and spleen; and a fall in bone and skin 65Zn at wk 4. Thus a wide-ranging disturbance in Zn homeostasis appears during ALDOST to include its translocation from plasma to injured heart, kidneys and skin and noninjured liver, skeletal muscle and spleen, together with a resorption of stored Zn in bone at wk 4. Zinc dyshomeostasis is an integral feature of chronic aldosteronism. PMID:18427278

  9. High-strain-rate brain injury model using submerged acute rat brain tissue slices.

    PubMed

    Sarntinoranont, Malisa; Lee, Sung J; Hong, Yu; King, Michael A; Subhash, Ghatu; Kwon, Jiwoon; Moore, David F

    2012-01-20

    Blast-induced traumatic brain injury (bTBI) has received increasing attention in recent years due to ongoing military operations in Iraq and Afghanistan. Sudden impacts or explosive blasts generate stress and pressure waves that propagate at high velocities and affect sensitive neurological tissues. The immediate soft tissue response to these stress waves is difficult to assess using current in vivo imaging technologies. However, these stress waves and resultant stretching and shearing of tissue within the nano- to microsecond time scale of blast and impact are likely to cause initial injury. To visualize the effects of stress wave loading, we have developed a new ex vivo model in which living tissue slices from rat brain, attached to a ballistic gelatin substrate, were subjected to high-strain-rate loads using a polymer split Hopkinson pressure bar (PSHPB) with real-time high-speed imaging. In this study, average peak fluid pressure within the test chamber reached a value of 1584±63.3 psi. Cavitation due to a trailing underpressure wave was also observed. Time-resolved images of tissue deformation were collected and large maximum eigenstrains (0.03-0.42), minimum eigenstrains (-0.33 to -0.03), maximum shear strains (0.09-0.45), and strain rates (8.4×10³/sec) were estimated using digital image correlation (DIC). Injury at 4 and 6 h was quantified using Fluoro-Jade C. Neuronal injury due to PSHPB testing was found to be significantly greater than injury associated with the tissue slice paradigm alone. While large pressures and strains were encountered for these tests, this system provides a controllable test environment to study injury to submerged brain slices over a range of strain rate, pressure, and strain loads. PMID:21970544

  10. In vivo glucose utilization in rat tissues during the three phases of starvation

    SciTech Connect

    Cherel, Y.; Burnol, A.F.; Leturque, A.; Le Maho, Y.

    1988-11-01

    Three phases of starvation have been described from changes in protein and lipid utilization in birds and mammals. In the present study, tissue glucose utilization was measured in vivo during these three phases, using a 2-deoxy-(1-3H)glucose technique in the anesthetized rat. According to this technique, the term glucose utilization therefore refers to transport and phosphorylation of glucose in tissues, ie, whatever is the fate of glucose. Whole-body glucose turnover rate, which was determined by a continuous infusion of (3-3H)glucose, decreased by 40% during the first two days of starvation (phase 1); it did not change thereafter, neither in the protein-sparing phase 2 nor in phase 3, which is marked by an increase in net protein breakdown. Two days of starvation caused a marked decrease in the glucose utilization in skeletal muscles; this decrease was higher in oxidative muscles (65% in diaphragm, 66% in soleus) than in glycolytic muscles (31% in extensor digitorum longus, 34% in epitrochlearis). Glucose utilization also decreased in heart atria (75%), heart ventricles (93%), and white adipose tissue (54%); by contrast, there was a two-fold increase in glucose utilization in brown adipose tissue and no change in brain and skin. No variations were observed in glucose utilization in any of the tissues from phase 1 to phase 2. However, phase 3 was marked by a decrease in glucose utilization in extensor digitorum longus (45%), brown adipose tissue (76%), brain (29%), and skin (40%), whereas there was a 2.3- and 3.4-fold increase in glucose utilization in diaphragm and heart ventricles, respectively.

  11. Zinc asparaginate supplementation induces redistribution of toxic trace elements in rat tissues and organs.

    PubMed

    Skalny, Andrey A; Tinkov, Alexey A; Medvedeva, Yulia S; Alchinova, Irina B; Karganov, Mikhail Yu; Ajsuvakova, Olga P; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-09-01

    The primary objective of the current study was the investigation of the influence of zinc asparaginate supplementation for 7 and 14 days on toxic metal and metalloid content in rat organs and tissues. Rats obtained zinc asparaginate in doses of 5 and 15 mg/kg/day for 7 and 14 days. At the end of the experiment rat tissues and organs (liver, kidney, heart, m. gastrocnemius, serum, and hair) were collected for subsequent analysis. Estimation of Zn, Al, As, Li, Ni, Sn, Sr content in the harvested organs was performed using inductively coupled plasma mass spectrometry at NexION 300D. The obtained data showed that intragastric administration of zinc significantly increased liver, kidney and serum zinc concentrations. Seven-day zinc treatment significantly affected the toxic trace element content in the animals' organs. Zinc supplementation significantly decreased particularly liver aluminium, nickel, and tin content, whereas lead tended to increase. Zinc-induced changes in kidney metal content were characterized by elevated lithium and decreased nickel concentration. Zinc-induced alteration of myocardical toxic element content was multidirectional. Muscle aluminium and lead concentration were reduced in response to zinc supplementation. At the same time, serum and hair toxic element concentrations remained relatively stable after 7-day zinc treatment. Zinc asparaginate treatment of 14 days significantly depressed liver and elevated kidney lithium content, whereas a significant zinc-associated decrease was detected in kidney strontium content. Zinc supplementation for 14 days resulted also in multidirectional changes in the content of heart toxic elements. At the same time, significant zinc-associated decrease in muscle lithium and nickel levels was observed. Fourteen-day zinc treatment resulted in significantly increased serum arsenic and tin concentrations, whereas hair trace element content remained relatively stable. Generally, the obtained data indicate a

  12. Zinc asparaginate supplementation induces redistribution of toxic trace elements in rat tissues and organs

    PubMed Central

    Skalny, Andrey A.; Medvedeva, Yulia S.; Alchinova, Irina B.; Karganov, Mikhail Yu.; Ajsuvakova, Olga P.; Skalny, Anatoly V.; Nikonorov, Alexandr A.

    2015-01-01

    The primary objective of the current study was the investigation of the influence of zinc asparaginate supplementation for 7 and 14 days on toxic metal and metalloid content in rat organs and tissues. Rats obtained zinc asparaginate in doses of 5 and 15 mg/kg/day for 7 and 14 days. At the end of the experiment rat tissues and organs (liver, kidney, heart, m. gastrocnemius, serum, and hair) were collected for subsequent analysis. Estimation of Zn, Al, As, Li, Ni, Sn, Sr content in the harvested organs was performed using inductively coupled plasma mass spectrometry at NexION 300D. The obtained data showed that intragastric administration of zinc significantly increased liver, kidney and serum zinc concentrations. Seven-day zinc treatment significantly affected the toxic trace element content in the animals’ organs. Zinc supplementation significantly decreased particularly liver aluminium, nickel, and tin content, whereas lead tended to increase. Zinc-induced changes in kidney metal content were characterized by elevated lithium and decreased nickel concentration. Zinc-induced alteration of myocardical toxic element content was multidirectional. Muscle aluminium and lead concentration were reduced in response to zinc supplementation. At the same time, serum and hair toxic element concentrations remained relatively stable after 7-day zinc treatment. Zinc asparaginate treatment of 14 days significantly depressed liver and elevated kidney lithium content, whereas a significant zinc-associated decrease was detected in kidney strontium content. Zinc supplementation for 14 days resulted also in multidirectional changes in the content of heart toxic elements. At the same time, significant zinc-associated decrease in muscle lithium and nickel levels was observed. Fourteen-day zinc treatment resulted in significantly increased serum arsenic and tin concentrations, whereas hair trace element content remained relatively stable. Generally, the obtained data indicate a

  13. Tissue dyslipidemia in salmonella-infected rats treated with amoxillin and pefloxacin

    PubMed Central

    2012-01-01

    Background This study investigated the effects of salmonella infection and its chemotherapy on lipid metabolism in tissues of rats infected orally with Salmonella typhimurium and treated intraperitoneally with pefloxacin and amoxillin. Methods Animals were infected with Salmonella enterica serovar Typhimurium strain TA 98. After salmonellosis was confirmed, they were divided into 7 groups of 5 animals each. While one group served as infected control group, three groups were treated with amoxillin (7.14 mg/kg body weight, 8 hourly) and the remaining three groups with pefloxacin (5.71mg/kg body weight, 12 hourly) for 5 and 10 days respectively. Uninfected control animals received 0.1ml of vehicle. Rats were sacrificed 24h after 5 and 10 days of antibiotic treatment and 5 days after discontinuation of antibiotic treatment. Their corresponding controls were also sacrificed at the same time point. Blood and tissue lipids were then evaluated. Results Salmonella infection resulted in dyslipidemia characterised by increased concentrations of free fatty acids (FFA) in plasma and erythrocyte, as well as enhanced cholesterogenesis, hypertriglyceridemia and phospholipidosis in plasma, low density lipoprotein-very low density lipoprotein (LDL-VLDL), erythrocytes, erythrocyte ghost and the organs. The antibiotics reversed the dyslipidemia but not totally. A significant correlation was observed between fecal bacterial load and plasma cholesterol (r=0.456, p<0.01), plasma triacyglycerols (r=0.485, p<0.01), plasma phospholipid (r=0.414, p<0.05), plasma free fatty acids (r=0.485, p<0.01), liver phospholipid (r=0.459, p<0.01) and brain phospholipid (r=0.343, p<0.05). Conclusion The findings of this study suggest that salmonella infection in rats and its therapy with pefloxacin and amoxillin perturb lipid metabolism and this perturbation is characterised by cholesterogenesis. PMID:23137290

  14. Hepatocyte growth factor-modified adipose tissue-derived stem cells improve erectile function in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Tao; Peng, Yifeng; Jia, Chao; Fang, Xiang; Li, Jing; Zhong, Wan

    2015-01-01

    TGFβ1-Smad signaling pathway is closely related to various tissues fibrosis. Hepatocyte growth factor (HGF) has been shown to antagonize TGFβ1-Smad signaling and may improve kidney tissue fibrosis in diabetic models. Penile fibrosis is a pathological condition which occurs during diabetic erectile dysfunction (ED). The aim of this study was to examine the effect of the treatment of ED in diabetic rats with a combination of HGF and adipose tissue-derived stem cells (ADSC). In this diabetes model, rats were injected intraperitoneally with 60 mg streptozotocin (STZ) to induce diabetes. Three months later, the diabetic rats were divided into a negative control(NC) group, an ADSC-treated group and an ADSC + HGF-treated group while normal rats were assigned into a sham group. Rats in the sham and NC groups were injected in the corpus cavernosum with phosphate-buffered saline, while rats in the other groups were injected with either ADSC or ADSC + HGF. One month later, erectile function was examined in each group and penile tissues were collected for experiments. The expression of smooth muscle actin (SMA) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) was analyzed by Western blotting. The smooth muscle and collagen deposition in corpus cavernosum was evaluated by Masson staining, while endothelial changes were assessed immunohistochemically. Cell apoptosis was detected by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. The results revealed that ADSC alone can significantly improve erectile function in diabetic rats, but in combination with HGF the improvement was more prominent, showing higher content of smooth muscle and endothelial cells and lower cell apoptotic index in corpus cavernosum. Treatment with HGF can significantly enhance the beneficial effect of ADSC on erectile function in diabetic rats, and this effect might be closely related to the down-regulation of TGFβ1-Smad signaling. PMID:26339935

  15. A monoclonal antibody against rat platelets. I. Tissue distribution in vitro and in vivo.

    PubMed Central

    Bagchus, W M; Jeunink, M F; Rozing, J; Elema, J D

    1989-01-01

    In this study we describe a new monoclonal antibody (MoAb PL.1) against rat platelets. Immunohistology of various rat tissues showed staining of platelets, especially in the spleen, and staining of megakaryocytes in bone marrow and spleen red pulp. In the liver small platelet aggregates and endothelial cells were stained. After in-vivo administration of MoAb PL.1 an acute severe thrombocytopenia was observed. In general the distribution of the antibody and/or antibody-coated platelet aggregates showed the same pattern as after in-vitro incubation, i.e. staining of rat platelets and platelet aggregates in spleen red pulp, and staining of megakaryocytes in spleen and bone marrow. Platelet aggregates were observed in the liver and electron microscopy indicated that they were associated with Kupffer cells. Furthermore, liver endothelial cells were positively stained. Comparison of the molecular weight of the antigens recognized by this MoAb and by human anti-platelet MoAbs, as well as comparison of staining patterns of megakaryocytes indicated that MoAb PL.1 is probably directed to a GPIIb/IIIa complex analogue. Since MoAb PL.1 is of the non-complement-binding mouse IgG1 isotype, it can be used for studying clearance of platelet aggregates by Fc-receptors of the MPS. It also promises to be a useful tool in the study of platelet involvement in rats with experimental nephritis. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:2649291

  16. In vitro glutathione conjugation of methyl iodide in rat, rabbit, and human blood and tissues.

    PubMed

    Poet, Torka S; Wu, Hong; Corley, Richard A; Thrall, Karla D

    2009-05-01

    Methyl iodide (MeI) is an intermediate in the manufacture of some pesticides and pharmaceuticals, and is under review for US registration as a non-ozone depleting alternative for methyl bromide for pre-plant soil fumigation. MeI is primarily metabolized via conjugation with glutathione (GSH), with further metabolism to S-methyl cysteine and methanethiol. To facilitate extrapolations of animal pharmacokinetic data to humans, rate constants for the GSH metabolism of MeI were determined in cytosols prepared from the liver and kidneys of rats, human donors, female rabbits, and rabbit fetuses, from rabbit olfactory and respiratory epithelium, and from rabbit and rat blood using a headspace vial equilibration technique and two-compartment mathematical model. MeI was metabolized in liver and kidney from adults of all three species, but metabolism was not detectable in fetal rabbit kidney. Maximal metabolic rates (V(max)) were similar in liver from rat and human donors (approximately 40 and 47 nmol/min/mg, respectively) whereas the V(max) rates in kidney cytosols varied approximately three-fold between the three species. No difference was observed in the loss of MeI from active and inactive whole blood from either rats or rabbits. The metabolism in olfactory and respiratory epithelial cytosol had Michaelis-Menten constant (K(m)) values that were several times higher than for any other tissue, suggesting essentially first-order metabolism in the nose. The metabolism of MeI in human liver cytosol prepared from five individual donors indicated two potential populations, one high affinity/low capacity and one with a lower affinity but higher capacity. PMID:19519152

  17. Changes in Metallothionein Level in Rat Hepatic Tissue after Administration of Natural Mouldy Wheat

    PubMed Central

    Vasatkova, Anna; Krizova, Sarka; Adam, Vojtech; Zeman, Ladislav; Kizek, Rene

    2009-01-01

    Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. This work was aimed at investigation of influence of mouldy wheat contaminated by pathogenic fungi producing mycotoxins on metallothionein levels in hepatic tissue of rats. The rats were administrating feed mixtures with different contents of vitamins or naturally mouldy wheat for 28 days. It was found that the wheat contained deoxynivalenol (80 ± 5 μg per kg of mouldy wheat), zearalenone (56 ± 3 μg/kg), T2-toxin (20 ± 2 μg/kg) and aflatoxins as a sum of B1, B2, G1 and G2 (3.9 ± 0.2 μg/kg). Rats were fed diets containing 0, 33, 66 and 100% naturally moulded wheat. Control group 0, 33, 66 and 100% contained vitamins according to Nutrient Requirements of Rats (NRC). Other four groups (control group with vitamins, vit33, vit66 and vit100%) were fed on the same levels of mouldy wheat, also vitamins at levels 100% higher than the previous mixtures. We determined weight, feed conversion and performed dissection to observe pathological processes. Changes between control group and experimental groups exposed to influence of mouldy wheat and experimental groups supplemented by higher concentration of vitamins and mouldy wheat were not observed. Livers were sampled and did not demonstrate significant changes in morphology compared to control either. In the following experiments the levels of metallothionein as a marker of oxidative stress was determined. We observed a quite surprising trend in metallothionein levels in animals supplemented with increased concentration of vitamins. Its level enhanced with increasing content of mouldy wheat. It was possible to determine a statistically significant decline (p<0.05) between control group and groups of animals fed with 33, 66 and 100% mouldy wheat. It is likely that some mycotoxins presented in mouldy wheat are able to block the mechanism of metallothionein synthesis. PMID:19399242

  18. Experimental Toxoplasmosis in Rats Induced Orally with Eleven Strains of Toxoplasma gondii of Seven Genotypes: Tissue Tropism, Tissue Cyst Size, Neural Lesions, Tissue Cyst Rupture without Reactivation, and Ocular Lesions

    PubMed Central

    Dubey, Jitender P.; Ferreira, Leandra R.; Alsaad, Mohammad; Verma, Shiv K.; Alves, Derron A.; Holland, Gary N.; McConkey, Glenn A.

    2016-01-01

    Background The protozoan parasite Toxoplasma gondii is one of the most widely distributed and successful parasites. Toxoplasma gondii alters rodent behavior such that infected rodents reverse their fear of cat odor, and indeed are attracted rather than repelled by feline urine. The location of the parasite encysted in the brain may influence this behavior. However, most studies are based on the highly susceptible rodent, the mouse. Methodology/Principal Findings Latent toxoplasmosis was induced in rats (10 rats per T. gondii strains) of the same age, strain, and sex, after oral inoculation with oocysts (natural route and natural stage of infection) of 11 T. gondii strains of seven genotypes. Rats were euthanized at two months post inoculation (p.i.) to investigate whether the parasite genotype affects the distribution, location, tissue cyst size, or lesions. Tissue cysts were enumerated in different regions of the brains, both in histological sections as well in saline homogenates. Tissue cysts were found in all regions of the brain. The tissue cyst density in different brain regions varied extensively between rats with many regions highly infected in some animals. Overall, the colliculus was most highly infected although there was a large amount of variability. The cerebral cortex, thalamus, and cerebellum had higher tissue cyst densities and two strains exhibited tropism for the colliculus and olfactory bulb. Histologically, lesions were confined to the brain and eyes. Tissue cyst rupture was frequent with no clear evidence for reactivation of tachyzoites. Ocular lesions were found in 23 (25%) of 92 rat eyes at two months p.i. The predominant lesion was focal inflammation in the retina. Tissue cysts were seen in the sclera of one and in the optic nerve of two rats. The choroid was not affected. Only tissue cysts, not active tachyzoite infections, were detected. Tissue cysts were seen in histological sections of tongue of 20 rats but not in myocardium and leg

  19. Evaluation of peripheral vasodilative indices in skin tissue of type 1 diabetic rats by use of RGB images

    NASA Astrophysics Data System (ADS)

    Tanaka, Noriyuki; Nishidate, Izumi; Nakano, Kazuya; Aizu, Yoshihisa; Niizeki, Kyuichi

    2016-04-01

    We investigated a method to evaluate the arterial inflow and the venous capacitance in the skin tissue of streptozotocin-induced type 1 diabetic rats from RGB digital color images. The arterial inflow and the venous capacitance in the dorsal reversed McFarlane skin flap are calculated based on the responses of change in the total blood concentration to occlusion of blood flow to and from the flap tissues at a pressure of 50 mmHg. The arterial inflow and the venous capacitance in the skin flap tissue were significantly reduced in type 1 diabetic rat group compared with the non-diabetic rat group. The results of the present study indicate the possibility of using the proposed method for evaluating the peripheral vascular dysfunctions in diabetes mellitus.

  20. EGFP gene transfection into the synovial joint tissues of rats with rheumatoid arthritis by ultrasound-mediated microbubble destruction

    PubMed Central

    JING, XIANG-XIANG; LIU, JIE; YANG, BING-ANG; FU, SHAO-QING; WU, TANG-NA; WANG, DONG-LIN

    2014-01-01

    The aim of the present study was to explore the feasibility of enhancing green fluorescent protein (EGFP) gene transfection into the synovial joint tissues of rats with rheumatoid arthritis (RA) by ultrasound-mediated microbubble destruction. An optimal SonoVue dose was determined using 40 normal rats categorized into five groups according to the various doses of microbubbles used. At 1 week after ultrasound irradiation, the rats were sacrificed. Damage to the joint synovial tissues was observed with hematoxylin and eosin histopathological staining under a microscope. A further 44 normal rats were used to establish a rat model of RA, and were then categorized into four groups: EGFP, ultrasound + EGFP, microbubbles + EGFP and ultrasound + microbubbles + EGFP. The last group was irradiated with ultrasound for 10 min following the injection of 300 μl SonoVue and 10 μg EGFP into the joint cavity. Rats were sacrificed after 3 days and synovial tissue was collected from the knee joints for observation of EGFP with fluorescence microscopy and analysis by quantitative polymerase chain reaction. EGFP expression was observed in the synovial tissues of all groups. However, high EGFP expression levels were observed in the ultrasound + microbubbles + EGFP group. No statistically significant differences (P>0.05) were observed in the EGFP expression levels between the EGFP, ultrasound + EGFP and microbubbles + EGFP groups. However, EGFP expression levels in the EGFP, ultrasound + EGFP and microbubbles + EGFP groups significantly differed (P<0.05) from that in the ultrasound + microbubbles + EGFP group. Therefore, ultrasound-mediated microbubble destruction improved EGFP transfection efficiency into the joint synovial tissues of rats with RA. PMID:24940446

  1. A comparison of tissue engineering based repair of calvarial defects using adipose stem cells from normal and osteoporotic rats

    PubMed Central

    Pei, Ming; Li, Jingting; McConda, David B.; Wen, Sijin; Clovis, Nina B.; Danley, Suzanne S.

    2015-01-01

    Repairing large bone defects presents a significant challenge, especially in those people who have a limited regenerative capacity such as in osteoporotic (OP) patients. The aim of this study was to compare adipose stem cells (ASCs) from both normal (NORM) and ovariectomized (OVX) rats in osteogenic potential using both in vitro and in vivo models. After successful establishment of a rat OP model, we found that ASCs from OVX rats exhibited a comparable proliferation capacity to those from NORM rats but had significantly higher adipogenic and relatively lower osteogenic potential. Thirty-two weeks post-implantation with poly (lactic-co-glycolic acid) (PLGA) alone or PLGA seeded with osteogenic-induced ASCs for critical-size calvarial defects, the data from Herovici’s collagen staining and micro-computed tomography suggested that the implantation of ASC-PLGA constructs exhibited a higher bone volume density compared to the PLGA alone group, especially in the NORM rat group. Intriguingly, the defects from OVX rats exhibited a higher bone volume density compared to NORM rats, especially for implantation of the PLGA alone group. Our results indicated that ASC based tissue constructs are more beneficial for the repair of calvarial defects in NORM rats while implantation of PLGA scaffold contributed to defect regeneration in OVX rats. PMID:25940459

  2. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue.

    PubMed

    Petridou, Anatoli; Tsalouhidou, Sofia; Tsalis, George; Schulz, Thorsten; Michna, Horst; Mougios, Vassilis

    2007-08-01

    The aim of the present study was to examine the effect of 8 weeks of voluntary wheel running on the gene expression, at the protein level, of 2 enzymes involved in lipogenesis (fatty acid synthase [FAS] and diacylglycerol acyl transferase 1), 2 proteins involved in lipolysis (hormone-sensitive lipase [HSL] and perilipin), and 3 transcription factors mediating the induction of genes involved in lipid metabolism (the alpha, gamma, and delta members of the peroxisome proliferator-activated receptor, or PPAR, family) in rat liver, gastrocnemius muscle, epididymal fat, and subcutaneous fat. Proteins were measured through Western blot analysis in the tissues of 11 trained and 14 untrained rats. The trained rats had lower FAS in the liver; higher FAS, HSL, and perilipin in epididymal fat; and higher HSL in subcutaneous fat. In addition, the trained rats had higher total protein concentrations in both fat depots. No significant differences in the liver, muscle, or adipose tissue PPAR contents were found between groups. However, the DNA binding activity of PPARgamma, measured through an enzyme immunoassay-based method, was higher in both fat depots of the trained rats. Our findings suggest that long-term wheel running had significant effects on the concentrations of proteins playing key roles in lipogenesis and lipolysis in rat liver and adipose tissue. These effects may be due to PPAR activation rather than induction, rendering the transcriptional regulation of target genes more economical and flexible. The activation of PPARgamma with exercise may mediate its beneficial effect on insulin sensitivity. PMID:17618946

  3. Changes in tissue distribution of rat alpha 1-macroglobulin and pregnancy-associated alpha 1-glycoprotein after inflammatory injury.

    PubMed Central

    Zorin, N. A.; Zhabin, S. G.; Belogorlova, T. I.; Chirikova, T. S.; Krayushkina, N. A.; Lykova, O. F.

    1994-01-01

    Antiserum against rat alpha 1-macroglobulin (alpha 1MG) was produced in rabbits. Antiserum against rat pregnancy-associated alpha 1-glycoprotein (PAG) was obtained by immunization with a partly purified PAG preparation and absorption of the serum with male rat serum. Acute inflammation was produced in non-pregnant female rats by a single intramuscular injection of turpentine. The concentrations of both macroglobulins in the serum and in tissue extracts were measured by rocket immunoelectrophoresis at various times up to 7 days after injury. Inflammation produced in the rats resulted in moderately elevated serum levels of these proteins soon after injury. At first, alpha 1MG levels in a number of tissues (heart, lung, kidney, spleen, pancreas, uterus and ovary) were depressed markedly; they then stabilized. The elevated serum concentrations of alpha 1MG remained unchanged during inflammation. The store of PAG in the tissues was rapidly depleted and its serum level decreased to a normal value 7 days after injury. Our findings indicate that alpha 1MG plays a more important role in maintenance of the proteinase inhibitory potential in the rat than does PAG. Images Figure 1 Figure 2 PMID:7537521

  4. The antioxidant effects of dry apricot in the various tissues of rats with induced cold restraint stress.

    PubMed

    Uguralp, S; Ozturk, F; Aktay, G; Cetin, A; Gursoy, S

    2012-01-01

    α-Tocopherol and β-carotene are the best known and most widely used natural antioxidant substances. Apricot contains β-carotene, tocopherols and flavonoids. This experimental study was designed to investigate the protective effect of Malatya kabashi apricot in stress-induced injury in various tissues of rats. In total, 32 male Wistar albino rats were divided into four groups: control, apricot, stress and apricot-stress groups. Apricot was administrated to rats by gavage for 10 days in the apricot and apricot-stress groups. Then rats were kept at 4°C for 4 h in stress and apricot-stress groups. The rats were killed at the end of the experiment for biochemical and histological examinations. This study shows apricot supplementation decreased oxidative stress injury in both the stomach and intestine. PMID:21985499

  5. Tissue Responses to Postoperative Laser Therapy in Diabetic Rats Submitted to Excisional Wounds

    PubMed Central

    de Loura Santana, Cristiano; de Fátima Teixeira Silva, Daniela; Deana, Alessandro Melo; Prates, Renato Araujo; Souza, Amanda Pires; Gomes, Mariana Teixeira; de Azevedo Sampaio, Brunna Pileggi; Shibuya, Josiane Ferraretto; Bussadori, Sandra Kalil; Mesquita-Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos; França, Cristiane Miranda

    2015-01-01

    In a previous study about low-level laser therapy biomodulation on a full-thickness burn model we showed that single and fractionated dose regimens increased wound healing and leukocyte influx similarly when compared with untreated control. In order to verify if this finding would be similar in an impaired wound model, we investigated the effect of single and multiple irradiations on wound closure rate, type of inflammatory infiltrate, myofibroblasts, collagen deposition, and optical retardation of collagen in diabetic rats. Female Wistar rats in the same estrous cycle had diabetes induced with streptozotocin and an 8-mm excisional wound performed with a punch. The experimental groups were: control group – untreated ulcer; single-dose group – ulcer submitted to single dose of diode laser therapy (λ = 660 ± 2 nm; P = 30 mW; energy density: 4 J/cm2) and fractionated-dose group – ulcer submitted to 1 J/cm2 laser therapy on Days 1, 3, 8, and 10. The ulcers were photographed on the experimental days and after euthanasia tissue samples were routinely processed for histological and immunohistochemistry analyses. Independently of the energy density, laser therapy accelerated wound closure by approximately 40% in the first three days in comparison to the control group. Laser therapy increased acute inflammatory infiltrate until Day 3. Both laser groups exhibited more myofibroblasts and better collagen organization than the control group. The findings demonstrate that low-level laser therapy in the immediate postoperative period can enhance the tissue repair process in a diabetes model. Similar effects were achieved with laser therapy applied a single time with an energy density of 4 J/cm2 and applied four times with an energy density of 1 J/cm2. The application of laser therapy in the inflammatory phase was the most important factor to the enhancement of the tissue repair process. PMID:25909480

  6. Fisetin averts oxidative stress in pancreatic tissues of streptozotocin-induced diabetic rats.

    PubMed

    Prasath, Gopalan Sriram; Sundaram, Chinnakrishnan Shanmuga; Subramanian, Sorimuthu Pillai

    2013-10-01

    Persistent hyperglycemia is associated with chronic oxidative stress which contributes to the development and progression of diabetes-associated complications. The sensitivity of pancreatic β-cells to oxidative stress has been attributed to their low content of antioxidants compared with other tissues. Bioactive compounds with potent antidiabetic properties have been shown to ameliorate hyperglycemia mediated oxidative stress. Recently, we have reported that oral administration of fisetin (10 mg/Kg b.w.), a bioflavonoid found to be present in strawberries, persimmon, to STZ-induced experimental diabetic rats significantly improved normoglycemia. The present study was aimed to evaluate the antioxidant potential of fisetin in both in vitro and in vivo. Diabetes was induced by single intraperitoneal injection of streptozotocin (50 mg/kg body weight). Fisetin was administered orally for 30 days. At the end of the study, all animals were killed. Blood samples were collected for the biochemical estimations. The antioxidant status was evaluated. Histological examinations were performed on pancreatic tissues. Fisetin treatment showed a significant decline in the levels of blood glucose, glycosylated hemoglobin (HbA1c), NF-kB p65 unit (in pancreas) and IL-1β (plasma), serum nitric oxide (NO) with an elevation in plasma insulin. The treatment also improved the antioxidant status in pancreas as well as plasma of diabetic rats indicating the antioxidant potential of fisetin. In addition, the results of DPPH and ABTS assays substantiate the free radical scavenging activity of fisetin. Histological studies of the pancreas also evidenced the tissue protective nature of fisetin. It is concluded that, fisetin possesses antioxidant and anti-inflammatory property and may be considered as an adjunct for the treatment of diabetes. PMID:23277230

  7. A magnetic resonance imaging study on changes in rat mandibular bone marrow and pulp tissue after high-dose irradiation

    PubMed Central

    Lee, Wan; Lee, Byung-Do; Lee, Kang-Kyoo

    2014-01-01

    Purpose This study was designed to evaluate whether magnetic resonance imaging (MRI) is appropriate for detecting early changes in the mandibular bone marrow and pulp tissue of rats after high-dose irradiation. Materials and Methods The right mandibles of Sprague-Dawley rats were irradiated with 10 Gy (Group 1, n=5) and 20 Gy (Group 2, n=5). Five non-irradiated animals were used as controls. The MR images of rat mandibles were obtained before irradiation and once a week until week 4 after irradiation. From the MR images, the signal intensity (SI) of the mandibular bone marrow and pulp tissue of the incisor was interpreted. The MR images were compared with the histopathologic findings. Results The SI of the mandibular bone marrow had decreased on T2-weighted MR images. There was little difference between Groups 1 and 2. The SI of the irradiated groups appeared to be lower than that of the control group. The histopathologic findings showed that the trabecular bone in the irradiated group had increased. The SI of the irradiated pulp tissue had decreased on T2-weighted MR images. However, the SI of the MR images in Group 2 was high in the atrophic pulp of the incisor apex at week 2 after irradiation. Conclusion These patterns seen on MRI in rat bone marrow and pulp tissue were consistent with histopathologic findings. They may be useful to assess radiogenic sclerotic changes in rat mandibular bone marrow. PMID:24701458

  8. The distribution and localization of /sup 127/m tellurium in normal and pathological nervous tissues of young and adult rats

    SciTech Connect

    Duckett, S.

    1982-11-01

    An equal amount (per weight) of /sup 127/m tellurium (Te) was injected IP into weanling and adult rats, some intoxicated with a diet containing Te, others not. The young intoxicated rats presented a segmental demyelination of the sciatic nerve and paralysis of the hind limbs; the adult intoxicated rats did not. Quantitation of 127m Te in nervous and other tissues was done with a gamma counter. Correlative morphological examination of the nervous tissues was done with light and electron microscopy. This study shows that Te crosses the vascular wall without injuring endothelial cells and invades the surrounding sciatic nerve parenchyma following administration of 127m Te to a weanling or adult rat. However, Te damages the endothelium, crosses the vascular wall of endo and perineurial vessels in weanling rats, causes a perivascular oedema, cytoplasmic anomalies in the Schwann cells, destruction of myelin and apparently invades axones--according to autoradiographic studies--following the administration of 127m Te plus the Te-diet. It is concluded that Te penetrates more quickly and in larger amounts the walls of blood vessels in the sciatic nerve of weanling rats intoxicated with Te, than the same nerve in the other weanling and adults rats. Te in the amounts indicated here penetrates the parenchyma of the CNS but apparently does not cause injury.

  9. Development of a liquid chromatography with mass spectrometry method for the determination of gelsemine in rat plasma and tissue: Application to a pharmacokinetic and tissue distribution study.

    PubMed

    Zhang, Shuangshuang; Hu, Shuping; Yang, Xiangxiang; Shen, Jiaqi; Zheng, Xiaoyong; Huang, Kexin; Xiang, Zheng

    2015-03-01

    Gelsemine from Gelsemium elegans Benth is a potential anesthetic and analgesic agent with no physical dependence and opiate addiction. This study was aimed at developing an ultrafast liquid chromatography coupled to tandem mass spectrometry method to quantify gelsemine in rat plasma and tissues. Plasma and tissues were processed with acetonitrile precipitation, and dendrobine was chosen as the internal standard. Sample separation was performed on an ACQUITY HSS T3 column. The mobile phase consisted of acetonitrile and 0.1% formic acid aqueous solution. Multiple reactions monitoring mode was utilized to detect the compounds of interest. The mass spectrometer was operated in the positive ion mode for detection. The MS/MS ion transitions monitored were m/z 323.2→70.5 for gelsemine and 264.2→108.05 for dendrobine, respectively. The calibration curves were linear over the range of 1-500 ng/mL in all biological matrices. The lower limit of quantification for rats plasma and tissues was 1.0 ng/mL. The values for inter- and intraday precision and accuracy were well within the ranges acceptable (< 15%). It was successfully applied to the pharmacokinetic and tissue distribution studies of gelsemine after intravenous doses of 5, 2, and 0.5 mg/kg in rats. These data of gelsemine would be useful for clinical application and further development. PMID:25580713

  10. Effects of a ketogenic diet on adipose tissue, liver, and serum biomarkers in sedentary rats and rats that exercised via resisted voluntary wheel running.

    PubMed

    Holland, Angelia Maleah; Kephart, Wesley C; Mumford, Petey W; Mobley, Christopher Brooks; Lowery, Ryan P; Shake, Joshua J; Patel, Romil K; Healy, James C; McCullough, Danielle J; Kluess, Heidi A; Huggins, Kevin W; Kavazis, Andreas N; Wilson, Jacob M; Roberts, Michael D

    2016-08-01

    We investigated the effects of different diets on adipose tissue, liver, serum morphology, and biomarkers in rats that voluntarily exercised. Male Sprague-Dawley rats (∼9-10 wk of age) exercised with resistance-loaded voluntary running wheels (EX; wheels loaded with 20-60% body mass) or remained sedentary (SED) over 6 wk. EX and SED rats were provided isocaloric amounts of either a ketogenic diet (KD; 20.2%-10.3%-69.5% protein-carbohydrate-fat), a Western diet (WD; 15.2%-42.7-42.0%), or standard chow (SC; 24.0%-58.0%-18.0%); n = 8-10 in each diet for SED and EX rats. Following the intervention, body mass and feed efficiency were lowest in KD rats, independent of exercise (P < 0.05). Absolute and relative (body mass-adjusted) omental adipose tissue (OMAT) masses were greatest in WD rats (P < 0.05), and OMAT adipocyte diameters were lowest in KD-fed rats (P < 0.05). None of the assayed OMAT or subcutaneous (SQ) protein markers were affected by the diets [total acetyl coA carboxylase (ACC), CD36, and CEBPα or phosphorylated NF-κB/p65, AMPKα, and hormone-sensitive lipase (HSL)], although EX unexpectedly altered some OMAT markers (i.e., higher ACC and phosphorylated NF-κB/p65, and lower phosphorylated AMPKα and phosphorylated HSL). Liver triglycerides were greatest in WD rats (P < 0.05), and liver phosphorylated NF-κB/p65 was lowest in KD rats (P < 0.05). Serum insulin, glucose, triglycerides, and total cholesterol were greater in WD and/or SC rats compared with KD rats (P < 0.05), and serum β-hydroxybutyrate was greater in KD vs. SC rats (P < 0.05). In conclusion, KD rats presented a healthier metabolic profile, albeit the employed exercise protocol minimally impacts any potentiating effects that KD has on fat loss. PMID:27357802

  11. Determination of piceid in rat plasma and tissues by high-performance liquid chromatographic method with UV detection.

    PubMed

    Lv, Chunyan; Zhang, Lantong; Wang, Qiao; Liu, Weina; Wang, Chunying; Jing, Xiujuan; Liu, Yang

    2006-11-01

    A rapid, sensitive and selective HPLC method was developed and validated for determination of piceid in rat plasma and tissues. The drug was isolated from plasma and tissues by a simple protein precipitation procedure. Chromatographic separation was performed on a C(18) column with acetonitrile-water (26:74, v/v) as mobile phase. The method was successfully applied to the pharmacokinetics and tissue distribution research after oral administration of a 50 mg/kg dose of piceid to healthy male Wistar rats. The pharmacokinetic parameters showed that piceid was quickly absorbed, distributed and eliminated within 4 h after oral administration. The tissue distribution results showed that, at 10 min, the concentrations of piceid in most tissues reached peak level except in heart and testis. The highest level of piceid was found in stomach, then in small intestine, spleen, lung, brain, testis, liver, kidney and heart. The amount of piceid in testis and heart reached the peak level at 30 min. At 120 min, the amount of piceid in all tissues decreased to a low percentage of the initial concentration. Piceid was absorbed throughout the gastrointestinal tract with considerable absorption taking place in the stomach and small intestine. There was no long-term accumulation of piceid in rat tissues. PMID:16883546

  12. Effect of exercise training on the fatty acid composition of lipid classes in rat liver, skeletal muscle, and adipose tissue.

    PubMed

    Petridou, Anatoli; Nikolaidis, Michalis G; Matsakas, Antonis; Schulz, Thorsten; Michna, Horst; Mougios, Vassilis

    2005-05-01

    The aim of the present study was to examine the effects of 8 weeks of exercise training on the fatty acid composition of phospholipids (PL) and triacylglycerols (TG) in rat liver, skeletal muscle (gastrocnemius medialis), and adipose tissue (epididymal and subcutaneous fat). For this purpose, the relevant tissues of 11 trained rats were compared to those of 14 untrained ones. Training caused several significant differences of large effect size in the concentrations and percentages of individual fatty acids in the aforementioned lipid classes. The fatty acid composition of liver PL, in terms of both concentrations and percentages, changed with training. The TG content of muscle and subcutaneous adipose tissue decreased significantly with training. In contrast to the liver, where no significant differences in the fatty acid profile of TG were found, muscle underwent more significant differences in TG than PL, and adipose tissue only in TG. Most differences were in the same direction in muscle and adipose tissue TG, suggesting a common underlying mechanism. Estimated fatty acid elongase activity was significantly higher, whereas Delta(9)-desaturase activity was significantly lower in muscle and adipose tissue of the trained rats. In conclusion, exercise training modified the fatty acid composition of liver PL, muscle PL and TG, as well as adipose tissue TG. These findings may aid in delineating the effects of exercise on biological functions such as membrane properties, cell signaling, and gene expression. PMID:15682327

  13. Decreased sulfhydryl groups in the reperfused myocardial tissue of a rat model of myocardial infarction.

    PubMed

    Maezawa, H; Manaka, K; Yamakawa, K; Ogawa, K; Iizuka, M

    1997-02-01

    The aim of this study was to determine whether myocardial injury resulting from temporary ischemia followed by reperfusion can be measured by assaying sulfhydryl groups in the affected tissue of a rat model of myocardial infarction. We studied 3 groups: a control group (n = 6), which underwent surgery without left coronary artery (LCA) ligation; group NoR (n = 9), in which the LCA was ligated for 3 h; and group I + R (n = 7), in which 30 min LCA ligation was followed by 3 h reperfusion. The sulfhydryl group content of myocardial tissue was assayed by measuring the fluorescence produced by incubating heart sections with N-(7-dimethylamino-4-methyl-3-coumarinyl) maleimide (DACM), which binds sulfhydryl groups. The fluorescence intensity (FI) of normal and infarcted myocardium was quantified by our computerized system of microscopic fluorophotometry. Indices such as sulfhydryl group content, the size of the low-FI area [% AREA(lower FI)] and the relative decrease in FI [%FI(decrease)]) in the infarct zone were calculated. Both %AREA(lower FI) and %FI(decrease) were significantly higher in the infarcted zone of animals in NoR and I + R groups than in control animals. Both indices were higher in infarct tissue from animals in the I + R group than in the NoR group. These changes suggest that sulfhydryl group content is significantly reduced in tissue that has been subjected to ischemia-reperfusion. Microscopic fluorophotometry, as defined by DACM staining of myocardial tissue, may help to delineate areas of myocardial reperfusion injury. PMID:9070971

  14. Chemical nature of nitric oxide storage forms in rat vascular tissue

    PubMed Central

    Rodriguez, Juan; Maloney, Ronald E.; Rassaf, Tienush; Bryan, Nathan S.; Feelisch, Martin

    2003-01-01

    Endothelial NO production results in local formation of adducts that may act as storage forms of NO. Because little is known about their chemical nature, concentrations, and possible role in vascular biology, we sought to characterize those species basally present in rat aorta, using two independent approaches. In the first approach, tissue homogenates were analyzed by using chemiluminescence- and ion-chromatography-based techniques that allow trace-level quantification of NO-related compounds in complex biological matrices. In the second approach, NO stores were characterized by their ability to release NO when illuminated with light and subsequently relax vascular smooth muscle (photorelaxation). The latter included a careful assessment of action spectra for photorelaxation, taking into account the light-scattering properties of the tissue and the storage depletion rates induced by exposure to controlled levels of light. Biochemical analyses revealed that aortic tissues contained 10 ± 1 μM nitrite, 42 ± 7 μM nitrate, 40 ± 6 nM S-nitroso, and 33 ± 6 nM N-nitroso compounds (n = 4–8). The functional data obtained suggest that the NO photolytically released in the tissue originated from species with photophysical properties similar to those reported for low-molecular-weight S-nitrosothiols, as well as from nitrite. The relative contribution of these potential NO stores to the extent of photorelaxation was consistent with their concentrations detected biochemically in vascular tissue when their photoactivity was taken into account. We conclude that intravascular nitroso species and nitrite both have the potential to release physiologically relevant quantities of NO independent of enzymatic control by NO synthase. PMID:12502793

  15. Hyaluronic acid hydrogels with IKVAV peptides for tissue repair and axonal regeneration in an injured rat brain

    NASA Astrophysics Data System (ADS)

    Wei, Y. T.; Tian, W. M.; Yu, X.; Cui, F. Z.; Hou, S. P.; Xu, Q. Y.; Lee, In-Seop

    2007-09-01

    A biocompatible hydrogel of hyaluronic acid with the neurite-promoting peptide sequence of IKVAV was synthesized. The characterization of the hydrogel shows an open porous structure and a large surface area available for cell interaction. Its ability to promote tissue repair and axonal regeneration in the lesioned rat cerebrum is also evaluated. After implantation, the polymer hydrogel repaired the tissue defect and formed a permissive interface with the host tissue. Axonal growth occurred within the microstructure of the network. Within 6 weeks the polymer implant was invaded by host-derived tissue, glial cells, blood vessels and axons. Such a hydrogel matrix showed the properties of neuron conduction. It has the potential to repair tissue defects in the central nervous system by promoting the formation of a tissue matrix and axonal growth by replacing the lost tissue.

  16. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats.

    PubMed Central

    Escobar-Morreale, H F; Obregón, M J; Escobar del Rey, F; Morreale de Escobar, G

    1995-01-01

    We have studied whether, or not, tissue-specific regulatory mechanisms provide normal 3,5,3'-triiodothyronine (T3) concentrations simultaneously in all tissues of a hypothyroid animal receiving thyroxine (T4), an assumption implicit in the replacement therapy of hypothyroid patients with T4 alone. Thyroidectomized rats were infused with placebo or 1 of 10 T4 doses (0.2-8.0 micrograms per 100 grams of body weight per day). Placebo-infused intact rats served as controls. Plasma and 10 tissues were obtained after 12-13 d of infusion. Plasma thyrotropin and plasma and tissue T4 and T3 were determined by RIA. Iodothyronine-deiodinase activities were assayed using cerebral cortex, liver, and lung. No single dose of T4 was able to restore normal plasma thyrotropin, T4 and T3, as well as T4 and T3 in all tissues, or at least to restore T3 simultaneously in plasma and all tissues. Moreover, in most tissues, the dose of T4 needed to ensure normal T3 levels resulted in supraphysiological T4 concentrations. Notable exceptions were the cortex, brown adipose tissue, and cerebellum, which maintained T3 homeostasis over a wide range of plasma T4 and T3 levels. Deiodinase activities explained some, but not all, of the tissue-specific and dose related changes in tissue T3 concentrations. In conclusion, euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy. Images PMID:8675653

  17. Hard tissue formation of STRO-1-selected rat dental pulp stem cells in vivo.

    PubMed

    Yang, Xuechao; Walboomers, X Frank; van den Beucken, Jeroen J J P; Bian, Zhuan; Fan, Mingwen; Jansen, John A

    2009-02-01

    The objective of this study was to examine hard tissue formation of STRO-1-selected rat dental pulp-derived stem cells, seeded into a calcium phosphate ceramic scaffold, and implanted subcutaneously in mice. Previously, STRO-1 selection was used to obtain a mesenchymal stem cell progenitor subpopulation from primary dental pulp-derived stem cells. In the current study, these cells were cultured with three different media: "BMP-plus" medium containing dexamethasone and 100 ng/mL of rhBMP-2, "odontogenic" medium containing dexamethasone, and "control" medium without supplements. The cell-scaffold complexes were cultured in these media for 1, 4, or 8 days before implantation. Histological analysis demonstrated that the cultures with BMP-plus and 4 days of culture gave the highest percentage of hard tissue formation per implant (36 +/- 9% of pore area). Real-time PCR confirmed these results. In conclusion, STRO-1-selected dental pulp stem cells show effective hard tissue formation in vivo, and a short in vitro culture period and addition of BMP-2 can enhance this effect. PMID:18652538

  18. Electrospun fibrinogen: feasibility as a tissue engineering scaffold in a rat cell culture model.

    PubMed

    McManus, Michael C; Boland, Eugene D; Simpson, David G; Barnes, Catherine P; Bowlin, Gary L

    2007-05-01

    Fibrinogen has a well-established tissue engineering track record because of its ability to induce improved cellular interaction and scaffold remodeling compared to synthetic scaffolds. While the feasibility of electrospinning fibrinogen scaffolds of submicron diameter fibers and their mechanical properties have been demonstrated, in vitro cellular interaction has not yet been evaluated. The goal of this study was to demonstrate, based on cellular interaction and scaffold remodeling, that electrospun fibrinogen can be used successfully as a tissue engineering scaffold. Electrospun fibrinogen scaffolds were disinfected, seeded with neonatal rat cardiac fibroblasts, and cultured for 2, 7, and 14 days. Cultures were treated to regulate scaffold degradation by either supplementing serum-containing media with aprotinin or crosslinking the scaffolds with glutaraldehyde vapor. Biocompatibility was assessed through a WST-1 cell proliferation assay. Postculture scaffolds were evaluated by scanning electron microscopy and histology. Cell culture demonstrated that fibroblasts readily migrate into and remodel electrospun fibrinogen scaffolds with deposition of native collagen. Supplementation of culture media with different concentrations of aprotinin-modulated scaffold degradation in a predictable fashion, but glutaraldehyde vapor fixation was less reliable. Based on the observed cellular interactions, there is tremendous potential for electrospun fibrinogen as a tissue engineering scaffold. PMID:17120217

  19. LC-MS-MS Analysis of Brodifacoum Isomers in Rat Tissue.

    PubMed

    Hauck, Zane Z; Feinstein, Douglas L; van Breemen, Richard B

    2016-05-01

    Brodifacoum (BDF) is a second-generation anticoagulant rodenticide structurally related to warfarin but containing two chiral centers. Highly stable, BDF can contaminate food and water supplies causing accidental poisoning of humans and nontarget animals. To determine the distribution of BDF isomers in serum and tissues, a quantitative method was developed and validated according to FDA guidelines based on high-performance liquid chromatography-tandem mass spectrometry. A single liquid-liquid extraction step provided recoveries exceeding 93%. Reversed-phase chromatographic separations required <6 min, and quantitative analysis utilized a triple-quadrupole mass spectrometer equipped with negative ion electrospray and selected reaction monitoring. The standard curve had a linear regression coefficient of 0.999 and intra- and inter-assay variations of <10%. The chromatographic method enabled the resolution and measurement of pairs of BDF diastereomers in commercial materials as well as in rat tissues. This method is suitable for measuring BDF exposure as well as basic science studies of the distribution and elimination of BDF diastereomers to various tissues. PMID:26912564

  20. Histological changes in connective tissue of rat tails after bipolar radiofrequency treatment.

    PubMed

    Beltrán-Frutos, E; Bernal-Mañas, C M; Navarro, S; Zuasti, A; Ferrer, C; Canteras, M; Seco-Rovira, V; García-Collado, A J; Pastor, L M

    2012-09-01

    Radiofrequency (RF) has been included in the techniques used in aesthetic surgery/medicine. To date, no studies have performed a histological assessment of changes in the tissue after application of bipolar radiofrequency (BRF) with low energy and frequency. The aim of this study was to examine changes that are produced in connective tissue, principally in the fibroblasts, following BRF treatment. Four groups of rats received a different number of RF sessions (1, 2, 3 and 5). The following parameters were determined: the number of fibroblasts/unit area (FA), the proliferation index (PI), the Heat shock Protein 47 index (HSPI) and the percentage of connective tissue (PC). For statistical analysis, two subgroups (A and B) were made for the variables FA, PI and PC, and another two subgroups (C and D) for the variable HSPI. Significant differences for FA, PI and PC were observed between subgroups A and B, FA and PI having higher values in A, while PC had higher values in B. The HSPI in subgroup C showed significantly higher values than in D. Low energy and frequency BRF led to an increase in the number, proliferation and biosynthetic activity of fibroblasts. The resulting stress suffered by fibroblasts as a result of heat may be associated with the phenomenon of hormesis. PMID:22806911

  1. Plasma Pharmacokinetics and Tissue Disposition of Novel Dextran- Methylprednisolone Conjugates with Peptide Linkers in Rats

    PubMed Central

    Penugonda, Suman; Agarwal, Hitesh K.; Parang, Keykavous; Mehvar, Reza

    2012-01-01

    The plasma and tissue disposition of two novel dextran prodrugs of methylprednisolone (MP) containing one (DMP-1) or five (DMP-5) amino acids as linkers were studied in rats. Single 5-mg/kg doses (MP equivalent) of each prodrug or MP were administered intravenously, and blood and tissue samples were collected. Prodrug and drug concentrations were quantitated using HPLC, and non-compartmental pharmacokinetic parameters were estimated. Whereas conjugation of MP with dextran in both prodrugs substantially decreased the clearance of the drug by ~200 fold, the accumulations of the drug in the liver, spleen, and kidneys were significantly increased by conjugation. However, the extent of accumulation of DMP-1 in these tissues was substantially greater than that for DMP-5. Substantial amounts of MP were regenerated from both prodrugs in the liver and spleen, with the rate of release from DMP-5 being twice as fast as that from DMP-1. However, the AUCs of MP regenerated from DMP-1 in the liver and spleen were substantially higher than those after DMP-5. In contrast, in the kidneys, the AUC of MP regenerated from DMP-5 was higher than that after DMP-1 administration. These data suggest that DMP-1 may be more suitable than DMP-5 for targeting immunosuppression to the liver and spleen. PMID:19780131

  2. Fibronectin and the adhesive properties of rat lymphocytes obtained from different peripheral lymphoid tissues.

    PubMed

    Altankov, G; Kostadinov, A; Marinova, L

    1990-01-01

    A comparative investigation has been carried out on the effect of plasma fibronectin (Fn) on the adhesive properties of normal rat lymphocytes obtained from different lymphoid tissues: blood, spleen, mesenteric and tonsillar lymph nodes. Fn was immobilized on the basis of its ability to bind to gelatin. We established that concentrations of 40-50 micrograms/ml are sufficient for a saturation effect on Fn coating. For spleen cells an adhesion of 55.7 +/- 9.3%, for mesenteric lymph nodes 34.5 +/- 8.7% and for tonsillar cells 33.8 +/- 3.2% was observed. Blood lymphocytes showed the lowest adhesion, 21.3 +/- 4.2%. Compared to the other lymphoid tissues, the spleen cells exhibited a "basal" adherence to surfaces coated with gelatin only: 19.2 +/- 4.1%. T lymphocytes participate to a greater extent in the process, since their number was significantly reduced in cell suspensions after adhesion to both gelatin and gelatin-Fn coated surfaces. The addition of soluble Fn leads to a competitive inhibition of the lymphocyte adhesion to gelatin-Fn coated surfaces. The data demonstrated the important role of Fn for the adhesive interactions of lymphocytes during their functional distribution in the tissues. PMID:2076848

  3. Cigarette smoke-induced DNA adducts in the respiratory and nonrespiratory tissues of rats

    SciTech Connect

    Gairola, C.G.; Gupta, R.C. )

    1991-01-01

    Formation of DNA adducts is regarded as an essential initial step in the process of chemical carcinogenesis. To determine how chronic exposure to cigarette smoke affects the distribution of DNA adducts in selected respiratory and nonrespiratory tissues. The authors exposed male Sprague-Dawley rats daily to fresh mainstream smoke from the Univ. of Kentucky reference cigarettes (2R1) in a nose-only exposure system for 32 weeks. Blood carboxyhemoglobin, total particulate matter (TPM) intake, and pulmonary aryl hydrocarbon hydroxylase values indicated effective exposure of animals to cigarette smoke. DNA was extracted from three respiratory (larynx, trachea, and lung) and three nonrespiratory (liver, heart, and bladder) tissues and analyzed for DNA adducts by the {sup 32}P-postlabeling assay under conditions capable of detecting low levels of diverse aromatic/hydrophobic adducts. Data showed that the total DNA adducts in the lung, heart, and trachea, and larynx were increased by 10- to 20-fold in the smoke-exposed group. These data suggest selective formation of DNA adducts in the tissues.

  4. Chronic cadmium exposure in rats produces pancreatic impairment and insulin resistance in multiple peripheral tissues.

    PubMed

    Treviño, Samuel; Waalkes, Michael P; Flores Hernández, José Angel; León-Chavez, Bertha Alicia; Aguilar-Alonso, Patricia; Brambila, Eduardo

    2015-10-01

    Previous studies have linked cadmium exposure to disturbances in carbohydrate and lipid metabolism. In this study we investigate the effects in Wistar rats of an oral cadmium exposure in drinking water on carbohydrates, lipids and insulin release. Also, using mathematical models we studied the effect of cadmium on insulin resistance and sensitivity in liver, muscle, adipose and cardiovascular tissue. Cadmium exposure induced hyperglycemia, increased insulin release after a glucose load, and caused increases in serum triglycerides, cholesterol, LDL-C and VLDL-C, and a decrease of HDL-C. In addition, there was an accumulation of cadmium in pancreas and an increase of insulin. After exposure, HOMA-IR was increased, while the HOMA-S%, QUICKI and Matsuda-DeFronzo indexes showed decreases. A decrease of insulin sensitivity was shown in muscle and liver. Additionally, cadmium increases insulin resistance in the liver, adipose tissue and cardiovascular system. Finally, β-cell functioning was evaluated by HOMA-B% index and insulin disposition index, which were decreased, while insulin generation index increased. In conclusion, cadmium increases insulin release, induces hyperglycemia and alters lipid metabolism. These changes likely occur as a consequence of reduced sensitivity and increased insulin resistance in multiple insulin-dependent and non-dependent tissues, producing a biochemical phenotype similar to metabolic syndrome and diabetes. PMID:26253262

  5. Multiple implants do not aggravate the tissue reaction in rat brain.

    PubMed

    Lind, Gustav; Gällentoft, Lina; Danielsen, Nils; Schouenborg, Jens; Pettersson, Lina M E

    2012-01-01

    Chronically implanted microelectrodes are an invaluable tool for neuroscientific research, allowing long term recordings in awake and behaving animals. It is known that all such electrodes will evoke a tissue reaction affected by its' size, shape, surface structure, fixation mode and implantation method. However, the possible correlation between tissue reactions and the number of implanted electrodes is not clear. We implanted multiple wire bundles into the brain of rats and studied the correlation between the astrocytic and microglial reaction and the positioning of the electrode in relation to surrounding electrodes. We found that an electrode implanted in the middle of a row of implants is surrounded by a significantly smaller astrocytic scar than single ones. This possible interaction was only seen between implants within the same hemisphere, no interaction with the contralateral hemisphere was found. More importantly, we found no aggravation of tissue reactions as a result of a larger number of implants. These results highlight the possibility of implanting multiple electrodes without aggravating the glial scar surrounding each implant. PMID:23091629

  6. Effect of air, heliox, and oxygen breathing on air bubbles in aqueous tissues in the rat.

    PubMed

    Hyldegaard, O; Madsen, J

    1994-12-01

    Our purpose was to examine the behavior of air bubbles in three non-lipid tissues (skeletal muscle, tendon, and the anterior chamber of the eye) during breathing of air, helium-oxygen (heliox, 80:20), or oxygen. Air bubbles were injected into skeletal muscle or tendon in rats after decompression from a 1-h air exposure at 3.5 atm abs (355 kPa) or into the anterior chamber of the rat eye without any previous pressure exposure. The bubbles were studied by photomicroscopy at 1 atm abs (101 kPa) during either air breathing or during air breathing followed by heliox or O2 breathing. Muscle: during air breathing, all bubbles initially increased in size for a period of 55-100 min after decompression and then started to shrink. Both heliox and O2 breathing increased the shrinking rate as compared to air. Bubble size decreased more rapidly during O2 than heliox breathing. Tendon: during air breathing, bubble size decreased at a constant rate; in one bubble the decrease was preceded by a small increase. During heliox breathing most bubbles decreased faster than during breathing of air. O2 breathing caused a short-term increase in bubble size in 4 out of 10 bubbles. Otherwise, the shrinkage rate was increased in six bubbles and uninfluenced in four bubbles during breathing of O2. Rat eye: during air breathing all bubbles shrank in the observation period. When heliox breathing was started, all bubbles transiently grew for 10-35 min, after which they began shrinking faster than during air breathing. When O2 breathing was started, five out of seven bubbles initially grew or stopped shrinking for 5-15 min, after which they decreased in size faster than during both air and heliox breathing. We conclude that breathing of either heliox or O2 will cause air bubbles in aqueous tissues to disappear faster than during breathing of air. Since heliox breathing promoted bubble shrinking in both muscle and tendon, gas exchange was probably not primarily limited by extravascular diffusion in

  7. Tissue specific characteristics of cells isolated from human and rat tendons and ligaments

    PubMed Central

    Scutt, N; Rolf, CG; Scutt, A

    2008-01-01

    Background Tendon and ligament injuries are common and costly in terms of surgery and rehabilitation. This might be improved by using tissue engineered constructs to accelerate the repair process; a method used successfully for skin wound healing and cartilage repair. Progress in this field has however been limited; possibly due to an over-simplistic choice of donor cell. For tissue engineering purposes it is often assumed that all tendon and ligament cells are similar despite their differing roles and biomechanics. To clarify this, we have characterised cells from various tendons and ligaments of human and rat origin in terms of proliferation, response to dexamethasone and cell surface marker expression. Methods Cells isolated from tendons by collagenase digestion were plated out in DMEM containing 10% fetal calf serum, penicillin/streptomycin and ultraglutamine. Cell number and collagen accumulation were by determined methylene blue and Sirius red staining respectively. Expression of cell surface markers was established by flow cytometry. Results In the CFU-f assay, human PT-derived cells produced more and bigger colonies suggesting the presence of more progenitor cells with a higher proliferative capacity. Dexamethasone had no effect on colony number in ACL or PT cells but 10 nM dexamethasone increased colony size in ACL cultures whereas higher concentrations decreased colony size in both ACL and PT cultures. In secondary subcultures, dexamethasone had no significant effect on PT cultures whereas a stimulation was seen at low concentrations in the ACL cultures and an inhibition at higher concentrations. Collagen accumulation was inhibited with increasing doses in both ACL and PT cultures. This differential response was also seen in rat-derived cells with similar differences being seen between Achilles, Patellar and tail tendon cells. Cell surface marker expression was also source dependent; CD90 was expressed at higher levels by PT cells and in both humans and

  8. Direct examination of cadmium bonding in rat tissues dosed with mine wastes and cadmium-containing solutions

    SciTech Connect

    Diacomanolis, V.; Ng, J. C.; Sadler, R.; Harris, H. H.; Nomura, M.; Noller, B. N.

    2010-06-23

    Direct examination by XANES and EXAFS of metal bonding in tissue can be demonstrated by examining cadmium uptake and bonding in animal tissue maintained at cryogenic temperatures. XANES at the K-edge of cadmium were collected at the Photon Factory Advanced Ring (PF-AR), NW10A beam line at KEK-Tsukuba-Japan. Rats fed with 1g mine waste containing 8-400 mg/kg cadmium per 200g body weight (b.w.) or dosed by oral gavage with either cadmium chloride solution alone (at 6 mg/kg b.w.) or in combination with other salts (As, Cu or Zn), 5 days/week for 6 weeks, had 0.1-7.5 and 8-86 mg/kg cadmium in the liver or kidney, respectively. Rats given intraperitoneally (ip) or intravenously (iv) 1-4 times with 1 mg/kg b.w. cadmium solution had 30-120 mg/kg cadmium in the liver or kidney. Tissues from rats were kept and transferred at cryogenic temperature and XANES were recorded at 20 K. The spectra for rat liver samples suggested conjugation of cadmium with glutathione or association with the sulfide bond (Cd-S) of proteins and peptides. EXAFS of rat liver fed by Cd and Zn solutions showed that Cd was clearly bound to S ligands with an inter-atomic distance of 2.54 A ring for Cd-S that was similar to cadmium sulfide with an inter-atomic distance of 2.52 A ring for Cd-S. Liver or kidney of rats fed with mine wastes did not give an edge in the XANES spectra indicating little uptake of cadmium by the animals. Longer and higher dosing regimen may be required in order to observe the same Cd-S bond in the rat tissue from mine wastes, including confirmation by EXAFS.

  9. Hydrolysis of pyrethroids by human and rat tissues: Examination of intestinal, liver and serum carboxylesterases

    SciTech Connect

    Crow, J. Allen; Borazjani, Abdolsamad; Potter, Philip M.; Ross, Matthew K. . E-mail: mross@cvm.msstate.edu

    2007-05-15

    Hydrolytic metabolism of pyrethroid insecticides in humans is one of the major catabolic pathways that clear these compounds from the body. Rodent models are often used to determine the disposition and clearance rates of these esterified compounds. In this study the distribution and activities of esterases that catalyze pyrethroid metabolism have been investigated in vitro using several human and rat tissues, including small intestine, liver and serum. The major esterase in human intestine is carboxylesterase 2 (hCE2). We found that the pyrethroid trans-permethrin is effectively hydrolyzed by a sample of pooled human intestinal microsomes (5 individuals), while deltamethrin and bioresmethrin are not. This result correlates well with the substrate specificity of recombinant hCE2 enzyme. In contrast, a sample of pooled rat intestinal microsomes (5 animals) hydrolyze trans-permethrin 4.5-fold slower than the sample of human intestinal microsomes. Furthermore, it is demonstrated that pooled samples of cytosol from human or rat liver are {approx} 2-fold less hydrolytically active (normalized per mg protein) than the corresponding microsomal fraction toward pyrethroid substrates; however, the cytosolic fractions do have significant amounts ({approx} 40%) of the total esteratic activity. Moreover, a 6-fold interindividual variation in carboxylesterase 1 protein expression in human hepatic cytosols was observed. Human serum was shown to lack pyrethroid hydrolytic activity, but rat serum has hydrolytic activity that is attributed to a single CE isozyme. We purified the serum CE enzyme to homogeneity to determine its contribution to pyrethroid metabolism in the rat. Both trans-permethrin and bioresmethrin were effectively cleaved by this serum CE, but deltamethrin, esfenvalerate, alpha-cypermethrin and cis-permethrin were slowly hydrolyzed. Lastly, two model lipase enzymes were examined for their ability to hydrolyze pyrethroids. However, no hydrolysis products could be

  10. Application of Prospective ECG-Gated High-Pitch 128-Slice Dual-Source CT Angiography in the Diagnosis of Congenital Extracardiac Vascular Anomalies in Infants and Children

    PubMed Central

    Wang, Ximing; Duan, Yanhua; Xu, Wenjian; Li, Haiou; Cao, Ting; Liu, Xuejun; Ji, Xiaopeng; Cheng, Zhaoping; Wang, Anbiao

    2014-01-01

    Purpose To investigate the value of prospective ECG-gated high-pitch 128-slice dual-source CT (DSCT) angiography in the diagnosis of congenital extracardiac vascular anomalies in infants and children in comparison with transthoracic echocardiography (TTE). Methods Eighty consecutive infants or children clinically diagnosed of congenital heart disease and suspected with extracardiac vascular anomaly were enrolled, and 75 patients were finally included in this prospective study. All patients underwent prospective ECG-gated high-pitch DSCT angiography after TTE with an interval of 1–7 days. The diagnostic accuracy and sensitivity of high-pitch DSCT angiography and TTE were compared according to the surgical/CCA findings. The image quality of DSCT was assessed using a five-point scale. The effective radiation dose (ED) was calculated. Results A total of 17 congenital heart diseases and 162 separate extracardiac vascular anomalies were confirmed by surgical/CCA findings in 75 patients. The diagnostic accuracy of high-pitch DSCT angiography and TTE was 99.67% and 97.89%, respectively. The sensitivity of high-pitch DSCT angiography and TTE was 97.53% and 79.62%, respectively. There was significant difference regarding to the diagnostic accuracy and the sensitivity between high-pitch DSCT angiography and TTE (χ2 = 23.561 and 28.013, P<0.05). The agreement on the image quality scoring of DSCT between the two observers was excellent (κ = 0.81), and the mean score of image quality was 4.1±0.7. The mean ED of DSCT was 0.29±0.08 mSv. Conclusions Prospective ECG-gated high-pitch 128-slice DSCT angiography with low radiation dose and high diagnostic accuracy has higher sensitivity compared to TTE in the detection of congenital extracardiac vascular anomalies in infants and children. PMID:25546178

  11. Therapeutic efficacy of amniotic membrane stem cells and adipose tissue stem cells in rats with chemically induced ovarian failure.

    PubMed

    Fouad, Hanan; Sabry, Dina; Elsetohy, Khaled; Fathy, Naglaa

    2016-03-01

    The present study was conducted to compare between the therapeutic efficacies of human amniotic membrane-derived stem cells (hAM-MSCs) vs. adipose tissue derived stem cells (AD-MSCs) in cyclophosphamide (CTX)-induced ovarian failure in rats. Forty-eight adult female rats were included in the study; 10 rats were used as control group. Thirty-eight rats were injected with CTX to induce ovarian failure and divided into four groups: ovarian failure (IOF) (IOF group), IOF + phosphate buffer saline (PBS group), IOF + hAM-MSCs group and IOF + AD-MSCs group. Serum levels of FSH and estradiol (E2) were assessed. Histopathological examination of the ovarian tissues was performed and quantitative gene expressions of Oct-4, Stra8 and integrin beta-1 genes were conducted by quantitative real time PCR. Results showed that IOF and IOF + PBS rat groups exhibited decreased ovarian follicles, increased interstitial fibrosis with significant decrease of serum E2, significant increase serum FSH level and significant down-regulation of Stra8 and integrin beta-1. In hAM-MSCs and AD-MSCs rat groups, there were increased follicles and corpora with evident the presence of oocytes, significant increase in serum E2, significant decrease in serum FSH levels (in hAM-MSCs treated group only) and significant up-regulation of the three studied genes with higher levels in hAM-MSCs treated rats group when compared to AD-MSCs treated rats group. In Conclusion, administration of either hAM-derived MSCs or AD-MSCs exerts a significant therapeutic efficacy in chemotherapy induced ovarian insult in rats. hAM-MSCs exert higher therapeutic efficacy as compared to AD-MSCs. PMID:26966564

  12. Controlled temperature tissue fusion: Ho:YAG laser welding of rat intestine in vivo

    NASA Astrophysics Data System (ADS)

    Cilesiz, Inci F.; Chan, Eric K.; Welch, Ashley J.; Thomsen, Sharon L.

    1995-05-01

    The results of a closed loop thermal feedback controlled laser-assisted tissue welding study in vivo are reported. A series of experiments was carried out to study and compare the weld strength and healing response of sutured and laser welded rat enterotomies with and without temperature feedback control (TFC) using a cryogenically cooled Ho:YAG laser. Although assignment of animals to three groups (control sutured, laser welded with and without TFC) and four observation periods (1, 3, 7, and 21 days) was randomized, several laser welded enterotomies without TFC had complications resulting in death of the animals. Those experiments were repeated. From the failure rates encountered, it is shown that TFC improves the quality of laser-assisted enterotomy closures.

  13. Tissue-specific alternative RNA splicing of rat vesicle-associated membrane protein-1 (VAMP-1).

    PubMed

    Mandic, R; Trimble, W S; Lowe, A W

    1997-10-15

    The vesicle-associated membrane protein (VAMP) family is essential to vesicle-mediated protein transport. Three mammalian isoforms, VAMP-1, VAMP-2, and cellubrevin, play a role in protein transport to the plasma membrane. In this study, we describe a new rat VAMP-1 isoform produced by alternative pre-mRNA splicing. Only one VAMP-1 isoform dominates in each tissue. Analysis of the nucleotide sequence for the newly discovered isoform, VAMP-1b, reveals that its expression is determined by whether an intron is retained or removed. The predicted amino acid sequences for the VAMP-1 isoforms differ at the carboxy-terminal end of the protein. A similar process has been described for VAMPs in Drosophila melanogaster and suggests a conserved function for the carboxy-terminal domain that can be modulated. PMID:9358054

  14. [Effects of different form calcium on growth and tissue calcium level in rats].

    PubMed

    Xu, Q; Yin, S A; Hu, S; Zhao, X; Meng, J; Ge, K Y

    1997-01-01

    In order to solve the problem of calcium deficiency and to look for economic and efficient source of calcium, the effects of calcium carbonate, active calcium and calcium lactate on growth, development and tissue calcium level in rats were compared. Fifty-six 3-week old weaning rats were fed with calcium deficient diet (containing vitamin D 500 IU per kg diet) for 3 weeks, and then were divided into four groups randomly with 14 rats in each group, half male and half female. The diet of control group (A) was the basic diet, while the three experiment diets were supplemented with calcium carbonate (B), active calcium (C) and calcium lactate (D) (3000 mg calcium per kg diet), respectively. The experiment term was 12 weeks. The results showed that the body weight and length of calcium supplemented group were significantly higher than that of control group (P<0.05). Among the calcium supplemented groups, no significant differences were observed except the difference of body length between the group D and the group A in female. Calcium deficiency dramatically hindered the development with reduced dietary intake and decreased food consumption efficiency. The calcium levels in plasma, red blood cells and liver were significantly higher in the supplemented groups than that in the control group (P<0.05), however, there was no difference among the supplemented groups. No significant difference of calcium levels in muscle and heart was observed among all groups. Based on needs for reaching the RDA with additional 400 mg/d from present calcium status in Chinese population, the calcium carbonate is the most economic one and the ideal calcium source for supplementation. PMID:15747462

  15. Responses of the Insulin Signaling Pathways in the Brown Adipose Tissue of Rats following Cold Exposure

    PubMed Central

    Wang, Xiaofei; Wahl, Richard

    2014-01-01

    The insulin signaling pathway is critical for the control of blood glucose levels. Brown adipose tissue (BAT) has also been implicated as important in glucose homeostasis. The effect of short-term cold exposure on this pathway in BAT has not been explored. We evaluated the effect of 4 hours of cold exposure on the insulin pathway in the BAT of rats. Whole genomic microarray chips were used to examine the transcripts of the pathway in BAT of rats exposed to 4°C and 22°C for 4 hours. The 4 most significantly altered pathways following 4 hours of cold exposure were the insulin signaling pathway, protein kinase A, PI3K/AKT and ERK/MAPK signaling. The insulin signaling pathway was the most affected. In the documented 142 genes of the insulin pathway, 42 transcripts (29.6%) responded significantly to this cold exposure with the least false discovery rate (Benjamini-Hochberg Multiple Testing: −log10 (p-value)  = 7.18). Twenty-seven genes (64%) were up-regulated, including the insulin receptor (Insr), insulin substrates 1 and 2 (Irs1 and Irs2). Fifteen transcripts (36%) were down-regulated. Multiple transcripts of the primary target and secondary effector targets for the insulin signaling were also up-regulated, including those for carbohydrate metabolism. Using western blotting, we demonstrated that the cold induced higher Irs2, Irs1, and Akt-p protein levels in the BAT than in the BAT of controls maintained at room temperature, and higher Akt-p protein level in the muscle. Conclusion: this study demonstrated that 4 hours of cold exposure stimulated the insulin signaling pathway in the BAT and muscle of overnight fasted rats. This raises the possibility that acute cold stimulation may have potential to improve glucose clearance and insulin sensitivity. PMID:24915042

  16. Characterization of p75{sup +} ectomesenchymal stem cells from rat embryonic facial process tissue

    SciTech Connect

    Wen, Xiujie; Liu, Luchuan; Deng, Manjing; Zhang, Li; Liu, Rui; Xing, Yongjun; Zhou, Xia; Nie, Xin

    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. 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.

  17. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  18. Early Chronotype and Tissue-Specific Alterations of Circadian Clock Function in Spontaneously Hypertensive Rats

    PubMed Central

    Sládek, Martin; Polidarová, Lenka; Nováková, Marta; Parkanová, Daniela; Sumová, Alena

    2012-01-01

    Malfunction of the circadian timing system may result in cardiovascular and metabolic diseases, and conversely, these diseases can impair the circadian system. The aim of this study was to reveal whether the functional state of the circadian system of spontaneously hypertensive rats (SHR) differs from that of control Wistar rat. This study is the first to analyze the function of the circadian system of SHR in its complexity, i.e., of the central clock in the suprachiasmatic nuclei (SCN) as well as of the peripheral clocks. The functional properties of the SCN clock were estimated by behavioral output rhythm in locomotor activity and daily profiles of clock gene expression in the SCN determined by in situ hybridization. The function of the peripheral clocks was assessed by daily profiles of clock gene expression in the liver and colon by RT-PCR and in vitro using real time recording of Bmal1-dLuc reporter. The potential impact of the SHR phenotype on circadian control of the metabolic pathways was estimated by daily profiles of metabolism-relevant gene expression in the liver and colon. The results revealed that SHR exhibited an early chronotype, because the central SCN clock was phase advanced relative to light/dark cycle and the SCN driven output rhythm ran faster compared to Wistar rats. Moreover, the output rhythm was dampened. The SHR peripheral clock reacted to the dampened SCN output with tissue-specific consequences. In the colon of SHR the clock function was severely altered, whereas the differences are only marginal in the liver. These changes may likely result in a mutual desynchrony of circadian oscillators within the circadian system of SHR, thereby potentially contributing to metabolic pathology of the strain. The SHR may thus serve as a valuable model of human circadian disorders originating in poor synchrony of the circadian system with external light/dark regime. PMID:23056539

  19. Tissue-selective inflammation in the oral cavity of the rat.

    PubMed

    Frade, Taíssa Iolanda Checón; Dos Reis, Diego Carlos; Cassali, Geovanni Dantas; Bakhle, Yeshwant S; de Francischi, Janetti Nogueira

    2016-08-01

    In the current study, carrageenan (CG; 100-1000 μg/site) was injected intraorally in the cheeks of Holtzman or Wistar rats to evaluate the consequences of administration of a non-immunogenic stimulus in the orofacial region. Subsequent inflammation was measured as oedema (increased thickness of the cheek wall using digital calipers), relative to the other cheek injected with saline. Oedema formation and tissue collection for histopathological studies were assessed at 0.5, 1, 2, 3, 4, 6, 24, 48, 72, 96, 120 and 144 h after injection. In parallel, other groups of rats were injected with CG in the hind paw, to provide a reference response. The inhibitor of prostaglandin biosynthesis, indomethacin, and antagonists of histamine, serotonin and NK1 receptors were injected s.c., 0.5 h before CG. CG induced a dose-related oedema more rapidly from 0 to 2 h which lasted for at least 72 h, showing a biphasic profile (peak at 2 and 24 h), compared with the monophasic oedema induced in rat paws (maximal duration of 24 h). Histopathological analysis of the CG-injected cheek revealed oedema formation with little leukocyte recruitment at 1-3 h, mast cell degranulation at 6 h, and a mixed polymorphonuclear and mononuclear cell infiltrate by 24 h. Histamine and serotonin antagonists and indomethacin, but not the NK1 antagonist, decreased cheek oedema in the first 4 h following carrageenan. Taken together, our data indicated important differences in the pattern of inflammation between the oral cavity and the paw which will determine the therapeutic approach to the treatment of inflammatory conditions in the oral cavity. PMID:27324249

  20. Pharmacokinetics, tissue distribution, and excretion of nomegestrol acetate in female rats.

    PubMed

    Huang, Qingbiao; Chen, Xiaoke; Zhu, Yan; Cao, Lin; Riviere, Jim E

    2015-12-01

    Nomegestrol acetate (NOMAC), a synthetic progestogen derived from 19-norprogesterone, is an orally active drug with a strong affinity for the progesterone receptor. NOMAC inhibits ovulation and is devoid of undesirable androgenic and estrogenic activities. The aim of this study was to evaluate the pharmacokinetics, tissue distribution, and excretion of NOMAC in female rats. Sprague-Dawley female rats were orally administered a single dose of NOMAC (10, 20 or 40 mg/kg) and drug plasma concentrations at different times were determined by RP-HPLC. Tissue distribution at 1, 2, and 4 h and excretion of NOMAC into bile, urine, and feces after dosing were investigated. The results showed that NOMAC was rapidly absorbed after oral administration, with [Formula: see text] of 1-2 h. The plasma concentration-time curves were fitted in a two-compartment model. The exposure to NOMAC ([Formula: see text] and [Formula: see text]) increased dose proportionally from 10 to 40 mg/kg. The average CL and [Formula: see text] were 5.58 L/(h·kg) and 10.8 h, respectively. The highest concentrations of NOMAC in ovary, liver, kidney, lung, heart, brain, spleen, muscle, and uterus were observed at 2 h, whereas the highest concentrations in stomach, pituitary, and hypothalamus appeared at 1 h. The total cumulative excretion of NOMAC in feces (0-72 h), urine (0-72 h), and bile (0-48 h) was ~1.06, 0.03, and 0.08 % of the oral administered dose, respectively. This study indicated that NOMAC had a widespread distribution in tissues, including ovary, pituitary, and hypothalamus, which are main target tissues where NOMAC inhibits ovulation. NOMAC was excreted via both feces and urine with few unchanged NOMAC excreted. Enterohepatic circulation was found in the drug elimination; however, it did not significantly affect [Formula: see text]. PMID:25168884

  1. Calcium-activated chloride currents prolongs the duration of contractions in pregnant rat myometrial tissue.

    PubMed

    Young, Roger C; Bemis, Adam

    2009-08-01

    We investigated the importance of pharmacologically blocking calcium-activated chloride (I(Cl(Ca))) and L-type calcium currents on isometric contractions of strips of D21 pregnant rat myometrial tissue, while simultaneously measuring the electrical activity of the tissue strips with extracellular contact electrodes. When measured with contact electrodes, the duration of the spiking activity directly reflects the duration of the tissue-level plateau potential. We correlated the number of spikes, durations of spiking activity, and the spiking frequencies with changes of the area under the force curves as a function of exposure to low doses of anthracene-9-carboxylate (9-AC, a non-specific Cl channel blocker), chlorotoxin (a specific I(Cl(Ca)) blocker) and nifedipine (an L-type calcium channel blocker). The area under the force curve was measured only during spiking electrical activity, thereby separating pharmacological effects on tissue relaxation from those that modulate force production. Blocking chloride channels reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes generated in each contraction. This was observed without a change in the frequency of spike production or a reduction of peak force. Nifedipine reduced impulse, shortened the duration of spiking activity, and reduced the number of spikes. In contrast to chloride channel blockade, nifedipine reduced maximum spike frequency and peak force. Taken together, our data suggest that blocking L-type calcium channels reduces impulse directly by reducing peak force, and indirectly by reducing activation of I(Cl(Ca)) , which shortens the duration of the contraction. PMID:19380901

  2. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins.

    PubMed

    Rajesh, Parsanathan; Sathish, Sampath; Srinivasan, Chinnapaiyan; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2013-03-01

    Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP-induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. PMID:22991202

  3. Clearing-factor lipase in adipose tissue. A medium in which the enzyme activity of tissue from starved rats increases in vitro

    PubMed Central

    Salaman, M. R.; Robinson, D. S.

    1966-01-01

    1. When epididymal fat bodies from starved rats are incubated for 3·5hr. at 37° in a defined medium in vitro the total clearing-factor lipase activity rises to approximately twice its initial value. 2. During the incubation period part of the tissue clearing-factor lipase activity appears in the medium. 3. Heparin, glucose, insulin, and HCO3− and K+ ions are shown to be important medium constituents. PMID:5964961

  4. Quantitative analysis of phenibut in rat brain tissue extracts by liquid chromatography-tandem mass spectrometry.

    PubMed

    Grinberga, Solveiga; Zvejniece, Liga; Liepinsh, Edgars; Dambrova, Maija; Pugovics, Osvalds

    2008-12-01

    Phenibut (3-phenyl-4-aminobutyric acid) is a gamma-aminobutyric acid mimetic drug, which is used clinically as a mood elevator and tranquilizer. In the present work, a rapid, selective and sensitive liquid chromatography-tandem mass spectrometry method for quantification of phenibut in biological matrices has been developed. The method is based on protein precipitation with acidic acetonitrile followed by isocratic chromatographic separation using acetonitrile-formic acid (0.1% in water; 8:92, v/v) mobile phase on a reversed-phase column. Detection of the analyte was performed by electrospray ionization mass spectrometry in multiple reaction monitoring mode with the precursor-to-product ion transition m/z 180.3 --> m/z 117.2. The calibration curve was linear over the concentration range 50-2000 ng/mL. The lower limit of quantification for phenibut in rat brain extracts was 50 ng/mL. Acceptable precision and accuracy were obtained over the whole concentration range. The validated method was successfully applied in a pharmacological study to analyze phenibut concentration in rat brain tissue extract samples. PMID:19034959

  5. Effects of fibre-enriched diets on tissue lipid profiles of MSG obese rats.

    PubMed

    Rotimi, O A; Olayiwola, I O; Ademuyiwa, O; Balogun, E A

    2012-11-01

    In order to investigate the influence of some fibre-enriched diets on tissue lipids in an animal model of obesity induced by the administration of monosodium glutamate (MSG), obese rats were fed diets containing 30% of Acha, Cassava, Maize and Plantain for five weeks and weight gain, feed intake and lee index were recorded. The lipid profiles of plasma, erythrocytes, kidney, heart and liver as well as hepatic 3-hydroxyl-3-methylglutaryl-CoA (HMG-CoA) reductase activity were measured. The diets significantly (p<0.05) reduced weight gain and lee index in the obese rats. Obesity-induced increase in plasma and erythrocytes lipid levels was significantly (p<0.05) reduced by these diets. MSG-induced obesity also resulted in a significant increase (p<0.05) in hepatic cholesterol level which was reduced by the diets. MSG-obesity was characterised by a significant (p<0.05) increase in cholesterol, triacylglycerol and phospholipids in kidney and this was reversed by the diets except Maize which did not reverse the increased cholesterol level. Only Acha reversed the obesity-induced increase in heart cholesterol and phospholipids. The increased activity of hepatic HMG-CoA reductase associated with obesity was also significantly (p<0.05) reduced by the diets. In conclusion, dyslipidemia associated with MSG-induced obesity could be attenuated by consumption of fibre-enriched diets. PMID:22898616

  6. Role of acid sphingomyelinase in the age-dependent dysregulation of sphingolipids turnover in the tissues of rats.

    PubMed

    Babenko, Nataliya A; Garkavenko, Vladimir V; Storozhenko, Galina V; Timofiychuk, Olga A

    2016-04-01

    Old age-associated pathologies usually coincide with altered sphingolipid metabolism. In the present article, the role of acid sphingomyelinase (ASMase) in the age-dependent changes of sphingomyelin (SM) and ceramide contents in the tissues has been investigated by means of ASMase inhibitors, imipramine and zoledronic acid. It has been determined that ceramide content and ceramide/SM ratio increased, while SM level decreased in the heart, liver, blood serum and skeletal muscles of 24-month old rats in contrast to 3-month old animals. Injections of imipramine or zoledronic acid to 24-month old rats resulted in significant downregulation of ASMase in the liver and skeletal and heart muscles. The both inhibitors decreased the ceramide content and ceramide/SM ratio and increased the SM content in all tissues studied, except the heart, of old rats to the levels close to those observed in the young animals. Long-term treatment of rats by inhibitors, which have different mechanisms of action on ASMase, exerts the similar, but not equal effects on enzyme activity and SM turnover. In summary, the data above strongly suggest that the age-dependent up-regulation of ASMase plays an important role in the modulation of ceramide and SM contents in rat tissues and that imipramine and zoledronic acid are useful tools for SM turnover manipulation at old age. PMID:26830134

  7. Effect of an aqueous extract of Scoparia dulcis on plasma and tissue glycoproteins in streptozotocin induced diabetic rats.

    PubMed

    Latha, M; Pari, L

    2005-02-01

    The influence of Scoparia dulcis, a traditionally used plant for the treatment of diabetes mellitus, was examined in streptozotocin diabetic rats on dearrangement in glycoprotein levels. Diabetes was induced in male Wistar rats by a single intraperitoneal injection of streptozotocin. An aqueous extract of Scoparia dulcis plant was administered orally for 6 weeks. The effect of the Scoparia dulcis extract on blood glucose, plasma insulin, plasma and tissue glycoproteins studied was in comparison to glibenclamide. The levels of blood glucose and plasma glycoproteins were increased significantly whereas the level of plasma insulin was significantly decreased in diabetic rats. There was a significant decrease in the level of sialic acid and elevated levels of hexose, hexosamine and fucose in the liver and kidney of streptozotocin diabetic rats. Oral administration of Scoparia dulcis plant extract (SPEt) to diabetic rats led to decreased levels of blood glucose and plasma glycoproteins. The levels of plasma insulin and tissue sialic acid were increased whereas the levels of tissue hexose, hexosamine and fucose were near normal. The present study indicates that Scoparia dulcis possesses a significant beneficial effect on glycoproteins in addition to its antidiabetic effect. PMID:15739907

  8. Low-Level Laser Stimulation on Adipose-Tissue-Derived Stem Cell Treatments for Focal Cerebral Ischemia in Rats

    PubMed Central

    Shen, Chiung-Chyi; Yang, Yi-Chin; Chiao, Ming-Tsang; Chan, Shiuh-Chuan; Liu, Bai-Shuan

    2013-01-01

    This study investigated the effects of large-area irradiation from a low-level laser on the proliferation and differentiation of i-ADSCs in neuronal cells. MTT assays indicated no significant difference between the amount of cells with (LS+) and without (LS−) laser treatment (P > 0.05). However, immunofluorescent staining and western blot analysis results indicated a significant increase in the neural stem-cell marker, nestin, following exposure to low-level laser irradiation (P < 0.05). Furthermore, stem cell implantation was applied to treat rats suffering from stroke. At 28 days posttreatment, the motor functions of the rats treated using i-ADSCs (LS+) did not differ greatly from those in the sham group and HE-stained brain tissue samples exhibited near-complete recovery with nearly no brain tissue damage. However, the motor functions of the rats treated using i-ADSCs (LS−) remained somewhat dysfunctional and tissue displayed necrotic scarring and voids. The western blot analysis also revealed significant expression of oligo-2 in the rats treated using i-ADSCs (LS+) as well as in the sham group (P < 0.05). The results demonstrated that low-level laser irradiation exerts a positive effect on the differentiation of i-ADSCs and can be employed to treat rats suffering from ischemic stroke to regain motor functions. PMID:24363769

  9. White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

    PubMed

    Bueno, Allain Amador; Habitante, Carlos Alexandre; Oyama, Lila Missae; Estadella, Débora; Ribeiro, Eliane Beraldi; Oller do Nascimento, Cláudia Maria

    2011-01-01

    The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time. PMID:21140253

  10. Beta-adrenergic blockade and lipoprotein lipase activity in rat tissues after acute exercise.

    PubMed

    Paulin, A; Lalonde, J; Deshaies, Y

    1991-10-01

    The present experiments were aimed at evaluating the acute effects of exercise on lipoprotein lipase (LPL) activity in untrained rats. The activity of LPL was measured in postheparin plasma (PHP) before and at various times after a 1-h run on a treadmill (22 m/min, O degrees grade). LPL in PHP was 50% below pre-exercise levels immediately and 3 h after the run but was increased 65% over resting levels 24 h postexercise. To further characterize the very early fall in LPL activity in response to exercise and to assess the possible involvement therein of the beta-adrenergic pathway, LPL in heart, vastus lateralis muscle (VLM), and white (WAT) and brown (BAT) adipose tissues was determined at rest and immediately after exercise in rats that were treated or not with nadolol (25 mg.kg-1.day-1 for 30 days). Immediately after 1 h of exercise, there was a reduction in total enzyme activity in WAT (40% below resting levels), BAT (-58%), VLM (-53%), and heart (-30%). Exercise reduced serum triacylglycerol levels (-64%) and doubled those of nonesterified fatty acids. beta-Adrenergic blockade did not affect any of these variables. Both exercise and nadolol lowered serum cholesterol levels by approximately 20%, but the effects were not additive. These results show that the global intravascular pool of LPL undergoes divergent, time-dependent alterations in response to a single bout of moderate exercise. The acute downregulation of postheparin plasma LPL immediately after exercise reflected a fall in the total enzyme pool of all tissues studied.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1681747

  11. The Effects of Levofloxacin on Testis Tissue and Spermatogenesis in Rat.

    PubMed

    Ahmadi, Ramesh; Ahmadifar, Mehdi; Safarpour, Elham; Vahidi-Eyrisofla, Nazila; Darab, Mehraneh; Eini, Ali Mohammad; Alizadeh, AliReza

    2016-01-01

    Levofloxacin is one of the Fluroquinoline antibiotic groups, which affect on controlling infections, especially in reproductive organs. It has therapeutic use in numerous countries, but little information exists on the effects of Levofloxacin on spermatogenesis when it is used for infectious treatment. The current study was designed to determine whether Levofloxacin influences testis tissue and spermatogenesis in rats. In this survey 50 male Wistar rats 6-8 weeks (250 ± 10 g) were used: normal salin as sham and control groups and 3 treatment groups (0.03, 0.06 and 0.08 mg Levofloxacin\\kg body weight) during 60 days. The experimental groups were daily gavages. After 60 days, they were anesthetized with ether and testes were taken for histopathology studies, sperm parameters evaluation and several hormone concentrations. Although testosterone concentration was not affected by Levofloxacin levels, follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentration significantly increased by Levofloxacin consumption in 0.03 and 0.06 mg Levofloxacin\\kg body weight groups (P<0.01). Moreover, sperm concentration decreased linearly as Levofloxacin was increased (200, 192, 170, 128 and 75×10(6) sperm for control, sham, 0.03, 0.06 and 0.08 mg Levofloxacin\\kg body weight, respectively, P<0.05). Testis tissue cuts in experimental group when the amount dosage of Levofloxacin increased cells solidarity to the primary and secondary spermatogonia. Adding Levofloxacin linearly reduced spermatocyte cells and amount of all cells in semenifer pipes tube (P<0.05). Levofloxacin as an antibiotic has histopathology effects on the spermatocyte cells, especially in high dose. Therefore, it might reduce fertility in male that requires further studies. PMID:27054126

  12. Rat subcutaneous tissue response to calcium silicate containing different arsenic concentrations

    PubMed Central

    MINOTTI, Paloma Gagliardi; ORDINOLA-ZAPATA, Ronald; MIDENA, Raquel Zanin; MARCIANO, Marina Angélica; CAVENAGO, Bruno Cavalini; BRAMANTE, Clovis Monteiro; GARCIA, Roberto Brandão; DUARTE, Marco Antonio Hungaro; de MORAES, Ivaldo Gomes

    2015-01-01

    Objective To evaluate the response of rat subcutaneous tissue in implanted polyethylene tubes that were filled with GMTA Angelus and Portland cements containing different arsenic concentrations. Material and Methods Atomic absorption spectrophotometry was utilized to obtain the values of the arsenic concentration in the materials. Thirty-six rats were divided into 3 groups of 12 animals for each experimental period. Each animal received two implants of polyethylene tubes filled with different test cements and the lateral of the tubes was used as a control group. After 15, 30 and 60 days of implantation, the animals were killed and the specimens were prepared for descriptive and morphometric analysis considering: inflammatory cells, collagen fibers, fibroblasts, blood vessels and other components. The results were analyzed utilizing the Kuskal-Wallis test and the Dunn´s Multiple test for comparison (p<0.05). Results The materials showed, according to atomic absorption spectrophotometry, the following doses of arsenic: GMTA Angelus: 5.01 mg/kg, WPC Irajazinho: 0.69 mg/kg, GPC Minetti: 18.46 mg/kg and GPC Votoran: 10.76 mg/kg. In a 60-day periods, all specimens displayed a neoformation of connective tissue with a structure of fibrocellular aspect (capsule). Control groups and MTA Angelus produced the lower amount of inflammatory reaction and GPC Minetti, the highest reaction. Conclusions There was no direct relationship between the concentration of arsenic present in the composition of the materials and the intensity of the inflammatory reactions. Higher values, as 18.46 mg/kg of arsenic in the cement, produce characteristics of severe inflammation reaction at the 60-day period. The best results were found in MTA angelus. PMID:25075671

  13. Lipopolysaccharide induces catecholamine production in mesenteric adipose tissue of rats previously exposed to immobilization stress.

    PubMed

    Vargovic, P; Laukova, M; Ukropec, J; Manz, G; Kvetnansky, R

    2016-07-01

    Catecholamines (CAs) are mainly produced by sympathoadrenal system but their de novo production has been also observed in adipose tissue cells. The aim of this work was to investigate whether immune challenge induced by lipopolysaccharide (LPS) modulates biosynthesis of CAs in mesenteric adipose tissue (MWAT), as well as whether previous exposure to immobilization (IMO) stress could modulate this process. Sprague-Dawley rats were exposed to single (2 h) or repeated (2 h/7 days) IMO and afterwards injected with LPS (i.p., 100 μg/kg body weight) and sacrificed 3 h later. LPS did not alter CA biosynthesis in MWAT in control rats. Single and repeated IMO elevated CAs and expression of CA biosynthetic enzymes in MWAT, including adipocyte and stromal/vascular fractions (SVF). Repeated IMO followed by LPS treatment led to the up-regulation of CA-biosynthetic enzymes expression, elevation of CAs in SVF but depletion of norepinephrine and epinephrine in adipocyte fraction. Prior IMO caused a marked LPS-induced macrophage infiltration in MWAT as evaluated by F4/80 expression. A positive correlation between expression of tyrosine hydroxylase and F4/80 suggests macrophages as the main source of LPS-induced CA production in MWAT. Furthermore, prior exposure to the single or repeated IMO differently affected immune responses following LPS treatment by modulation of inflammatory cytokine expression. These data suggest that stress might be a significant modulator of immune response in MWAT via stimulation of the macrophage infiltration associated with cytokine response and de novo production of CAs. PMID:27314578

  14. The Effects of Levofloxacin on Testis Tissue and Spermatogenesis in Rat

    PubMed Central

    Ahmadi, Ramesh; Ahmadifar, Mehdi; Safarpour, Elham; Vahidi-eyrisofla, Nazila; Darab, Mehraneh; Eini, Ali Mohammad; Alizadeh, AliReza

    2016-01-01

    Levofloxacin is one of the Fluroquinoline antibiotic groups, which affect on controlling infections, especially in reproductive organs. It has therapeutic use in numerous countries, but little information exists on the effects of Levofloxacin on spermatogenesis when it is used for infectious treatment. The current study was designed to determine whether Levofloxacin influences testis tissue and spermatogenesis in rats. In this survey 50 male Wistar rats 6-8 weeks (250 ± 10 g) were used: normal salin as sham and control groups and 3 treatment groups (0.03, 0.06 and 0.08 mg Levofloxacin\\kg body weight) during 60 days. The experimental groups were daily gavages. After 60 days, they were anesthetized with ether and testes were taken for histopathology studies, sperm parameters evaluation and several hormone concentrations. Although testosterone concentration was not affected by Levofloxacin levels, follicle stimulating hormone (FSH) and luteinizing hormone (LH) concentration significantly increased by Levofloxacin consumption in 0.03 and 0.06 mg Levofloxacin\\kg body weight groups (P<0.01). Moreover, sperm concentration decreased linearly as Levofloxacin was increased (200, 192, 170, 128 and 75×106 sperm for control, sham, 0.03, 0.06 and 0.08 mg Levofloxacin\\kg body weight, respectively, P<0.05). Testis tissue cuts in experimental group when the amount dosage of Levofloxacin increased cells solidarity to the primary and secondary spermatogonia. Adding Levofloxacin linearly reduced spermatocyte cells and amount of all cells in semenifer pipes tube (P<0.05). Levofloxacin as an antibiotic has histopathology effects on the spermatocyte cells, especially in high dose. Therefore, it might reduce fertility in male that requires further studies. PMID:27054126

  15. Transforming growth factor-alpha in vivo stimulates epithelial cell proliferation in digestive tissues of suckling rats.

    PubMed Central

    Hormi, K; Lehy, T

    1996-01-01

    BACKGROUND: The role that exogenous transforming growth factor-alpha (TGF-alpha) may exert on cell proliferation in vivo is poorly understood. AIM: To investigate the effect of rat TGF-alpha on epithelial cell proliferation in all suckling rat digestive tissues and to compare it with that of rat epidermal growth factor (EGF). ANIMAL AND METHODS: TGF-alpha and EGF were given three times daily either subcutaneously (10 or 20 micrograms/kg) or intraperitoneally (100 micrograms/kg) to rats from the ninth postnatal day. Cell proliferation was assessed through 5-bromo- 2-deoxyuridine incorporation and estimation of labelling indices. RESULTS: For both growth factors, the highest dose given for only two days significantly increased stomach and intestinal weights compared with controls (p < 0.05 to p < 0.001). The proliferative responded depended on the dose given, colonic mucosa being the most sensitive whereas oxyntic mucosa remained unresponsive. TGF-alpha was as potent as EGF in stimulating epithelial cell proliferation in antral, duodenal, and colonic mucosae. However, EGF was more active on oesophageal and jejunal cell proliferation whereas TGF-alpha was more active on pancreatic exocrine cell proliferation and the differences between the two growth factor treated groups were significant. CONCLUSIONS: These results prove for the first time the stimulating effect in vivo of exogenous rat TGF-alpha on epithelial cell proliferation in rat digestive tissues during the developmental period and support a functional role for TGF-alpha at that time. PMID:8944561

  16. Protective Nature of Mangiferin on Oxidative Stress and Antioxidant Status in Tissues of Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Sellamuthu, Periyar Selvam; Arulselvan, Palanisamy; Kamalraj, Subban; Fakurazi, Sharida; Kandasamy, Murugesan

    2013-01-01

    Oxidative stress plays an important role in the progression of diabetes complications. The aim of the present study was to investigate the beneficial effect of oral administration of mangiferin in streptozotocin (STZ)-induced diabetic rats by measuring the oxidative indicators in liver and kidney as well as the ameliorative properties. Administration of mangiferin to diabetic rats significantly decreased blood glucose and increased plasma insulin levels. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) and level of reduced glutathione (GSH) were significantly (P < 0.05) decreased while increases in the levels of lipidperoxidation (LPO) markers were observed in liver and kidney tissues of diabetic control rats as compared to normal control rats. Oral treatment with mangiferin (40 mg/kg b.wt/day) for a period of 30 days showed significant ameliorative effects on all the biochemical and oxidative parameters studied. Diabetic rats treated with mangiferin restored almost normal architecture of liver and kidney tissues, which was confirmed by histopathological examination. These results indicated that mangiferin has potential ameliorative effects in addition to its antidiabetic effect in experimentally induced diabetic rats. PMID:24167738

  17. Tissue Distribution and Urinary Excretion of Dimethylated Arsenic and Its Metabolites in Dimethylarsinic acid- or Arsenate-treated Rats - MCEARD

    EPA Science Inventory

    Adult female Fisher 344 rats received drinking water containing 0, 4, 40, 100, or 200 parts per million of dimethylarsinic acid or 100 parts per million of arsenate for 14 days. Urine was collected during the last 24 h of exposure. Tissues were then taken for analysis of dimethy...

  18. EFFECTS OF NEONATAL METHYLMERCURY EXPOSURE ON ADRENERGIC RECEPTOR BINDING SITES IN PERIPHERAL TISSUES OF THE DEVELOPING RAT

    EPA Science Inventory

    Neonatal exposure to methylmercury produces changes in patterns of tissue growth and function, in part, due to alterations in adrenergic neuronal input. To explore the mechanisms by which these changes come about, newborn rats were exposed to methylmercury (1 or 2.5 mg/kg/day) th...

  19. 32P-POSTLABELING DNA ADDUCT ASSAY: CIGARETTE SMOKE-INDUCED DNA ADDUCTS IN THE RESPIRATORY AND NONRESPIRATORY RAT TISSUES

    EPA Science Inventory

    An analysis of the tissue DNA adducts in rats by the sensitive 32P-postlabeling assay showed one to eight detectable DNA adducts in lung, trachea, larynx, heart and bladder of the sham controls. hronic exposure of animals to mainstream cigarette smoke showed a remarkable enhancem...

  20. Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Phylloquinone (PK) is converted into menaquinone-4 (MK-4) via side chain removal-addition. Stable isotope use is an effective approach to identify the tissue location of this conversion, which is currently unknown. Following a 14 d PK-deficient diet, male Fischer 344 rats (8 mo; n=15) were fed 1.6 m...

  1. Fluorescence polarization spectroscopy and time-resolved fluorescence kinetics of native cancerous and normal rat kidney tissues.

    PubMed Central

    Tata, D B; Foresti, M; Cordero, J; Tomashefsky, P; Alfano, M A; Alfano, R R

    1986-01-01

    Steady state fluorescence polarization spectra and time-resolved emission decay kinetics have been measured in vitro from malignant and normal rat kidney tissue. The degrees of polarization and emission lifetimes from the cancerous and normal systems are different. The spectroscopic differences are attributed to environmental transformations local to the native flavin and porphyrin fluorophors' binding sites. PMID:3489490

  2. PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    PERIPUBERTAL DI (2-ETHYLHEXYL) PHTHALATE EXPOSURE INHIBITS ANDROGEN SENSITIVE TISSUE DEVELOPMENT AND DELAYS PUBERTY IN MALE SPRAGUE-DAWLEY RATS

    Nigel Noriega, Jonathan Furr, Christy Lambright, Vickie Wilson, L. Earl Gray Jr.

    The plasticizer Di (2-ethylhexyl) phtha...

  3. Protective effects of protocatechuic acid on TCDD-induced oxidative and histopathological damage in the heart tissue of rats.

    PubMed

    Ciftci, Osman; Disli, Olcay Murat; Timurkaan, Necati

    2013-10-01

    2,3,7,8-Tetracholorodibenzo-p-dioxin (TCDD) is a highly toxic environmental contaminant that causes severe toxic effects in animal and human. In this study, we investigated the toxic effects of TCDD and the preventive effects of protocatechuic acid (PCA), a widespread phenolic compound, in the heart tissue of rats. For this purpose, 3-4 months old 28 rats with 280-310 g body weights were equally divided into 4 groups (control, TCDD, PCA, TCDD + PCA group). A 2 μg/kg dose of 2,3,7,8-TCDD and 100 mg/kg dose of PCA were dissolved in corn oil and given orally to the rats for 45 days. The results indicated that TCDD induced oxidative stress by increasing the level of thiobarbituric acid reactive substance and by decreasing the levels of glutathione, catalase, glutathione peroxidase and superoxide dismutase in the heart tissue of rats. In contrast, PCA treatment prevents the toxic effects of TCDD on oxidative stress. In addition, histopathological alterations such as necrosis and hemorrhage occurred in TCDD group, and PCA treatment partially prevents these alterations in heart tissue. In this study, it was concluded that TCDD exposure led to toxic effects in heart tissue and PCA treatment could prevent the toxicity of TCDD. PMID:22495517

  4. An immunocytochemical method for localization of estrogen receptors in rat tissues using a dinitrophenyl (DNP)-labeled rat monoclonal primary antibody.

    PubMed

    Gee, J M; Nicholson, R I; Jasani, B; Newman, G R; Amselgruber, W M

    1990-01-01

    We have developed an immunocytochemical method to demonstrate estrogen receptor in hormone-sensitive tissues of the rat using a dinitrophenyl (DNP) hapten-labeled rat antihuman estrogen receptor monoclonal antibody (MAb), H222. Mouse IgM anti-DNP was used secondarily, followed by a DNP/peroxidase conjugate, diaminobenzidine/hydrogen peroxide chromogen, and silver intensification. This method was applied to tissues from intact female rats and showed that estrogen receptor was localized in the nuclei of the stromal and glandular components of the uterine endometrium. Reduced receptor staining was observed in the luminal epithelium, with minimal myometrial staining. Anterior pituitary glands showed heterogeneous immunostaining and ovaries expressed the receptor predominantly in the interstitial cells; fallopian tubes demonstrated substantial epithelial staining. Uteri from chemically castrated rats showed reduced estrogen receptor immunostaining in both stromal and luminal cells, whereas staining was enhanced in the glandular elements. Classical estrogen-unresponsive tissues (heart, lung, and spleen) were unstained. Antibody controls involved pre-blocking antibody recognition sites on the receptor with unlabeled antibodies to estrogen receptor (H222, H226, and D547), as well as use of an inappropriate DNP-labeled antibody to metallothionein. These controls illustrated the specific nature of the DNP-H222 binding. PMID:1688451

  5. Does prolonged radiofrequency radiation emitted from Wi-Fi devices induce DNA damage in various tissues of rats?

    PubMed

    Akdag, Mehmet Zulkuf; Dasdag, Suleyman; Canturk, Fazile; Karabulut, Derya; Caner, Yusuf; Adalier, Nur

    2016-09-01

    Wireless internet (Wi-Fi) providers have become essential in our daily lives, as wireless technology is evolving at a dizzying pace. Although there are different frequency generators, one of the most commonly used Wi-Fi devices are 2.4GHz frequency generators. These devices are heavily used in all areas of life but the effect of radiofrequency (RF) radiation emission on users is generally ignored. Yet, an increasing share of the public expresses concern on this issue. Therefore, this study intends to respond to the growing public concern. The purpose of this study is to reveal whether long term exposure of 2.4GHz frequency RF radiation will cause DNA damage of different tissues such as brain, kidney, liver, and skin tissue and testicular tissues of rats. The study was conducted on 16 adult male Wistar-Albino rats. The rats in the experimental group (n=8) were exposed to 2.4GHz frequency radiation for over a year. The rats in the sham control group (n=8) were subjected to the same experimental conditions except the Wi-Fi generator was turned off. After the exposure period was complete the possible DNA damage on the rat's brain, liver, kidney, skin, and testicular tissues was detected through the single cell gel electrophoresis assay (comet) method. The amount of DNA damage was measured as percentage tail DNA value. Based on the DNA damage results determined by the single cell gel electrophoresis (Comet) method, it was found that the% tail DNA values of the brain, kidney, liver, and skin tissues of the rats in the experimental group increased more than those in the control group. The increase of the DNA damage in all tissues was not significant (p>0.05). However the increase of the DNA damage in rat testes tissue was significant (p<0.01). In conclusion, long-term exposure to 2.4GHz RF radiation (Wi-Fi) does not cause DNA damage of the organs investigated in this study except testes. The results of this study indicated that testes are more sensitive organ to RF

  6. Morphological and biochemical examination of Cosmos 1887 rat heart tissue. Part 1: Ultrastructure

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Popova, I. A.; Kato, K.; Stevenson, J.; Miquel, J.; Sapp, W.

    1990-01-01

    Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel. Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space.

  7. The relationship between decorrelation time and sample thickness in acute rat brain tissue slices (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Brake, Joshua; Jang, Mooseok; Yang, Changhuei

    2016-03-01

    The optical opacity of biological tissue has long been a challenge in biomedical optics due to the strong scattering nature of tissue in the optical regime. While most conventional optical techniques attempt to gate out multiply scattered light and use only unscattered light, new approaches in the field of wavefront shaping exploit the time reversible symmetry of optical scattering in order to focus light inside or through scattering media. While these approaches have been demonstrated effectively on static samples, it has proven difficult to apply them to dynamic biological samples since even small changes in the relative positions of the scatterers within will cause the time symmetry that wavefront shaping relies upon to decorrelate. In this paper we investigate the decorrelation curves of acute rat brain slices for thicknesses in the range 1-3 mm (1/e decorrelation time on the order of seconds) using multi-speckle diffusing wave spectroscopy (MSDWS) and compare the results with theoretical predictions. The results of this study demonstrate that the 1/L^2 relationship between decorrelation time and thickness predicted by diffusing wave spectroscopy provides a good rule of thumb for estimating how the decorrelation of a sample will change with increasing thickness. Understanding this relationship will provide insight to guide the future development of biophotonic wavefront shaping tools by giving an estimate of how fast wavefront shaping systems need to operate to overcome the dynamic nature of biological samples.

  8. Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

    SciTech Connect

    Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.; Smith, Jordan N.; Timchalk, Charles; Laskin, Julia

    2013-01-15

    Imaging mass spectrometry offers simultaneous detection of drugs, drug metabolites and endogenous substances in a single experiment. This is important when evaluating effects of a drug on a complex organ system such as the brain, where there is a need to understand how regional drug distribution impacts function. Nicotine is an addictive drug and its action in the brain is of high interest. Here we use nanospray desorption electrospray ionization, nano-DESI, imaging to discover the localization of nicotine in rat brain tissue after in vivo administration of nicotine. Nano-DESI is a new ambient technique that enables spatially-resolved analysis of tissue samples without special sample pretreatment. We demonstrate high sensitivity of nano-DESI imaging that enables detection of only 0.7 fmole nicotine per pixel in the complex brain matrix. Furthermore, by adding deuterated nicotine to the solvent, we examined how matrix effects, ion suppression, and normalization affect the observed nicotine distribution. Finally, we provide preliminary results suggesting that nicotine localizes to the hippocampal substructure called dentate gyrus.

  9. Studies of Hard and Soft Tissue Elemental Compositions in Mice and Rats Subjected to Simulated Microgravity

    NASA Astrophysics Data System (ADS)

    Mehta, Rahul; Lane, Ryan A.; Fitch, Hannah M.; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2009-03-01

    Microgravity has profound effects on skeletal as well as other body systems. To investigate the effect of microgravity, we have used a NASA validated Hind-limb suspension (HLS) animal model of simulated weightlessness. Groups of mice and rats were subjected to hind limb suspension between 1 and 14 days while the control groups were maintained without suspension for the same duration. To study the effect of diet, some groups of animals were fed on a special diet with defined composition. At term, the animals were sacrificed and the tibia, femur, and skull bones were collected. In addition, soft tissues from pancreas and muscles were also collected. All of the bones and tissues samples were analyzed for elemental analysis using Energy Dispersive Spectroscopy (EDS) equipped on a Scanning Electron Microscope (SEM). In the EDS, 10-20 keV electrons bombarded the samples and a Si (Li) detector measured K-, L- and M-shell x-rays. Independently, X-Ray Fluorescence (XRF) provided the data for comparison and normalization. Flame software, with Fuzzy Logic, was used to form elemental ratios. Elemental analysis of bone samples indicated a variation in the compositional ratios of calcium, potassium, oxygen and carbon in the leg bones and skulls of the HLS versus control specimens. These variations showed dependence on sample position in the bone.

  10. Preparation and evaluation of enrofloxacin microspheres and tissue distribution in rats

    PubMed Central

    Yang, Fan; Kang, Jijun; Yang, Fang; Zhao, Zhensheng; Kong, Tao

    2015-01-01

    New enrofloxacin microspheres were formulated, and their physical properties, lung-targeting ability, and tissue distribution in rats were examined. The microspheres had a regular and round shape. The mean diameter was 10.06 µm, and the diameter of 89.93% of all microspheres ranged from 7.0 µm to 30.0 µm. Tissue distribution of the microspheres was evaluated along with a conventional enrofloxacin preparation after a single intravenous injection (7.5 mg of enrofloxacin/kg bw). The results showed that the elimination half-life (t1/2β) of enrofloxacin from lung was prolonged from 7.94 h for the conventional enrofloxacin to 13.28 h for the microspheres. Area under the lung concentration versus time curve from 0 h to ∞ (AUC0-∞) was increased from 11.66 h·µg/g to 508.00 h·µg/g. The peak concentration (Cmax) in lung was increased from 5.95 µg/g to 93.36 µg/g. Three lung-targeting parameters were further assessed and showed that the microspheres had remarkable lung-targeting capabilities. PMID:25643802

  11. Surface fluorescence studies of tissue mitochondrial redox state in isolated perfused rat lungs.

    PubMed

    Staniszewski, Kevin; Audi, Said H; Sepehr, Reyhaneh; Jacobs, Elizabeth R; Ranji, Mahsa

    2013-04-01

    We designed a fiber-optic-based optoelectronic fluorometer to measure emitted fluorescence from the auto-fluorescent electron carriers NADH and FAD of the mitochondrial electron transport chain (ETC). The ratio of NADH to FAD is called the redox ratio (RR = NADH/FAD) and is an indicator of the oxidoreductive state of tissue. We evaluated the fluorometer by measuring the fluorescence intensities of NADH and FAD at the surface of isolated, perfused rat lungs. Alterations of lung mitochondrial metabolic state were achieved by the addition of rotenone (complex I inhibitor), potassium cyanide (KCN, complex IV inhibitor) and/or pentachlorophenol (PCP, uncoupler) into the perfusate recirculating through the lung. Rotenone- or KCN-containing perfusate increased RR by 21 and 30%, respectively. In contrast, PCP-containing perfusate decreased RR by 27%. These changes are consistent with the established effects of rotenone, KCN, and PCP on the redox status of the ETC. Addition of blood to perfusate quenched NADH and FAD signal, but had no effect on RR. This study demonstrates the capacity of fluorometry to detect a change in mitochondrial redox state in isolated perfused lungs, and suggests the potential of fluorometry for use in in vivo experiments to extract a sensitive measure of lung tissue health in real-time. PMID:23238793

  12. Pressure-Mediated Oligonucleotide Transfection of Rat and Human Cardiovascular Tissues

    NASA Astrophysics Data System (ADS)

    Mann, Michael J.; Gibbons, Gary H.; Hutchinson, Howard; Poston, Robert S.; Hoyt, E. Grant; Robbins, Robert C.; Dzau, Victor J.

    1999-05-01

    The application of gene therapy to human disease is currently restricted by the relatively low efficiency and potential hazards of methods of oligonucleotide or gene delivery. Antisense or transcription factor decoy oligonucleotides have been shown to be effective at altering gene expression in cell culture expreriments, but their in vivo application is limited by the efficiency of cellular delivery, the intracellular stability of the compounds, and their duration of activity. We report herein the development of a highly efficient method for naked oligodeoxynucleotide (ODN) transfection into cardiovascular tissues by using controlled, nondistending pressure without the use of viral vectors, lipid formulations, or exposure to other adjunctive, potentially hazardous substances. In this study, we have documented the ability of ex vivo, pressure-mediated transfection to achieve nuclear localization of fluorescent (FITC)-labeled ODN in approximately 90% and 50% of cells in intact human saphenous vein and rat myocardium, respectively. We have further documented that pressure-mediated delivery of antisense ODN can functionally inhibited target gene expression in both of these tissues in a sequence-specific manner at the mRNA and protein levels. This oligonucleotide transfection system may represent a safe means of achieving the intraoperative genetic engineering of failure-resistant human bypass grafts and may provide an avenue for the genetic manipulation of cardiac allograft rejection, allograft vasculopathy, or other transplant diseases.

  13. Different exercise protocols improve metabolic syndrome markers, tissue triglycerides content and antioxidant status in rats

    PubMed Central

    2011-01-01

    Background An increase in the prevalence of obesity entails great expenditure for governments. Physical exercise is a powerful tool in the combat against obesity and obesity-associated diseases. This study sought to determine the effect of three different exercise protocols on metabolic syndrome and lipid peroxidation markers and the activity of antioxidant enzymes in adult Wistar rats (120 days old). Methods Animals were randomly divided into four groups: the control (C) group was kept sedentary throughout the study; the aerobic group (A) swam1 h per day, 5 days per week, at 80% lactate threshold intensity; the strength group (S) performed strength training with four series of 10 jumps, 5 days per week; and the Concurrent group (AS) was trained using the aerobic protocol three days per week and the strength protocol two days per week. Results Groups A and S exhibited a reduction in body weight compared to group C. All exercised animals showed a reduction in triglyceride concentrations in fatty tissues and the liver. Exercised animals also exhibited a reduction in lipid peroxidation markers (TBARS) and an increase in serum superoxide dismutase activity. Animals in group A had increased levels of liver catalase and superoxide dismutase activities. Conclusions We concluded that all physical activity protocols improved the antioxidant systems of the animals and decreased the storage of triglycerides in the investigated tissues. PMID:22182600

  14. Acceleration of healing of gastric ulcers induced in rats by liquid diet: importance of tissue contraction.

    PubMed

    Tsukimi, Y; Okabe, S

    1994-12-01

    We examined the effect of a liquid diet or a combined diet of liquid plus cellulose on the healing of gastric ulcers induced in rats in comparison with that of solid chow. Ulcers were induced in the fundus of the stomach by luminal application of an acetic acid solution. The healing of ulcers could be divided into two phases based on the healing rate: early phase (days 1 to 10) and late phase (days 10 to 20). The liquid diet, but not the combined one, administered for 10 days significantly accelerated ulcer healing in both the early and late phases. The length of the ruptured muscularis mucosa decreased only in the liquid diet group in both phases. Regeneration of the ulcerated mucosa in the chow diet group was observed only in the late phase, it being markedly inhibited in the liquid diet group. The serum gastrin level significantly decreased in the liquid and combined diet groups in contrast to that in the chow group. The liquid and combined diets significantly reduced gastric mucosal DNA synthesis. We conclude that 1) the healing in this gastric ulcer model comprises two phases, and 2) tissue contraction is a major factor for the healing of gastric ulcers in the early phase, while both tissue contraction and regeneration of the ulcerated mucosa are involved in the healing in the late phase. PMID:7723215

  15. The natural xanthone alpha-mangostin reduces oxidative damage in rat brain tissue.

    PubMed

    Márquez-Valadez, Berenice; Lugo-Huitrón, Rafael; Valdivia-Cerda, Verónica; Miranda-Ramírez, Luis Rubén; Pérez-De La Cruz, Verónica; González-Cuahutencos, Octavio; Rivero-Cruz, Isabel; Mata, Rachel; Santamaría, Abel; Pedraza-Chaverrí, José

    2009-02-01

    The antiperoxidative properties of alpha-mangostin, a xanthone isolated from mangosteen fruit, were tested for the first time in nerve tissue exposed to different toxic insults. Two reliable biological preparations (rat brain homogenates and synaptosomal P2 fractions) were exposed to the toxic actions of a free radical generator (ferrous sulfate), an excitotoxic agent (quinolinate), and a mitochondrial toxin (3-nitropropionate). alpha-Mangostin decreased the lipoperoxidative action of FeSO(4) in both preparations in a concentration-dependent manner, and completely abolished the peroxidative effects of quinolinate, 3-nitropropionate and FeSO(4) + quinolinate at all concentrations tested. Interestingly, when tested alone in brain homogenates, alpha-mangostin significantly decreased the lipoperoxidation even below basal levels. alpha-Mangostin also prevented the decreased reductant capacity of mitochondria in synaptosomal fractions. Our results suggest that alpha-mangostin exerts a robust antiperoxidative effect in brain tissue preparations probably through its properties as a free radical scavenger. In light of these findings, this antioxidant should be tested in other neurotoxic models involving oxidative stress. PMID:19178790

  16. Effects of pristane on cytochrome P450 isozyme expression in rat tissues.

    PubMed

    Howard, Carolyn B; Samuel, Jacqueline; Henderson, Shalonda B; Stevens, Jacqueline; Thomas, Paul E; Cuchens, Marvin A

    2005-04-01

    Chemical carcinogenesis studies are powerful tools to obtain information on potential mechanisms of chemical factors for malignancies. In this study Western blot analyses, using monoclonal antibodies specific for three different cytochrome P450 (CYP) isozymes (CYP1A1, CYP1A2 and CYP2B), were employed to examine the effect(s) of 3-methylcholanthrene and/or pristane (2,6,10,14-tetramethylpentadecane) on the basal and inducible levels of expression of CYP proteins within Copenhagen rat tissues. Pristane exposure led to tissue specific differences in the CYP isozymes expressed and elicited increased CYP protein expression over 3-methylcholanthrene induced levels in microsomes isolated from liver, Peyer's Patches, and thymus. Within the context of the chemical carcinogenesis model employed in this study, these observations correlated with the induction of B-cell malignancies by low doses of 3-methylcholanthrene and of thymic lymphomas by a high 3-methylcholanthrene dose. The data suggest that pristane treatment affects CYP isozyme expression. This pristane-mediated effect clearly could be a contributing factor in the chemical carcinogenesis of the previously observed lymphoid malignancies, and a possible basis for the tumor enhancing effects of pristane. PMID:16708425

  17. Radiation-Induced Oxidative Stress at Out-of-Field Lung Tissues after Pelvis Irradiation in Rats

    PubMed Central

    Najafi, Masoud; Fardid, Reza; Takhshid, Mohammad Ali; Mosleh-Shirazi, Mohammad Amin; Rezaeyan, Abol-Hassan; Salajegheh, Ashkan

    2016-01-01

    Objective The out-of-field/non-target effect is one of the most important phenomena of ionizing radiation that leads to molecular and cellular damage to distant non-irradiated tissues. The most important concern about this phenomenon is carcinogenesis many years after radiation treatment. In vivo mechanisms and consequences of this phenomenon are not known completely. Therefore, this study aimed to evaluate the oxidative damages to out-of-field lung tissues 24 and 72 hours after pelvic irradiation in rats. Materials and Methods In this experimentalinterventional study, Sprague-Dawleymale rats (n=49) were divided into seven groups (n=7/each group), including two groups of pelvis- exposed rats (out-of-field groups), two groups of whole bodyexposed rats (scatter groups), two groups of lung-exposed rats (direct irradiation groups), and one control sham group. Out- of-field groups were irradiated at a 2×2 cm area in the pelvis region with 3 Gy using 1.25 MeV cobalt-60 gamma-ray source, and subsequently, malondialdehyde (MDA) and glutathione (GSH) levels as well as superoxide dismutase (SOD) activity in out-of-field lung tissues were measured. Results were compared to direct irradiation, control and scatter groups at 24 and 72 hours after exposure. Data were analyzed using Mann-Whitney U test. Results SOD activity decreased in out-of-field lung tissue 24 and 72 hours after irradiation as compared with the controls and scatter groups. GSH level decreased 24 hours after exposure and increased 72 hours after exposure in the out-of-field groups as compared with the scatter groups. MDA level in out-of-field groups only increased 24 hours after irradiation. Conclusion Pelvis irradiation induced oxidative damage in distant lung tissue that led to a dramatic decrease in SOD activity. This oxidative stress was remarkable, but it was less durable as compared to direct irradiation. PMID:27602315

  18. Effects of Diaceto-Dipropyl-Disulphide on Plasma Sialic Acid and Renal Tissue Thiol Levels in Alloxan Diabetic Rats

    PubMed Central

    Vickram; Thirumalarao, Kashinath Rattihalli; Raiker, Veena Gajana; Puttaswamy, Sandhya Hanumanthappa

    2016-01-01

    Introduction Plasma sialic acid levels are elevated in Diabetes Mellitus (DM) patients with proteinuria. Renal damage is mainly caused by free radicals that are excessively generated in DM. Thiols play an important role in the cellular antioxidative defence mechanisms mainly through thiol-disulphide exchange reaction. Diallyl disulphide, a garlic oil principle component, is known for its anti-diabetic properties. Its structural analogue, Diaceto-Dipropyl Disulphide (DADPDS), is a less toxic and more palatable disulphide and possesses similar anti-diabetic actions. Aim This study was undertaken to assess the usefulness of DADPDS in prevention of de-sialation of Glomerular Basement Membrane (GBM) in alloxan diabetic rats and to assess effect of DADPDS on renal tissue thiol levels. Materials and Methods Rats were divided into Normal, Diabetic and DADPDS treated diabetic groups. Diabetes was induced by intraperitoneal injection (IP) of alloxan. DADPDS was fed by gastric intubation. Plasma Sialic acid was determined by Ehrlich’s method and renal tissue thiol levels by Nitroprusside reaction method. Results This study showed a significant decrease (p<0.001) in plasma sialic acid, plasma glucose and renal tissue TBARS levels along with significant increase (p<0.001) in renal tissue thiol levels in DADPDS treated alloxan diabetic rats when compared to diabetic control rats. Conclusion Hence it may be concluded that DADPDS helps in preventing de-sialation of GBM in alloxan diabetic rats and improves renal tissue antioxidant defence mechanisms, may be through thiol-disulphide exchange reaction and thereby exhibits a possible clinical use in prevention of renal complications like diabetic nephropathy. PMID:27504279

  19. Brain Tissue Hypoxia and Oxidative Stress Induced by Obstructive Apneas is Different in Young and Aged Rats

    PubMed Central

    Dalmases, Mireia; Torres, Marta; Márquez-Kisinousky, Leonardo; Almendros, Isaac; Planas, Anna M.; Embid, Cristina; Martínez-Garcia, Miguel Ángel; Navajas, Daniel; Farré, Ramon; Montserrat, Josep Maria

    2014-01-01

    Study Objectives: To test the hypotheses that brain oxygen partial pressure (PtO2) in response to obstructive apneas changes with age and that it might lead to different levels of cerebral tissue oxidative stress. Design: Prospective controlled animal study. Setting: University laboratory. Participants: Sixty-four male Wistar rats: 32 young (3 mo old) and 32 aged (18 mo). Interventions: Protocol 1: Twenty-four animals were subjected to obstructive apneas (50 apneas/h, lasting 15 sec each) or to sham procedure for 50 min. Protocol 2: Forty rats were subjected to obstructive apneas or sham procedure for 4 h. Measurements and Results: Protocol 1: Real-time PtO2 measurements were performed using a fast-response oxygen microelectrode. During successive apneas cerebral cortex PtO2 presented a different pattern in the two age groups; there was a fast increase in young rats, whereas it remained without significant changes between the beginning and the end of the protocol in the aged group. Protocol 2: Brain oxidative stress assessed by lipid peroxidation increased after apneas in young rats (1.34 ± 0.17 nmol/mg of protein) compared to old ones (0.63 ± 0.03 nmol/mg), where a higher expression of antioxidant enzymes was observed. Conclusions: The results suggest that brain oxidative stress in aged rats is lower than in young rats in response to recurrent apneas, mimicking obstructive sleep apnea. This could be due to the different PtO2 response observed between age groups and the increased antioxidant expression in aged rats. Citation: Dalmases M, Torres M, Márquez-Kisinousky L, Almendros I, Planas AM, Embid C, Martínez-Garcia MA, Navajas D, Farré R, Montserrat JM. Brain tissue hypoxia and oxidative stress induced by obstructive apneas is different in young and aged rats. SLEEP 2014;37(7):1249-1256. PMID:25061253

  20. Tissue-specific expression and developmental regulation of the rat apolipoprotein B gene.

    PubMed Central

    Demmer, L A; Levin, M S; Elovson, J; Reuben, M A; Lusis, A J; Gordon, J I

    1986-01-01

    Expression of the apolipoprotein B (apoB) gene was examined in a variety of fetal, neonatal, and adult rat tissues by probing RNA blots with a cloned rat apoB cDNA. Among 10 adult male tissues surveyed, small intestine had the highest concentration of apoB mRNA. Its abundance in liver and adrenal gland was 40% and 0.5%, respectively, of that in small bowel, while none was detected in colon, kidney, testes, spleen, lung, heart, or brain. ApoB mRNA is as abundant in 18-day fetal liver as at any subsequent period of hepatic development. In contrast, the concentration of apoB mRNA remains low in fetal intestine until the last (21st) day of gestation, when it increases sharply to levels that are several-fold higher than in the liver. ApoB mRNA levels in fetal membranes harvested during this late gestational period were 10 times greater than in fetal liver. Since the major lipoprotein species in 19-day fetal plasma is low density lipoprotein, these observations suggest that fetal liver, and particularly its functional homologue, the yolk sac, are the principal sites of fetal lipoprotein synthesis at this stage of development. A 20-fold increase in placental apoB mRNA concentrations during the last 48 hr of pregnancy (to a level that is 50% of that encountered in fetal membrane RNA) suggests a specific role for this organ in maternal-fetal lipid transport immediately prior to parturition. Pulse-labeling experiments using 21-day fetal tissue slices showed that the liver synthesizes both apoB-100 (B-PI) and apoB-48 (B-PIII) albeit in somewhat different ratios than the adult organ. Fetal intestine produces almost exclusively the smaller apoB species, while fetal membranes and placenta synthesize only the larger peptide. The postnatal pattern of apoB mRNA accumulation is similar in liver and intestine. Profound decreases were observed during the late suckling and weaning periods, followed by an increase to adult levels. These final concentrations were similar to those

  1. Decreased plasma and tissue isoleucine levels after simulated gastrointestinal bleeding by blood gavages in chronic portacaval shunted rats.

    PubMed Central

    Olde Damink, S W; Dejong, C H; Deutz, N E; Soeters, P B

    1997-01-01

    BACKGROUND: Previously, arterial concentrations of the essential branched chain amino acid isoleucine (Ile) were found to have decreased by more than 50% after gastrointestinal haemorrhage in patients and after intragastric blood administration in healthy humans and pigs. Hypothetically, this induced hypoisoleucinaemia could deplete tissue Ile pools. AIMS: To study the effect of repeated blood gavages on arterial and tissue Ile levels during normal and impaired liver function. SUBJECTS: Male Wistar rats. METHODS: 14 days after portacaval shunting or sham surgery, rats received 3 ml bovine erythrocytes or saline at 0, 1, 2, and 3 hours via a gastrostomy catheter in the duodenum. At 0, 2, 4, 6 and 8 hours arterial blood and at 8 hours intestine, liver, muscle, and cerebral cortex were sampled for determination of ammonia and amino acid concentrations. RESULTS: In both groups repeated blood administration resulted in a marked decrease in plasma Ile (40-60%). This was accompanied by decreased tissue Ile concentrations in liver (50%), muscle (40-60%), and cerebral cortex (40-50%), but unaltered intestinal Ile levels. In contrast, the arterial and tissue concentrations of ammonia, urea, and of most amino acids increased, most strikingly of the other two branched chain amino acids, valine and leucine. CONCLUSIONS: Simulated gastrointestinal bleeding by blood gavages in rats with and without impaired liver function leads to hypoisoleucinaemia and decreased tissue Ile pools. PMID:9135535

  2. Amygdalin (Laetrile) and prunasin beta-glucosidases: distribution in germ-free rat and in human tumor tissue.

    PubMed Central

    Newmark, J; Brady, R O; Grimley, P M; Gal, A E; Waller, S G; Thistlethwaite, J R

    1981-01-01

    Amygdalin, the gentiobioside derivative of mandelonitrile commonly referred to as Laetrile, is presently under intensive investigation as a potential cancer chemotherapeutic agent. Because of this interest, we investigated the activity of beta-glucosidases that cleave glucose from amygdalin and from prunasin (mandelonitrile monoglucoside) in tissues from germ-free rats and in normal and neoplastic human tissues. Rat and human small intestinal mucosa contain high levels of activity of glucosidases that act on both of these cyanogenic glucosides. Release of glucose from these compounds was not detected in any of the human neoplastic tissues examined in the present study. These observations are consistent with reports of cyanide toxicity through the oral use of amygdalin or prunasin and pose serious questions concerning the alleged tumoricidal effect of amygdalin. PMID:6796962

  3. Tissue distribution of berberine and its metabolites after oral administration in rats.

    PubMed

    Tan, Xiang-Shan; Ma, Jing-Yi; Feng, Ru; Ma, Chao; Chen, Wen-Jing; Sun, Yu-Peng; Fu, Jie; Huang, Min; He, Chi-Yu; Shou, Jia-Wen; He, Wen-Yi; Wang, Yan; Jiang, Jian-Dong

    2013-01-01

    Berberine (BBR) has been confirmed to have multiple bioactivities in clinic, such as cholesterol-lowering, anti-diabetes, cardiovascular protection and anti- inflammation. However, BBR's plasma level is very low; it cannot explain its pharmacological effects in patients. We consider that the in vivo distribution of BBR as well as of its bioactive metabolites might provide part of the explanation for this question. In this study, liquid chromatography coupled to ion trap time-of-flight mass spectrometry (LC/MS(n)-IT-TOF) as well as liquid chromatography that coupled with tandem mass spectrometry (LC-MS/MS) was used for the study of tissue distribution and pharmacokinetics of BBR in rats after oral administration (200 mg/kg). The results indicated that BBR was quickly distributed in the liver, kidneys, muscle, lungs, brain, heart, pancreas and fat in a descending order of its amount. The pharmacokinetic profile indicated that BBR's level in most of studied tissues was higher (or much higher) than that in plasma 4 h after administration. BBR remained relatively stable in the tissues like liver, heart, brain, muscle, pancreas etc. Organ distribution of BBR's metabolites was also investigated paralleled with that of BBR. Thalifendine (M1), berberrubine (M2) and jatrorrhizine (M4), which the metabolites with moderate bioactivity, were easily detected in organs like the liver and kidney. For instance, M1, M2 and M4 were the major metabolites in the liver, among which the percentage of M2 was up to 65.1%; the level of AUC (0-t) (area under the concentration-time curve) for BBR or the metabolites in the liver was 10-fold or 30-fold higher than that in plasma, respectively. In summary, the organ concentration of BBR (as well as its bioactive metabolites) was higher than its concentration in the blood after oral administration. It might explain BBR's pharmacological effects on human diseases in clinic. PMID:24205048

  4. Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

    PubMed

    Peplow, Philip V

    2015-04-01

    Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). PMID:25952122

  5. Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices – an experimental study in the rat

    PubMed Central

    2014-01-01

    Introduction Within the last decades, collagen types I and III have been established as a sufficient biomaterial for GBR and GTR procedures. They might also be an adequate matrix for soft tissue augmentations. However, collagen materials differ significantly regarding resorption time, biodegradation pattern and the invasion of inflammatory cells. The aim of the present study was to compare the biodegradation and tissue integration of native, differently processed and cross-linked collagen scaffolds in rats. Methods Four experimental porcine collagen matrices of 1.0 mm thickness, developed for soft tissue augmentation procedures, were tested. Based on the same native dermal Type I and III collagen, native (ND, Mucoderm® prototype), specifically defatted (DD), ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL) dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two specimens of 1 × 1 cm were fixed around a non-absorbable spacer using non-absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each. After each period, eight rats were sacrificed and explanted specimens were prepared for histological analysis. The following parameters were evaluated: membrane thickness as a sign of biodegradation and volume stability, cell ingrowth, vascularization, tissue integration and foreign body reaction. Results Biodegradation pattern of the non cross-linked collagen scaffolds differed only slightly in terms of presence of inflammatory cells and cell invasion into the matrix. In terms of biodegradation, ECL displayed a considerable slower resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide showed a significant higher invasion of inflammatory cells. Conclusion Within the limits of the present study it was concluded that the

  6. Changes in the masticatory muscles, periodontal tissues, and the pharyngeal ring in Wistar rats in chronic psychophysical stress.

    PubMed

    Antonova, I N

    2008-11-01

    Experimental studies performed on 120 male Wistar rats using morphometric and histological methods demonstrated changes in oral cavity tissues on exposure to chronic psychophysical stress (dosed swimming). The masticatory muscles showed foci of non-infective inflammation, dystrophic changes in muscle fibers, and contractures. The periodontal ligament showed impairments to the microcirculation with congestion of the venous bed, local bleeding into the tissue, changes in the directions of bundles of collagen fibers, and deformation of bundles. The tissues of the pharyngeal ring showed decreases in lymphocyte content, progressive loosening of connective tissue, and decreases in non-degranulated mast cell numbers, as compared with controls. The intensity of these changes depended on the level of physical loading and the individual adaptive capacity of the animals. These structural changes in the tissues may be the etiopathogenetic basis of the development of chronic inflammatory periodontal diseases. PMID:18975112

  7. Effect of exercise training on the density of endothelial cells in the white adipose tissue of rats.

    PubMed

    Hatano, D; Ogasawara, J; Endoh, S; Sakurai, T; Nomura, S; Kizaki, T; Ohno, H; Komabayashi, T; Izawa, T

    2011-12-01

    We examined the effects of a 9-week exercise training (TR) in Wistar male rats, beginning at 4 weeks of age, on the density of endothelial cells (ECs) in epididymal white adipose tissue (WAT) and the mRNA expression of angiogenic factors in adipose tissue stromal vascular fraction (SVF) cells. The number of ECs and mRNA expressions were assessed by lectin staining and real-time reverse transcriptase-polymerase chain reaction, respectively. Compared with control (CR) rats, TR rats gained weight more slowly and had significantly lower final weight of WAT due to the reduction in the size and the number of adipocytes. TR significantly increased the number of ECs per square millimeter and per adipocyte (1.37- and 1.23-fold, respectively) in WAT. This is probably because the number of adipocytes is fewer while the number of ECs is constant in the WAT of TR rats, because the regression line of TR rats for adipocyte number-dependent EC number was shifted toward the left without significant differences in the slopes between groups. TR also induced the upregulation of mRNA expression of vascular endothelial growth factor (Vegf)-A and Vegf-receptor-2 in SVF cells, thereby retaining a constant number of ECs in the WAT. PMID:20807385

  8. Morphological Study of the Articular Disc and Capillary of the Retrodiscal Tissue in a Type 2 Spontaneous Diabetes Mellitus Rat Model.

    PubMed

    Uemura, Mamoru; Toda, Isumi; Kawashima, Wataru; Yoshimoto, Gaku; Fang, Yi-Ru; Xu, Yuan Jin; Liu, Yuan; Zhang, Lei; Takemura, Akimichi

    2016-01-01

    The objective of this study was to evaluate morphological changes at the articular disc of the temporomandibular joint and capillary of the retrodiscal tissue in a rat model for type 2 spontaneous diabetes mellitus (DM) (i.e., Goto-Kakizaki [GK] rats) compared to normal Wistar rats. A total of 20 experimental rats were used in this study; the rats were categorized into the normal (n = 10 male 8-week-old Wistar rats) and DM (n = 10 male 8-week-old GK rats) groups. Hematoxylin-eosin stained specimens were obtained from 5 rats from each group. Image analyses of the hematoxylin-eosin stained specimens were conducted using light micrographs, which allowed comparisons of the thickness of the anterior, central, and posterior parts of the articular disc. Afterwards, the microvascular corrosion cast specimens were obtained from 5 rats from each group. The diameter of the capillary of the retrodiscal tissue was determined by analyzing scanning electron micrographs of the microvascular corrosion cast specimens. Student's t-test was used to test for statistical significant differences between the 2 groups. Differences were considered significant when p < 0.01. We found that the thickness of the anterior, central, and posterior parts of the articular disc, and the diameter of the capillary of the retrodiscal tissue was significantly lower in the DM vs. normal group. Therefore, we consider that DM-associated the hyperglycemia causes atrophy of the articular disc and microangiopathy of the capillary of the retrodiscal tissue in GK rats. PMID:27319300

  9. Dietary fatty acid composition alters 11β-hydroxysteroid dehydrogenase type 1 gene expression in rat retroperitoneal white adipose tissue.

    PubMed

    Vara Prasad, Sakamuri S S; Jeya Kumar, Shanmugam S; Kumar, Putcha Uday; Qadri, Syed S Y H; Vajreswari, Ayyalasomayajula

    2010-01-01

    The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) amplifies intracellular glucocorticoid action by converting inactive glucocorticoids to their active forms in vivo. Adipose-specific overexpression of 11β-HSD1 induces metabolic syndrome in mice, whereas 11β-HSD1 null mice are resistant to it. Dietary trans and saturated fatty acids (TFAs and SFAs) are involved in the development of metabolic syndrome, whereas polyunsaturated fatty acids (PUFA) offer protection against this. Here, we report the effects of chronic feeding of different diets containing vanaspati (TFA rich), palm oil (SFA rich) and sunflower oil (PUFA rich) at 10%level on 11β-HSD1 gene expression in rat retroperitoneal adipose tissue. 11β-HSD1 gene expression was significantly higher in TFA rich diet-fed rats compared to SFA rich diet-fed rats, which in turn was significantly higher than PUFA rich diet-fed rats. Similar trend was observed in the expression of CCAAT-enhancer binding protein-α (C/EBP-α), the main transcription factor required for the expression of 11β-HSD1. We propose that TFAs and SFAs increase local amplification of glucocorticoid action in adipose tissue by upregulating 11β-HSD1 by altering C/EBP-α-gene expression. The increased levels of glucocorticoids in adipose tissue may lead to development of obesity and insulin resistance, thereby increasing the risk of developing metabolic syndrome. PMID:20932307

  10. Double immunofluorescent staining of rat macrophages in formalin-fixed paraffin-embedded tissue using two monoclonal mouse antibodies.

    PubMed

    Isidro, Raymond A; Isidro, Angel A; Cruz, Myrella L; Hernandez, Siomara; Appleyard, Caroline B

    2015-12-01

    The conventional approach of double immunostaining to visualize more than one protein in tissues or cells using antibodies from two different host species is not always feasible due to limitations with antibody availability. Previously reported methodologies for performing multiple immunostains on the same tissue or cells with antibodies originating from the same species are varied in their complexity, sensitivity, and approach to prevent unwanted interactions between antibodies. In the ever-expanding field of macrophage biology, much more is known about mouse and human macrophages than their rat counterparts. The limited availability of validated and well-characterized monoclonal antibodies from different species is one factor responsible for preventing advances in rat macrophage biology. Here we describe an immunostaining method for identifying and examining rat macrophages that is sufficiently sensitive for use in formalin-fixed paraffin-embedded tissue and that uses only commercially available reagents and antibodies. This method can be used to help characterize both physiological and pathophysiological processes in rat macrophages and can be adapted for use with any two antibodies from the same species of origin as long as one of the antibodies is biotinylated. PMID:26403093

  11. Effects of antibodies to adipocytes on body weight, food intake, and adipose tissue cellularity in obese rats.

    PubMed

    Flint, D J

    1998-11-01

    Female Wistar rats were fed on a high fat diet for 18 weeks, during which their energy intake increased by 25% and body weight by 50% due to a doubling of adipose tissue tissue stores. Animals were then treated with increasing doses of a sheep polyclonal antiserum to rat adipocytes on days 1-4 and 7 after which they remained untreated for 14 weeks. Antibody treatment reduced body weight by 10% and the weight of parametrial and subcutaneous adipose tissue by 30-40%. This decrease was explicable entirely in terms of a decrease in the number of adipocytes presumably due to adipocyte lysis. These favourable changes in body fat mass were accompanied by improvement in at least one metabolic factor associated with obesity - serum leptin concentrations were significantly reduced in treated animals compared with high fat controls. Genetically obese Zucker rats also showed decreases in the number of adipocytes after treatment with antibodies but in contrast to diet-induced obese rats, they showed a compensatory increase in adipocyte volume which attenuated the effects on body fat mass. These results demonstrate for the first time, the potential to treat diet-induced obesity with antibodies to adipocytes by producing long-term reductions in the number of adipocytes, with minimal side-effects. PMID:9813180

  12. Immunization of Wistar female rats with 255-Gy-irradiated Toxoplasma gondii: Tissue parasitic load and lactogenic quantification.

    PubMed

    Camossi, Lucilene Granuzzio; Fornazari, Felipe; Richini-Pereira, Virgínia Bodelão; Costa da Silva, Rodrigo; Cardia, Daniel Fontana Ferreira; Langoni, Helio

    2015-07-01

    Toxoplasma gondii is one of the most significant parasite, due its importance in veterinary medicine and in public health, considered a food-borne pathogens, there is no available drug treatments to eliminate it from animal tissue, this reinforce the search for a vaccine against this parasite. This study was aimed to evaluate the dynamic of the distribution of T. gondii in tissues of female Wistar rats and their milk, after the immunization by oral rote with irradiated tachyzoites. One week after pregnancy confirmation, rats was challenged by gavage with T. gondii bradyzoites, oocysts or tachyzoites of T. gondii. Forty-eight pregnant rats were grouped as follows: immunized and challenged with bradyzoites (BZ*); non-immunized and challenged with bradyzoites (BZ); immunized and challenged with oocysts (OC*); non-immunized and challenged with oocysts (OC); immunized and challenged with tachyzoites (TZ*); non-immunized and challenged with tachyzoites (TZ); only immunized (I); control group (C). After parturition, milk samples were collected for 3 weeks and then rats were sacrificed and the tissues and milk samples were researched for T. gondii parasite load determined by the quantitative PCR (qPCR). It was verified that the immunization with irradiated tachyzoites of T. gondii induced the reduction of parasitic load in muscle samples in rats challenged by bradyzoites and oocysts, although not enabled the development of sterile immunity. The detection of parasite DNA in milk was found throughout the lactation period, from immunized and non-immunized rats, however no differences were found in the parasite load caused by immunization. PMID:25936982

  13. 32P analysis of DNA adducts in tissues of benzene-treated rats.

    PubMed

    Reddy, M V; Blackburn, G R; Schreiner, C A; Mehlman, M A; Mackerer, C R

    1989-07-01

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene. The carcinogenic activity of benzene is thought to be caused by activation to toxic metabolites that can interact with DNA, forming covalent adducts. A nuclease P1-enhanced 32P-postlabeling assay, having a sensitivity limit of 1 adduct in 10(9-10) DNA nucleotides, was found suitable for measuring aromatic DNA adducts derived in vitro from catechol, benzenetriol (BT), phenol, hydroquinone (HQ), and benzoquinone (BQ), potential metabolites of benzene. When DNA specimens isolated from tissues of female Sprague-Dawley rats at 24 hr after an oral gavage dose of 200 to 500 mg/kg, 5 days/week, in olive oil (3 mL/kg) for 1 day, 1 week, 5 weeks, and 10 weeks were analyzed by the 32P-postlabeling procedure, no aromatic adducts were detected unequivocally with DNA samples of liver, kidney, bone marrow, and mammary gland. With Zymbal gland DNA, three weak spots at levels totaling four lesions per 10(9) DNA nucleotides were seen only after 10 weeks of treatment, and these adducts did not correspond chromatographically to major adducts in vitro from the above specified compounds. Consequently, this finding requires confirmatory experiments. This distinct adduct pattern may relate to tumor induction in this organ following benzene administration. Our results also indicate that DNA adducts derived from catechol, BT, phenol, HQ, and BQ are either not formed in vivo with benzene or formed at levels below the detection limit of 1 adduct per 10(9-10) DNA nucleotides. PMID:2792046

  14. 32P analysis of DNA adducts in tissues of benzene-treated rats.

    PubMed Central

    Reddy, M V; Blackburn, G R; Schreiner, C A; Mehlman, M A; Mackerer, C R

    1989-01-01

    Solid tumors have been reported in the Zymbal gland, oral and nasal cavities, liver, and mammary gland of Sprague-Dawley rats following chronic, high-dose administration of benzene. The carcinogenic activity of benzene is thought to be caused by activation to toxic metabolites that can interact with DNA, forming covalent adducts. A nuclease P1-enhanced 32P-postlabeling assay, having a sensitivity limit of 1 adduct in 10(9-10) DNA nucleotides, was found suitable for measuring aromatic DNA adducts derived in vitro from catechol, benzenetriol (BT), phenol, hydroquinone (HQ), and benzoquinone (BQ), potential metabolites of benzene. When DNA specimens isolated from tissues of female Sprague-Dawley rats at 24 hr after an oral gavage dose of 200 to 500 mg/kg, 5 days/week, in olive oil (3 mL/kg) for 1 day, 1 week, 5 weeks, and 10 weeks were analyzed by the 32P-postlabeling procedure, no aromatic adducts were detected unequivocally with DNA samples of liver, kidney, bone marrow, and mammary gland. With Zymbal gland DNA, three weak spots at levels totaling four lesions per 10(9) DNA nucleotides were seen only after 10 weeks of treatment, and these adducts did not correspond chromatographically to major adducts in vitro from the above specified compounds. Consequently, this finding requires confirmatory experiments. This distinct adduct pattern may relate to tumor induction in this organ following benzene administration. Our results also indicate that DNA adducts derived from catechol, BT, phenol, HQ, and BQ are either not formed in vivo with benzene or formed at levels below the detection limit of 1 adduct per 10(9-10) DNA nucleotides. Images FIGURE 1. FIGURE 2. FIGURE 3. PMID:2792046

  15. Uninephrectomy in rats on a fixed food intake results in adipose tissue lipolysis implicating spleen cytokines

    PubMed Central

    Arsenijevic, Denis; Cajot, Jean-François; Dulloo, Abdul G.; Montani, Jean-Pierre

    2015-01-01

    The role of mild kidney dysfunction in altering lipid metabolism and promoting inflammation was investigated in uninephrectomized rats (UniNX) compared to Sham-operated controls rats. The impact of UniNX was studied 1, 2, and 4 weeks after UniNX under mild food restriction at 90% of ad libitum intake to ensure the same caloric intake in both groups. UniNX resulted in the reduction of fat pad weight. UniNX was associated with increased circulating levels of beta-hydroxybutyrate and glycerol, as well as increased fat pad mRNA of hormone sensitive lipase and adipose triglyceride lipase, suggesting enhanced lipolysis. No decrease in fat pad lipogenesis as assessed by fatty acid synthase activity was observed. Circulating hormones known to regulate lipolysis such as leptin, T3, ghrelin, insulin, corticosterone, angiotensin 1, and angiotensin 2 were not different between the two groups. In contrast, a select group of circulating lipolytic cytokines, including interferon-gamma and granulocyte macrophage–colony stimulating factor, were increased after UniNX. These cytokine levels were elevated in the spleen, but decreased in the kidney, liver, and fat pads. This could be explained by anti-inflammatory factors SIRT1, a member of the sirtuins, and the farnesoid x receptor (FXR), which were decreased in the spleen but elevated in the kidney, liver, and fat pads (inguinal and epididymal). Our study suggests that UniNX induces adipose tissue lipolysis in response to increased levels of a subset of lipolytic cytokines of splenic origin. PMID:26217234

  16. Cloning and regulation of rat tissue inhibitor of metalloproteinases-2 in osteoblastic cells

    NASA Technical Reports Server (NTRS)

    Cook, T. F.; Burke, J. S.; Bergman, K. D.; Quinn, C. O.; Jeffrey, J. J.; Partridge, N. C.

    1994-01-01

    Rat tissue inhibitor of metalloproteinases-2 (TIMP-2) was cloned from a UMR 106-01 rat osteoblastic osteosarcoma cDNA library. The 969-bp full-length clone demonstrates 98 and 86% sequence identity to human TIMP-2 at the amino acid and nucleic acid levels, respectively. Parathyroid hormone (PTH), at 10(-8) M, stimulates an approximately twofold increase in both the 4.2- and 1.0-kb transcripts over basal levels in UMR cells after 24 h of exposure. The PTH stimulation of TIMP-2 transcripts was not affected by the inhibitor of protein synthesis, cycloheximide (10(-5) M), suggesting a primary effect of the hormone. This is in contradistinction to regulation of interstitial collagenase (matrix metalloproteinase-1) by PTH in these same cells. Nuclear run-on assays demonstrate that PTH causes an increase in TIMP-2 transcription that parallels the increase in message levels. Parathyroid hormone, in its stimulation of TIMP-2 mRNA, appears to act through a signal transduction pathway involving protein kinase A (PKA) since the increase in TIMP-2 mRNA is reproduced by treatment with the cAMP analogue, 8-bromo-cAMP (5 x 10(-3) M). The protein kinase C and calcium pathways do not appear to be involved due to the lack of effect of phorbol 12-myristate 13-acetate (2.6 x 10(-6) M) and the calcium ionophore, ionomycin (10(-7) M), on TIMP-2 transcript abundance. In this respect, regulation of TIMP-2 and collagenase in osteoblastic cells by PTH are similar. However, we conclude that since stimulation of TIMP-2 transcription is a primary event, the PKA pathway must be responsible for a direct increase in transcription of this gene.

  17. Radiochemical detection of dihydrodiol dehydrogenase: distribution of the indomethacin sensitive enzyme in rat tissues

    SciTech Connect

    Ivins, J.; Penning, T.

    1986-05-01

    Dihydrodiol dehydrogenase catalyzes the NADP/sup +/ dependent oxidation of trans-dihydrodiols of polycyclic aromatic hydrocarbons (PAH) which are potent proximate carcinogens. The authors have developed a highly sensitive radiochemical assay for this enzyme in which the oxidation of trans-1,2-dihydroxy-3,5-cyclohexadiene, a model substrate for trans-dihydrodiol proximate carcinogens, is coupled to O-methylation catalyzed by catechol O-methyl transferase. Using S-adenosyl-(/sup 3/H-methyl)-methionine as methyl donor at a specific activity of 0.1 nCi/pmol and extracting the product, /sup 3/H-o-methoxyphenol, the assay provides a 5000 fold increase in sensitivity over the existing spectrophotometric method. The radiochemical assay was validated by comparing the K/sub m/ and V/sub max/ values for rat liver cytosol with those derived spectrophotometrically. In both instances there was close agreement between values (K/sub m/ = 0.77 +/- 0.11 mM and V/sub max/ = 2.14 +/- 0.13 nmoles/min/mg protein determined radiochemically; K/sub m/ = 0.96 +/- 0.10 mM and V/sub max/ = 6.31 +/- 0.50 nmoles/min/mg protein determined spectrophotometrically). Using the radiochemical method, dihydrodiol dehydrogenase activity was detected in the following rat tissues: liver > lung > heart > small intestine > testis > seminal vesicle > bladder > prostate > spleen. Specific activities ranged between 0.944 and 0.016 nmoles/min/mg protein. In liver, lung, and testis, which are sites of PAH metabolism, the dehydrogenase is sensitive to inhibition by low ..mu..M concentrations of indomethacin, suggesting that this drug can prevent the detoxification of proximate carcinogens by this route.

  18. Proteomic study of periovarian adipose tissue in 17β-estradiol-treated and untreated ovariectomized rats.

    PubMed

    Amengual-Cladera, Emilia; Capllonch-Amer, Gabriela; Lladó, Isabel; Gianotti, Magdalena; Proenza, Ana M

    2016-04-01

    Taking into account the sexual dimorphism previously found in white adipose tissue (WAT) regarding mitochondrial function and biogenesis, as well as insulin sensitivity, the aim of this study was to go further into the role of sex hormones in this dimorphism. To achieve this objective, we used ovariectomized rats and performed a screening by means of proteomic analyses of the periovarian WAT, combined with a study of the protein levels of specific factors involved in mitochondrial function. Rats were ovariectomized at 5 weeks of age and subcutaneously injected every 48 h with corn-oil (OVX group) or with 17β-estradiol (E2, 10 μg/kg body mass; OVX + E2 group) for 4 weeks prior to sacrifice. Beside proteomic analysis, protein levels of Transcription Factor A, Mitochondrial (TFAM), cytochrome oxidase (COX)II, and COXIV were determined by Western blot, and mRNA levels of peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, ERα, ERβ, lipoprotein lipase (LPL), peroxisome proliferator-activated receptor-γ (PPARγ), and adiponectin were quantified by real-time PCR. Our results show that ovariectomy leads to an increase in anabolic processes and inflammatory protein levels as well as to a decrease in some of the markers of mitochondrial function, which are restored, at least in part, by E2 supplementation. Indeed, this E2 supplementation seems to be counteracted by a decline in ERα and in the ERα to ERβ ratio values that could be directed to avoid an over-stimulation of the E2 signaling pathway, given the possibility of an activation of extra-gonadal steroid biosynthetic pathways. PMID:26914441

  19. Quantitative analysis of tenuifolin concentrations in rat plasma and tissue using LC⬜MS/MS: application to pharmacokinetic and tissue distribution study.

    PubMed

    Ma, Bo; Li, Xiaotian; Li, Jing; Zhang, Qi; Liu, Yinhui; Yang, Xiaojing; Sun, Jingjing; Yao, Di; Liu, Lei; Liu, Xiaoxin; Ying, Hanjie

    2014-01-01

    A sensitive, reliable and accurate reversed-phased liquid chromatography with tandem mass spectrometry (LC⬜MS/MS) in negative ion mode was developed and validated for the quantification of tenuifolin in rat plasma and tissue. A single step protein precipitation by methanol was used to prepare plasma and tissue homogenate samples. Tenuifolin and polydatin (internal standard, IS) were separated by HPLC using a C18 column and an isocratic mobile phase consisted of acetonitrile and water containing 0.05% formic acid (42:58, v/v) running at a flow rate of 0.2 ml/min for 6 min. Detection and quantification were performed using a mass spectrometer by the multiple reaction monitoring (MRM) in negative electrospray ionization mode. The transition monitored were m/z [M↙H](↙) 679.4 ⠙ 455.4 for tenuifolin and m/z [M↙H](↙) 389.0 ⠙ 227.2 for IS, respectively. Calibration curves were recovered over a concentration range of 0.5⬜1000 ng/ml for plasma, heart, liver, lung and kidney, 0.5⬜200 ng/ml for spleen, and 0.5⬜50 ng/ml for brain, respectively. The lower limit of quantification was 0.5 ng/ml for plasma and tissue homogenates. The inter-day precision (R.S.D.) was less than 12.9% and intra-day precision R.S.D. was less than 13.4%, while the inter-day accuracy (R.E.) was ranged from ↙7.20 to 6.87% and intra-day accuracy (R.E.) was ranged from ↙6.20 to 8.04% in plasma and tissue homogenates. This method was successfully applied to the pharmacokinetic and tissue distribution study of pure tenuifolin in rat. The pharmacokinetic study indicated that poor absorption into systemic circulation was observed after rat was administered orally tenuifolin, and the absolute bioavailability was low (0.83 ± 0.28%). The results of tissue distribution showed the higher tenuifolin concentrations were found in liver, kidney and heart, and the small amount of drug was distributed quickly into the brain tissue at 5 min after the intravenous injection of tenuifolin

  20. Correlation of virtual touch tissue quantification and liver biopsy in a rat liver fibrosis model.

    PubMed

    Hu, Zhiwen; Luo, Jialun; Wei, Hongqin; Ou, Wencai; Xiao, Shuyi; Gan, Man; Ma, Suihong; He, Jingguang; Wu, Daihong; Feng, Guiying; Wei, Jinglu; Liu, Jianhua

    2015-05-01

    Liver fibrosis assessment is very important to the treatment of chronic liver disease. In the present study, Virtual Touch Tissue Quantification (VTQ) and eSie Touch™ elasticity imaging techniques were used to examine the rat liver fibrosis model. Rat liver fibrosis was induced with thioacetamide and the degree of liver fibrosis was determined using pathological diagnosis as a gold standard. The right lobe of the liver was also examined with the VTQ and eSie Touch™ techniques. The VTQ and serological results were correlated and analyzed. The results were compared with those obtained from liver biopsies to investigate the accuracy and diagnostic value of eSie Touch™ and VTQ on the classification of liver fibrosis in rats. A total of 30 successful modeling cases were obtained, with a success rate of 86%. The mean acoustic radiation force impulse (ARFI) elastography‑VTQ values were 1.08, 1.51, 1.88 and 2.50 m/sec for the normal and F1/F2, F3 and F4 fibrosis groups, respectively. A significant correlation (r = 0.969) was identified between the ARFI measurements and the degree of fibrosis assessed by pathological examination (P<0.001). The histological staging results correlated with those of the eSie Touch™ elasticity imaging of the biopsy site (r = 0.913, P<0.001). The predictive values of ARFI for various stages of fibrosis were as follows: F≥1 and 2 ‑ cut‑off >1.250 m/sec (when Vs >1.250 m/sec, the pathological grading was ≥F1/F2) [Area under receiver operating characteristic (AUROC) = 1.00], F≥3 ‑ cut‑off >1.685 m/sec (when Vs >1.685 m/sec, the pathological grading was ≥F3; AUROC = 1.00) and F≥4 ‑ cut‑off >2.166 m/sec (when Vs >2.166 m/sec, the pathological grading is cirrhosis; AUROC = 1.00). In conclusion, the eSie Touch™ elasticity imaging and VTQ techniques may be successfully adopted to assess the extent of liver stiffness. These techniques are expected to replace liver biopsy. PMID:25592825

  1. Tissue distribution and metabolism of guanosine in rats following intraperitoneal injection.

    PubMed

    Giuliani, P; Ballerini, P; Ciccarelli, R; Buccella, S; Romano, S; D'Alimonte, I; D' Alimonte, I; Poli, A; Beraudi, A; Peña, E; Jiang, S; Rathbone, M P; Caciagli, F; Di Iorio, P

    2012-01-01

    Guanosine has long been known as an endogenous purine nucleoside deeply involved in the modulation of several intracellular processes, especially G-protein activity. More recently, it has been reported to act as an extracellular signaling molecule released from neurons and, more markedly, from astrocytes either in basal conditions or after different kinds of stimulation including hypoxia. Moreover, in vivo studies have shown that guanosine plays an important role as both a neuroprotective and neurotrophic agent in the central nervous system. Specific high-affinity binding sites for this nucleoside have been found on membrane preparations from rat brain. The present study was undertaken to investigate the distribution and metabolic profiles of guanosine after administering the nucleoside to gain a better understanding of the biological effects of this potential drug candidate. Rats were given an intraperitonal (i.p.) injection of 2, 4, 8 or 16 mg/kg of guanosine combined with 0.05% of [3H]guanosine. Plasma samples were collected 7.5, 15, 30, 60 and 90 min after the guanosine-mixture administration and analyzed by either a liquid scintillation counter or by HPLC connected to a UV and to an on-line radiochemical detector to measure the levels of guanosine and its metabolic products guanine, xanthine and uric acid. The levels of guanosine, guanine and xanthine were also measured in brain, lung, heart, kidney and liver tissue homogenates at the defined time points after the injection of 8 mg/kg of the guanosine-mixture. We found that the levels of radioactivity in plasma increased linearly in a dose- and time-dependent manner. Guanosine was widely distributed in all tissues examined in the present study, at almost twice its usual levels. In addition, guanine levels dramatically increased in all the organs. Interestingly, enzymatic analysis of the plasma samples showed the presence of a soluble purine nucleoside phosphorylase, a key enzyme in the purine salvage pathway

  2. Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase activities in adipose tissue of rats.

    PubMed

    Martinelli, Marcela I; Mocchiutti, Norberto O; Bernal, Claudio A

    2010-09-01

    The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical with detrimental health effects. The present work was designed to asses some potential mechanisms by which DEHP causes, among others, a reduced body fat retention. Since this effect could be related to an alteration of adipocyte triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in adipose tissues upon (1) the number and size of fat cells; (2) the basal and stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of male Wistar rats were fed for 21 days a control diet alone (control group) or the same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues. These rats had significantly reduced weight in epididymal and lumbar tissues, together with reduced size of epididymal adipocytes. These alterations do not seem to be associated with higher lipid mobility because neither basal lipolysis nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified by DEHP. Based on these results, we concluded that the adipose tissue size reduction induced by DEHP intake is not due to changes in lipolysis nor to a decreased LPL activity. More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention. PMID:20144957

  3. Long-term biopersistence of tangled oxidized carbon nanotubes inside and outside macrophages in rat subcutaneous tissue

    PubMed Central

    Sato, Yoshinori; Yokoyama, Atsuro; Nodasaka, Yoshinobu; Kohgo, Takao; Motomiya, Kenichi; Matsumoto, Hiroaki; Nakazawa, Eiko; Numata, Tomoko; Zhang, Minfang; Yudasaka, Masako; Hara, Hideyuki; Araki, Rikita; Tsukamoto, Osamu; Saito, Hiroaki; Kamino, Takeo; Watari, Fumio; Tohji, Kazuyuki

    2013-01-01

    Because of their mechanical strength, chemical stability, and low molecular weight, carbon nanotubes (CNTs) are attractive biological implant materials. Biomaterials are typically implanted into subcutaneous tissue or bone; however, the long-term biopersistence of CNTs in these tissues is unknown. Here, tangled oxidized multi-walled CNTs (t-ox-MWCNTs) were implanted into rat subcutaneous tissues and structural changes in the t-ox-MWCNTs located inside and outside of macrophages were studied for 2 years post-implantation. The majority of the large agglomerates were present in the intercellular space, maintained a layered structure, and did not undergo degradation. By contrast, small agglomerates were found inside macrophages, where they were gradually degraded in lysosomes. None of the rats displayed symptoms of cancer or severe inflammatory reactions such as necrosis. These results indicate that t-ox-MWCNTs have high biopersistence and do not evoke adverse events in rat subcutaneous tissue in vivo, demonstrating their potential utility as implantable biomaterials. PMID:23981952

  4. Bone density and tissue lead accretion in growing rats fed low high calcium with or without supplemental clinoptilolite

    SciTech Connect

    Pond, W.G.; Ho, H.; Su, D.R.

    1996-12-31

    The toxicity of lead in animals and humans is well documented. The naturally occurring zeolite, clinoptilolite, is known to offer protection against ammonium ion toxicity in rats and sheep and to counteract cadmium-induced iron deficiency anemia in rats and swine. The cation-exchange and adsorption properties of clinoptilolite suggest is possible role in reducing tissue uptake of ingested lead by animals. Evidence supporting this role was reported in growing pigs whose liver and kidney concentrations of lead were significantly reduced by the addition of 1.0% clinoptilolite to diets containing 500 or 1000ppm of lead. The basal diet was a highly fortified milk-replacer containing about 1% calcium supplied by milk constituents. High dietary calcium is known to reduce tissue uptake of lead and protect the pig from the tissue pathology associated with lead ingestion. The objective of this experiment was to test the hypothesis that dietary clinoptilolite and calcium levels affect the growth, tissue uptake and bone morphology of growing rats fed diets containing toxic levels of lead. 20 refs., 3 tabs.

  5. PVP formulated Fullerene (C60) increases Rho-kinase dependent Vascular Tissue Contractility in Pregnant Sprague Dawley Rats

    PubMed Central

    Vidanapathirana, Achini K.; Thompson, Leslie C.; Mann, Erin. E.; Odom, Jillian T.; Holland, Nathan A.; Sumner, Susan J.; Han, Li; Lewin, Anita H.; Fennell, Timothy R.; Brown, Jared M.; Wingard, Christopher J.

    2014-01-01

    Pregnancy is a unique physiological state, in which C60 fullerene is reported to be distributed in both maternal and fetal tissues. Tissue distribution of C60 differs between pregnant and non-pregnant states, presumably due to functional changes in vasculature during pregnancy. We hypothesized that, polyvinylpyrorrolidone (PVP) formulated C60 (C60/PVP) increases vascular tissue contractility during pregnancy by increasing Rho-kinase activity. C60/PVP was administered intravenously to pregnant and non-pregnant female Sprague Dawley rats. Vascular responses were assessed using wire myography 24 hours post-exposure. Increased stress generation was observed in uterine artery, thoracic aorta and umbilical vein. Rho-Rho-kinase mediated force maintenance was increased in arterial segments from C60/PVP exposed pregnant rats when compared to PVP exposed rats. Our findings suggest that intravenous exposure to C60/PVP during pregnancy increases vascular tissue contractility of the uterine artery through elements of Rho-Rho-kinase signaling during late stages of pregnancy. PMID:25088243

  6. Soya protein ameliorates the metabolic abnormalities of dysfunctional adipose tissue of dyslipidaemic rats fed a sucrose-rich diet.

    PubMed

    Oliva, María E; Selenscig, Dante; D'Alessandro, María E; Chicco, Adriana; Lombardo, Yolanda B

    2011-04-01

    The present study investigates whether the replacement of dietary casein by soya protein isolate could be able to improve and/or even revert the morphological and metabolic abnormalities underlying the adipose tissue dysfunction of dyslipidaemic rats chronically fed (8 months) a sucrose-rich (62·5 %) diet (SRD). For this purpose, Wistar rats were fed a SRD for 4 months. From months 4 to 8, half the animals continued with the SRD and the other half were fed a SRD in which the source of protein, casein, was substituted by soya. The control group received a diet in which the source of carbohydrate was maize starch. Compared with the SRD-fed group, the results showed that: (1) soya protein decreased body-weight gain, limited the accretion of visceral adiposity and decreased adipose tissue cell volume without changes in total cell number; (2) soya protein increased the protein mass expression of PPARγ, which was significantly reduced in the fat pad of the SRD-fed rats; (3) the activity of the enzymes involved in the de novo lipogenesis of adipose tissue was significantly decreased/normalised; (4) soya protein corrected the inhibitory effect of SRD upon the anti-lipolytic action of insulin, reduced basal lipolysis and normalised the protein mass expression of GLUT-4. Dyslipidaemia, glucose homeostasis and plasma leptin levels returned to control values. The present study provides data showing the beneficial effects of soya protein to improve and/or revert the adipose tissue dysfunction of a dyslipidaemic insulin-resistant rat model and suggests that soya could maintain the functionality of the adipose tissue-liver axis improving/reverting lipotoxicity. PMID:21118606

  7. Autologous subcutaneous adipose tissue transplants improve adipose tissue metabolism and reduce insulin resistance and fatty liver in diet-induced obesity rats.

    PubMed

    Torres-Villalobos, Gonzalo; Hamdan-Pérez, Nashla; Díaz-Villaseñor, Andrea; Tovar, Armando R; Torre-Villalvazo, Ivan; Ordaz-Nava, Guillermo; Morán-Ramos, Sofía; Noriega, Lilia G; Martínez-Benítez, Braulio; López-Garibay, Alejandro; Torres-Landa, Samuel; Ceballos-Cantú, Juan C; Tovar-Palacio, Claudia; Figueroa-Juárez, Elizabeth; Hiriart, Marcia; Medina-Santillán, Roberto; Castillo-Hernández, Carmen; Torres, Nimbe

    2016-09-01

    Long-term dietary and pharmacological treatments for obesity have been questioned, particularly in individuals with severe obesity, so a new approach may involve adipose tissue transplants, particularly autologous transplants. Thus, the aim of this study was to evaluate the metabolic effects of autologous subcutaneous adipose tissue (SAT) transplants into two specific intraabdominal cavity sites (omental and retroperitoneal) after 90 days. The study was performed using two different diet-induced obesity (DIO) rat models: one using a high-fat diet (HFD) and the other using a high-carbohydrate diet (HCHD). Autologous SAT transplant reduced hypertrophic adipocytes, improved insulin sensitivity, reduced hepatic lipid content, and fasting serum-free fatty acids (FFAs) concentrations in the two DIO models. In addition, the reductions in FFAs and glycerol were accompanied by a greater reduction in lipolysis, assessed via the phosphorylation status of HSL, in the transplanted adipose tissue localized in the omentum compared with that localized in the retroperitoneal compartment. Therefore, the improvement in hepatic lipid content after autologous SAT transplant may be partially attributed to a reduction in lipolysis in the transplanted adipose tissue in the omentum due to the direct drainage of FFAs into the liver. The HCHD resulted in elevated fasting and postprandial serum insulin levels, which were dramatically reduced by the autologous SAT transplant. In conclusion, the specific intraabdominal localization of the autologous SAT transplant improved the carbohydrate and lipid metabolism of adipose tissue in obese rats and selectively corrected the metabolic parameters that are dependent on the type of diet used to generate the DIO model. PMID:27582062

  8. Alteration of tissue disposition of cadmium by chelating agents. [Mice; rats

    SciTech Connect

    Klaassen, C.D.; Waalkes, M.P.; Cantilena, L.R. Jr.

    1984-03-01

    The effect of several chelating agents (diethyldithiocarbamic acid, DDC; nitrilotriacetic acid, NTA; 2,3-dimercaptopropanol, BAL; d,l-penicillamine, PEN; 2,3-dimercaptosuccinic acid, DMSA; ethylenediaminetetraacetic acid, EDTA; and diethylenetriaminepentaacetic acid, DTPA) on the toxicity, distribution and excretion of cadmium (Cd) was determined in mice. When chelators were administered immediately after Cd, significant increases in survival were noted after treatment with DMSA, EDTA, and DTPA. DTPA, followed by EDTA and then DMSA, were consistently the most effective in decreasing the tissue concentrations of Cd and increasing the excretion of Cd. NTA, BAL, DDC and PEN had no beneficial effects. To determine the role of MT in the acute decrease in chelator efficacy following Cd poisoning, rats were injected IV with Cd followed by DTPA at various times after Cd. Although DTPA reduced Cd content in the various organs when given immediately after Cd, the chelator was ineffective at all later times. Increases in hepatic and renal metallothionein (MT) did not occur until 2 hr after Cd, and did not coincide with the earlier drop in chelator efficacy. Blockade of MT synthesis by actinomycin D failed to eliminate this decreased DTPA effectiveness. Therefore, it appears that MT does not play an important role in the acute decrease in efficacy of chelation therapy for Cd poisoning. The effect of repeated daily administration of chelators on the distribution and excretion of Cd was studied by administering chelators daily for 5 days starting 48 hr after Cd. DTPA, EDTA, DMSA and BAL significantly increased the urinary elimination of Cd. Thus, mobilization of Cd into urine occurs with repeated chelation therapy, which may decrease tissue concentrations of Cd and reduce the toxicity of the metal. 4 references, 15 figures, 2 tables.

  9. Transient solid-fluid interactions in rat brain tissue under combined translational shear and fixed compression.

    PubMed

    Haslach, Henry W; Leahy, Lauren N; Hsieh, Adam H

    2015-08-01

    An external mechanical insult to the brain may create internal deformation waves, which have shear and longitudinal components that induce combined shear and compression of the brain tissue. To isolate such interactions and to investigate the role of the extracellular fluid (ECF) in the transient mechanical response, translational shear stretch up to 1.25 under either 0 or 33% fixed normal compression is applied without preconditioning to heterogeneous sagittal slices which are nearly the full length of the rat brain cerebrum. The normal stress contribution is estimated by separate unconfined compression stress-stretch curves at 0.0667/s and 1/s engineering strain rates to 33% strain. Unconfined compression deformation causes lateral dimension expansion less than that predicted for an incompressible material under large deformation and often a visible loss of internal fluid from the specimen so that the bulk brain tissue is not incompressible in vitro, as sometimes assumed for mathematical modeling. The response to both slow 0.001/s and moderate 1/s shear translational stretch rates is deformation rate dependent and hardening under no compression but under 33% compression is nearly linear perhaps because of increased solid-solid friction. Both shear and normal stress relaxation are faster after the fast rate deformation possibly because higher deformation rates produce higher ECF hydrostatic pressure that primarily drives stress relaxation. The experimental results on ECF behavior guide the form of our nonlinear viscoelastic mathematical model. Our data are closely fit by non-equilibrium evolution equations that involve at most three specimen-specific empirical parameters and that are based on the idea that stretch of axons and glial processes resists load-induced ECF pressure. PMID:25913604

  10. In vivo corrosion behaviour of magnesium alloy in association with surrounding tissue response in rats.

    PubMed

    Miura, Chieko; Shimizu, Yoshinaka; Imai, Yoshimichi; Mukai, Toshiji; Yamamoto, Akiko; Sano, Yuya; Ikeo, Naoko; Isozaki, Shuji; Takahashi, Toru; Oikawa, Miho; Kumamoto, Hiroyuki; Tachi, Masahiro

    2016-04-01

    Biodegradable magnesium (Mg) alloys are the most promising candidates for osteosynthesis devices. However, their in vivo corrosion behaviour has not been fully elucidated. The aim of this study was to clarify the influence of the physiological environment surrounding Mg alloys on their corrosion behaviour. A Mg-1.0Al alloy with a fine-grained structure was formed into plates using titanium (Ti) as a control. These plates were implanted into the subperiosteum in the head, subcutaneous tissue of the back, and in the muscle of the femur of rats for 1, 2 and 4 weeks. The volumes of the remaining Mg alloy and of the insoluble salt deposition and gas cavities around the Mg alloy were determined by microtomography, and the volume losses were calculated. Then, the tissue response around the plates in each implantation site was examined histopathologically, and its relation to the respective volume loss was analyzed. These analyses determined that the Mg alloy was corroded fastest in the head, at an intermediate level in the back, and slowest in the femur. The insoluble salt deposition at the Mg alloy surface had no influence on the volume loss. Gas cavities formed around the Mg alloy at all implantation sites and decreased after 4 weeks. Histopathological examination revealed that the Mg alloy exhibited good biocompatibility, as was seen with Ti. In addition, vascularized fibrous capsules formed around the plates and became mature with time. Notably, the volume loss in the different anatomical locations correlated with capsule thickness. Together, our results suggest that, to facilitate the successful clinical application of Mg alloys, it will be necessary to further comprehend their interactions with specific in vivo environments. PMID:26947358

  11. Patagonfibrase modifies protein expression of tissue factor and protein disulfide isomerase in rat skin.

    PubMed

    Peichoto, María Elisa; Santoro, Marcelo Larami

    2016-09-01

    Patagonfibrase is a hemorrhagic metalloproteinase isolated from the venom of the South American rear-fanged snake Philodryas patagoniensis, and is an important contributor to local lesions inflicted by this species. The tissue factor (TF)-factor VIIa complex, besides triggering the coagulation cascade, has been demonstrated to be involved in inflammatory events. Our aim was to determine whether patagonfibrase affects the expression of TF and protein disulfide isomerase (PDI), an enzyme that controls TF biological activity, at the site of patagonfibrase injection, and thus if they may play a role in hemostatic and inflammatory events induced by snake venoms. Patagonfibrase (60 μg/kg) was administered s.c. to rats, and after 3 h blood was collected to evaluate hemostasis parameters, and skin fragments close to the site of injection were taken to assess TF and PDI expression. Patagonfibrase did not alter blood cell counts, plasma fibrinogen levels, or levels of TF activity in plasma. However, by semiquantitative Western blotting, patagonfibrase increased TF expression by 2-fold, and decreased PDI expression by 3-fold in skin samples. In agreement, by immunohistochemical analyses, prominent TF expression was observed in the subcutaneous tissue. Thus, patagonfibrase affects the local expression of TF and PDI without inducing any systemic hemostatic disturbance, although that they may be involved in the local inflammatory events induced by hemorrhagic metalloproteinases. Once antivenom therapy is not totally effective to treat the local injury induced by snake venoms, modulation of the activity and expression of TF and/or PDI might become a strategy for treating snake envenomation. PMID:27390042

  12. Sympathetic activation by chemical stimulation of white adipose tissues in rats.

    PubMed

    Shi, Zhen; Chen, Wei-Wei; Xiong, Xiao-Qing; Han, Ying; Zhou, Ye-Bo; Zhang, Feng; Gao, Xing-Ya; Zhu, Guo-Qing

    2012-03-01

    Injection of leptin into white adipose tissue (WAT) increases sympathetic outflow. The present study was designed to determine the effects of capsaicin and other chemicals in WAT on the sympathetic outflow and blood pressure and the roles of WAT afferents and hypothalamic paraventricular nucleus (PVN) in the adipose afferent reflex (AAR). The AAR was induced by injection of capsaicin, bradykinin, adenosine, adenosine triphosphate (ATP), or leptin into inguinal WAT (iWAT) or retroperitoneal WAT (rWAT) in anesthetized rats. The iWAT injection of capsaicin increased the renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) but not the heart rate. Bradykinin, adenosine, or leptin but not ATP in the iWAT caused similar effects to capsaicin on the RSNA and MAP. Intravenous, intramuscular, or intradermal injection of capsaicin had no significant effects on the RSNA and MAP. The effects of capsaicin in rWAT were similar to that in iWAT on the RSNA and MAP. Furthermore, injection of capsaicin into the iWAT increased the WAT afferent nerve activities, WAT efferent nerve activity, and brown adipose tissue efferent nerve activity. The iWAT denervation or chemical lesion of the PVN neurons with kainic acid abolished the AAR induced by the iWAT injection of capsaicin. These results indicate that the stimulation of iWAT afferents with capsaicin, bradykinin, adenosine, or leptin reflexly increases the RSNA and blood pressure. The iWAT afferents and the PVN are involved in the AAR induced by capsaicin in the iWAT. PMID:22223453

  13. Comparative pharmacokinetic and tissue distribution profiles of four major bioactive components in normal and hepatic fibrosis rats after oral administration of Fuzheng Huayu recipe.

    PubMed

    Yang, Tao; Liu, Shan; Wang, Chang-Hong; Tao, Yan-Yan; Zhou, Hua; Liu, Cheng-Hai

    2015-10-10

    Fuzheng Huayu recipe (FZHY) is a herbal product for the treatment of liver fibrosis approved by the Chinese State Food and Drug Administration (SFDA), but its pharmacokinetics and tissue distribution had not been investigated. In this study, the liver fibrotic model was induced with intraperitoneal injection of dimethylnitrosamine (DMN), and FZHY was given orally to the model and normal rats. The plasma pharmacokinetics and tissue distribution profiles of four major bioactive components from FZHY were analyzed in the normal and fibrotic rat groups using an ultrahigh performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Results revealed that the bioavailabilities of danshensu (DSS), salvianolic acid B (SAB) and rosmarinic acid (ROS) in liver fibrotic rats increased 1.49, 3.31 and 2.37-fold, respectively, compared to normal rats. There was no obvious difference in the pharmacokinetics of amygdalin (AMY) between the normal and fibrotic rats. The tissue distribution of DSS, SAB, and AMY trended to be mostly in the kidney and lung. The distribution of DSS, SAB, and AMY in liver tissue of the model rats was significantly decreased compared to the normal rats. Significant differences in the pharmacokinetics and tissue distribution profiles of DSS, ROS, SAB and AMY were observed in rats with hepatic fibrosis after oral administration of FZHY. These results provide a meaningful basis for developing a clinical dosage regimen in the treatment of hepatic fibrosis by FZHY. PMID:26048667

  14. A HPLC-MS/MS method for determination of 6'''-feruloylspinosin in rat plasma and tissues: Pharmacokinetics and tissue distribution study.

    PubMed

    Qiao, Longdong; Liu, Yan; Chen, Xiaoyan; Xie, Junbo; Zhang, Yanqing; Yang, Ke; Zhou, Hongjian; Duan, Yayun; Zheng, Wei; Xie, Wenlin

    2016-03-20

    A sensitive, reliable and accurate HPLC-MS/MS method was developed and validated for the quantification of 6'''-feruloylspinosin in rat plasma and tissues with puerarin as the internal standard. The separation was performed on a Proshell 120 EC-C18 column (4.6×150 mm, 2.7 μm) with a mobile phase consisting of acetonitrile and 0.1% formic acid (20:80, v/v) at 0.3 mL/min. The quantification was performed by MRM with m/z [M-H](-) 783.3→427.2 for 6'''-feruloylspinosin and m/z [M-H](-) 415.4→295.4 for the internal standard, respectively. The calibration curves covered over a concentration range of 20-2000 ng/mL in plasma and various tissues samples (heart, liver, spleen, lung, kidney, stomach, intestine, muscle, cerebrum and cerebellum) with good linearity (r(2)≥0.9914). Both the intra- and inter-day precisions were less than 14.70%, and the accuracy (RE%) ranged from -5.80% to 4.93%. The extraction recoveries were within 75.21-92.96%, and the matrix effect ranged from 87.21% to 113.44%. Compared with spinosin, 6'''-feruloylspinosin was distributed in rats faster whereas more slowly eliminated from the plasma. 6'''-Feruloylspinosin could be distributed rapidly and widely in various tissues, and transfer across the blood-brain barrier. In addition, both 6'''-feruloylspinosin and spinosin could enhance the expression of GABAAα1, GABAAα5, GABABR1 mRNA in rat hippocampal neurons significantly, indicating the bioactivity mechanism of 6'''-feruloylspinosin was involved in the GABA receptors. PMID:26780157

  15. Monocytic Tissue Transglutaminase in a Rat Model for Reversible Acute Rejection and Chronic Renal Allograft Injury

    PubMed Central

    Zakrzewicz, Anna; Atanasova, Srebrena; Padberg, Winfried

    2015-01-01

    Acute rejection is a major risk factor for chronic allograft injury (CAI). Blood leukocytes interacting with allograft endothelial cells during acute rejection were suggested to contribute to the still enigmatic pathogenesis of CAI. We hypothesize that tissue transglutaminase (Tgm2), a multifunctional protein and established marker of M2 macrophages, is involved in acute and chronic graft rejection. We focus on leukocytes accumulating in blood vessels of rat renal allografts (Fischer-344 to Lewis), an established model for reversible acute rejection and CAI. Monocytes in graft blood vessels overexpress Tgm2 when acute rejection peaks on day 9 after transplantation. Concomitantly, caspase-3 is activated, suggesting that Tgm2 expression is linked to apoptosis. After resolution of acute rejection on day 42, leukocytic Tgm2 levels are lower and activated caspase-3 does not differ among isografts and allografts. Cystamine was applied for 4 weeks after transplantation to inhibit extracellular transglutaminase activity, which did, however, not reduce CAI in the long run. In conclusion, this is the first report on Tgm2 expression by monocytes in vivo. Tgm2 may be involved in leukocytic apoptosis and thus in reversion of acute rejection. However, our data do not support a role of extracellular transglutaminase activity as a factor triggering CAI during self-limiting acute rejection. PMID:26063971

  16. Spontaneous cutaneous soft tissue sarcoma with differentiation into fibroblasts in a Sprague-Dawley rat.

    PubMed

    Ogawa, Takashi; Onozato, Tomoya; Okuhara, Yuji; Nagasawa, Tatsuya; Tamura, Toru; Hayashi, Morimichi

    2016-04-01

    A small mass with an ulcer was found in the skin of the dorsal cervix of a 7-month-old male Sprague-Dawley rat. Histologically, the central region of the tumor showed a high cellular density with oval-shaped tumor cells arranged in an alveolar pattern and thin collagen fiber bundles. The peripheral region of the tumor had a low cellular density with short spindle- or polygonal-shaped tumor cells surrounded by abundant collagen fiber bundles. Immunohistochemically, the tumor cells were strongly positive for vimentin and proliferating cell nuclear antigen, and a portion of the short spindle- or polygonal-shaped cells located in the peripheral region of the tumor were positive for S100A4. However, the tumor cells were negative for alpha-smooth muscle actin, desmin, S100, chromogranin A, neurofilament, CD68, Iba-1, cytokeratin 20, von Willebrand factor, melanosome, and anti-melanoma. Electron microscopically, the tumor cells had an abundance of rough endoplasmic reticulum, the Golgi apparatus, and a few intracellular collagen fibrils, showing fibroblastic features. Considering the lack of diagnostic differentiation, the tumor was diagnosed as an undifferentiated malignant mesenchymal tumor and classified as a soft tissue sarcoma with differentiation into fibroblasts in a portion of the tumor cells. PMID:27182117

  17. Expression and distribution of acyl-CoA thioesterases in the white adipose tissue of rats.

    PubMed

    Ohtomo, Takayuki; Hoshino, Atsuko; Yajima, Masako; Tsuchiya, Akiharu; Momose, Atsushi; Tanonaka, Kouichi; Toyoda, Hiroo; Kato, Tetsuta; Yamada, Junji

    2013-08-01

    Acyl-CoA thioesterases (Acots) are enzymes that catalyze the hydrolysis of fatty acyl-CoAs to free fatty acids and coenzyme A, and have the potential to regulate the intracellular levels of these molecules. In this study, we show that a cytosolic isoform, Acot1, is expressed and distributed in immature adipocytes located in the perivascular region of the white adipose tissue (WAT) of rats. Immunoblot analyses detected Acot1 in all of the WATs examined, while immunohistochemistry revealed positively stained layered structures surrounding the adventitia of blood vessels in the subcutaneous WAT. When the subcutaneous WAT was digested with collagenase and centrifuged, Acot1 was recovered in the stromal vascular fraction (SVF), and not in the large mature adipocytes. In the SVF, undigested cells attached to short tubular fragments of blood vessels showed positive immunostaining, as well as a proportion of the dispersed cells. These fibroblast-like cells contained fine particulate lipid droplets, stained by oil-red O dye, in their cytoplasm, or expressed fatty acid-binding protein 4, an adipocyte marker. After induction of adipocyte differentiation following a 15-day preculture without insulin, the dedifferentiated cells showed increased Acot1 expression with a diffuse distribution throughout the cytosol. These findings suggest that Acot1 expression is transiently upregulated at an early stage of adipocyte maturation, possibly to maintain cytosolic acyl-CoAs below a certain level until the cells acquire their full capability for fat storage. PMID:23385637

  18. Dynamic effects of point source electroporation on the rat brain tissue.

    PubMed

    Sharabi, Shirley; Last, David; Guez, David; Daniels, Dianne; Hjouj, Mohammad Ibrahim; Salomon, Sharona; Maor, Elad; Mardor, Yael

    2014-10-01

    In spite of aggressive therapy, existing treatments offer poor prognosis for glioblastoma multiforme due to tumor infiltration into the surrounding brain as well as poor blood-brain barrier penetration of most therapeutic agents. In this paper we present a novel approach for a minimally invasive treatment and a non-invasive response assessment methodology consisting of applying intracranial point-source electroporation and assessing treatment effect volumes using magnetic resonance imaging. Using a unique setup of a single intracranial electrode and an external surface electrode we treated rats' brains with various electroporation protocols and applied magnetic resonance imaging to study the dependence of the physiological effects on electroporation treatment parameters. The extent of blood-brain barrier disruption and later volumes of permanent brain tissue damage were found to correlate significantly with the treatment voltages (r(2)=0.99, p<0.001) and the number of treatment pulses (r(2)=0.94, p<0.002). Blood-brain barrier disruption depicted 3.2±0.3 times larger volumes than the final permanent damage volumes (p<0.0001). These results indicate that it may be beneficial to use more than one modality of electroporation when planning a treatment for brain tumors. PMID:24976141

  19. Low dose irradiation profoundly affects transcriptome and microRNAme in rat mammary gland tissues

    PubMed Central

    Luzhna, Lidia; Kovalchuk, Olga

    2014-01-01

    Ionizing radiation has been successfully used in medical tests and treatment therapies for a variety of medical conditions. However, patients and health-care workers are greatly concerned about overexposure to medical ionizing radiation and possible cancer induction due to frequent mammographies and/or CT scans. Diagnostic imaging involves the use of low doses of ionizing radiation, and its potential carcinogenic role creates a cancer risk concern for exposed individuals. In this study, the effects of X-ray exposure of different doses on the gene expression patterns and the micro-RNA expression patterns in normal breast tissue were investigated in rats. Our results revealed the activation of immune response pathways upon low dose of radiation exposure. These included natural killer mediated cytotoxicity pathways, antigen processing and presentation pathways, chemokine signaling pathways, and T- and B-cell receptor signaling pathways. Both high and low doses of radiation led to miRNA expression alterations. Increased expression of miR-34a may be linked to cell cycle arrest and apoptosis. Up-regulation of miR-34a was correlated with down-regulation of its target E2F3 and up-regulation of p53. This data suggests that ionizing radiation at specific high and low doses leads to cell cycle arrest and a possible initiation of apoptosis. PMID:25594002

  20. Analysis and distribution of esculetin in plasma and tissues of rats after oral administration.

    PubMed

    Kim, Ji-Sun; Ha, Tae-Youl; Ahn, Jiyun; Kim, Suna

    2014-12-01

    In this study, we developed a method to quantify esculetin (6,7-dihydroxycoumarin) in plasma and tissues using HPLC coupled with ultraviolet detection and measured the level of esculetin in rat plasma after oral administration. The calibration curve for esculetin was linear in the range of 4.8 ng/mL to 476.2 ng/mL, with a correlation coefficient (r(2)) of 0.996, a limit of detection value of 33.2 ng/mL, and a limit of quantification value of 100.6 ng/mL. Recovery rates for the 95.2 ng/mL and 190.5 ng/mL samples were 95.2% and 100.3%, within-runs and 104.8% and 101.0% between-runs, respectively. The relative standard deviation was less than 7% for both runs. In the pharmacokinetic analysis, the peak plasma esculetin level was reached 5 min after administration (Cmax=173.3 ng/mL; T1/2=45 min; AUC0 ~180 min=5,167.5 ng · min/mL). At 180 min post-administration (i.e., after euthanasia), esculetin was only detectable in the liver (30.87±11.33 ng/g) and the kidney (20.29±7.02 ng/g). PMID:25580397

  1. Perivascular Adipose Tissue Inhibits Endothelial Function of Rat Aortas via Caveolin-1

    PubMed Central

    Lee, Michelle Hui-Hsin; Chen, Shiu-Jen

    2014-01-01

    Perivascular adipose tissue (PVAT)-derived factors have been proposed to play an important role in the pathogenesis of atherosclerosis. Caveolin-1 (Cav-1), occupying the calcium/calmodulin binding site of endothelial NO synthase (eNOS) and then inhibiting nitric oxide (NO) production, is also involved in the development of atherosclerosis. Thus, we investigated whether PVAT regulated vascular tone via Cav-1 and/or endothelial NO pathways. Isometric tension studies were carried out in isolated thoracic aortas from Wistar rats in the presence and absence of PVAT. Concentration-response curves of phenylephrine, acetylcholine, and sodium nitroprusside were illustrated to examine the vascular reactivity and endothelial function. The protein expressions of eNOS and Cav-1 were also examined in aortic homogenates. Our results demonstrated that PVAT significantly enhanced vasoconstriction and inhibited vasodilatation via endothelium-dependent mechanism. The aortic NO production was diminished after PVAT treatment, whereas protein expression and activity of eNOS were not significantly affected. In addition, Cav-1 protein expression was significantly increased in aortas with PVAT transfer. Furthermore, a caveolae depleter methyl-β-cyclodextrin abolished the effect of PVAT on the enhancement of vasoconstriction, and reversed the impairment of aortic NO production. In conclusion, unknown factor(s) released from PVAT may inhibit endothelial NO production and induce vasocontraction via an increase of Cav-1 protein expression. PMID:24926683

  2. Molecular detection and extraction of pyrene in plasma and tissues of Sprague-Dawley rats.

    PubMed

    Bao, C; Dong, X; Tao, J; Lu, J; Luo, T; Liu, J

    2016-01-01

    In this paper, an efficient method for determination of total pyrene concentration in the biological samples including plasma, liver, spleen, lung and kidney of Sprague-Dawley rats were investigated and established using steady-state fluorescence method. Equilibrium dialysis method was applied to determine plasma protein binding rate of pyrene. The results illustrated that the protein binding rate depends on the concentration of pyrene in plasma. Extraction of pyrene in plasma was studied by using biomedical nanopartical which was prepared from synthesized associating polymer poly(ethylene glycol) end-capped by hexadecane. The Critical Micelle Concentration (CMC) of the polymeric micelle in aqueous solution was determined to equal 0.0063 mg/mL using 1-pyrenemethanol as a fluorescent probe. The distribution of free pyrene and pyrene loaded nanoparticals in blood were determined. The results showed that over 95% of the free pyrene was distributed into the erythrocyte, and the pyrene-loaded nanoparticles were less distributed in to the erythrocyte than free pyrene, but it was higher than 60%. This study provides an efficient method to detect pyrene in different tissues as well as an extraction method at the molecular level, which might contribute to the development of modern molecular diagnosis and identification in vivo. PMID:27064868

  3. Argon cluster ion source evaluation on lipid standards and rat brain tissue samples.

    PubMed

    Bich, Claudia; Havelund, Rasmus; Moellers, Rudolf; Touboul, David; Kollmer, Felix; Niehuis, Ewald; Gilmore, Ian S; Brunelle, Alain

    2013-08-20

    Argon cluster ion sources for sputtering and secondary ion mass spectrometry use projectiles consisting of several hundreds of atoms, accelerated to 10-20 keV, and deposit their kinetic energy within the top few nanometers of the surface. For organic materials, the sputtering yield is high removing material to similar depth. Consequently, the exposed new surface is relatively damage free. It has thus been demonstrated on model samples that it is now really possible to perform dual beam depth profiling experiments in organic materials with this new kind of ion source. Here, this possibility has been tested directly on tissue samples, 14 μm thick rat brain sections, allowing primary ion doses much larger than the so-called static secondary ion mass spectrometry (SIMS) limit and demonstrating the possibility to enhance the sensitivity of time-of-flight (TOF)-SIMS biological imaging. However, the depth analyses have also shown some variations of the chemical composition as a function of depth, particularly for cholesterol, as well as some possible matrix effects due to the presence or absence of this compound. PMID:23875833

  4. Spontaneous cutaneous soft tissue sarcoma with differentiation into fibroblasts in a Sprague-Dawley rat

    PubMed Central

    Ogawa, Takashi; Onozato, Tomoya; Okuhara, Yuji; Nagasawa, Tatsuya; Tamura, Toru; Hayashi, Morimichi

    2016-01-01

    A small mass with an ulcer was found in the skin of the dorsal cervix of a 7-month-old male Sprague-Dawley rat. Histologically, the central region of the tumor showed a high cellular density with oval-shaped tumor cells arranged in an alveolar pattern and thin collagen fiber bundles. The peripheral region of the tumor had a low cellular density with short spindle- or polygonal-shaped tumor cells surrounded by abundant collagen fiber bundles. Immunohistochemically, the tumor cells were strongly positive for vimentin and proliferating cell nuclear antigen, and a portion of the short spindle- or polygonal-shaped cells located in the peripheral region of the tumor were positive for S100A4. However, the tumor cells were negative for alpha-smooth muscle actin, desmin, S100, chromogranin A, neurofilament, CD68, Iba-1, cytokeratin 20, von Willebrand factor, melanosome, and anti-melanoma. Electron microscopically, the tumor cells had an abundance of rough endoplasmic reticulum, the Golgi apparatus, and a few intracellular collagen fibrils, showing fibroblastic features. Considering the lack of diagnostic differentiation, the tumor was diagnosed as an undifferentiated malignant mesenchymal tumor and classified as a soft tissue sarcoma with differentiation into fibroblasts in a portion of the tumor cells. PMID:27182117

  5. Effect of the acute crowding stress on the rat brown adipose tissue metabolic function.

    PubMed

    Djordjevic, Jelena; Cvijic, Gordana; Petrovic, Natasa; Davidovic, Vukosava

    2005-12-01

    Our previous results have shown that metabolic and thermal stressors influence interscapular brown adipose tissue (IBAT) metabolic activity by increasing oxygen consumption and, consequently, altering the toxic reactive oxygen species (ROS) production and the antioxidative system activity. Since there is not enough evidence about the effect of psychosocial stressors on these processes, we studied the effect of acute crowding stress on the IBAT and hypothalamic monoamine oxidase (MAO) activity as well as IBAT antioxidative enzymes, manganese (MnSOD), copper-zinc superoxide dismutase (CuZnSOD) and catalase (CAT), as the relevant indicators of IBAT metabolic alternations under the stress exposure and the returning of animals to control conditions. The results indicated that acute crowding stress did not change the hypothalamic and IBAT MAO activities, the generation of ROS and, consequently, the IBAT CuZnSOD and CAT activities. However, all three antioxidative enzymes were affected only after the recovery period. It seems that peripheral overheating of rats during acute crowding changes the stress nature, by becoming more thermal than psychosocial and by suppression the hypothalamic efferent pathways involved in the IBAT thermogenesis regulation. However, it seems that returning of the animals to the control conditions after the stress termination causes the reactivation of IBAT thermogenesis with tendency to normalise the body temperature. PMID:16309937

  6. Analysis of Tyrosine Kinase Inhibitor-Mediated Decline in Contractile Force in Rat Engineered Heart Tissue

    PubMed Central

    Cuello, Friederike; Luther, Pradeep; Schulze, Thomas; Eder, Alexandra; Streichert, Thomas; Mannhardt, Ingra; Hirt, Marc N.; Schaaf, Sebastian; Stenzig, Justus; Force, Thomas

    2016-01-01

    Introduction Left ventricular dysfunction is a frequent and potentially severe side effect of many tyrosine kinase inhibitors (TKI). The mode of toxicity is not identified, but may include impairment of mitochondrial or sarcomeric function, autophagy or angiogenesis, either as an on-target or off-target mechanism. Methods and Results We studied concentration-response curves and time courses for nine TKIs in three-dimensional, force generating engineered heart tissue (EHT) from neonatal rat heart cells. We detected a concentration- and time-dependent decline in contractile force for gefitinib, lapatinib, sunitinib, imatinib, sorafenib, vandetanib and lestaurtinib and no decline in contractile force for erlotinib and dasatinib after 96 hours of incubation. The decline in contractile force was associated with an impairment of autophagy (LC3 Western blot) and appearance of autophagolysosomes (transmission electron microscopy). Conclusion This study demonstrates the feasibility to study TKI-mediated force effects in EHTs and identifies an association between a decline in contractility and inhibition of autophagic flux. PMID:26840448

  7. Low-affinity hemoglobin increases tissue PO2 and decreases arteriolar diameter and flow in the rat cremaster muscle.

    PubMed

    Kunert, M P; Liard, J F; Abraham, D J; Lombard, J H

    1996-07-01

    The hypothesis that tissue oxygen delivery in excess of metabolic demand results in vasoconstriction and reduced blood flow was tested in the cremaster muscle of anesthetized Sprague-Dawley rats by studying the effects of an intravenous infusion of RSR-13, an allosteric effector of hemoglobin. RSR-13 reduces the affinity of hemoglobin for oxygen, causing a right shift in the oxygen dissociation curve. Thus, oxygen delivery to the tissues was increased without elevations in blood flow or blood pressure. Tissue PO2, arteriolar diameter, and RBC velocity were measured and volume flow was calculated from diameter and RBC velocity in third-order arterioles. In rats receiving RSR-13 at a rate of 200 mg kg-1 in 15 min (n = 18) P50 (the PO2 at which hemoglobin is 50% saturated) increased from 36 +/- 1 to 52 +/- 3 mm Hg, and tissue PO2 increased to a maximum of 146 +/- 12% above its control value. P50 and tissue PO2 did not change in the control group (n = 8) receiving vehicle at a rate equivalent to that in the experimental group. In a separate group of rats receiving RSR-13 (n = 7), P50 increased from 38 +/- 1 to 51 +/- 3 mm Hg, calculated arteriolar flow decreased from 9 +/- 3 to a minimum of 1.4 +/- 1 nl sec-1, and arteriolar diameter decreased from 27 +/- 3 to a minimum of 13 +/- 3 micrograms P50, volume flow, and arteriolar diameter did not change in the control group (n = 10). These results suggest that an increased tissue oxygen delivery, caused by a right shift in the oxygen dissociation curve, may cause an increase in vascular resistance independent of an elevated blood flow. PMID:8812756

  8. Pharmacokinetics in rats and tissue distribution in mouse of magnoflorine by ultra performance liquid chromatography-tandem mass spectrometry

    PubMed Central

    Bao, Shihui; Geng, Peiwu; Wang, Shuanghu; Zhou, Yunfang; Hu, Lufeng; Yang, Xuezhi

    2015-01-01

    Magnoflorine is one of the most widespread aporphine alkaloids. In this work, a sensitive and selective ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of magnoflorine in rat plasma and mouse tissue have been developed and validated. After addition of nuciferine as an internal standard (IS), protein precipitation by acetonitrile-methanol (9:1, v/v) was used for samples treatment. Chromatographic separation was achieved on a UPLC BEH C18 column (2.1 mm×100 mm, 1.7 μm) with 0.1% formic acid and acetonitrile as the mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reactions monitoring (MRM) mode was used for quantification using target fragment ions m/z 342.8→298.2 for magnoflorine and m/z 296.0→265.1 for IS. Calibration plots were linear throughout the range 2-2000 ng/mL for magnoflorine in rat plasma and tissue. Mean recoveries of magnoflorine in rat plasma were better than 83.0%. RSD of intra-day and inter-day precision were both less than 9%. The accuracy of the method was between 95.5% and 107.5%. The method was successfully applied to pharmacokinetics and tissue distribution study of magnoflorine. The absolute bioavailability of magnoflorine was reported as 22.6%. The magnoflorine underwent a rapid and wide distribution to tissues; the level of magnoflorine in liver is highest, then followed by heart, spleen and lung. Based on tissue distribution data, a back-propagation artificial neural network (BP-ANN) method was developed and it could be used to predict the concentrations of magnoflorine in tissues. PMID:26884929

  9. A Simplified Workflow for Protein Quantitation of Rat Brain Tissues Using Label-Free Proteomics and Spectral Counting.

    PubMed

    Boutté, Angela M; Grant, Shonnette F; Dave, Jitendra R

    2016-01-01

    Mass spectrometry-based proteomics is an increasingly valuable tool for determining relative or quantitative protein abundance in brain tissues. A plethora of technical and analytical methods are available, but straightforward and practical approaches are often needed to facilitate reproducibility. This aspect is particularly important as an increasing number of studies focus on models of traumatic brain injury or brain trauma, for which brain tissue proteomes have not yet been fully described. This text provides suggested techniques for robust identification and quantitation of brain proteins by using molecular weight fractionation prior to mass spectrometry-based proteomics. Detailed sample preparation and generalized protocols for chromatography, mass spectrometry, spectral counting, and normalization are described. The rat cerebral cortex isolated from a model of blast-overpressure was used as an exemplary source of brain tissue. However, these techniques may be adapted for lysates generated from several types of cells or tissues and adapted by the end user. PMID:27604744

  10. Excised segments of rat small intestine in Ussing chamber studies: A comparison of native and stripped tissue viability and permeability to drugs.

    PubMed

    Sjögren, Erik; Eriksson, Johanna; Vedin, Charlotta; Breitholtz, Katarina; Hilgendorf, Constanze

    2016-05-30

    Excised rat intestinal tissue mounted in an Ussing chamber can be used for intestinal permeability assessments in drug development. The outer layer of the intestine, the serosa and part of the muscle layer, is traditionally removed since it is considered a barrier to the diffusion of nutrients and oxygen as well as to that of pharmaceutical substances. However, the procedure for removing the serosal-muscle layer, i.e. stripping, is a technically challenging process in the pre-experimental preparation of the tissue which may result in tissue damage and reduced viability of the segment. In this study, the viability of stripped and native (non-stripped) rat small intestine tissue segments mounted in Ussing chambers was monitored and the apparent permeability of the tissue to a set of test compounds across both tissue preparations was determined. Electrical measurements, in particular the potential difference (PD) across the intestinal membrane, were used to evaluate the viability. In this study, there were no differences in initial PD (health status of the tissue) or PD over time (viability throughout the experiment) between native and stripped rat jejunum segments. Overall, there were also no significant differences in permeability between stripped and native rat intestinal tissue for the compounds in this study. Based on these results, we propose that stripping can be excluded from the preparation procedures for rat jejunal tissue for permeability studies when using the Ussing chamber technique. PMID:27073083

  11. Hypoglycaemic and Tissue-Protective Effects of the Aqueous Extract of Persea Americana Seeds on Alloxan-Induced Albino Rats

    PubMed Central

    EZEJIOFOR, Anthonet Ndidi; OKORIE, Abednego; ORISAKWE, Orish Ebere

    2013-01-01

    Background: The tissue-protective potential of Persea americana necessitated a look into the histopathological effects of the plant extract on the pancreas, liver, and kidneys. This study was conceived and designed based on the gaps in the research that has been performed and what is known about the plant. The hypoglycaemic and tissue-protective effects of hot aqueous Persea americana (avocado pear) seed extracts on alloxan-induced albino rats were investigated. Methods: Persea americana seeds were extracted using hot water, and different concentrations of the extract were prepared. The effects of different concentrations (20, 30, 40 g/L) of the hot aqueous P. americana seed extract on alloxan-induced Wistar albino rats were compared with those of a reference drug, glibenclamide. The glucose level of the rats was measured daily, and the weight of the animal was monitored on a weekly basis for 21 days. The oral glucose tolerance test (OGTT) was performed at 0, 30, 60, 90 and 120 minutes, and the histopathologies of the liver, kidneys, and pancreas were investigated. Phytochemical analysis of P. americana seed extracts indicated the presence of glycosides, tannins, saponins, carbohydrates, flavonoids, and alkaloids. Results: The results showed that the extract possessed a significant hypoglycaemic (P < 0.05) effect and reversed the histopathological damage that occurred in alloxan-induced diabetic rats, comparable to the effects glibenclamide. The seeds of P. americana also had anti-diabetic and protective effects on some rat tissues such as the pancreas, kidneys, and liver. Conclusion: In conclusion, the present study provides a pharmacological basis for the folkloric use of the hot-water extract of P. americana seeds in the management of diabetes mellitus. PMID:24643349

  12. Preparation of four fluorine-18-labeled estrogens and their selective uptakes in target tissues of immature rats

    SciTech Connect

    Kiesewetter, D.O.; Kilbourn, M.R.; Landvatter, S.W.; Heiman, D.F.; Katzenellenbogen, J.A.; Welch, M.J.

    1984-11-01

    Four fluorine-18-labeled estrogens have been prepared by simple displacement reactions utilizing reactive trifluoromethane sulfonate (triflate) precursors and F-18 fluoride ion. All four fluoroestrogens have high affinity for the estrogen receptor. In immature female rats, they are taken up by target tissues, such as the uterus, with very high selectivity: uterus-to-blood ratios at 1 hr are: Compound 1, 39; Compound 2, 12; Compound 3, 13; and Compound 4, 19. That the uptake process involves an estrogen-specific binder of limited capacity is demonstrated by the suppressive effect of coadministered unlabeled estradiol on target tissue uptake.

  13. Expression of ATF4 and RUNX2 in periodontal tissue of pressure side during orthodontic tooth movement in rat

    PubMed Central

    Han, Jinyou; Xu, Xiaodong; Zhang, Bin; Chen, Baoxing; Hang, Wangyan

    2015-01-01

    Objective: This study aims to explore the expression levels of ATF4 and RUNX and their interactions in periodontal tissue of the pressure side during orthodontic tooth movement. Methods: A total of 72 SPF level male Sprague Dawley rats were used in this study, they were divided into 9 groups randomly and 8 rats in each group. The expression changes of ATF4 and RUNX2 in periodontal tissue of pressure side at different straining time point were detected with RT-PCR and Western blotting methods. The morphological changes of cells in the tissue samples were observed by HE staining. The data were analyzed with SPSS 19.0 software. Results: The expression levels of ATF4 and RUNX2 increased during orthodontic tooth movement and were related with the movement time. They reached highest after straining for 24 h and began to decrease after straining for 12 d. Conclusions: The expression levels of ATF4 and RUNX2 in periodontal tissue can increase transiently induced by stress, which play a role in the process of osteogenesis and reconstruction of periodontal tissue during orthodontic tooth movement. PMID:25785078

  14. Label-free profiling of white adipose tissue of rats exhibiting high or low levels of intrinsic exercise capacity.

    PubMed

    Bowden-Davies, Kelly; Connolly, Joanne; Burghardt, Paul; Koch, Lauren G; Britton, Steven L; Burniston, Jatin G

    2015-07-01

    Divergent selection has created rat phenotypes of high- and low-capacity runners (HCR and LCR, respectively) that have differences in aerobic capacity and correlated traits such as adiposity. We analyzed visceral adipose tissue of HCR and LCR using label-free high-definition MS (elevated energy) profiling. The running capacity of HCR was ninefold greater than LCR. Proteome profiling encompassed 448 proteins and detected 30 significant (p <0.05; false discovery rate <10%, calculated using q-values) differences. Approximately half of the proteins analyzed were of mitochondrial origin, but there were no significant differences in the abundance of proteins involved in aerobic metabolism. Instead, adipose tissue of LCR rats exhibited greater abundances of proteins associated with adipogenesis (e.g. cathepsin D), ER stress (e.g. 78 kDa glucose response protein), and inflammation (e.g. Ig gamma-2B chain C region). Whereas the abundance antioxidant enzymes such as superoxide dismutase [Cu-Zn] was greater in HCR tissue. Putative adipokines were also detected, in particular protein S100-B, was 431% more abundant in LCR adipose tissue. These findings reveal low running capacity is associated with a pathological profile in visceral adipose tissue proteome despite no detectable differences in mitochondrial protein abundance. PMID:25758023

  15. Recovery of fertility in azoospermia rats after injection of adipose-tissue-derived mesenchymal stem cells: the sperm generation.

    PubMed

    Cakici, Cihangir; Buyrukcu, Bugra; Duruksu, Gokhan; Haliloglu, Ahmet Hakan; Aksoy, Ayca; Isık, Ayca; Uludag, Orhan; Ustun, Huseyin; Subası, Cansu; Karaoz, Erdal

    2013-01-01

    The recent reports on the treatment of azoospermia patients, in which spermatozoa could not be traced in their testes, are focused more on the potential use of adult stem cells, like mesenchymal stem cells (MSCs). The aim of this study was to demonstrate the potential use of MSCs derived from adipose tissue in the treatment of azoospermia using rat disease models. After busulfan application, the rats (n = 20) were injected with the GFP(+) MSCs into left rete testes. After 12 weeks, the testes with cell injection (right testes) were compared to control (left testes) after dimensional and immunohistochemical analyses. Testes treated with MSCs appeared morphologically normal, but they were atrophic in rats without stem cell treatment, in which the seminiferous tubules were empty. Spermatogenesis was detected, not in every but in some tubules of cell-treated testes. GFP(+)/VASA(+) and GFP(+)/SCP1(+) cells in testes indicated the transdifferentiation of MSCs into spermatogenetic cells in the appropriate microenvironment. Rats with cell treatment were mated to show the full recovery of spermatogenesis, and continuous generations were obtained. The expression of GFP was detected in the mesenchymal stem cells derived from adipose tissue and bone marrow and also in the sperms of offspring. In conclusion, MSCs might be studied for the same purpose in humans in future. PMID:23509736

  16. Early and late effects of prenatal corticosteroid treatment on the microRNA profiles of lung tissue in rats

    PubMed Central

    YU, HONG-REN; LI, SUNG-CHOU; TSENG, WAN-NING; TAIN, YOU-LIN; CHEN, CHIH-CHENG; SHEEN, JIUNN-MING; TIAO, MAO-MENG; KUO, HO-CHANG; HUANG, CHAO-CHENG; HSIEH, KAI-SHENG; HUANG, LI-TUNG

    2016-01-01

    Glucocorticoids have been administered to mothers at risk of premature delivery to induce maturation of preterm fetal lungs and prevent the development of respiratory distress syndrome. Micro (mi)RNAs serve various crucial functions in cell proliferation, differentiation and organ development; however, few studies have demonstrated an association between miRNAs and lung development. The aim of the present study was to investigate alterations in the miRNA profiles of rat lung tissue following prenatal glucocorticoid therapy for fetal lung development. The differences in miRNA expression profiles were compared between postnatal days 7 (D7) and 120 (D120) rat lung tissues, followed by validation using reverse transcription-quantitative polymerase chain reaction. The miRNA profiles of rat lung tissues following prenatal dexamethasone (DEX) therapy were also investigated. miRNAs with 2-fold changes were selected for further analysis. At D120, 6 upregulated and 6 downregulated miRNAs were detected, compared with D7. Among these differentially expressed miRNAs, miR-101-3p and miR-99b-5p were associated with the lowest and highest expressions of miRNA at D7, respectively. A limited impact on the miRNA profiles of rat lung tissues was observed following prenatal DEX treatment, which may help to further clarify the mechanisms underlying normal lung development. However, the results of the present study cannot entirely elucidate the effects of prenatal DEX treatment on the lung development of premature infants, and further studies investigating the impact of prenatal corticosteroids on fetal lung miRNA profiles are required. PMID:26997989

  17. Endurance exercise training ameliorates insulin resistance and reticulum stress in adipose and hepatic tissue in obese rats.

    PubMed

    da Luz, Gabrielle; Frederico, Marisa J S; da Silva, Sabrina; Vitto, Marcelo F; Cesconetto, Patricia A; de Pinho, Ricardo A; Pauli, José R; Silva, Adelino S R; Cintra, Dennys E; Ropelle, Eduardo R; De Souza, Cláudio T

    2011-09-01

    Obesity-induced endoplasmatic reticulum (ER) stress has been demonstrated to underlie the induction of obesity-induced JNK and NF-κB activation inflammatory responses, and generation of peripheral insulin resistance. On the other hand, exercise has been used as a crucial tool in obese and diabetic patients, and may reduce inflammatory pathway stimulation. However, the ability of exercise training to reverse endoplasmatic reticulum stress in adipose and hepatic tissue in obesity has not been investigated in the literature. Here, we demonstrate that exercise training ameliorates ER stress and insulin resistance in DIO-induced rats. Rats were fed with standard rodent chow (3,948 kcal kg(-1)) or high-fat diet (5,358 kcal kg(-1)) for 2 months. After that rats were submitted to swimming training (1 h per day, 5 days for week with 5% overload of the body weight for 8 weeks). Samples from epididymal fat and liver were obtained and western blot analysis was performed. Our results showed that swimming protocol reduces pro-inflammatory molecules (JNK, IκB and NF-κB) in adipose and hepatic tissues. In addition, exercise leads to reduction in ER stress, by reducing PERK and eIF2α phosphorylation in these tissues. In parallel, an increase in insulin pathway signaling was observed, as confirmed by increases in IR, IRSs and Akt phosphorylation following exercise training in DIO rats. Thus, results suggest that exercise can reduce ER stress, improving insulin resistance in adipose and hepatic tissue. PMID:21249392

  18. Organotin speciation and tissue distribution in rat dams, fetuses, and neonates following oral administration of tributyltin chloride.

    PubMed

    Cooke, Gerard M; Forsyth, Don S; Bondy, Genevieve S; Tachon, Romain; Tague, Brett; Coady, Laurie

    2008-01-01

    Tributyltin (TBT) is a biocide that contaminates human foodstuffs, especially shellfish. TBT is an endocrine disrupter, producing imposex in several marine gastropods. Previous studies showed that oral dosing of rat dams with TBT chloride leads to abnormal fetal and postnatal development. In this study, the tissue distribution and speciation of organotins in tissues were examined in dams, fetuses, and neonates following dosing of rat dams commencing on gestational day (GD) 8 by oral gavage with TBT in olive oil at 0, 0.25, 2.5, or 10 mg/kg body weight (BW)/d. Dams' body weights were significantly reduced by the 10-mg/kg BW/d TBT treatment. At GD20, there were no significant effects of any TBT treatment on pup weights, litter size, sex ratio, or tissue weights. However, at postnatal day (PND) 6 and 12, neonatal pup weights were reduced by the 10-mg/kg BW/d TBT treatment but tissue weights were unaffected, except for the liver weight of female pups, which was reduced by the 10-mg/kg BW/d TBT treatment. Tissues harvested on GD20 and PND6 and PND12 were extracted for determination of organotins by gas chromatography-atomic emission detection (GC-AED). In most tissues, TBT and its metabolite dibutyltin (DBT) were evident but monobutyltin (MBT) was rarely measured above the detection limit. The livers and brains of fetuses contained TBT and DBT at levels that were approximately 50% of the equivalent tissues in the dams. Furthermore, these tissues appeared to preferentially absorb/retain organotins, since the concentrations were greater than were found for the total loading in whole pups. The placenta also contained relatively large quantities of TBT and DBT. Postnatally, the TBT levels in pups decreased markedly, a probable consequence of the extremely low levels of organotins in rat milk. However, DBT levels in pups livers and brains were maintained, probably due to metabolism of TBT to DBT. Similarly, while dams' spleens contained significant quantities of organotins

  19. Systemically alendronate was incorporated into dental tissues but did not cause morphological or mechanical changes in rats teeth.

    PubMed

    Nelson-Filho, Paulo; Lucisano, Marília Pacífico; Da Silva, Raquel Assed Bezerra; Da Silva, Roberto Santana; Serra, Mônica Campos; Gerlach, Raquel Fernanda; Neto, Francisco Carlos Rehder; Carneiro, Zumira Aparecida; Zamarioli, Ariane; Morse, Leslie; Battaglino, Ricardo

    2012-09-01

    This study evaluated the effect of the systemic use of sodium alendronate in rats in vivo. Forty-five Wistar rats aged 36 to 42 days and weighing 200 to 230 g were randomly assigned to a control group (n = 20), which received distilled water, and an experimental group (n = 25), which received 2 weekly doses of 1 mg/kg of chemically pure sodium alendronate. The animals were killed after 60 days of treatment. The tibias were removed for analysis of bone mineral density by dual-energy X-ray absorptiometry (DXA). Then, the maxillary incisors were extracted for analysis of the mineralized dental tissues using fluorescence spectroscopy (FS), scanning electron microscopy (SEM), bright field microscopy (BFM), and cross-sectional microhardness (CSMH) testing. DXA and CSMH data were subjected to statistical analysis by Kruskal-Wallis test (5% significance level). The experimental group presented higher bone mineral density than the control group by DXA. FS analysis revealed presence of alendronate in the mineralized dental tissues of the specimens of the experimental group. Significant morphological differences were not found by SEM and BFM. Enamel and dentin (100 and 300 μm from the dentinoenamel junction) CSMH data did not show significant difference between the control and experimental groups. Based on the obtained results, we conclude that while alendronate increased the bone mineral density and was incorporated into the mineralized dental tissues it did not cause significant alterations in the morphology and microhardness of rat incisor enamel and dentin. PMID:22508272

  20. Effects of pulse current on endurance exercise and its anti-fatigue properties in the hepatic tissue of trained rats.

    PubMed

    Chang, Qi; Miao, Xinfang; Ju, Xiaowei; Zhu, Lvgang; Huang, Changlin; Huang, Tao; Zuo, Xincheng; Gao, Chunfang

    2013-01-01

    Fatigue is synonymous with a wide spectrum of familiar physiological conditions, from pathology and general health, to sport and physical exercise. Strenuous, prolonged exercise training causes fatigue. Although several studies have investigated the effects of electrical stimulation frequency on muscle fatigue, the effects of percutaneous pulse current stimulation on fatigue in the hepatic tissue of trained rats is still unclear. In order to find an effective strategy to prevent fatigue or enhance recovery, the effects of pulse current on endurance exercise and its anti-fatigue properties in exercised rats were studied. Rats were subjected to one, three or five weeks of swimming exercise training. After exercise training, rats in the treated group received daily applications of pulse current. All rats were sacrificed after one, three or five weeks of swimming exercise, and the major biochemical indexes were measured in serum and liver. The results demonstrate that pulse current could prolong the exhaustion swimming time, as well as decrease serum ALT, AST and LD levels and liver MDA content. It also elevated serum LDH activity, liver SOD activity and glycogen content. Furthermore, pulse current increased the expression of Bcl-2 and decreased the expression of Bax. Taken together, these results show that pulse current can elevate endurance capacity and facilitate recovery from fatigue. PMID:24116026

  1. Transcriptional Alterations of ET-1 Axis and DNA Damage in Lung Tissue of a Rat Obesity Model

    PubMed Central

    Cabiati, Manuela; Salvadori, Costanza; Guiducci, Letizia; Caselli, Chiara; Prescimone, Tommaso; Facioni, Maria Sole; Azzarà, Alessia; Chiaramonte, Anna; Mazzoni, Stefano; Bruschi, Fabrizio; Giannessi, Daniela

    2015-01-01

    Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (COfc-Ofc) or acute hyperglycemia (COAH-OAH). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in OAH rats were significantly higher (p=0.019) than in the corresponding CO and COAH rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection. PMID:25517973

  2. Functional synergy of anti-mir221 and nanohydroxyapatite scaffold in bone tissue engineering of rat skull.

    PubMed

    Sadeghi, Mahya; Bakhshandeh, Behnaz; Dehghan, Mohammad Mehdi; Mehrnia, Mohammad Reza; Khojasteh, Arash

    2016-08-01

    An appropriate cell source, effective cell modification, and proper supportive matrices are the main bases of tissue engineering. The effectiveness of anti-mir221 or hydroxyapatite (HA) in improving the osteogenic differentiation of mesenchymal stem cells (MSCs) has been reported previously. Herein, simultaneous application of these osteogenic inducers was investigated in vivo. The Poly-caprolactone (PCL)/HA nanofibers were characterized using contact angle measurement, tensile test, Fourier transform infrared spectroscopy, and electron microscopy. Rat MSCs were isolated, characterized and transfected with anti-mir221. The rats were divided into 4 groups and an 8 mm defect were created in the mid-calvaria of each rat by trephine bur. Group 1 received (PCL)/HA nanofibers, group 2 received (PCL)/HA nanofibers plus autologous MSCs, group 3 received (PCL)/HA nanofibers plus MSCs transfected with anti-mir221, and group 4 rats were left empty as an additional control group. Histomorphometric and radiomorphometric evaluation after 4 and 8 weeks revealed more new bone formation in the cell-treated groups compared to the scaffold alone group. There was evidence for a combination of increased osteoclasts and osteoblast vascular lake containing red blood cells in the anti-mir221 transfected group. New bone penetration into the scaffolds empirically demonstrated the capability of this combination for efficient osteointegration. Altogether, the co-application of HA and anti-mir221 transfected cells can enhance bone healing of the rat skull. PMID:27412651

  3. Identification of Coordinately Regulated Functional Modules in Thyroid Tissues from Rats Exposed to a Tumorigenic and a Non-Tumorigenic Conazole Fungicide Using Oncomine®

    EPA Science Inventory

    Conazoles are triazole- or imidazole-containing fungicides used in agriculture and medicine. Using transcriptomic analysis of rat thyroid tissues exposed to either tumorigenic or non-tumorigenic structurally related conazoles, we identified new findings on thyroid gene expressio...

  4. Pharmacokinetics and tissue distribution of intraperitoneal 5-fluorouracil with a novel carrier solution in rats

    PubMed Central

    Wei, Zhi-Gang; Li, Guo-Xin; Huang, Xiang-Cheng; Zhen, Li; Yu, Jiang; Deng, Hai-Jun; Qing, Shan-Hua; Zhang, Ce

    2008-01-01

    AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9% sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats. METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12, 18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by high-performance liquid chromatography. RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAES-steri than those with physiologic saline at 1, 6, 12, 18, and 24 h (P = 0.047, 0.009, 0.005, 0.005 and 0.005 respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7 ± 9.7, 23.0 ± 2.8 vs 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3, 12 and 18 h (P = 0.009, 0.009 and 0.005 respectively, the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fluorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L vs 0.0000 ± 0

  5. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons

    PubMed Central

    Liu, Zhenyi; Brown, Andrew; Fisher, Dan; Wu, Yumei; Warren, Joe; Cui, Xiaoxia

    2016-01-01

    The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson’s disease. PMID:26886559

  6. Tissue Specific Expression of Cre in Rat Tyrosine Hydroxylase and Dopamine Active Transporter-Positive Neurons.

    PubMed

    Liu, Zhenyi; Brown, Andrew; Fisher, Dan; Wu, Yumei; Warren, Joe; Cui, Xiaoxia

    2016-01-01

    The rat is a preferred model system over the mouse for neurological studies, and cell type-specific Cre expression in the rat enables precise ablation of gene function in neurons of interest, which is especially valuable for neurodegenerative disease modeling and optogenetics. Yet, few such Cre rats are available. Here we report the characterization of two Cre rats, tyrosine hydroxylase (TH)-Cre and dopamine active transporter (DAT or Slc6a3)-Cre, by using a combination of immunohistochemistry (IHC) and mRNA fluorescence in situ hybridization (FISH) as well as a fluorescent reporter for Cre activity. We detected Cre expression in expected neurons in both Cre lines. Interestingly, we also found that in Th-Cre rats, but not DAT-Cre rats, Cre is expressed in female germ cells, allowing germline excision of the floxed allele and hence the generation of whole-body knockout rats. In summary, our data demonstrate that targeted integration of Cre cassette lead to faithful recapitulation of expression pattern of the endogenous promoter, and mRNA FISH, in addition to IHC, is an effective method for the analysis of the spatiotemporal gene expression patterns in the rat brain, alleviating the dependence on high quality antibodies that are often not available against rat proteins. The Th-Cre and the DAT-Cre rat lines express Cre in selective subsets of dopaminergic neurons and should be particularly useful for researches on Parkinson's disease. PMID:26886559

  7. Effects of ulinastatin administered at different time points on the pathological morphologies of the lung tissues of rats with hyperthermia

    PubMed Central

    QIN, ZAI-SHENG; TIAN, PEI; WU, XIA; YU, HONG-MEI; GUO, NA

    2014-01-01

    Hyperthermia not only directly induces cell injury of body tissues, but also causes the body to release large amounts of inflammatory mediators and cells with extensive biological activities to induce a systemic inflammatory response and immune dysfunction. Thus, hyperthermia causes systemic inflammatory response syndrome, aggravating injuries to various organs. This study aimed to observe the effects of ulinastatin (UTI) administered at different time points on the cellular morphologies of the lung tissues of rats with systemic hyperthermia. A total of 40 male Sprague Dawley rats were randomly divided into five groups: The normal control group (C group), the hyperthermia group without medication (H group), the hyperthermia and UTI pre-treatment group (HU group), the group treated with UTI at 1 h after hyperthermia (HU1 group), and the group treated with UTI at 2 h after hyperthermia (HU2 group). The systemic hyperthermia rat model was established in a heating chamber with a biological oxygen supply. For the HU, HU1 and HU2 groups, UTI (5×104 U/kg) was administered at different time points. For the C and H groups, an equivalent volume of normal saline was administered. During heating, the respiratory frequency and rectal temperature were measured and recorded once every 30 min. After 2.5 h of heating, the wet/dry weight (W/D) ratio of the lung tissues of the rats was measured. Additionally, the cellular morphologies of the lung tissues were observed under light and electron microscopes. The respiratory frequencies and lung tissue W/D ratios of the rats in the various hyperthermia groups were significantly higher than those of the rats in the C group (all P<0.05). The respiratory frequencies and lung tissue W/D values of the HU and HU1 groups were significantly lower than those of the H group (all P<0.05). Under the light microscope, the bronchial surrounding tissues of the HU and HU1 groups were loose, and the majority of the pulmonary alveolar structures were

  8. Natural variation in maternal care and cross-tissue patterns of oxytocin receptor gene methylation in rats.

    PubMed

    Beery, Annaliese K; McEwen, Lisa M; MacIsaac, Julia L; Francis, Darlene D; Kobor, Michael S

    2016-01-01

    This article is part of a Special Issue "Parental Care". Since the first report of maternal care effects on DNA methylation in rats, epigenetic modifications of the genome in response to life experience have become the subject of intense focus across many disciplines. Oxytocin receptor expression varies in response to early experience, and both oxytocin signaling and methylation status of the oxytocin receptor gene (Oxtr) in blood have been related to disordered social behavior. It is unknown whether Oxtr DNA methylation varies in response to early life experience, and whether currently employed peripheral measures of Oxtr methylation reflect variation in the brain. We examined the effects of early life rearing experience via natural variation in maternal licking and grooming during the first week of life on behavior, physiology, gene expression, and epigenetic regulation of Oxtr across blood and brain tissues (mononucleocytes, hippocampus, striatum, and hypothalamus). Rats reared by "high" licking-grooming (HL) and "low" licking-grooming (LL) rat dams exhibited differences across study outcomes: LL offspring were more active in behavioral arenas, exhibited lower body mass in adulthood, and showed reduced corticosterone responsivity to a stressor. Oxtr DNA methylation was significantly lower at multiple CpGs in the blood of LL versus HL males, but no differences were found in the brain. Across groups, Oxtr transcript levels in the hypothalamus were associated with reduced corticosterone secretion in response to stress, congruent with the role of oxytocin signaling in this region. Methylation of specific CpGs at a high or low level was consistent across tissues, especially within the brain. However, individual variation in DNA methylation relative to these global patterns was not consistent across tissues. These results suggest that blood Oxtr DNA methylation may reflect early experience of maternal care, and that Oxtr methylation across tissues is highly concordant

  9. Effects of beta-endorphin on ornithine decarboxylase in tissues of developing rats: a potential role for this endogenous neuropeptide in the modulation of tissue growth.

    PubMed

    Bartolome, J V; Bartolome, M B; Daltner, L A; Evans, C J; Barchas, J D; Kuhn, C M; Schanberg, S M

    1986-06-23

    Ornithine decarboxlyase (ODC) catalyzes the initial step in the bio-synthesis of the polyamines spermidine and spermine, which are key regulators of cell growth, proliferation and differentiation. Intracisternal administration of beta-endorphin (1 microgram) to 6 day-old rats markedly decreased brain, liver, heart and kidney ODC activity. Conversely, subcutaneous administration of beta-endorphin increased ODC activity in the heart and liver. Thus, ODC inhibition in peripheral organs in rat pups given beta-endorphin intracisternally appears to reflect central effects of this neuropeptide. Experiments were also carried out to test whether opioid receptors are involved in these tissue ODC responses. Naloxone prevented the decreases in brain ODC indicating the participation of opioid receptors in that process. In contrast, naloxone did not alter ODC responses in peripheral organs in rat pups given beta-endorphin intracisternally, indicating that these effects are independent of its classical opioid character. These results support the view that endogenous beta-endorphin may play an important role in organogenesis by modulating the growth-related enzyme ODC. The data also suggest that the regulation of peripheral organ development by beta-endorphin may be mediated through the release of growth regulatory substances from the CNS. PMID:2941633

  10. On-Tissue Derivatization via Electrospray Deposition for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Endogenous Fatty Acids in Rat Brain Tissues.

    PubMed

    Wu, Qian; Comi, Troy J; Li, Bin; Rubakhin, Stanislav S; Sweedler, Jonathan V

    2016-06-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is used for the multiplex detection and characterization of diverse analytes over a wide mass range directly from tissues. However, analyte coverage with MALDI MSI is typically limited to the more abundant compounds, which have m/z values that are distinct from MALDI matrix-related ions. On-tissue analyte derivatization addresses these issues by selectively tagging functional groups specific to a class of analytes, while simultaneously changing their molecular masses and improving their desorption and ionization efficiency. We evaluated electrospray deposition of liquid-phase derivatization agents as a means of on-tissue analyte derivatization using 2-picolylamine; we were able to detect a range of endogenous fatty acids with MALDI MSI. When compared with airbrush application, electrospray led to a 3-fold improvement in detection limits and decreased analyte delocalization. Six fatty acids were detected and visualized from rat cerebrum tissue using a MALDI MSI instrument operating in positive mode. MALDI MSI of the hippocampal area allowed targeted fatty acid analysis of the dentate gyrus granule cell layer and the CA1 pyramidal layer with a 20-μm pixel width, without degrading the localization of other lipids during liquid-phase analyte derivatization. PMID:27181709

  11. Quantitative determination of periplocymarin in rat plasma and tissue by LC-MS/MS: application to pharmacokinetic and tissue distribution study.

    PubMed

    Yan, Kaijing; Wang, Xiangyang; Jia, Yumeng; Chu, Yang; Guan, Xiufeng; Ma, Xiaohui; Li, Wei; Pan, Guixiang; Zhou, Shuiping; Sun, He; Liu, Changxiao

    2016-08-01

    A simple, rapid and sensitive liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the determination of periplocymarin in biological samples was developed and successfully applied to the pharmacokinetic and tissue distribution study of periplocymarin after oral administration of periplocin. Biological samples were processed with ethyl acetate by liquid-liquid extraction, and diazepam was used as the internal standard. Periplocymarin was analyzed on a C18 column with isocratic eluted mobile phase composed of methanol and water (containing 0.1% formic acid) at a flow rate of 0.2 mL/min (73:27, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer using positive-ion mode electrospray ionization in the selected reaction monitoring mode. The MS/MS ion transitions monitored were m/z 535.3→355.1 and 285.1→193.0 for periplocymarin and diazepam, respectively. Good linearity was observed over the concentration ranges. The lower limit of quantification was 0.5 ng/mL in plasma and tested tissues. The intra-and inter-day precisions (relative standard deviation) were <10.2 and 10.5%, respectively, and accuracies (relative error) were between -6.8 and 8.9%. Recoveries in plasma and tissue were >90%. The validated method was successfully applied to the pharmacokinetic and tissue distribution studies of periplocymarin in rats. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26663385

  12. On-Tissue Derivatization via Electrospray Deposition for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging of Endogenous Fatty Acids in Rat Brain Tissues

    PubMed Central

    2016-01-01

    Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) is used for the multiplex detection and characterization of diverse analytes over a wide mass range directly from tissues. However, analyte coverage with MALDI MSI is typically limited to the more abundant compounds, which have m/z values that are distinct from MALDI matrix-related ions. On-tissue analyte derivatization addresses these issues by selectively tagging functional groups specific to a class of analytes, while simultaneously changing their molecular masses and improving their desorption and ionization efficiency. We evaluated electrospray deposition of liquid-phase derivatization agents as a means of on-tissue analyte derivatization using 2-picolylamine; we were able to detect a range of endogenous fatty acids with MALDI MSI. When compared with airbrush application, electrospray led to a 3-fold improvement in detection limits and decreased analyte delocalization. Six fatty acids were detected and visualized from rat cerebrum tissue using a MALDI MSI instrument operating in positive mode. MALDI MSI of the hippocampal area allowed targeted fatty acid analysis of the dentate gyrus granule cell layer and the CA1 pyramidal layer with a 20-μm pixel width, without degrading the localization of other lipids during liquid-phase analyte derivatization. PMID:27181709

  13. Influence of feeding graded levels of canned sardines on the inflammatory markers and tissue fatty acid composition of Wistar rats.

    PubMed

    Rodrigues, Pedro O; Martins, Susana V; Lopes, Paula A; Ramos, Cristina; Miguéis, Samuel; Alfaia, Cristina M; Pinto, Rui M A; Rolo, Eva A; Bispo, Paulo; Batista, Irineu; Bandarra, Narcisa M; Prates, José A M

    2014-08-14

    Canned sardines are a ready-to-use fish product with excellent nutritional properties owing to its high n-3 long-chain PUFA content, mainly EPA (20 : 5n-3) and DHA (22 : 6n-3). The present study aimed to assess the effect of two dosages of canned sardines, recommended for the primary and secondary prevention of human CVD, on the inflammatory marker concentrations and fatty acid composition of erythrocytes and key metabolic tissues (liver, muscle, adipose tissue and brain) in the rat model. Wistar rats were fed a diet containing 11 % (w/w) of canned sardines (low-sardine (LS) diet) and a diet containing 22 % (w/w) of canned sardines (high-sardine (HS) diet) for 10 weeks. Daily food intake, weight gain, and organ and final body weights were not affected by the dietary treatments. The concentrations of total cholesterol, HDL-cholesterol and LDL-cholesterol decreased in both the LS and HS groups, while those of alanine aminotransferase and adiponectin increased. The concentrations of IL-1β increased only with the highest dosage of sardine. The dose-dependent influence of the graded levels of EPA+DHA was tissue specific. Compared with that of other tissues and erythrocytes, the fatty acid composition of the brain was less affected by the canned sardine-supplemented diets. In contrast, the retroperitoneal adipose tissue was highly responsive. The deposition ratios of EPA and DHA indicated that the LS diet was optimal for DHA deposition across the tissues, except in the retroperitoneal adipose tissue. Taken together, our findings indicate that a LS diet positively affects plasma lipid profiles and inflammatory mediators, whereas a HS diet has contradictory effects on IL-1β, which, in turn, is not associated with variations in the concentrations of other pro-inflammatory cytokines. This finding requires further investigation and pathophysiological understanding. PMID:24775714

  14. Fat tissue morphology of long-term sex steroid deficiency and estrogen treatment in female rats.

    PubMed

    Santana, Aluana Carlos; Soares da Costa, Carlos Alberto; Armada, Luciana; de Paula Lopes Gonzalez, Gabrielle; dos Santos Ribeiro, Mariana; de Sousa dos Santos, Aline; de Carvalho, Jorge Jose; do Nascimento Saba, Celly Cristina A

    2011-03-15

    After long-term estradiol deficiency, female rats displayed body mass gain accompanied by an increase in the size of adipocytes, an increase in hyperglycemia, and a decrease in insulinemia. The effects were reversed by daily estradiol treatment. Adiposity was suggested by the increased vascular endothelial growth factor expression in castrated rats, whereas the proliferative effect of estradiol was suggested by the increased fibronectin expression in treated rats. PMID:21315340

  15. Tissue Distribution and Pharmacokinetics of Stable Polyacrylamide Nanoparticles Following Intravenous Injection in the Rat

    PubMed Central

    WENGER, Yvan; SCHNEIDER, Randal J.; REDDY, G. Ramachandra; KOPELMAN, Raoul; JOLLIET, Olivier; PHILBERT, Martin A.

    2011-01-01

    A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles (~31 nm average diameter). PAA-NPs and polyethylene glycol-coated PAA-NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 minutes to 120 hours and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000 %-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage. PMID:21134391

  16. Tissue distribution and pharmacokinetics of stable polyacrylamide nanoparticles following intravenous injection in the rat

    SciTech Connect

    Wenger, Yvan; Schneider, Randal J.; Reddy, G. Ramachandra; Kopelman, Raoul; Jolliet, Olivier; Philbert, Martin A.

    2011-03-15

    A variety of polymer nanoparticles (NP) are under development for imaging and therapeutic use. However, little is known about their behavior. This study examined pharmacokinetics, distribution and elimination of stable polyacrylamide (PAA) nanoparticles ({approx} 31 nm average diameter). PAA NPs and polyethylene glycol-coated PAA NPs were injected into the tail veins of healthy male rats. Blood, tissues and excreta were collected at times ranging from 5 min to 120 h and their radioactive content was quantified. A mathematical model was then applied to analyze the distribution dynamics of both NPs. Elimination from the blood could be accounted for by a quick but finite relocation to the major organs (about 20%, 0.6 to 1.3 h half-lives), and a slower distribution to the carcass (about 70%, 35 to 43 h half-lives). Excreted urinary levels correlated with blood concentrations. Combined cumulative urinary and fecal output accounted for less than 6% of the dose at 120 h. Compared to five other polymeric nanoparticles, the studied particles are at the highest half-lives and Area Under the Curve (4000 to 5000%-h). These two parameters decrease by three orders of magnitude when nanoparticle size increases from the 30 nm range up to 250 nm. For similar sizes, pegylated nanoparticles are more persistent in the blood than non-pegylated ones, but this difference is much smaller in the 30 nm and relatively high dose range than above 100 nm. Persistence of PAA NPs is not associated with acute toxicity signs as measured by typical serum markers of inflammation and cellular damage.

  17. ECRG4 Expression in Normal Rat Tissues: Expression Study and Literature Review

    PubMed Central

    Porzionato, A.; Rucinski, M.; Macchi, V.; Sarasin, G.; Malendowicz, L.K.; De Caro, R.

    2015-01-01

    The Esophageal Cancer Related Gene 4 (ECRG4) is a highly conserved tumour suppressor gene encoding various peptides (augurin, CΔ16 augurin, ecilin, argilin, CΔ16 argilin) which can be processed and secreted. In the present work, we examined ECRG4 expression and location in a wide range of rat organs and reviewed the available literature. ECRG4 mRNA was identified in all examined tissues by quantitative PCR (qPCR). ECRG4 immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, ECRG4 immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, ECRG4 immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal zona glomerularis and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function), although it is up-regulated in papillary thyroid cancer (oncogenic role). ECRG4 expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of ECRG4 in many structures suggests the involvement of ECRG4 in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of ECRG4 in neurons and endocrine cells and the fact that it can be secreted, its role as a neurotransmitter

  18. ECRG4 expression in normal rat tissues: expression study and literature review.

    PubMed

    Porzionato, A; Rucinski, M; Macchi, V; Sarasin, G; Malendowicz, L K; De Caro, R

    2015-01-01

    The Esophageal Cancer Related Gene 4 (ECRG4) is a highly conserved tumour suppressor gene encoding various peptides (augurin, CΔ16 augurin, ecilin, argilin, CΔ16 argilin) which can be processed and secreted. In the present work, we examined ECRG4 expression and location in a wide range of rat organs and reviewed the available literature. ECRG4 mRNA was identified in all examined tissues by quantitative PCR (qPCR). ECRG4 immunoreaction was mainly cytoplasmic, and was detected in heart and skeletal muscles, smooth muscle cells showing only weak reactions. In the digestive system, ECRG4 immunostaining was stronger in the esophageal epithelium, bases of gastric glands, hepatocytes and pancreatic acinar epithelium. In the lymphatic system, immunoreactive cells were detectable in the thymus cortex, lymph node medulla and splenic red pulp. In the central and peripheral nervous systems, different neuronal groups showed different reaction intensities. In the endocrine system, ECRG4 immunoreaction was detected in the hypothalamic paraventricular and supraoptic nuclei, hypophysis, thyroid and parathyroid glands, adrenal zona glomerularis and medulla and Leydig cells, as well as in follicular and luteal cells of the ovary. In the literature, ECRG4 has been reported to inhibit cell proliferation and increase apoptosis in various cell types. It is down-regulated, frequently due to hypermethylation, in esophageal, prostate, breast and colon cancers, together with glioma (oncosuppressor function), although it is up-regulated in papillary thyroid cancer (oncogenic role). ECRG4 expression is also higher in non-proliferating cells of the lymphatic system. In conclusion, our identification of ECRG4 in many structures suggests the involvement of ECRG4 in the tumorigenesis of other organs and also the need for further research. In addition, on the basis of the location of ECRG4 in neurons and endocrine cells and the fact that it can be secreted, its role as a neurotransmitter

  19. Chronic Brain Tissue Remodeling after Stroke in Rat: A One Year Multiparametric Magnetic Resonance Imaging Study

    PubMed Central

    Karki, Kishor; Knight, Robert A.; Shen, Li Hong; Kapke, Alissa; Lu, Mei; Li, Yi; Chopp, Michael

    2010-01-01

    Rats subjected to 2 hours of transient middle cerebral artery occlusion were studied temporally over 1 year by magnetic resonance imaging (MRI) and behavioral testing. Multiparameter MRI measures of T2, T1, T1 in the presence of off-resonance saturation of the bound proton signal (T1sat), apparent diffusion coefficient (ADC) and susceptibility-weighted imaging (SWI) were obtained at 1 day, 1, 2, 3 and 4 weeks, and 3, 6, 9 and 12 months post-ischemia. Regions of interest included: ischemic core (damaged both at 1 day and later); new lesion (normal at 1 day, but damaged later); and recovery (damaged at 1 day, but normal later) areas. Hematoxylin and eosin, Prussian blue and ED-1, a monoclonal antibody murine macrophage marker, stainings were performed for histological assessment. Core area T2 and ADC values increased until ~6 months, and T1 and T1sat until ~12 months. New lesion area MRI parameter values increased until ~6 months (T2, T1 and ADC), or ~1 year (T1sat). Lesion area was largest at 1 day (mean±SD: 37.0±13.7 mm2) and smallest at 1 year (18.1±10.5 mm2). Recovery area was largest at 3 weeks (8.9±3.8 mm2) and smallest at 1 year (6.4±3.3 mm2). The ipsilateral/contralateral ventricle area ratio was 0.7±0.2 at 1 day and increased significantly at 1 year (2.4±0.7). Iron-laden macrophages, histologically confirmed at 1 year, were detected in the lesion borders by SWI at 3, 6, 9 and 12 months. Our data indicate that MRI detectable changes of ischemia-damaged brain tissue continue for at least 1 year post-ischemia. PMID:20828544

  20. Pharmacokinetics, bioavailability, tissue distribution, excretion, and metabolite identification of methoxyflavones in Kaempferia parviflora extract in rats.

    PubMed

    Mekjaruskul, Catheleeya; Jay, Michael; Sripanidkulchai, Bungorn

    2012-12-01

    Kaempferia parviflora (KP) is an herbal plant in the family of Zingiberaceae. KP mainly contains methoxyflavones, especially 5,7-dimethoxyflavone (DMF), 5,7,4'-trimethoxyflavone (TMF), and 3,5,7,3',4'-pentamethoxyflavone (PMF). The present study was designed to characterize the pharmacokinetics, including bioavailability, distribution, excretion, and identification of metabolites after administration of a KP ethanolic extract. Male rats were orally or intravenously administered a 250 mg/kg concentration of a KP extract, and blood samples were obtained at selected times to determine pharmacokinetic parameters of PMF, TMF, and DMF. For distribution and excretion studies, the organs, urine, and feces samples were collected at various times after oral administration of a larger (750 mg/kg) dose of KP extract. Methoxyflavones in the biological samples were quantified by high-performance liquid chromatography-UV, and the metabolites in urine and feces were further identified by using liquid chromatography-tandem mass spectrometry. After oral administration, concentrations of the three methoxyflavones quickly approached their maximal concentration, ranging from 0.55 to 0.88 μg/ml within 1 to 2 h after administration, and then were gradually excreted with half-lives of 3 to 6 h. The methoxyflavones showed low oral bioavailability of 1 to 4%. Three methoxyflavones were detected at their highest levels in liver followed by kidney. They were also found in lung, testes, and brain. After absorption, organ distribution, and metabolism, the components of KP were mainly eliminated through urine in the forms of demethylated, sulfated, and glucuronidated products and as demethylated metabolites in the feces. The parent compounds were found to have 0.79, 1.76, and 3.10% dose recovery in urine and 1.06, 1.77, and 0.96% dose recovery in feces for PMF, TMF, and DMF, respectively. These studies are the first to describe the pharmacokinetics of KP extract to provide the information on

  1. Dietary Triacylglycerols with Palmitic Acid in the sn-2 Position Modulate Levels of N-Acylethanolamides in Rat Tissues

    PubMed Central

    Lisai, Sara; Sirigu, Annarita; Piras, Antonio; Collu, Maria; Batetta, Barbara; Gambelli, Luisa; Banni, Sebastiano

    2015-01-01

    Background Several evidences suggest that the position of palmitic acid (PA) in dietary triacylglycerol (TAG) influences different biological functions. We aimed at evaluating whether dietary fat with highly enriched (87%) PA in sn-2 position (Hsn-2 PA), by increasing PA incorporation into tissue phospholipids (PL), modifies fatty acid profile and biosynthesis of fatty acid—derived bioactive lipids, such as endocannabinoids and their congeners. Study Design Rats were fed for 5 weeks diets containing Hsn-2 PA or fat with PA randomly distributed in TAG with 18.8% PA in sn-2 position (Lsn-2 PA), and similar total PA concentration. Fatty acid profile in different lipid fractions, endocannabinoids and congeners were measured in intestine, liver, visceral adipose tissue, muscle and brain. Results Rats on Hsn-2 PA diet had lower levels of anandamide with concomitant increase of its congener palmitoylethanolamide and its precursor PA into visceral adipose tissue phospholipids. In addition, we found an increase of oleoylethanolamide, an avid PPAR alpha ligand, in liver, muscle and brain, associated to higher levels of its precursor oleic acid in liver and muscle, probably derived by elongation and further delta 9 desaturation of PA. Changes in endocannabinoids and congeners were associated to a decrease of circulating TNF alpha after LPS challenge, and to an improved feed efficiency. Conclusions Dietary Hsn-2 PA, by modifying endocannabinoids and congeners biosynthesis in different tissues may potentially concur in the physiological regulation of energy metabolism, brain function and body fat distribution. PMID:25775474

  2. Cytochemical demonstration of constitutive H2O2 production by macrophages in synovial tissue from rats with adjuvant arthritis.

    PubMed Central

    Hoffstein, S. T.; Gennaro, D. E.; Meunier, P. C.

    1988-01-01

    Generation of toxic oxygen metabolites by inflammatory cells is considered to be one of the mechanisms by which inflammation produces tissue injury. This concept is based on in vitro studies of purified leukocyte populations because it has not been possible to assess production of these metabolites in tissues. In order to determine whether or not inflammatory cells in tissue generate H2O2, the authors modified an earlier cytochemical method for the localization of H2O2. The incubation medium consists of 0.5 mM CeCl3 in a Hepes-buffered balanced salt solution with Cl- as the only anion. Synovial tissue from the knees of normal and 16-day adjuvant arthritic rats was incubated in this medium for 30 minutes and then fixed and processed for electron microscopy. No H2O2 reaction product was visible in normal synovium. In contrast, patchy deposits of H2O2 reaction product were seen adjacent to a subpopulation of synovial lining macrophages in synovium from inflamed knee joints. These data show that rat synovial macrophages are capable of generating H2O2 when appropriately stimulated and that such a stimulus is present in adjuvant arthritis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:3257356

  3. Tissue-specific regulation of expression and activity of P-glycoprotein in adjuvant arthritis rats.

    PubMed

    Achira, Meguru; Totsuka, Ryuichi; Fujimura, Hisako; Kume, Toshiyuki

    2002-07-01

    Cyclosporine A and steroids are effective against rheumatoid arthritis and also known as substrates of P-glycoprotein (P-gp). We investigated the effect of arthritis on the hepatic and intestinal P-gp activity in rats, and substantiated the expression level of the hepatic P-gp. Doxorubicin was used as a P-gp substrate. Cumulative biliary excretion and intestinal exsorption of doxorubicin following intravenous administration were compared between adjuvant arthritis (AA) and normal rats. Intestinal P-gp activity was also investigated by intestinal everted sac method, and hepatic P-gp was detected by FITC-labeled antibody and visualized using a confocal laser microscope system. Biliary clearance of doxorubicin in AA rats was significantly decreased from that in normal rats. The expression level of the hepatic P-gp in AA rats was very low compared to normal rats, indicating down-regulation. Intestinal exsorption clearance was not different between AA and normal rats. Permeability of doxorubicin across intestinal everted sac was comparable between AA and normal rats, corresponding to in vivo study. In AA rats, hepatic P-gp activity was decreased due to the reduction of expression level, but intestinal P-gp activity was not changed. Different regulation systems may be involved in liver and intestine. PMID:12113888

  4. Betaine (trimethylglycine) as a nutritional agent prevents oxidative stress after chronic ethanol consumption in pancreatic tissue of rats.

    PubMed

    Kanbak, Gungör; Dokumacioglu, Ali; Tektas, Aysegul; Kartkaya, Kazim; Erden Inal, Mine

    2009-03-01

    In this study, we investigated the free radical-mediated cytotoxic effects of chronic ethanol consumption on the pancreatic tissue and a possible cytoprotective effect of betaine as a methyl donor and an important participant in the methionine cycle. Twenty-four male Wistar rats were divided into control, ethanol, and ethanol+betaine groups. Prior to sacrifice, all groups were fed 60 mL/diet per day for two months. Rats in the ethanol group were fed with ethanol 8 g/kg/day. The ethanol+betaine groups were fed ethanol plus betaine (0.5 % w/v). Malondialdehyde levels and adenosine deaminase, superoxide dismutase, and xanthine oxidase activities were determined in pancreatic tissues of rats. Compared to control group, MDA levels increased significantly in the ethanol group (p<0.05). MDA levels in the ethanol+betaine group were significantly decreased compared to the ethanol group (p<0.05). ADA activity in the ethanol+betaine group decreased significantly when compared to the ethanol group (p<0.05). XO activities in ethanol-fed rats were decreased significantly compared to the control group (p<0.05). XO activity in the betaine group was increased significantly (p<0.05) compared to the ethanol group. SOD activity in the ethanol group decreased significantly compared to control group (p<0.001). SOD activity in the ethanol+betaine group decreased significantly (p<0.05) compared to the control group. We think that betaine, as a nutritional methylating agent, may be effective against ethanol-mediated oxidative stress in pancreatic tissue. PMID:20108209

  5. Decreased expression of Ras-GRF1 in the brain tissue of the intractable epilepsy patients and experimental rats.

    PubMed

    Zhu, Qiong; Wang, Liang; Xiao, Zheng; Xiao, Fei; Luo, Jing; Zhang, Xiaogang; Peng, Xi; Wang, Xuefeng; Sun, Hongbin

    2013-02-01

    Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) is present mainly at synaptosome and its expression after birth increases in parallel with the development of neuronal circuitry. Evidences suggested that Ras-GRF1 could mediate forms of synaptic plasticity and might participate in the regulation of neuronal excitability and neurite outgrowth though various signal transduction pathway. The aim of this study was to measure Ras-GRF1 expression in brain tissue of patients with drug-refractory temporal lobe epilepsy (TLE) and lithium chloride-pilocarprine kindled rats using double-label immunofluorescence, immunohistochemistry and Western blotting and to discuss the possible role of Ras-GRF1 in TLE. We randomly selected 30 temporal neocortices tissues from patients with TLE and 9 histologically normal temporal neocortices samples from controls. Meanwhile, we investigated the distribution and level of Ras-GRF1 protein expression during the different phases (the acute period, the latent period and the chronic phase) in the epileptic and control rats. Ras-GRF1 was mainly expressed in the plasma membrane and dendrite of neurons, but it was not co-expressed with GFAP-positive astrocytes in the brain tissue of patients and epileptic rats. Compared with controls, Ras-GRF1 expression was significantly decreased in TLE patients. Ras-GRF1 expression in epileptic rats was already reduced at 1 day post-seizures, then gradually decreased during the latent period and reached a minimum level during the chronic phase. These results demonstrated that the decreased expression of Ras-GRF1 could be involved in the pathogenesis of human TLE. PMID:23200899

  6. Carbohydrate feeding increases total body and specific tissue 3,5,3'-triiodothyronine neogenesis in the rat

    SciTech Connect

    Gavin, L.A.; Moeller, M.; McMahon, F.A.; Castle, J.N.; Gulli, R.; Cavalieri, R.R.

    1988-08-01

    The glucose-fed rat, in contrast to the chow-fed animal, has a higher serum total T3 concentration and an increase in the hepatic content of T4 5'-deiodinase (type I) activity. The mechanism and significance of these glucose-induced changes in T3 metabolism are elucidated in this study. To focus on extrathyroidal thyroid hormone metabolism the kinetic parameters were determined in thyroidectomized T4-replaced rats (1.25 micrograms T4/100 g BW.day). Kinetics of T4 and T3 were studied separately by infusing labeled hormone to equilibrium. Glucose feeding for 72 h (G) significantly increased both the total and free serum T3 concentrations compared to the respective means in the chow-fed control group (P). The glucose-induced changes in serum T3 reflect the approximate doubling of T3 production to 14.7 +/- 0.6 ng/h.100 g in G rats compared to 7.6 +/- 0.7 ng/h.100 g in P rats. The higher T3 production rate in the G group is due to a significant increase in the fractional total body T4 to T3 conversion (0.33 +/- 0.02) compared to that in the P group (0.19 +/- 0.02). The tissue (liver, kidney, brain, and brown adipose tissue) concentration of T4 (nanograms per g wet wt) was significantly increased in the G group. The increase ranged from 54% in liver to 80% in kidney, brain, and brown adipose tissue. The tissue concentration of T3 (nanograms per g wet wt) was even more dramatically increased by glucose feeding than was T4. The glucose-induced increment in organ T3 ranged from 2.5-fold (kidney, muscle, and brain) to 5-fold (liver and white adipose tissue) to 12-fold (brown adipose tissue). These data indicate that the increase in serum total and free T3 concentrations associated with glucose feeding reflects augmented total body T3 production from T4. The effect of the enhanced T3 neogenesis was generalized, as the T3 content was increased in each organ studied. Thus, glucose feeding has unique effects on T3 metabolism.

  7. Silver nanoparticle based surface enhanced Raman scattering spectroscopy of diabetic and normal rat pancreatic tissue under near-infrared laser excitation

    NASA Astrophysics Data System (ADS)

    Huang, H.; Shi, H.; Feng, S.; Lin, J.; Chen, W.; Huang, Z.; Li, Y.; Yu, Y.; Lin, D.; Xu, Q.; Chen, R.

    2013-04-01

    This paper presents the use of high spatial resolution silver nanoparticle based near-infrared surface enhanced Raman scattering (SERS) from rat pancreatic tissue to obtain biochrmical information about the tissue. A high quality SERS signal from a mixture of pancreatic tissues and silver nanoparticles can be obtained within 10 s using a Renishaw micro-Raman system. Prominent SERS bands of pancreatic tissue were assigned to known molecular vibrations, such as the vibrations of DNA bases, RNA bases, proteins and lipids. Different tissue structures of diabetic and normal rat pancreatic tissues have characteristic features in SERS spectra. This exploratory study demonstrated great potential for using SERS imaging to distinguish diabetic and normal pancreatic tissues on frozen sections without using dye labeling of functionalized binding sites.

  8. Coronary atherosclerosis burden is not advanced in patients with β-thalassemia despite premature extracardiac atherosclerosis: a coronary artery calcium score and carotid intima-media thickness study

    PubMed Central

    Hahalis, George; Zacharioglou, Evangelia; Xanthopoulou, Ioanna; Koniari, Ioanna; Kalogeropoulou, Chistina; Tsota, Irene; Rigopoulou, Aspasia; Diamantopoulos, Athanasios; Gkizas, Vasilios; Davlouros, Periklis; Akinosoglou, Karolina; Leopoulou, Marianna; Gogos, Charalampos; Alexopoulos, Dimitrios

    2016-01-01

    Background Thalassemic patients demonstrate an increased rate of extracardiac vascular complications and increased carotid wall intima-media thickness (cIMT), but very low prevalence of coronary artery disease (CAD). We investigated the atheroma burden by assessing the coronary artery calcium (CAC) and cIMT in these patients. Methods We examined 37 patients with β-thalassemia and 150 healthy control volunteers with multi-detector computer tomography (CT) and ultrasonography to determine CAC score and cIMT, respectively. Results Propensity score matching (C-statistic: 0.88; 95% CI: 0.83–0.93) resulted in 27 pairs of patients; severe CAC was observed in 2 (7.4%) and 0 of β-thalassemia patients and healthy volunteers respectively (P = 0.5). Median calcium score was 0 (0–0) in β-thalassemia patients and 0 (0–4) in healthy volunteers (P = 0.8). Median intima-media thickness was higher in β-thalassemia patients compared to control group [0.45 (0.06–0.65) vs. 0.062 (0.054–0.086); P = 0.04]. Conclusions Patients with β–thalassemia in comparison with healthy control subjects exhibit similar CAC score and increased cIMT. Our findings indicate a disparate rate of progression of atherosclerosis between coronary and extracardiac arteries in these patients lending support to the epidemiological evidence. PMID:27168742

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