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Sample records for rat extracardiac tissues

  1. Extracardiac off-pump fontan completion for single ventricle with dextrocardia.

    PubMed

    Goksel, Onur S; Gok, Emre; Tireli, Emin; Dayioglu, Enver

    2013-01-01

    Extracardiac off-pump is reported to result in better early hemodynamics and shorter mechanical ventilation periods. We present a case report of extracardiac off-pump Fontan in a 5-year-old girl with single ventricle and dextrocardia.

  2. Hemothorax in Three Dogs with Intrathoracic Extracardiac Hemangiosarcoma.

    PubMed

    Rutherford, Lynda; Stell, Anneliese; Smith, Ken; Kulendra, Nicola

    2016-01-01

    Intrathoracic extracardiac hemangiosarcoma (HSA) is rare in dogs. This report describes three dogs with acute onset dyspnea due to hemorrhagic pleural effusion resulting from intrathoracic extracardiac masses, which were confirmed as HSA by histopathology. The dogs were stabilized with thoracocentesis and intravascular fluid resuscitation. Computed tomography identified intrathoracic masses, which were not originating from the heart or pulmonary parenchyma. Surgical exploration was performed in all cases. Case 1 was euthanized intraoperatively as the tumor could not be dissected from the aorta. In cases 2 and 3, hemostasis and resection of the tumors was successful. Case 2 was euthanized 1 mo after surgery and case 3 was alive at the time of writing, 5 mo postoperatively. Intrathoracic extracardiac HSA should be considered as a differential for nontraumatic hemothorax and surgical treatment can be palliative.

  3. Rat tissue reaction to MTA FILLAPEX®.

    PubMed

    Gomes-Filho, João Eduardo; Watanabe, Simone; Lodi, Carolina Simonetti; Cintra, Luciano Tavares Angelo; Nery, Mauro Juvenal; Filho, José Arlindo Otoboni; Dezan, Elói; Bernabé, Pedro Felício Estrada

    2012-12-01

    The aim of this study was to evaluate the rat subcutaneous tissue reaction to implanted polyethylene tubes filled with mineral trioxide aggregate (MTA) FILLAPEX® compared to the reaction to tubes filled with Sealapex® or Angelus MTA® . These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7, 15, 30, 60, and 90 days. The specimens were stained with hematoxylin and eosin or Von Kossa or left unstained for examination under polarized light. Qualitative and quantitative evaluations of the reaction were performed. All materials caused moderate reactions after 7 days, which decreased with time. The reactions were moderate and similar to that evoked by the control and Sealapex® on the 15th day. MTA FILLAPEX(®) and Angelus MTA caused mild reactions beginning after 15 days. Mineralization and granulation birefringent to polarized light were observed with all materials. It was concluded that MTA FILLAPEX® was biocompatible and stimulated mineralization.

  4. Extra-cardiac stimulators: what do cardiologists need to know?

    PubMed

    Guinand, Alexandre; Noble, Stéphane; Frei, Angela; Renard, Julien; Tramer, Martin R; Burri, Haran

    2016-09-01

    For several decades, treating patients with pacemakers has been the privilege of cardiologists. However, in the last 30 years, researchers have found new targets for electrical stimulation in different clinical subspecialities, such as deep brain stimulation (for the treatment of Parkinson's disease, essential tremor, dystonia, and some psychiatric illnesses); spinal cord stimulation (for refractory angina, chronic pain, and peripheral artery disease); and sacral (for diverse urologic and proctologic conditions), vagal (for epilepsy), and phrenic nerve stimulation (for sleep apnoea). The purpose of this article is to familiarize cardiologists with these 'extra-cardiac pacemakers' and to discuss potential issues that must be addressed when these patients undergo cardiac procedures. PMID:27234870

  5. Bis-(5'-guanosyl) tetraphosphatase in rat tissues.

    PubMed Central

    Cameselle, J C; Costas, M J; Sillero, M A; Sillero, A

    1982-01-01

    The occurrence and distribution of bis-(5'-guanosyl) tetraphosphatase activity towards dinucleoside tetraphosphates between the 27 000 g supernatant and sedimented fraction were studied in liver, kidney, brain, muscle and intestinal mucosa from rat. The p1p4-bis-(5'-guanosyl) tetraphosphate-hydrolysing activities found in total homogenates were 0.77, 1.44, 0.39, 0.36 and 2.14 units (mumol/min)/g respectively. The activities found in the 27000 g-sedimented fractions were 74, 49, 11, 4 and 96% of those present in the homogenates respectively. The properties of the soluble enzymes were investigated. All of them have low Km values for p1p4-bis-(5'-guanosyl) tetraphosphate (from 2 to 50 microM), are competitively inhibited by guanosine 5'-tetraphosphate with K1 values from 10 to 160 nM, have molecular weights of about 21 000, require Mg2+ or Mn2+ and are inhibited by Ca2+. These properties show that bis-(5'-guanosyl) tetraphosphatase (EC 3.6.1.17), an enzyme previously characterized in Artemia salina and rat liver [Warner & Finamore (1965) Biochemistry 4, 1568-1575; Vallejo, Sillero & Sillero (1974) Biochim, Biophys. Acta 358, 117-125; Lobatón, Vallejo, Sillero & Sillero (1975) Eur. J. Biochem. 50, 495-501], is present in all the rat tissues examined. The inhibition of the enzyme by Ca2+ could be related to the effect of p1p4-bis-(5'-adenosyl) tetraphosphate as a trigger of DNA synthesis [Grummt, Waltl, Jantzen, Hamprecht, Huebscher & Kuenzle (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 6081-6085]. PMID:6282267

  6. Extracardiac-Lodged Mesenchymal Stromal Cells Propel an Inflammatory Response Against Myocardial Infarction via Paracrine Effects.

    PubMed

    Peng, Yi; Pan, Wei; Ou, Yali; Xu, Weifang; Kaelber, Sussannah; Borlongan, Cesario V; Sun, Meiqin; Yu, Guolong

    2016-01-01

    Transplantation of stem cells, including mesenchymal stromal cells (MSCs), improves the recovery of cardiac function after myocardial infarction (MI) in experimental studies using animal models and in patients. However, the improvement of cardiac function following MSC transplantation remains suboptimal in both preclinical and clinical studies. Understanding the mechanism of cell therapy may improve its therapeutic outcomes, but the mode of action mediating stem cell promotion of cardiac repair is complex and not fully understood. Recent studies suggest that the immunomodulatory effects of MSCs on the macrophage M1/M2 subtype transition allow the transplanted stem cells to inhibit inflammation-induced injury and promote cardiac repair in acute MI. However, equally compelling evidence shows that there is poor survival and minimal graft persistence of transplanted MSCs within the infarcted heart tissues, negating the view that graft survival per se is required for the observed high rate and long duration of the transition from proinflammatory M1 to reparative M2 macrophages in the infarcted myocardium. Therefore, we raised a novel hypothesis that the therapeutic effects of MSC transplantation for acute MI depends not primarily on the grafted cells in infarct myocardium, but that MSCs migrating to and being lodged in the extracardiac organs, demonstrating good graft survival and persistence, may render the therapeutic effects in MI. More specifically, MSC transplantation promotes the transition from M1 to M2 in extracardiac organs, such as spleen and bone marrow, and therapeutic effects are conferred to the infarcted myocardium via paracrine effects. In MSC transplantation, the conversion from proinflammatory M1 to anti-inflammatory M2 monocytes may occur remotely from the heart and may serve as one of the major pathways in regulating the dual effects of inflammation. This hypothesis, if proven valid, may represent an important new mechanism of action to be considered

  7. 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

  8. 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.

  9. 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

  10. Prevalence of extracardiac findings in the evaluation of ischemic heart disease by multidetector computed tomography

    PubMed Central

    Cho, Jeong-Hwan; Park, Jong-Seon; Shin, Dong-Gu; Kim, Young-Jo; Lee, Sang-Hee; Choi, Yoon-Jung; Cho, Ihn-Ho

    2013-01-01

    Objective Multidector computed tomography (MDCT) is now commonly used for the evaluation of coronary artery disease. Because MDCT images include many non-cardiac organs and the patient population evaluated is highly susceptible to extracardiac diseases, this study was designed to evaluate the prevalence of extracardiac findings in the MDCT evaluation of ischemic heart disease. Methods From March 2007 to March 2008, a total of six-hundred twenty patients, who underwent 64-slice MDCT evaluations for chest pain, or dyspnea, were enrolled in this study. Cardiac and non-cardiac findings were comprehensively evaluated by a radiologist. Results Enrolled patients included 306 men (49.4%), with a mean age of 66 years. Significant coronary artery stenosis was found in 41.6% of the patients. A total of 158 extracardiac findings were observed in 110 (17.7%) patients. Commonly involved extracardiac organs were lung (36.7%), hepatobiliary system (21.5%), thyroid (19.6%), kidney (10.8%), spine (9.7%) and breast (0.6%). Of those 110 patients, 50 (45.5%) patients underwent further diagnostic investigations. Malignant disease was detected in three (2.7%) patients (lung cancer, pancreatic cancer, and thyroid cancer). Conclusions Extracardiac findings are frequently present and should be a concern in the MDCT evaluation of chest pain syndrome. PMID:24133511

  11. Characteristic lesion pattern and echocardiographic findings in extra-cardiac shunt-related stroke.

    PubMed

    Mun, Jun Kyu; Park, Sung Ji; Kim, Suk Jae; Bang, Oh Young; Chung, Chin-Sang; Lee, Kwang Ho; Kim, Gyeong-Moon

    2016-10-15

    Among embolic strokes of undetermined source, under-recognized etiology such as extra-cardiac shunt could be a potential risk factor. We sought to characterize infarction patterns on diffusion-weighted imaging (DWI) and transesophageal echocardiography (TEE) findings in extra-cardiac shunt-related stroke. We enrolled 96 consecutive patients with cryptogenic stroke who had an extra- or intra-cardiac shunt. Diagnosis of the shunt was performed using TEE with agitated saline contrast and pulmonary vein isolation. Infarction patterns on DWI and total lesion volume were analyzed. Bubble amounts through the shunt were classified via the International Consensus Criteria (ICC). Short-term prognosis, patterns and size of DWI lesions, and involved vascular territories were not significantly different between two groups. Multivariate analysis revealed that extra-cardiac shunt group has a smaller total infarct volume (odds ratio [OR]=0.427, 95% confidence interval [95% CI] 0.228-0.799, p=0.008), and significantly higher bubble grade during resting state and lower grade during the Valsalva maneuver (OR= 0.539, 95% CI 0.438-0.663, p<0.001). Stroke related to an extra-cardiac shunt presented smaller infarct volume, favorable clinical outcomes and characteristic finding on TEE with agitated saline contrast. Further study is needed to confirm whether the extra-cardiac shunt is an independent risk factor. PMID:27653885

  12. 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.

  13. 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

  14. Normal Sinus Rhythm-Sinus Bradycardia is Common in Young Children Post-extracardiac Fontan.

    PubMed

    Evans, William N; Acherman, Ruben J; Restrepo, Humberto

    2016-10-01

    We hypothesized that normal sinus rhythm-sinus bradycardia is common in young children following extracardiac Fontan. After excluding patients with sinus pauses, junctional rhythm, tachy-brady syndrome, frequent ectopics, or ectopic atrial rhythm, we found an ambulatory 24-h Holter monitor average heart rate of 78 ± 12 beats per minute (bpm) in 33 post-extracardiac Fontan children with a median age of 6 years (5-10). A 24-h average heart rate of 78 ± 12 bpm is statistically significantly lower than a 24-h average heart rate value of 90 ± 10 bpm derived from a similarly aged control population (p < 0.01). We conclude that after excluding those with significant arrhythmias, normal sinus rhythm-sinus bradycardia is common in children post-extracardiac Fontan.

  15. Biocompatibility evaluation of alendronate paste in rat's subcutaneous tissue.

    PubMed

    Mori, Graziela Garrido; de Moraes, Ivaldo Gomes; Nunes, Daniele Clapes; Castilho, Lithiene Ribeiro; Poi, Wilson Roberto; Capaldi, Maria Luciana P Manzoli

    2009-04-01

    Alendronate is a known inhibitor of root resorption and the development of alendronate paste would enhance its utilization as intracanal medication. Therefore, this study aimed to investigate the biocompatibility of experimental alendronate paste in subcutaneous tissue of rats, for utilization in teeth susceptible to root resorption. The study was conducted on 15 male rats, weighing approximately 180-200 grams. The rats' dorsal regions were submitted to one incision on the median region and, laterally to the incision, the subcutaneous tissue was raised and gently dissected for introduction of two tubes, in each rat. The tubes were sealed at one end with gutta-percha and taken as control. The tubes were filled with experimental alendronate paste. The animals were killed at 7, 15 and 45 days after surgery and the specimens were processed in laboratory. The histological sections were stained with hematoxylin-eosin and analyzed by light microscopy. Scores were assigned to the inflammatory process and statistically compared by the Tukey test (P < 0.05). Alendronate paste promoted severe inflammation process at 7 days, with statistically significant difference compared to the control (P < 0.05%). However, at 15 days, there was a regression of inflammation and the presence of connective tissue with collagen fibers, fibroblasts and blood vessels was observed. After 45 days, it was observed the presence of well-organized connective tissue, with collagen fibers and fibroblasts, and few inflammatory cells. No statistical difference was observed between the control and experimental paste at 15 and 45 days. The experimental alendronate paste was considered biocompatible with subcutaneous tissue of rat.

  16. Zinc supplement on tissue arsenic concentration in rats.

    PubMed

    Kamaluddin, M; Misbahuddin, M

    2006-12-01

    To examine the effect of zinc in the removal of accumulated arsenic from different tissues (liver, kidneys, spleen and lungs), rats were initially allowed to drink high concentration (400 microg/kg/day) of arsenic for two months followed by a period of cessation (one month). Administration of zinc (2 mg/kg/day) during the third month in arsenic-treated and non-treated groups were compared. In arsenic-treated rats, the mean (+/- SD) amounts of total arsenic in liver, kidneys, spleen and lungs were 12.3 +/- 0.7, 20.5 +/- 1.0, 31.4 +/- 1.0 and 25.6 +/- 1.1 microg/g of tissues respectively. Administration of zinc to arsenic-treated rats reduced the arsenic concentrations of those tissues to 7.8, 10.7, 23.0 and 14.0 microg/g of tissues. This in vivo study suggests that zinc removes the accumulated arsenic from different tissues significantly (p < 0.001).

  17. Localization of calmodulin in rat tissues.

    PubMed Central

    Harper, J F; Cheung, W Y; Wallace, R W; Huang, H L; Levine, S N; Steiner, A L

    1980-01-01

    The localization of calmodulin, a calcium-dependent modulator of many enzymes, was studied in rat liver, skeletal muscle, and adrenal slices. Calmodulin is found in liver cytoplasm, nucleus, and plasma membrane. Much of the cytoplasmic calmodulin is associated with glycogen particles presumably bound to enzymes involved in glycogen metabolism. Skeletal muscle calmodulin is found on the I-band, also associated with glycogen particles. Intermyofibrillar staining that is not glycogen associated is also observed. Calmodulin is localized in the cytoplasm and nucleus of adrenal cortex cells. Injection of corticotropin leads to a greatly increased localization of calmodulin in nuclei of the adrenal cortex. These observations suggest that one role of calmodulin may be the regulation of hormone effects on nuclear processes. Images PMID:6987650

  18. 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

  19. Rat and human membrane dipeptidase: tissue distribution and developmental changes.

    PubMed

    Kera, Y; Liu, Z; Matsumoto, T; Sorimachi, Y; Nagasaki, H; Yamada, R H

    1999-05-01

    Distribution and developmental changes in membrane dipeptidase activity were examined in rat and human tissues. The activity to hydrolyze glycyl-D-alanine in rat and human tissues was completely or almost completely inhibited by 5 mM cilastatin, suggesting that the activity was due to membrane dipeptidase and that the contribution of leucine aminopeptidase to the activity was minor. In 8-week-old rats, the activity was high in lung, kidney, pancreas and testis, and in each pooled sample of ileal mucosa, duodenal mucosa, jejunal mucosa and adrenal mucosa. A low activity was found in spleen, liver, serum and heart. The activity in lung, kidney, adrenal and intestinal mucosa increased up to the age of 5 or 8 weeks, while that in pancreas, testis and spleen reached a maximal level at around 3 weeks and declined thereafter. The distribution profile of the enzyme in postmortem tissues of adult humans was similar to that in rat, except for an extremely low activity in lung. The enzyme was also found in serum and urine from healthy volunteers. In urine, the activity was significantly correlated to the creatinine content. No clear dependence of the activity on gender or age was observed in urine and serum.

  20. Stereological determination of the volume of the rat hemimandible tissues.

    PubMed

    Silva, M A; Merzel, J

    2001-07-01

    Rodent incisors are useful models to study the development and behavior of dental and periodontal tissues. Some studies require three-dimensional reconstructions of the tooth but none of the described methods yield actual volumetric data. Unlike the rat lower incisors the hemimandible can be easily isolated and its volume was determined by Cavalieri's geometrical principle. This method associated with point-counting volumetry was used to calculate the volume of the structures found in that bone mainly those related to the lower incisor. For 172 g male rats the mean volume of the hemimandible was 182.7 mm(3), statistically not different from 184.9 mm(3) the mean volume of the same hemimandibles determined by Archimedes' principle. The coefficients of error (CE) of Cavalieri's estimates for the hemimandible, incisor as a whole (the tooth itself, odontogenic region and periodontium) and bone tissue were less than 0.04. For the incisor individual tissues the CEs were usually above 0.05, however their calculated volumes are probably not different from the actual ones. The data for incisors and their periodontal tissues and for bone, because of continuous growth of these structures, are meaningful only for rats of the same gender, strain and weight range. PMID:11455534

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. Lability of renal papillary tissue composition in the rat.

    PubMed Central

    Atherton, J C

    1978-01-01

    1. The acute effects of (a) a minor operative procedure using ether as the anaesthetic, and (b) the administration of 0.9% saline as a single I.V. injection in the conscious rat, on renal tissue composition were studied in hydropenic and normally hydrated rats. 2. The operative procedure and anaesthesia induced a rapid and transient decrease in papillary osmolality in both hydropenic and normally hydrated animals, the important contributing factor being a significant decrease in urea content. 3. Administration of a small volume of saline caused a rapid decrease in urea content, and an increase in water content. 4. It is concluded that papillary composition is extremely labile, large changes being produced by relatively minor experimental procedures. PMID:624997

  7. Biocompatibility of acetazolamide pastes in the subcutaneous tissue of rats.

    PubMed

    Mori, Graziela Garrido; Moraes, Ivaldo Gomes de; Nunes, Daniele Clapes; Castilho, Lithiene Ribeiro; Poi, Wilson Roberto

    2009-01-01

    This aim of this study was to investigate the biocompatibility of two experimental acetazolamide (AZ)-based pastes in the subcutaneous tissue of rats. Both pastes contained AZ as the main component in similar concentration. The vehicle in experimental paste 1 was saline, while experimental paste 2 was prepared with propylene glycol. Sixty polyethylene tubes were sealed at one end with gutta-percha (GP), which served as a control. Half of the tubes were filled with paste 1 and half with paste 2. The tubes were implanted in the subcutaneous tissue of 15 rats, being 4 tubes for each animal. The animals were killed 7, 15 and 45 days after surgery and the specimens were processed in laboratory. The histological sections were stained with hematoxylin and eosin and were analyzed by light microscopy. Scores were assigned to level of inflammatory process: 1- none; 2- mild; 3- moderate; 4- severe. The data were analyzed statistically by the Kruskal-Wallis test (p< or =0.05). Paste 1 produced an inflammatory process at 7 days. However, the intensity of this inflammation decreased with time and was nearly absent at 45 days. No statistically significant difference (p>0.05) was observed between the control (GP) and paste 1. However, paste 2 produced inflammatory response at all study periods and differed significantly (p<0.05) from the control. In conclusion, in the present study, the experimental AZ-based paste 1 was considered as biocompatible as the control matrial (GP), while experimental paste 2 was irritating to rat subcutaneous tissue.

  8. 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.

  9. Pharmacological interference with tissue hypercatabolism in tumour-bearing rats.

    PubMed Central

    Tessitore, L; Costelli, P; Baccino, F M

    1994-01-01

    Marked loss of body weight and profound waste of both skeletal muscle and white adipose tissue occur in rats into which the ascites hepatoma Yoshida AH-130 has been transplanted, associated with marked perturbations in the hormonal homoeostasis and the presence of circulating tumour necrosis factor and high plasma levels of prostaglandin E2 [Tessitore, Costelli and Baccino (1993) Br. J. Cancer 67, 15-23]. On the basis of previous findings, the present study examined whether the development of cachexia in this model system could be significantly affected by adrenalectomy or by pharmacological treatments that may interfere with proximal or distal mediators of tissue hypercatabolism. In no instance was tumour growth modified. Medroxyprogesterone acetate, an anabolic-hormone-like drug, was completely ineffective. In adrenalectomized animals, although changes such as the elevation of plasma triacylglycerols and corticosterone were corrected, the general course of cachexia was not modified. A partial prevention of muscle waste was observed with acetylsalicylic acid, a non-steroidal anti-inflammatory drug, or with leupeptin, a proteinase inhibitor. Insulin afforded the most significant preservation of muscle protein and adipose-tissue mass, which were maintained close to control values even 10 days after transplantation. The effects of insulin on gastrocnemius muscle and liver protein content were exerted by slowing down protein turnover, mainly enhancing synthesis. Consistently, the total free amino acid concentration in the gastrocnemius of insulin-treated rats 10 days after tumour transplantation was close to that of controls. Although treatment with insulin decreased plasma corticosterone to normal values, it did not modify the circulating level of tumour necrosis factor. On the whole these data show that it seems possible to prevent, at least in part, the tissue waste that characterizes cancer cachexia by purely pharmacological means. PMID:8166661

  10. Extracardiac autologous pericardial tunnel Fontan allows implantation of an endocardial atrial lead for sinus node dysfunction.

    PubMed

    Newcombe, Jennifer; Gordon, Brent; Razzouk, Anees; Bailey, Leonard; Mandapati, Ravi

    2014-09-01

    Sinus node dysfunction is common after the Fontan procedure, and pacemaker implantation has been reported in 9.2% of Fontan patients. The two options for pacemaker implantation for sinus node dysfunction after the Fontan operation are epicardial lead placement, which allows for dual-chamber pacing, or transvenous atrial pacing. We report the first successful implantation of an endocardial atrial lead for sinus node dysfunction in a patient with an extracardiac lateral tunnel Fontan.

  11. Prostaglandin F receptor expression in intrauterine tissues of pregnant rats

    PubMed Central

    Kanca, Halit; Yar, Atiye Seda; Helvacioğlu, Fatma; Menevşe, Sevda; Çalgüner, Engin; Erdoğan, Deniz

    2014-01-01

    In this investigation, we studied the expression and localization of rat prostaglandin F (FP) receptor in uterine tissues of rats on gestational Days 10, 15, 18, 20, 21, 21.5 and postpartal Days 1 and 3 using Western blotting analysis, real-time PCR, and immunohistochemistry. A high level of immunoreactivity was observed on gestational Days 20, 21, and 21.5 with the most significant signals found on Day 20. FP receptor protein was expressed starting on gestational Day 15, and a fluctuating unsteady increase was observed until delivery. Uterine FP receptor mRNA levels were low between Days 10 and 18 of gestation (p < 0.05). The transcript level increased significantly on Day 20 and peaked on Day 21.5 just before labor (p < 0.05). There was a positive correlation between FP receptor mRNA expression and serum estradiol levels (rs = 0.78; p < 0.01) along with serum estradiol/progesterone ratios (rs = 0.79; p < 0.01). In summary, we observed an increase FP receptor expression in rat uterus with advancing gestation, a marked elevation of expression at term, and a concominant decrease during the postpartum period. These findings indicate a role for uterine FP receptors in the mediation of uterine contractility at term. PMID:24136214

  12. 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.

  13. Tissue decorporation of polonium-210 in rats by DMPA

    SciTech Connect

    Aposhian, H.V.; Dart, R.C.; Aposhian, M.M.; Dawson, B.V.

    1987-11-01

    Polonium-210 exposures, although rare, have occurred due to accidents in nuclear working environments. This alpha emitting radioactive element can bind thiols and thiol-containing proteins in vivo. Since thiol-containing chelating agents compete with many thiols for heavy metals, a number of these chelating agents have been investigated as protective agents against the lethal effects of /sup 210/Po and as tissue decorporating agents for it. Rats given /sup 210/Po (40 microCi/kg) ip had a median survival time (mst) of 39 days. The mst was increased to 106 days when N-(2,3-dimercaptopropyl)phthalamidic acid (DMPA), meso-dimercaptosuccinic acid (DMSA) or the Na salt of 2,3-dimercapto-1-propanesulfonic acid (DMPS) was administered sc (p less than .002). Decorporation studies were performed by giving rats /sup 210/Po (0.4 microCi) sc, followed by a series of thiol injections beginning one hour later. After 21 days, kidney levels of /sup 210/Po in rats given DMPA were only 28% of those of the untreated controls and significantly lower than those receiving DMSA, DMPS, N-acetyl-L-cysteine, or WR2721. After DMPA treatment, the /sup 210/Po levels of the spleen were 25% of the saline-treated control. DMPA appears to be a new and consistent decorporating agent for polonium-210.

  14. Tissue perfusion inhomogeneity during early tumor growth in rats.

    PubMed

    Endrich, B; Reinhold, H S; Gross, J F; Intaglietta, M

    1979-02-01

    Tissue perfusion in BA 1112 sarcomas of WAG inbred Rijswijk rats was determined from in vivo measurements of capillary density, length, and erythrocyte velocity in modified Algire chamber preparations. Studies were done with the use of television techniques in situ during a period of 26 days, both in control chambers and after implantation of a 0.1-mm3 piece of tumor tissue. Perfusion in control areas void of tumor tissue. Perfusion in control areas void of tumor was approximately 8-10 ml/minute/100 g of tissue. Flow in active tumor growth regions on the outward side of the tumor edge was through undifferentiated channels and had characteristics of flow through a porous medium. Despite enhanced arterial supply, the stabilized tumor microcirculation at the inward side of the growing tumor retained its perfusion rate constant (15-18 ml/min/100 g). Perfusion in central portions of the tumor was about 2-4 ml/minute/100 g during 12 days, whereas the tumor doubled in diameter. Our findings support the concept of temporal and functional blood flow inhomogeneity in the microcirculation of spreading tumors. PMID:283271

  15. 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.

  16. 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.

  17. 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.

  18. Elenoside, a new cytotoxic drug, with cardiac and extracardiac activity.

    PubMed

    Navarro, Eduardo; Alonso, Simeona Josefina; Trujillo, Juan; Jorge, Elena; Pérez, Cirilo; Hernández-Calzadilla, Carlos

    2002-08-01

    This paper deals with the effects of elenoside, (3-hidroxymethyl-1-methoxy-5,6-methylene-dioxy-4-(3,4-methylenedioxyphenyl)-2-naftoic acid lactone-beta-D-glucoside) an arylnaphthalene lignan with broad spectrum cytotoxicity in a human tumor cell line panel, isolated from Justicia hyssopifolia (Acanthaceae) grown in the Canary Islands (Spain), on isolated cardiac auricle of rabbits, urinary excretion of rats, and on isolated rat ileum. These effects, using a vehicle (propylene glycol-ethanol-plant oil-Tween 80 (40:10:50:2) as a standard, are presented. Elenoside at concentrations of 3.2x10(-4), 6.4 x 10(-4), and 1.2 x 10(-3) M produced an increase in the contraction force of auricles in a concentration-dependent way. At doses of 25 and 50 mg/kg, an antidiuretic effect and a decrease in sodium excretion were observed. Elenoside at concentrations of 3.2 x 10(-4), 6.4 x 10(-4) and 1.2 x 10(-3) M produced an increase in the contraction force of ileum in a concentration-dependent manner. Elenoside produced the concentration dependent inhibition of 86Rb uptake. These results indicate that elenoside has digitalis-like activity similar to mammalian lignans. Moreover, this lignan has an irritant effect on the gastrointestinal tract.

  19. Comparative analysis of tissue reactions to anesthetic solutions: histological analysis in subcutaneous tissue of rats.

    PubMed Central

    Ribeiro, Paulo Domingos; Sanches, Marcio Giampietro; Okamoto, Tetuo

    2003-01-01

    Postanesthetic pain is a relatively common complication after local anesthesia. This complication may be caused by the anesthetic technique or by the anesthetic solution used. Tissue reactions induced by the anesthetic solutions may be one of the factors resulting in pain after anesthesia. The objective of this study was to comparatively analyze tissue reactions induced by different anesthetic solutions in the subcutaneous tissue of rats. The following solutions were utilized: 2% lidocaine without vasoconstrictor; a 0.5% bupivacaine solution with 1:200,000 adrenaline; a 4% articaine solution and 2% mepivacaine, both with 1:100,000 adrenaline; and a 0.9% sodium chloride solution as a control. Sterilized absorbent paper cones packed inside polyethylene tubes were soaked in the solutions and implanted in the subcutaneous region. The sacrifice periods were 1, 2, 5, and 10 days after surgery. The specimens were prepared and stained with hematoxylin and eosin for histological analysis. The results showed that there is a difference in tissue irritability produced by the local anesthetic solutions. The results also showed that there is no relation between the concentration of the drug and the inflammatory intensity, that the mepivacaine and articaine solutions promoted less inflammatory reaction than the bupivacaine, and that the lidocaine solution produced the least intense inflammation. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 PMID:14959905

  20. Distribution of biglycan and decorin in rat dental tissue.

    PubMed

    Tenório, D M H; Santos, M F; Zorn, T M T

    2003-08-01

    Biglycan and decorin are small leucine-rich proteoglycans that play several biological and structural roles in different tissues and organs. Several reports have indicated that biglycan participates in odontoblast and ameloblast differentiation and in the calcification process. In the present study we show that the expression of biglycan changes from within the ameloblasts and odontoblasts to the extracellular space according to the stage of animal development. In predentin and in the pulp space, however, biglycan was continually expressed throughout the period of investigation. In contrast, decorin was absent in odontoblasts and in ameloblasts and was exclusively expressed in predentin throughout the period of observation. In young rats, however, decorin was expressed in the extracellular spaces of the pulp, where it was concentrated mainly in the peripheral pulp.

  1. 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.

  2. Giant Cardiac Lipoma: Refined Hypothesis Proposes Invagination from Extracardiac to Intracardiac Sites

    PubMed Central

    Rainer, W. Gerald; Bailey, David J.

    2016-01-01

    Cardiac lipomas are rare and usually present as benign, encapsulated masses outside the heart; however, they can also be found within the atria. No single theory—including molecular genetic mutation—adequately explains why this occurs. Extensive career experience and broadened knowledge in embryology and cardiac physiology have helped us to develop a hypothesis based on invagination of extracardiac tumors. This report describes a vexing case of a giant right atrial lipoma, from 1985, in which the diagnosis was made incidentally during management of a patient's acute limb ischemia. In addition, we discuss the imaging and treatment of cardiac lipoma. PMID:27777537

  3. 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.

  4. 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.

  5. Calcium and magnesium content in hard tissues of rats under condition of subchronic lead intoxication.

    PubMed

    Todorovic, Tatjana; Vujanovic, Dragana; Dozic, Ivan; Petkovic-Curcin, Aleksandra

    2008-03-01

    Lead manifests toxic effects in almost all organs and tissues, especially in: the nervous system, hematopoietic system, kidney and liver. This metal has a special affinity for deposition in hard tissue, i.e., bones and teeth. It is generally believed that the main mechanism of its toxicity relies on its interaction with bioelements, especially with Ca and Mg. This article analyses the influence of Pb poisoning on Ca and Mg content in hard tissues, (mandible, femur, teeth and skull) of female and young rats. Experiments were carried out on 60 female rats, AO breed, and on 80 of their young rats (offspring). Female rats were divided into three groups: the first one was a control group, the second one received 100 mg/kg Pb2+ kg b.wt. per day in drinking water, the third one received 30 mg/kg Pb(2+) kg b.wt. per day in drinking water. Young rats (offspring) were divided into the same respective three groups. Lead, calcium and magnesium content in hard tissues (mandible, femur, teeth-incisors and skull) was determined by flame atomic absorption spectrophotometry in mineralized samples. There was a statistically significant Pb deposition in all analyzed female and young rat hard tissues. Ca and Mg contents were significantly reduced in all female and young rat hard tissues. These results show that Pb poisoning causes a significant reduction in Ca and Mg content in animal hard tissues, which is probably the consequence of competitive antagonism between Pb and Ca and Mg.

  6. Analysis of Parathyroid Hormone and Its Fragments in Rat Tissues

    PubMed Central

    D'Amour, Pierre; Segre, Gino V.; Roth, Sanford I.; Potts, John T.

    1979-01-01

    After intravenous injection of [125I]-iodo-parathyroid hormone in the rat, uptake of the hormone was greatest in the liver and kidneys. Uptake was rapid, reaching a maximal concentration by 4 and 8 min, respectively. Extracts, prepared from both these organs at intervals soon after the injection of intact hormone, showed three main radioactive peaks when samples were subjected to gel filtration under protein-denaturing conditions. The first peak coeluted with intact hormone. The second eluted at a position corresponding to the carboxy-terminal fragments previously described in plasma, and the last eluted at the salt volume of the column. Microsequence analysis of the radioiodinated fragments, a method that has proved valuable for chemically defining the circulating fragments resulting from metabolism of injected hormone, showed that extracts of liver and kidney, prepared at 4 and 8 min after injection of the intact hormone, contained different fragments. The radioiodinated fragments in liver extracts were identical to those previously reported in the plasma of rats and dogs, fragments resulting principally from proteolysis between positions 33 and 34, and 36 and 37 of the intact hormone. Although the same fragments were also present in the kidneys, they constituted less than 15% of the amount present in the liver. More than 50% of the labeled renal fragments consisted of a peptide whose amino-terminal amino acid was position 39 of the intact hormone, a fragment not present in plasma. The rate of appearance of radioiodinated fragments that were chemically identical to those in plasma was more rapid in the liver than in plasma. Correlation of these chemical analyses with studies of the localization of 125I by autoradiography showed that at the times when the intact hormone and the carboxy-terminal fragments comprised nearly all of the 125I-labeled moieties in the tissues, the proximal convoluted tubules of the kidney and sinusoidal lining cells of the liver, which

  7. Effect of zinc-deficient diet on oral tissues and periodontal indices in rats.

    PubMed

    Seyedmajidi, Seyed Ali; Seyedmajidi, Maryam; Moghadamnia, Aliakbar; Khani, Zohreh; Zahedpasha, Samir; Jenabian, Niloofar; Jorsaraei, Gholamali; Halalkhor, Sohrab; Motallebnejad, Mina

    2014-01-01

    Zinc (Zn) as a nutritional factor affects the health of the oral tissues. This study was done for the evaluation of the effects of zinc deficiency on the oral tissues of rats. The study was carried out on 14 male Wistar rats, cessation of lactation on the 24(th) day after birth. The rats were randomly divided into two groups. Zinc deficient (ZD) diet was used for one group and another group was fed with a zinc-containing (ZC) diet. The alterations of the oral tissues in both groups were evaluated clinically after four weeks. Also the gingival index and periodontal pocket depth were recorded. The measurement of serum zinc level was done by atomic absorption spectrophotometry. The microscopic slides of oral tissue specimen were evaluated quantitatively. The serum zinc level of the ZD rats was lower than the ZC group (p< 0.001). According clinical findings, the gingival index was lower in ZC rat (p=0.001), but there was no significant difference regarding the periodontal pocket depth between two groups (p=0.07). Aphthous ulcer was observed in ZD rats on the floor of the mouth. There was no significant difference regarding the epithelial and keratin thickening between two groups. This study indicated that oral and periodontal health was better in ZC rats than in ZD rats. Aphthous lesions were more prominent in ZD rats. This study confirmed that zinc deficiency may endanger oral and periodo ntal structures.

  8. 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.

  9. Computational fluid dynamic simulations of cavopulmonary connections with an extracardiac lateral conduit.

    PubMed

    Migliavacca, F; de Leval, M R; Dubini, G; Pietrabissa, R; Fumero, R

    1999-04-01

    Complex congenital heart defects due to the absence of a ventricular chamber can often be treated by the Fontan surgical procedure. The objective of this work was to quantify the haemodynamics in the Fontan operation (cavopulmonary connection) with extracardiac lateral conduit. Four different models based on the finite element method were constructed with different lengths of inferior anastomosis (range 18-25 mm) and inclinations of the conduit (33 and 47.5 degrees). Mass conservation and Navier-Stokes equations were solved by means of the FIDAP code, based on the finite element method. The left-to-right pulmonary flow ratio and percentage inferior caval blood to the left lung were the highest with the smallest anastomosis and highest inclination: 1.35 and 83.26%, respectively. Dissipated power percentage was higher with the largest anastomosis than with the smallest (19.4 vs 15.8%). It was concluded that, when performing a total cavopulmonary connection, an extracardiac lateral conduit: (i) diverts more flow to the left lung, and (ii) shows higher energy losses when compared with a connection with intra-atrial tunnel. This study could be useful to evaluate the incidence of pulmonary arteriovenous malformations.

  10. [Treatment strategy for patients with extracardiac structural anomalies and congenital heart disease].

    PubMed

    Murakami, Arata

    2011-07-01

    The surgical treatment of patients with extracardiac structural anomalies and congenital heart disease often carries major risk and remains a challenging field. An appropriate, solid treatment plan should be developed during the early phase with interactive intelligence sharing between a pediatric surgery team and congenital heart surgery team. As the top of the chain of command, the role of a neonatologist is important. This article reviews the history of surgery for congenital heart disease and the progress of the Japan Congenital Cardiovascular Surgery Database. Finally, as an example of a combination of diseases, the clinical course and intelligence sharing during treatment of a patient with biliary atresia requiring living-donor liver transplantation and hypoplastic left heart syndrome is reported. The National Quality Forum provided structural measures, process measures, and outcome measures for congenital heart surgery. Structural measures provided by the National Quality Forum included participation in a preoperative multidisciplinary conference. To improve the outcome of surgical treatment of patients with congenital heart disease and extracardiac structural anomalies, the importance of a preoperative multidisciplinary conference involving not only pediatric surgeons, pediatric cardiologists, and pediatric cardiac surgeons but also neonatologists, anesthesiologists, and nurses cannot be overemphasized.

  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. Decomposition of α-Tocopheryl Glycosides in Rat Tissues

    PubMed Central

    Knaś, Małgorzata; Wałejko, Piotr; Maj, Jadwiga; Hryniewicka, Agnieszka; Witkowski, Stanisław; Borzym-Kluczyk, Małgorzata; Dudzik, Danuta; Zwierz, Krzysztof

    2008-01-01

    Background The aim of our investigation was to estimate the stability of α-tocopheryl O-glycosides in relation to activity of exoglycosidases in selected rat tissues. Material and Methods Acetylated glycosides were obtained in glucosidation of α-tocopherol using the Helferich method. The activity of exoglycosidases was determined by the Zwierz et al. method. Protein concentrations were determined by the biuret method. The concentration of released α-tocopherol was determined with the HPLC method. Results The comparison of the amount of released α-tocopherol with the amount of released p-nitrophenol shows that glycoside bound in 2a–5a derivatives of α-tocopherol undergoes hydrolysis significantly harder than in appropriate 2b–5b p-nitrophenyl derivatives. Conclusion The results indicate that tocopheryl O-glycosides are more resistant to enzymatic hydrolysis than appropriate p-nitrophenol O-glycosides 2a–5a. Among examined tocopheryl O-glycosides, galactoside 4 is the only compound that caused the significant increase in tocopherol concentration, as compared to its endogenic content. PMID:19696909

  13. 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

  14. 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

  15. Transplantation of adipose tissue protects BB/OK rats from type 1 diabetes development.

    PubMed

    Bahr, Jeanette; Klöting, Nora; Klöting, Ingrid; Follak, Niels

    2011-05-01

    B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to search for possibilities to avoid the loss of adipose tissue. BB/OK rats were subcutaneously grafted with visceral adipose tissue. In total, 34 (71%) out of 48 male and 23 (49%) out of 47 female BB/OK rats grafted with adipose tissue developed type 1 diabetes so that significantly more females than males were protected from diabetes development (p=0.03). In the control group, 17 (85%) out of 20 male and 20 (95%) out of 21 female BB/OK rats were diabetic. Adipose tissue transplantation can protect BB/OK rats from type 1 diabetes development in a sex specific manner. One could conclude that the manipulations have influenced fat accumulation and/or fat metabolism which prevent type 1 diabetes development in about 50% of BB/OK rats. This idea is supported by the finding that a mutation in the leptin receptor of NOD mice suppresses type 1 diabetes progression.

  16. 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.

  17. Contribution of mitochondria and peroxisomes to palmitate oxidation in rat and bovine tissues.

    PubMed

    Piot, C; Veerkamp, J H; Bauchart, D; Hocquette, J F

    1998-10-01

    Total and peroxisomal palmitate oxidation capacities and mitochondrial enzyme activities were compared in tissues from growing rats, preruminant calves and 15-month-old bulls. Total palmitate oxidation rates were 1.9-5.2-fold higher in rat than in bovine tissues and 1.7-fold higher in the heart and muscles from calves than from growing bulls. The peroxisomal contribution to palmitate oxidation was similar between rats and bovines (i.e. calves and bulls) in liver (35-51%), heart (26%) but not in muscles (14 +/- 3% in rats vs 33 +/- 4.5% in bovines, P < 0.05). Mitochondrial enzyme activities were 1.8-4.8-fold higher in rat than in bovine tissues but the citrate synthase to cytochrome-c oxidase ratio was the highest in the liver (17-38), intermediate in the heart and muscles from calves and rats (6-10) and the lowest in heart and muscles from bulls (2-3, P < 0.05). In all tissues and animal groups, palmitate oxidation rates were similar per unit cytochrome-c oxidase activity, but not always per unit citrate synthase activity. Therefore, differences in mitochondrial contents (as between rats and bovines) or in mitochondrial characteristics (as between liver and muscles) relate to the differences in palmitate oxidation capacity.

  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. 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.

  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 /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.

  1. 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. PMID:27652835

  2. 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.

  3. 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.

  4. 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.

  5. Influence of trichlorfon and fractionated irradiation on hydroproteolytic activity of pancreas and intestinal tissues of rats.

    PubMed

    Koćmierska-Grodzka, D

    1976-03-01

    Investigations into the hydroproteolytic activity of pancreas and intestinal tissues (small intestine and colon) of rats after fractionated irradiation (5 X 150 R) were carried out. There was found marked postirradiation enhancement of lipase activity in pancreas and duodenal part of intestine and increase of B-glucuronidase and acid phosphatase activity in nearly all parts of the examined intestinal tissues. Fractionated irradiation resulted in an increase of pancreatic catheptic (proteolytic) activity causing simultaneous decrease of proteolytic activity in intestine and colon. Preventive administration of Trichlorfon (ten days before irradiation) in the dose of 10 mg or 30 mg/kg evoked modification of hydroproteolytic activity in intestinal tissues of healthy and irradiated rats. Trichlorfon applied in the dose of 30 mg/kg exerted antilipolytic and anticatheptic effects in pancreas and intestinal tissues of irradiated rats. PMID:1258099

  6. [Concentration of prostaglandins and cyclic adenosine-3',5'-monophosphate in the tissues of rats].

    PubMed

    Komissarenko, V P; Slavnov, V N; Epsheĭn, E V; Malinkovich, V D

    1977-04-01

    The content of prostaglandines (PG) and cyclic 3',5'-adenosine monphosphate (cAMP) was investigated in rat tissues by the radioisotopic method of competitive binding. Maximum quantities of both PG and cAMP were revealed in the same most actively functioning organs: the brain, incretory glands, small intestine. Fatty tissue showed minimum quantities of these substances. Results indicate a close functional relationship between the PG synthesis and adenylatecyclase activity in the body tissues.

  7. Tissue response to implanted ceramic-coated titanium alloys in rats.

    PubMed

    Satomi, K; Akagawa, Y; Nikai, H; Tsuru, H

    1988-07-01

    In order to assess the tissue compatibility of the hybrid materials for the dental implant (hydroxyapatite, titanium oxide and titanium nitride coated titanium alloys), tissue response to these materials implanted in the rat subcutaneous tissue was histologically examined. Initial inflammatory response was less evident in titanium oxide coated and non-coated titanium alloys. All materials were encapsulated by thin fibrous connective tissues. The membrane thickness of hydroxyapatite coated titanium alloy was significantly higher than that of titanium nitride coated one. These results suggest that all materials possess favourable tissue compatibility and may encourage clinical use as the dental implant.

  8. Tissue bioavailability of anthocyanins from whole tart cherry in healthy rats.

    PubMed

    Kirakosyan, Ara; Seymour, E Mitchell; Wolforth, Janet; McNish, Robert; Kaufman, Peter B; Bolling, Steven F

    2015-03-15

    Our aim was to confirm and identify the presence of tart cherry anthocyanins in several target tissues of healthy rats. Liquid chromatography-mass spectrometry analysis was employed for detection and characterisation of anthocyanin metabolites. It was shown that four native anthocyanins, namely cyanidin 3-glucosylrutinoside, cyanidin 3-rutinoside, cyanidin 3-rutinoside 5-β-D-glucoside, and peonidin 3-rutinoside were differentially distributed among targeted tissues of rats. Bladder and kidney contained more total anthocyanins than all other tissues analysed. It was also revealed that the bioavailability pattern of these native anthocyanins among tissues is varied. The highest concentration of individual anthocyanin cyanidin 3-glucosylrutinoside (2339 picograms/gram of tissue) was detected in bladder, followed by cyanidin 3-rutinoside 5-β-d-glucoside (916 picograms/gram) in the liver of rats. Although the diverse distribution of tart cherry anthocyanins in different rat tissues still requires further explanation, it may provide an evidentiary link between tissue bioavailability and health-enhancing properties of anthocyanins at target sites. PMID:25308638

  9. 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.

  10. Arsenic increased lipid peroxidation in rat tissues by a mechanism independent of glutathione levels.

    PubMed Central

    Ramos, O; Carrizales, L; Yáñez, L; Mejía, J; Batres, L; Ortíz, D; Díaz-Barriga, F

    1995-01-01

    The role of lipid peroxidation in the mechanism of arsenic toxicity was investigated in female rats pretreated with N-acetylcysteine (NAC, a glutathione [GSH] inducer) or with buthionine sulfoximine (BSO, a GSH depletor). Rats were challenged with sodium arsenite, and sacrificed 1 hr after this treatment. Results showed that arsenic decreased GSH levels and increased lipid peroxidation in liver, kidney, and heart, with a larger effect at 18.2 mg/kg than at 14.8 mg/kg for lipid peroxidation induction. In the liver of rats treated with arsenic, pretreatment with NAC increased the levels of GSH and decreased lipid peroxidation. In kidney and heart, NAC pretreatment protected the tissues against arsenic-induced depletion of GSH levels, but the same degree of protection was not found for lipid peroxidation induction. In its turn, BSO had an additive effect with arsenic in lowering the levels of GSH in the liver and kidney, but an inverse correlation between GSH levels and lipid peroxidation was found only in liver. Arsenic content in tissues of rats pretreated with NAC was lower than in rats treated only with arsenic. In rats with depleted levels of GSH (BSO-pretreated rats), a shift in arsenic tissue distribution was found, with higher levels in skin and lower levels in kidney. A clear tendency for a positive correlation between arsenic concentration and lipid peroxidation levels was found in liver, kidney, and heart. PMID:7621808

  11. In vitro pulsatile flow visualization on extracardiac conduits for the right ventricular outflow tract reconstruction: qualitative considerations.

    PubMed

    Yuan, S M; Chang, Q; Guo, Y R; Guo, J Q

    1998-05-01

    Valved homograft conduits play an important role in the right ventricular outflow tract (RVOT) reconstruction for the surgical treatment of complex congenital heart disease. An excellent immediate rather than long-term outcome could be obtained. The hemodynamics for late failure, however, remained unclear. In vitro pulsatile flow visualization was not conducted before. A simplified right heart duplicator system was set up and driven under physiologic conditions. Polystyrene of 0.18 mm in diameter was applied as the tracing particle. Flow characteristics of models of normal pulmonary circulation as well as pulmonary artery atresia with the RVOT reconstructed utilizing valved and non-valved extracardiac conduits were observed. Flow patterns in the normal pulmonary circulatory model were mainly of axial flow associated with small scope of flow disturbances. A single vortex in the right ventricle was noted in diastole. In the pulmonary artery atresia model, a couple of vortexes were found in the right ventricle, a secondary flow in the main pulmonary artery, and a stronger secondary flow than in the normal pulmonary circulatory model in the two branches in both systole and diastole. A secondary flow was found in the proximal, an axial flow was observed in the distal portion of the extracardiac conduit with normal bioprosthetic valves and a secondary flow was observed in the entire conduit with stenotic bioprosthetic valves. The secondary flow intensity became stronger with the development of the stenosis. Severe insufficiency occurred in the bileaflet ceramic tilting-disc prosthesis during the entire cardiac circle, i.e., the prosthesis was in a maximum open position. Severe reverse flow could be found in the extracardiac conduit in the deceleration phase. Concavity of the crank shaft was found by examination to be filled with tracing particles and the prosthesis became stuck. Model of RVOT reconstruction with non-valved conduit yielded reverse flow inside the

  12. Down-regulation of Zac1 gene expression in rat white adipose tissue by androgens.

    PubMed

    Mirowska, Agnieszka; Sledzinski, Tomasz; Smolenski, Ryszard T; Swierczynski, Julian

    2014-03-01

    ZAC1 is a zinc-finger protein transcription factor, a transcriptional cofactor for nuclear receptors, and a co-activator of nuclear receptors, which interacts with multiple signaling pathways affecting apoptosis, cell cycle arrest, and metabolism. Some data suggest that ZAC1 regulates the expression of genes associated with function of adipose tissue. Since there is no information about the levels of Zac1 gene expression in white adipose tissue (WAT), and the expression of several genes associated with metabolic function of WAT is significantly lower in male than female animals, we have examined: (a) the relative ZAC1 mRNA levels in some organs/tissues, including three main depots of WAT, in 3-month-old male rats; (b) the relative ZAC1 mRNA levels in WAT of male and female rats; (c) the effect of orchidectomy and orchidectomy with concomitant testosterone treatment on ZAC1 mRNA and protein levels; (d) the effect of ovariectomy and ovariectomy with concomitant 17β-estradiol treatment on ZAC1 mRNA levels; (e) the effect of dihydrotestosterone on ZAC1 mRNA levels in isolated adipocytes. Our results indicate that: (a) ZAC1 mRNA levels are relatively high in WAT in comparison with other organs/tissues; (b) ZAC1 mRNA levels in subcutaneous WAT are approximately 2-fold lower than in epididymal and retroperitoneal adipose tissue; (c) ZAC1 mRNA levels in WAT of adult female rats are approximately 2-fold higher than in male rats; (d) testosterone is inversely related to ZAC1 mRNA and protein levels in WAT of male rats; and (e) dihydrotestosterone decreases the ZAC1 mRNA levels in adipocytes in dose dependent manner. In conclusion, Zac1 gene is highly expressed in white adipose tissue of adult rats. Androgens could play an important role in down-regulation of the ZAC1 mRNA and protein levels in rats.

  13. Decreased receptivity of pathway connective tissue to sympathetic nerve ingrowth in the developing rat.

    PubMed

    Hiebert, J M; Fan, Q; Smith, P G

    1997-05-20

    Sympathetic axons can form atypical pathways to denervated orbital targets in neonatal rats but not in rats aged 30 or more days. The objective of this study was to determine if connective tissue pathways that carry sympathetic nerves lose their ability to sustain axonal sprouting during the early postnatal period. Regions of periorbital sheath known to contain large numbers of sympathetic axons that travel to distal orbital targets were excised from rats (sympathectomized 3 days previously) on postnatal days 6-7, 14-15, 30-31, and 48-49 and placed in anterior chambers of adult host rats. Tissues were removed 3, 6, or 10 days post-transplant and sympathetic ingrowth was analyzed by catecholamine histofluorescence in whole-mount or cryosectioned specimens. Connective tissue transplants from 6-15-day-old donors showed significant fiber ingrowth by 3 days in oculo, and innervation was maximal by 6 days. In contrast, sprouting into 30-49-day-old tissue was significantly slower, with most transplants lacking fibers at 3 days, and with small numbers of short fibers present at 6 days. We conclude that maturational changes occur in periorbital connective tissue pathways in the early postnatal period which make them less receptive to ingrowth by sympathetic nerves. The findings that connective tissue pathways are better substrates for sympathetic sprouting in the neonatal rat supports the view that developmental changes in these tissues are likely to contribute to the impaired reinnervation of orbital targets by contralateral neurons in juvenile and adult rats. PMID:9174244

  14. Mechanical characterization of the rat and mice skin tissues using histostructural and uniaxial data

    PubMed Central

    Karimi, Alireza; Rahmati, Seyyed Mohammadali; Navidbakhsh, Mahdi

    2015-01-01

    The skin tissue has been shown to behave like a nonlinear anisotropic material. This study was aimed to employ a constitutive fiber family equation to characterize the nonlinear anisotropic mechanical behavior of the rat and mice skin tissues in different anatomical locations, including the abdomen and back, using histostructural and uniaxial data. The rat and mice skin tissues were excised from the animals’ body and then the histological analyses were performed on each skin type to determine the mean fiber orientation angle. Afterward, the preconditioned skin tissues were subjected to a series of quasi-static axial and circumferential loads until the incidence of failure. The crucial role of fiber orientation was explicitly added into a proposed strain energy density function. The material coefficients were determined using the constrained nonlinear optimization method based on the axial and circumferential extension data of the rat and mice samples at different anatomical locations. The material coefficients of the skins were given with R2 ≥ 0.998. The results revealed a significant load-bearing capacity and stiffness of the rat abdomen compared to the rat back tissues. In addition, the mice abdomen showed a higher stiffness in the axial direction in comparison with circumferential one, while the mice back displayed its highest stiffness in the circumferential direction. The material coefficients of the rat and mice skin tissues were determined and well compared to the experimental data. The optimized fiber angles were also compared to the experimental histological data, and in all cases less than 11.85% differences were observed in both the skin tissues. PMID:25837446

  15. Adequate evaluation of HSL mass and activity in rat adipose tissue in fasting and aging-related obesity.

    PubMed

    Tsujita, Takahiro; Sumiyoshi, Maho; Morimoto, Chie; Kameda, Kenji; Okuda, Hiromichi

    2002-04-01

    Adipose tissue is a unique tissue because its mass is readily changed by altering nutritional conditions. Therefore the activity and content of enzyme in the adipose tissue is significantly differed according to the way of their presentation: per g tissue, per whole tissue, or per cell number. In the present study, the effects of the ways of expressing the hormone sensitive lipase (HSL) activity and content were studied in rat by decreasing or increasing adipose tissue. Fasting caused a progressive decline in body weight and in the weight of the epididymal fat pad. When the HSL content was expressed per g of adipose tissue, the lipase activity and immunoreactive HSL protein content in fasting rats were higher than those in fed rats. On the other hand, when they were expressed as per fat pad, the lipase activity and immunoreactive HSL protein in fasting rats were lower than those in fed rats. The opposite results were observed in obesity. When the HSL content was expressed per g of adipose tissue, the lipase activity and immunoreactive HSL protein in obese rats were lower than in control rats. However, when the HSL content was expressed per fat pad, the lipase activity and immunoreactive HSL protein in the obese rats were higher than in the control rats. Therefore we must pay careful attention to the way of presentation of adipose tissue enzyme contents.

  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.

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

    PubMed

    Sjöqvist, Sebastian; Jungebluth, Philipp; Lim, Mei Ling; Haag, Johannes C; Gustafsson, Ylva; Lemon, Greg; Baiguera, Silvia; Burguillos, Miguel Angel; 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

    2014-04-15

    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.

  1. Radioimmunoassay of carbonic anhydrase III in rat tissues.

    PubMed Central

    Shiels, A; Jeffery, S; Wilson, C; Carter, N

    1984-01-01

    A specific and sensitive radioimmunoassay for the rat carbonic anhydrase III isoenzyme was developed. High concentrations of carbonic anhydrase III were detected in soleus muscle and male liver. Female liver and other skeletal muscles contained significantly lower concentrations, and only trace amounts were found in heart, prostate, kidney, brain, plasma, urine and, possibly, erythrocytes. PMID:6424658

  2. 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

  3. Proinsulin C-peptide inhibits lipolysis in diabetic rat adipose tissue through phosphodiestrase-3B enzyme.

    PubMed

    Ghorbani, A; Omrani, G R; Hadjzadeh, M A; Varedi, M

    2013-03-01

    We have previously reported that C-peptide modulates insulin-mediated inhibition of lipolysis and glucose consumption but has no significant effects per se on adipose tissue of normal rats. It has been repeatedly observed that certain actions of C-peptide are restricted to the diabetic states. In the present study, therefore, we examined whether C-peptide alters lipolysis in adipose tissue of diabetic rats. Rats were rendered diabetic by streptozotocin and divided into 2 groups; insulin treated and untreated. Retroperitoneal adipose tissue was excised aseptically, subjected to organ culture and incubated with rat C-peptide, insulin, or a combination of both peptides in the presence or absence of isoproterenol. Tissue lipolysis was assessed by the rate of glycerol release into the culture media. The cultures were pretreated with cilostamide, a phosphodiesterase-3B enzyme inhibitor, when the role of this enzyme was to be examined. C-Peptide on its own, like insulin, significantly inhibited isoproterenol-stimulated lipolysis in the adipose tissue of untreated diabetic rats. The effect was enhanced by a combination of C-peptide and insulin. Notably, the C-peptide's effect was totally blocked in the presence of cilostamide. In the adipose tissue of insulin treated rats, however, C-peptide failed to show any significant antilipolytic effects. These data show that C-peptide has the potential to act, conditionally, as an antilipolytic hormone by activating phosphodiesterase-3B and suggest that the action may contribute to the C-peptide's beneficial effects on diabetes-induced complications. PMID:22990990

  4. 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

  5. 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.

  6. Structural changes in femoral bone tissue of rats after subchronic peroral exposure to selenium

    PubMed Central

    2013-01-01

    Background The role of selenium (Se) on bone microarchitecture is still poorly understood. The present study aims to investigate the macroscopic and microscopic structures of femoral bone tissue in adult male rats after subchronic peroral administration of Se. Methods Twenty one-month-old male Wistar rats were randomly divided into two experimental groups. In the first group (Se group) young males were exposed to 5 mg Na2SeO3/L in drinking water, for 90 days. Ten one-month-old males without Se administration served as a control group. At the end of the experiment, macroscopic and microscopic structures of the femurs were analysed using analytical scales, sliding instrument, and polarized light microscopy. Results The body weight, femoral length and cortical bone thickness were significantly decreased in Se group rats. These rats also displayed different microstructure in the middle part of the femur, both in medial and lateral views, where vascular canals expanded into the central area of the bone while, in control rats, these canals occurred only near the endosteal surfaces. Additionally, a smaller number of primary and secondary osteons was identified in Se group rats. Histomorphometric analyses revealed significant increases for area, perimeter, maximum and minimum diameters of primary osteons’ vascular canals but significant reductions for all measured variables of Haversian canals and secondary osteons. Conclusions Se negatively affected the macroscopic and microscopic structures of femoral bone tissue in adult male rats. The results contribute to the knowledge on damaging impact of Se on bone. PMID:23369508

  7. 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

  8. Fetal and neonatal mortality in patients with isolated congenital heart diseases and heart conditions associated with extracardiac abnormalities.

    PubMed

    Marantz, Pablo; Sáenz Tejeira, M Mercedes; Peña, Gabriela; Segovia, Alejandra; Fustiñana, Carlos

    2013-10-01

    Congenital malformations are a known cause of intrauterine death; of them, congenital heart diseases (CHDs) are accountable for the highest fetal and neonatal mortality rates. They are strongly associated with other extracardiac malformations and an early fetal mortality. Two hundred and twenty fves cases of CHDs are presented. Of them, 155 were isolated CHDs (group A) and 70 were associated with extracardiac malformations, chromosomal disorders, or genetic syndromes (group B). The overall mortality in group B was higher than that observed in group A (p <0.01). Prenatal mortality was similar in both groups: A: 8.4% (13 out of 155); B: 15.7% (11 out of 70). Postnatal mortality was A: 16.8% (26 out of 155) (p <0.01), OR: 0.52 (95% CI: 0.16-1.7); B: 32.9% (23 out of 70) (p <0.01), OR: 0.41 (95% CI: 0.20-0.83). Heart diseases associated with extracardiac abnormalities had a higher mortality rate than isolated congenital heart diseases in the period up to 60 weeks of postmenstrual age (140 days post-term). No differences were observed between both groups of patients in terms of prenatal mortality.

  9. l-Arginine metabolism in cardiovascular and renal tissue from hyper- and hypothyroid rats

    PubMed Central

    Moliz, Juan N; Quesada, Andrés; Montoro-Molina, Sebastian; Vargas-Tendero, Pablo; Osuna, Antonio; Wangensteen, Rosemary; Vargas, Félix

    2015-01-01

    This study assessed the effects of thyroid hormones on the enzymes involved in l-arginine metabolism and the metabolites generated by the different metabolic pathways. Compounds of l-arginine metabolism were measured in the kidney, heart, aorta, and liver of euthyroid, hyperthyroid, and hypothyroid rats after 6 weeks of treatment. Enzymes studied were NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]), arginases I and II, ornithine decarboxylase (ODC), ornithine aminotransferase (OAT), and l-arginine decarboxylase (ADC). Metabolites studied were l-arginine, l-citrulline, spermidine, spermine, and l-proline. Kidney heart and aorta levels of eNOS and iNOS were augmented and reduced (P < 0.05, for each tissue and enzyme) in hyper- and hypothyroid rats, respectively. Arginase I abundance in aorta, heart, and kidney was increased (P < 0.05, for each tissue) in hyperthyroid rats and was decreased in kidney and aorta of hypothyroid rats (P < 0.05, for each tissue). Arginase II was augmented in aorta and kidney (P < 0.05, for each tissue) of hyperthyroid rats and remained unchanged in all organs of hypothyroid rats. The substrate for these enzymes, l-arginine, was reduced (P < 0.05, for all tissues) in hyperthyroid rats. Levels of ODC and spermidine, its product, were increased and decreased (P < 0.05) in hyper- and hypothyroid rats, respectively, in all organs studied. OAT and proline levels were positively modulated by thyroid hormones in liver but not in the other tissues. ADC protein levels were positively modulated by thyroid hormones in all tissues. According to these findings, thyroid hormone treatment positively modulates different l-arginine metabolic pathways. The changes recorded in the abundance of eNOS, arginases I and II, and ADC protein in renal and cardiovascular tissues may play a role in the hemodynamic and renal manifestations observed in thyroid disorders. Furthermore, the changes in ODC and spermidine might

  10. Tissue levels of (3(-14)C) coumarin in the rat: distribution and excretion.

    PubMed Central

    Piller, N. B.

    1977-01-01

    The benzo-pyrones (including coumarin) are a very effective therapy for mild thermal oedema and cases of acute and chronic lymphoedema. In this preliminary report the distribution of a single injected dose of coumarin was followed in normal tissues of rats for 100 hours. Comparisons are to be made later with drug levels in thermally injured and lymphoedematous tissues. The resluts show 7-4% of the injected dose to remain in the tissues after 100 h. During this time 30-9% was excreted in the faeces and approximately 47% excreted in the urine. At any given time most of the dose was present in the gut, muscular tissues, skin and liver. For the gut tissues this was 33%, for the muscular tissues 28%, for the skin 18% and for the liver 16%. The highest concentrations per gram of tissue were however in the kidney and liver, representing the two organs of metabolism and excretion of the coumarin. PMID:836764

  11. 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

  12. Biodegradation of a carbamate pesticide, Propoxur, in rat tissues.

    PubMed

    Kumar, R; Madhavi, N B; Sharma, C B

    1993-01-01

    Propoxur (Baygon, 2-isopropoxyphenyl N-methylcarbamate) is a carbamate pesticide commonly used against house insects. When the insecticide was administered intramuscularly in rats it was converted to a new metabolite which was found to be present in the serum, liver, kidney and brain 6 h after the administration of the pesticide. The metabolite was purified by high performance liquid to chromatography and comparison of the infrared spectra of Propoxur and the metabolite showed that a deamination reaction was responsible for the formation of the metabolite from the parent pesticide. The pesticide also induced haematological changes such as an increased level of total bilubrin, amylase and glutamic-oxalacetic transaminase and decrease of cholinesterase activity, indicating damage of the liver and nervous system in rats.

  13. The cardiodepressant and vasodepressant effects of tumour necrosis factor in rat isolated atrial and aortic tissues.

    PubMed Central

    Foulkes, R.; Shaw, S.

    1992-01-01

    1. The ability of recombinant human tumour necrosis factor-alpha (rec huTNF) to elicit cardiodepressor and vasodepressor effects in rat isolated tissues was investigated. 2. rec huTNF (3 x 10(-11)-3 x 10(-8) M) administered directly to the organ bath, caused a concentration-dependent relaxation of the isoprenaline-induced inotropic response in electrically stimulated rat left atria. This occurred within 20 min of administration. In contrast, rec huTNF was without effect on the chronotropic response to isoprenaline in isolated spontaneously beating atria. 3. rec huTNF (1 microgram kg-1) was also given systemically to rats and the atria studied in vitro. Only 60 min of rec huTNF pretreatment was sufficient to cause a marked attenuation of the isoprenaline-induced inotropic response. This effect was not further augmented when rats were pretreated with rec huTNF for 24 h. 4. In isolated aortic rings taken from rats 60 min after rec huTNF (1 microgram kg-1, i.v.) administration, there was no effect seen on the constriction induced by phenylephrine in either endothelium-intact or denuded tissues. In addition, any responses to L-arginine or NG-nitro-L-arginine methyl ester (L-NAME) administration were unaffected by rec huTNF pretreatment. 5. In aortic rings taken from rats 24 h after rec huTNF administration, the phenylephrine-induced constriction was significantly attenuated in tissues with an intact endothelium. Furthermore, the relaxation to subsequent L-arginine administration was greater in these tissues than in those saline-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1382789

  14. Metabolic disposition of ivermectin in tissues of cattle, sheep, and rats

    SciTech Connect

    Chiu, S.H.; Sestokas, E.; Taub, R.; Buhs, R.P.; Green, M.; Sestokas, R.; Vandenheuvel, W.J.; Arison, B.H.; Jacob, T.A.

    1986-09-01

    The metabolic disposition of ivermectin, a new antiparasitic drug, has been studied in cattle, sheep, and also in rats dosed with the drug labeled with tritium in the C-22,23 positions. In the edible tissues of these animals, the unaltered drug was the major tissue residue component and was quantitated by HPLC-reverse isotope dilution assay. The depletion half-lives of the drug ranged between 1 and 6 days, similar to those of the total tissue residue in these species. Most metabolites present in the liver tissues were more polar than the parent drug. Based on spectral (NMR, mass spectrometric) analysis and chromatographic comparison with authentic compounds prepared by in vitro rat or steer microsomal incubations, three of these metabolites have been isolated and identified as the hydroxylation derivatives of ivermectin, i.e. 24-hydroxymethyl-H/sub 2/B1a, its monosaccharide, and 24-hydroxymethyl-H/sub 2/B1b.

  15. 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

  16. 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.

  17. Altered expression of mitofusin 2 in penile tissues of diabetic rats.

    PubMed

    Yang, J; Wang, T; Zhang, Y; Li, R; Wang, S; Xu, H; Liu, J; Ye, Z

    2014-06-01

    Diabetic erectile dysfunction (ED) is a common complication in diabetes mellitus, and the efficacy of first-line therapies is not satisfactory. Recent studies revealed that corporal apoptosis was responsible for the nonresponsiveness of severe ED to phosphodiesterase type 5 inhibitors. Mitofusin 2 (Mfn2) is a versatile protein, regulating mitochondrial morphology and playing an important role in apoptosis. Several studies showed that expression of Mfn2 was decreased in STZ-induced diabetic rats' kidney, myocardium and retina, which was associated with diabetic nephropathy, cardiomyopathy and retinopathy respectively. In this study, our aim was to explore the expression of Mfn2 and apoptosis in diabetic rats' penes. We found that erectile function (ICP/MAP) elicited by electrical stimulation of cavernous nerve was markedly impaired in diabetic rats compared with the normal rats. The mRNA and protein levels of Mfn2 were found to be significantly reduced in diabetic rats' penile tissues. Compared with normal rats, the content of smooth muscle and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were dramatically decreased, and penile apoptotic index and expression of activated-caspase-3 were dramatically increased in diabetic rats. This data indicated that repression of Mfn2 in diabetic rats' penes might be associated with excessive apoptosis in diabetes-induced severe ED.

  18. Altered expression of mitofusin 2 in penile tissues of diabetic rats.

    PubMed

    Yang, J; Wang, T; Zhang, Y; Li, R; Wang, S; Xu, H; Liu, J; Ye, Z

    2014-06-01

    Diabetic erectile dysfunction (ED) is a common complication in diabetes mellitus, and the efficacy of first-line therapies is not satisfactory. Recent studies revealed that corporal apoptosis was responsible for the nonresponsiveness of severe ED to phosphodiesterase type 5 inhibitors. Mitofusin 2 (Mfn2) is a versatile protein, regulating mitochondrial morphology and playing an important role in apoptosis. Several studies showed that expression of Mfn2 was decreased in STZ-induced diabetic rats' kidney, myocardium and retina, which was associated with diabetic nephropathy, cardiomyopathy and retinopathy respectively. In this study, our aim was to explore the expression of Mfn2 and apoptosis in diabetic rats' penes. We found that erectile function (ICP/MAP) elicited by electrical stimulation of cavernous nerve was markedly impaired in diabetic rats compared with the normal rats. The mRNA and protein levels of Mfn2 were found to be significantly reduced in diabetic rats' penile tissues. Compared with normal rats, the content of smooth muscle and B-cell lymphoma 2 (Bcl-2)/Bcl-2-associated X protein (Bax) ratio were dramatically decreased, and penile apoptotic index and expression of activated-caspase-3 were dramatically increased in diabetic rats. This data indicated that repression of Mfn2 in diabetic rats' penes might be associated with excessive apoptosis in diabetes-induced severe ED. PMID:23682852

  19. 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.

  20. Distribution of 3H-nicotine in rat tissues under the influence of simulated microgravity.

    PubMed

    Chowdhury, P; Soulsby, M E; Pasley, J N

    1999-06-01

    Rat tail suspension offers a useful model to reproduce physiologic responses to weightlessness. The present study was conducted in the head-down-tilt (HDT) rat model to assess changes in metabolism of body tissues employing 3H-nicotine. Twelve male rats were used in the study. Half of the rats were tail suspended at 30 degrees for two weeks on a 12/12 light/dark cycle. During this period, body weight, food and fluid intakes were measured. At term, animals were anesthetized and injected i.v. with a solution containing 4 microcuries of nicotine. After 90 min the animals were sacrificed, exsanguinated and tissues (brain, blood, trachea, salivary gland, lung, heart, esophagus, spleen, kidneys and testes) were harvested. The distribution of 3H-nicotine per gram of each tissue was determined and calculated as percent of total injected radioactivity. Final body weights of suspended animals were significantly (P < 0.05) lower than those of controls (309 +/- 21 vs 350 +/- 11 g). 3H-Nicotine was retained in greatest amounts by the kidneys, followed in order by salivary glands, spleen, and gastrointestinal tissues. Compared to non-suspended control, the tissue retention of nicotine in suspended animals was decreased in the following tissues: esophagus (25%), aorta (25%), fundus (25%), trachea (22%), adrenals (18%), spleen (17%), and pancreas (12%). The decreased retention of nicotine in tissues from suspended animals may be indicative of the fluid shifts and changes in blood flow to those tissue beds. The lack of differences in nicotine retention in liver and kidney between control and suspended groups may implicate a normal metabolic function of these organs even under simulated weightlessness.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. Hypertension induces tissue-specific gene suppression of a fatty acid binding protein in rat aorta.

    PubMed Central

    Sarzani, R; Claffey, K P; Chobanian, A V; Brecher, P

    1988-01-01

    The effect of hypertension on the expression of a fatty acid binding protein localized in the rat aorta was studied. The presence of rat heart fatty acid binding protein (hFABP) was documented in aortic tissue by using a cDNA probe and polyclonal antibodies. Hypertension was induced in groups of rats by implantation of deoxycorticosterone acetate in conjunction with 1% salt in the drinking water (deoxycorticosterone/salt). By the third week of this treatment a marked reduction (by a factor of 20) in the expression of hFABP mRNA in aorta was found, concomitant with a reduction in immunologically detectable protein, suggesting transcriptional regulation. This effect was tissue specific, since no change in the normal amounts of hFABP mRNA in heart, skeletal muscle, or kidney was found. This reduction in aortic hFABP mRNA was also found in mildly hypertensive uninephrectomized rats given salt but no deoxycorticosterone and in normotensive rats given deoxycorticosterone but no excess salt intake. A marked decrease in aortic hFABP mRNA also was observed in the Goldblatt two kidney-one clip hypertensive model, and administration of angiotensin II for 6 days by osmotic minipump also caused a reduction. These findings suggest that hFABP is under complex regulation in aortic tissue and is suppressed by arterial hypertension. Images PMID:3174661

  6. The Role of Routine Whole Volume SPECT Reconstruction in Comparison to Cine Raw Data in the Detection of Extracardiac Uptake on Myocardial Perfusion Scans.

    PubMed

    Maharaj, M; Korowlay, N A

    2011-01-01

    The objective of this study was to determine the role of routine whole volume reconstructed single-photon emission tomography (rSPECT) compared to cine raw data to detect extracardiac uptake of Sestamibi (MIBI). In a retrospective study, the myocardial perfusion studies of 426 patients were inspected separately for extracardiac uptake on cine raw data and rSPECT. The acquisition parameters for all the images were done according to departmental protocol. The whole volume SPECT data was selected and processed by HOSEM iterative reconstruction using the HERMES computer software system. The images were assessed by two observers, a student in training and a senior consultant nuclear medicine physician. The overall mean age and standard deviation of the 426 patients at the time of the study was 60 ± 12 years. Statistical analysis was performed using the Kappa and McNemars tests. The clinical significance of the extracardiac uptake was evaluated using hospital folders and /or laboratory results after viewing images. rSPECT detected 25 patients (5.9%) and cine raw data identified 18 patients (4.2%) with extracardiac uptake. All the areas of extracardiac uptake noted on cine raw data were seen on the rSPECT images. Only 21 of the 25 patients had complete 5-year clinical follow-up. The value of the clinical significance of the extracardiac uptake was limited due to the study being retrospective. The proportion of positives identified by rSPECT was significantly larger than those identified by cine raw data (P = 0.0082). Although our study demonstrates that rSPECT is more sensitive than cine raw data in detecting extracardiac uptake, it also shows that there is no benefit in routine whole volume rSPECT in daily clinical practice.

  7. The effect of Mentha spicata Labiatae on uterine tissue in rats.

    PubMed

    Güney, Mehmet; Oral, Baha; Karahanli, Nermin; Mungan, Tamer; Akdogan, Mehmet

    2006-09-01

    The plant Mentha spicata, or peppermint, is commonly used in the treatment of loss of appetite, common cold, bronchitis, sinusitis, fever, nausea and vomiting, and indigestion as a herbal agent. In this study, we aimed to investigate the biochemical and histological effects of M. spicata Labiatae, growing on the Anamas high plateau of Yenisarbademli town, on rat uterine tissue. Twenty female Wistar albino rats weighing 160+/-10 g were used for this study. Rats were divided into two groups of ten animals: group I received no herbal tea (control group) and group II received 20 g/L M. spicata tea. Control group rats were given commercial drinking water (Hayat DANONESA water). Herbal tea was prepared daily and provided at all times to the rats over 30 days as drinking water. Plasma malondialdehyde (MDA) levels were determined. In addition, uterine tissues were submitted for histopathologic examination. MDA levels were increased in group II when compared with the control group. The difference between group II and the control group was statistically significant (P<0.01). In the M. spicata Labiatae-treated group, histopathological changes like apoptosis and diffuse eosinophil leucocyte infiltration in surface and stromal glandular epithelium were observed in both endometrium and endocervix. It was concluded that lipid peroxidation and uterine damage occurs after M. spicata administration in rat uterus. Despite the beneficial effects of M. spicata Labiatae in indigestion, we should also be aware of the toxic effects when it is not used in the recommended fashion, at the recommended dose.

  8. Effect of adipose tissue-derived stem cell injection in a rat model of urethral fibrosis

    PubMed Central

    Sangkum, Premsant; Yafi, Faysal A.; Kim, Hogyoung; Bouljihad, Mostafa; Ranjan, Manish; Datta, Amrita; Mandava, Sree Harsha; Sikka, Suresh C; Abdel-Mageed, Asim B.; Hellstrom, Wayne J.G.

    2016-01-01

    Introduction: We sought to evaluate the therapeutic effect of adi-pose tissue-derived stem cells (ADSCs) in a rat model of urethral fibrosis. Methods: Eighteen (18) male Sprague-Dawley rats (300‒350 g) were divided into three groups: (1) sham (saline injection); (2) urethral fibrosis group (10 μg transforming growth factor beta 1 (TGF-β1) injection); and (3) ADSCs group (10 μg TGF-β1 injection plus 2 × 105 ADSCs). Rat ADSCs were harvested from rat inguinal fat pads. All study animals were euthanized at two weeks after urethral injection. Following euthanasia, rat urethral tissue was harvested for histologic evaluation. Type I and III collagen levels were quantitated by Western blot analysis. Results: TGF-β1 injection induced significant urethral fibrosis and increased collagen type I and III expression (p<0.05). Significant decrease in submucosal fibrosis and collagen type I and III expression were noted in the ADSCs group compared with the urethral fibrosis group (p<0.05). TGF-β1 induced fibrotic changes were ameliorated by injection of ADSCs. Conclusions: Local injection of ADSCs in a rat model of urethral fibrosis significantly decreased collagen type I and III. These findings suggest that ADSC injection may prevent scar formation and potentially serve as an adjunct treatment to increase the success rate of primary treatment for urethral stricture disease. Further animal and clinical studies are needed to confirm these results.

  9. 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

  10. 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.

  11. 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.

  12. Effect of dietary manganese on tissue antioxidants in STZ diabetic rats

    SciTech Connect

    Thompson, K.H.; Lee, M. )

    1991-03-15

    The objective of this experiment was to investigate the effect of Mn deficiency on tissue antioxidant levels under conditions of STZ (streptozotocin)-induced diabetes. Weanling, male Sprague-Dawley rats were assigned randomly to 1 of 6 groups: (1) Mn+ (manganese-sufficient), nondiabetic; (2) Mn{minus} (manganese-deficient), nondiabetic; (3) Mn+, diabetic for 4 weeks; (4) Mn{minus}, diabetic for 4 weeks; (5) Mn+, diabetic for 8 weeks; and (6) Mn{minus}, diabetic for 8 weeks. Decreased Mn levels in all tissues of Mn{minus} rats were accompanied by decreased MnSOD activity in kidney and heart, but not in liver or pancreas. Hepatic vitamin E was progressively increased in 4 and 8-week diabetic rats. Overall, diabetogenic effects of STZ were not amplified by manganese deficiency.

  13. 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

  14. Plasma kinetics, tissue distribution, and cerebrocortical sources of reverse triiodothyronine in the rat

    SciTech Connect

    Obregon, M.J.; Larsen, P.R.; Silva, J.E.

    1985-06-01

    Studies in vitro have shown that rT3 is a potent and competitive inhibitor of T4 5'-deiodination (5'D). Recent studies in vivo have shown that cerebrocortical (Cx) T4 5'D-type II (5'D-II) activity (propylthiouracil (PTU) insensitive pathway), is reduced by T4 and rT3, the latter being more potent than T3 in Cx 5'D-II suppression. Some other reports had described rT3 production in rat brain as a very active pathway of thyroid hormone metabolism. To examine the possibility that rT3 plays a physiological role in regulating Cx 5'D-II, we have explored rT3 plasma kinetics, plasma to tissue exchange, and uptake by tissues in the rat, as well as the metabolic routes of degradation and the sources of rT3 in cerebral cortex (Cx). Plasma and tissue levels were assessed with tracer (/sup 125/I)rT3. Two main compartments were defined by plasma disappearance curves in euthyroid rats (K/sub 1/ = -6.2 h-1 and K/sub 2/ = -0.75 h-1). In Cx of euthyroid rats, (/sup 125/I)rT3 peaked 10 min after iv injection, tissue to plasma ratio being 0.016 +/- 0.004 (SE). In thyroidectomized rats, plasma and tissue (/sup 125/I)rT3 concentrations were higher than in euthyroid rats, except for the Cx that did not change. PTU caused further increases in all the tissues studied, except for the Cx and the pituitaries of thyroidectomized rats. From the effect of blocking 5'D-I with PTU or reducing its activity by making the animals hypothyroid, we concluded that 5'D-I accounts for most of the rT3 clearance from plasma. In contrast, in Cx and pituitary the levels of rT3 seem largely affected by 5'D-II activity. Since the latter results suggest that plasma rT3 does not play a major role in determining rT3 levels in these tissues, we explored the sources of rT3 in Cx using (/sup 125/I)T4. The (/sup 125/I)rT3 (T4) to (/sup 125/I)T4 ratio remained constant at 0.03 from 1 up to 5 h after injection of (/sup 125/I)T4.

  15. A study of the sulphur amino acids of rat tissues

    PubMed Central

    Gaull, Gerald E.; Gaitonde, M. K.

    1967-01-01

    1. In a study of the metabolism of l-[35S]methionine in vivo, the labelled sulphur compounds of rat liver and brain were separated first by ion-exchange chromatography into two fractions containing (i) free sulphur amino acids such as methionine, cystathionine, cyst(e)ine and homocyst(e)ine and (ii) glutathione. 2. Two-dimensional paper chromatography with butan-1-ol–acetic acid or propionic acid–water in the first direction and 80% acetone or acetone–ethyl methyl ketone–water in the second direction was found superior to other solvent systems for separating the sulphur amino acids. 3. At 10min. after injection of [35S]methionine only a small part of the 35S was found combined in free methionine or other free sulphur amino acids. 4. Evidence was obtained of the presence of adenosyl[35S]methionine and adenosyl[35S]homocysteine in perchloric acid extracts of rat liver and brain. 5. The trans-sulphuration pathway was active in brain as well as in liver. PMID:6030290

  16. Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress Induced Hypercholesterolemic Rats

    PubMed Central

    Deori, Meetali; Devi, Dipali; Kumari, Sima; Hazarika, Ankita; Kalita, Himadri; Sarma, Rahul; Devi, Rajlakshmi

    2016-01-01

    This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH) was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC) excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies.

  17. Antioxidant Effect of Sericin in Brain and Peripheral Tissues of Oxidative Stress Induced Hypercholesterolemic Rats

    PubMed Central

    Deori, Meetali; Devi, Dipali; Kumari, Sima; Hazarika, Ankita; Kalita, Himadri; Sarma, Rahul; Devi, Rajlakshmi

    2016-01-01

    This study evaluated the antioxidant effect of crude sericin extract (CSE) from Antheraea assamensis in high cholesterol fed rats. Investigation was conducted by administering graded oral dose of 0.25 and 0.5 gm/kg body weight (b.w.)/day of CSE for a period of 28 days. Experiments were conducted in 30 rats and were divided into five groups: normal control, high cholesterol fed (HCF), HCF + 0.065 gm/kg b.w./day fenofibrate (FF), HCF + sericin 0.25 gm/kg b.w./day (LSD), and HCF + sericin 0.5 gm/kg b.w./day (HSD). In brain, heart, liver, serum, and kidney homogenates nitric oxide (NO), thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC), superoxide dismutase, reduced glutathione (GSH) was measured. LSD treatment prevented the alterations in GSH and PCC levels in hypercholesterolemic (HyC) brain tissue homogenates of rats. CSE lowers the serum total cholesterol level in HyC rats by promoting fecal cholesterol (FC) excretion. CSE increases FC level by promoting inhibition of cholesterol absorption in intestine. The endogenous antioxidant reduced significantly and the oxidative stress marker TBARS level increases significantly in the peripheral tissue of HCF rats. However, the administration of LSD and HSD exhibited a good antioxidant activity by reducing the TBARS level and increasing the endogenous antioxidant in peripheral tissue. In addition, a histological examination revealed loss of normal liver and kidney architecture in cholesterol fed rats which were retained in sericin treated groups. The findings of this study suggested that CSE improves hypercholesterolemia in rats fed a HyC diet. Clinical relevance of this effect of CSE seems worthy of further studies. PMID:27695419

  18. Changes in diffuse reflectance intensity and autofluorescence for brain tissue in rats during loss of tissue viability

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Shima, Katsuji; Kikuchi, Makoto

    2006-02-01

    To investigate the correlation between light scattering and tissue viability of brains, we performed measurements of multiwavelength diffuse reflectance and autofluorescence for brains during loss of tissue viability. As a model temporally losing tissue viability of brain, a perfused brain in a rat was used. Diffuse reflectance at 620 nm, which is an isosbestic point of cytochrome oxidase (cyt. ox.), showed that a triphasic, drastic change in light scattering occurred 220 - 300 s after starting perfusion. After this event, light scattering stayed at a higher level than that before this event. We observed a different behavior between the reflectance at 620 nm and that at 605 nm, showing that the tissue absorption at 605 nm was increasing. This is attributable to the reduction of heme a+a 3 in cyt. ox., which preceded the triphasic change in light scattering. An important difference was also found between the reflectance at 620 nm and that at 800 nm, indicating that the absorption decrease at 800 nm presumably due to the reduction of copper A in cyt. ox. coincided with the triphasic change in light scattering; the reduction of copper A in cyt. ox. indicates the decrease in ATP production. Change in fluorescence of NADH did not correlate either with change in light scattering or with the reduction of cytochrome oxidase. These findings suggest that light scattering is useful as an indicator of brain tissue viability.

  19. 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.

  20. Lack of differences in blood and tissue concentrations of endogenous ethanol in conventional and germfree rats.

    PubMed

    Jones, A W; Ostrovsky YuM; Wallin, A; Midtvedt, T

    1984-01-01

    Headspace gas chromatography was used to determine the concentrations of endogenous ethanol in blood and tissue of conventional and germfree rats. In all biological specimens analysed, the four principal volatile endogenous substances were identified as methanol, acetaldehyde, ethanol and acetone. No statistically significant differences in the concentrations of endogenous ethanol were noted between conventional and germfree animals. In whole blood, liver, kidney, and brain of germfree rats the concentrations of endogenous ethanol were 4.2 +/- 0.19 microM, 5.1 +/- 0.55 microM, 8.2 +/- 0.59 microM and 4.4 +/- 0.17 microM (means +/- SE), respectively. The higher concentration in kidney was also observed in conventional rats. Our results suggest that ethanol is a normal metabolic intermediate in rats and does not exclusively arise from microbial fermentation reactions in the gastrointestinal tract.

  1. 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.

  2. 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.

  3. 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.

  4. [The effect of the amino acid combinations on cell proliferation in tissue cultures in old rats].

    PubMed

    Chalisova, N I; Kontsevaia, E A; Zhekalov, A N; Siniachkin, D A

    2012-01-01

    In organotypic tissue culture, the effect of the 20 coded amino acids combinations, in the effective concentration of 0.05 ng/ml, on the cell proliferation development in the spleen, myocardium, pancreas and brain cortex explants in 24 months rats was investigated. The combinations of two amino acids (stimulating and inhibiting proliferation) produced in the tissue culture the stimulating effect, exceeding by 8-10% as compared to the isolating effect of the stimulating amino acid. The results obtained form the base for the further synthesis of new effective dipeptides to be used to increase the regeneration of tissues when aging. PMID:23130534

  5. Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

    PubMed

    Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

    2010-06-01

    Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage. PMID:20047045

  6. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

    PubMed

    Wolvekamp, M C; Cleary, M L; Cox, S L; Shaw, J M; Jenkin, G; Trounson, A O

    2001-01-31

    The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for

  7. Follicular development in cryopreserved Common Wombat ovarian tissue xenografted to Nude rats.

    PubMed

    Wolvekamp, M C; Cleary, M L; Cox, S L; Shaw, J M; Jenkin, G; Trounson, A O

    2001-01-31

    The Northern Hairy-nosed Wombat (Lasiorhinus krefftii) is a highly endangered marsupial species and every possible option for sustaining the species needs to be explored. One important approach may be the development of assisted reproductive technologies in the non-endangered Common Wombat (Vombatus ursinus) and Southern Hairy-nosed Wombat (Lasiorhinus latifrons) for application in breeding the Northern Hairy-nosed Wombat. In this study, it was examined whether cryopreserved Wombat ovarian tissue would develop following xenografting to immunologically deficient rats. Ovarian tissue was collected from Common Wombats (n = 3) and cryopreserved as small cortical pieces. After thawing the cortical pieces were grafted underneath the kidney capsule of Nude rats (n = 16). The grafts were recovered at 2, 4, and 10 weeks after transplantation and their gross and histological appearance investigated. Two weeks after grafting (n = 2), the tissue was revascularized and healthy primordial follicles were present. At week 4 (n = 2), some follicular development was present. At week 10, six rats received human chorionic gonadotrophin (hCG) to trigger follicle and oocyte maturation while another six rats were not given any treatment. The administration of hCG did not induce preovulatory follicles and oocyte maturation although type 5 follicles were present in ovarian tissue collected 10 weeks posttransplantation in both treated and untreated groups. This study demonstrates for the first time that Wombat ovarian tissue can survive and function when grafted into immunocompromized rats and that Wombat ovarian follicles can be recruited to growth and development in an ovarian xenograft. This model system has the potential to produce mature oocytes from endangered species for use in assisted reproductive technologies such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and mature oocytes from non-endangered species for nuclear transfer which may be necessary for

  8. 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.

  9. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity.

    PubMed

    Sharifi, Ali M; Darabi, Radbod; Akbarloo, Nasrin

    2003-10-24

    Tribulus terrestris is a natural herb used for treating many diseases including hypertension. According to previous reports, aqueous extract of tribulus fruits may have some antihypertensive effect with an unknown mechanism. The present study investigated the antihypertensive mechanism of tribulus in 2K1C hypertensive rats by measurement of circulatory and local ACE activity in aorta, heart, kidney and lung. Four groups of rats were selected; control, sham, operated or hypertensive and tribulus treated hypertensive group. Hypertension was induced using silver clip on renal artery by surgery. Four weeks after surgery, a single daily dose of 10 mg/kg of lyophilized aqueous extract of tribulus fruit were given orally to 2K1C rats for four weeks. ACE activity was determined by high performance liquid chromatography (HPLC). Blood pressure was measured by the tail-cuff method. The systolic blood pressure (SBP) was significantly increased in 2K1C rats compared to control rats. The SBP of tribulus fed hypertensive rats was significantly decreased compared to hypertensive rats. The ACE activity in all tissues of 2K1C rats including: aorta, heart, kidney, lung as well as serum were significantly increased compared to normal rats. The ACE activity in all tissues of tribulus fed hypertensive rats was significantly lower than that of hypertensive rats, which was more pronounced in kidney. These results indicated that there is a negative correlation between consumption of tribulus and ACE activity in serum and different tissues in 2K1C rats.

  10. Novel Bioceramic Urethral Bulking Agents Elicit Improved Host Tissue Responses in a Rat Model.

    PubMed

    Mann-Gow, Travis K; King, Benjamin J; El-Ghannam, Ahmed; Knabe-Ducheyne, Christine; Kida, Masatoshi; Dall, Ole M; Krhut, Jan; Zvara, Peter

    2016-01-01

    Objectives. To test the physical properties and host response to the bioceramic particles, silica-calcium phosphate (SCPC10) and Cristobalite, in a rat animal model and compare their biocompatibility to the current clinically utilized urethral bulking materials. Material and Methods. The novel bulking materials, SCPC10 and Cristobalite, were suspended in hyaluronic acid sodium salt and injected into the mid urethra of a rat. Additional animals were injected with bulking materials currently in clinical use. Physiological response was assessed using voiding trials, and host tissue response was evaluated using hard tissue histology and immunohistochemical analysis. Distant organs were evaluated for the presence of particles or their components. Results. Histological analysis of the urethral tissue five months after injection showed that both SCPC10 and Cristobalite induced a more robust fibroblastic and histiocytic reaction, promoting integration and encapsulation of the particle aggregates, leading to a larger bulking effect. Concentrations of Ca, Na, Si, and P ions in the experimental groups were comparable to control animals. Conclusions. This side-by-side examination of urethral bulking agents using a rat animal model and hard tissue histology techniques compared two newly developed bioactive ceramic particles to three of the currently used bulking agents. The local host tissue response and bulking effects of bioceramic particles were superior while also possessing a comparable safety profile.

  11. Study of tanshinone IIA tissue distribution in rat by liquid chromatography-tandem mass spectrometry method.

    PubMed

    Bi, Hui-chang; Law, Francis C P; Zhong, Guo-ping; Xu, Chen-shu; Pan, Ying; Ding, Liang; Chen, Xiao; Zhao, Li-zi; Xu, Qiong; Huang, Min

    2007-05-01

    A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated for determining tanshinone IIA in rat tissues. After a single step liquid-liquid extraction with diethyl ether, tanshinone IIA and loratadine (internal standard) was subjected to LC/MS/MS analysis using positive electro-spray ionization under selected reaction monitoring mode. Chromatographic separation of tanshinone IIA and loratadine was achieved on a Hypersil BDS C(18) column (i.d. 2.1 x 50 mm, 5 microm) with a mobile phase consisting of methanol-1% formic acid (90:10, v/v) at a flow rate of 300 microL/min. The intra-day and inter-day precision of the method were less than 10.2 and 12.4%, respectively. The intra-day and inter-day accuracies ranged from 99.7 to 109.7%. The lowest limit of quantification for tanshinone IIA was 1 ng/mL. The method was applied to a tanshinone IIA tissue distribution study after an oral dose of 60 mg/kg to rats. Tanshinone IIA tissue concentrations decreased in the order of stomach > small intestine > lung > liver > fat > muscle > kidneys > spleen > heart > plasma > brain > testes. Tanshinone IIA still could be detected in most of the tissues at 20 h post-dosing. These results indicate that the LC/MS/MS method was rapid and sensitive to quantify tanshinone IIA in different rat tissues. PMID:17357178

  12. Novel Bioceramic Urethral Bulking Agents Elicit Improved Host Tissue Responses in a Rat Model.

    PubMed

    Mann-Gow, Travis K; King, Benjamin J; El-Ghannam, Ahmed; Knabe-Ducheyne, Christine; Kida, Masatoshi; Dall, Ole M; Krhut, Jan; Zvara, Peter

    2016-01-01

    Objectives. To test the physical properties and host response to the bioceramic particles, silica-calcium phosphate (SCPC10) and Cristobalite, in a rat animal model and compare their biocompatibility to the current clinically utilized urethral bulking materials. Material and Methods. The novel bulking materials, SCPC10 and Cristobalite, were suspended in hyaluronic acid sodium salt and injected into the mid urethra of a rat. Additional animals were injected with bulking materials currently in clinical use. Physiological response was assessed using voiding trials, and host tissue response was evaluated using hard tissue histology and immunohistochemical analysis. Distant organs were evaluated for the presence of particles or their components. Results. Histological analysis of the urethral tissue five months after injection showed that both SCPC10 and Cristobalite induced a more robust fibroblastic and histiocytic reaction, promoting integration and encapsulation of the particle aggregates, leading to a larger bulking effect. Concentrations of Ca, Na, Si, and P ions in the experimental groups were comparable to control animals. Conclusions. This side-by-side examination of urethral bulking agents using a rat animal model and hard tissue histology techniques compared two newly developed bioactive ceramic particles to three of the currently used bulking agents. The local host tissue response and bulking effects of bioceramic particles were superior while also possessing a comparable safety profile. PMID:27688751

  13. Novel Bioceramic Urethral Bulking Agents Elicit Improved Host Tissue Responses in a Rat Model

    PubMed Central

    Mann-Gow, Travis K.; King, Benjamin J.; El-Ghannam, Ahmed; Knabe-Ducheyne, Christine; Kida, Masatoshi; Dall, Ole M.; Krhut, Jan

    2016-01-01

    Objectives. To test the physical properties and host response to the bioceramic particles, silica-calcium phosphate (SCPC10) and Cristobalite, in a rat animal model and compare their biocompatibility to the current clinically utilized urethral bulking materials. Material and Methods. The novel bulking materials, SCPC10 and Cristobalite, were suspended in hyaluronic acid sodium salt and injected into the mid urethra of a rat. Additional animals were injected with bulking materials currently in clinical use. Physiological response was assessed using voiding trials, and host tissue response was evaluated using hard tissue histology and immunohistochemical analysis. Distant organs were evaluated for the presence of particles or their components. Results. Histological analysis of the urethral tissue five months after injection showed that both SCPC10 and Cristobalite induced a more robust fibroblastic and histiocytic reaction, promoting integration and encapsulation of the particle aggregates, leading to a larger bulking effect. Concentrations of Ca, Na, Si, and P ions in the experimental groups were comparable to control animals. Conclusions. This side-by-side examination of urethral bulking agents using a rat animal model and hard tissue histology techniques compared two newly developed bioactive ceramic particles to three of the currently used bulking agents. The local host tissue response and bulking effects of bioceramic particles were superior while also possessing a comparable safety profile. PMID:27688751

  14. Novel Bioceramic Urethral Bulking Agents Elicit Improved Host Tissue Responses in a Rat Model

    PubMed Central

    Mann-Gow, Travis K.; King, Benjamin J.; El-Ghannam, Ahmed; Knabe-Ducheyne, Christine; Kida, Masatoshi; Dall, Ole M.; Krhut, Jan

    2016-01-01

    Objectives. To test the physical properties and host response to the bioceramic particles, silica-calcium phosphate (SCPC10) and Cristobalite, in a rat animal model and compare their biocompatibility to the current clinically utilized urethral bulking materials. Material and Methods. The novel bulking materials, SCPC10 and Cristobalite, were suspended in hyaluronic acid sodium salt and injected into the mid urethra of a rat. Additional animals were injected with bulking materials currently in clinical use. Physiological response was assessed using voiding trials, and host tissue response was evaluated using hard tissue histology and immunohistochemical analysis. Distant organs were evaluated for the presence of particles or their components. Results. Histological analysis of the urethral tissue five months after injection showed that both SCPC10 and Cristobalite induced a more robust fibroblastic and histiocytic reaction, promoting integration and encapsulation of the particle aggregates, leading to a larger bulking effect. Concentrations of Ca, Na, Si, and P ions in the experimental groups were comparable to control animals. Conclusions. This side-by-side examination of urethral bulking agents using a rat animal model and hard tissue histology techniques compared two newly developed bioactive ceramic particles to three of the currently used bulking agents. The local host tissue response and bulking effects of bioceramic particles were superior while also possessing a comparable safety profile.

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Glycerolipid biosynthesis in rat adipose tissue. Influence of adipose-cell size and site of adipose tissue on triacylglycerol formation in lean and obese rats.

    PubMed

    Jamdar, S C

    1978-01-15

    The rates of lipid formation were compared in different fat-depots from lean and obese rats by using [14C]glycerol 3-phosphate, [14C]glucose or [14C]acetate as substrates. In lean animals, subcutaneous adipose tissue showed significantly lower rates of lipid synthesis than did perirenal and gonadal fat-tissue. In obese animals, the rates of lipid synthesis were significantly higher and did not vary from one fat-depot to another. Differences in the rates of lipid formation between lean and obese rats disappeared during dietary restriction of obese animals. The isolated adipocyte preparation did not reflect the true metabolic activity of the adipose organ, since this preparation was mainly derived from smaller adipocytes that were metabolically less active than larger adipocytes. The present study suggests that it is better to use whole tissue preparations to measure lipogenesis and esterification reactions, because these measurements represent the contribution of both larger and smaller adipocytes towards lipid formation.

  20. Immunolocalization of nitric oxide synthase isoforms in human archival and rat tissues, and cultured cells.

    PubMed

    Martins, Antonio R; Zanella, Cesar A B; Zucchi, Fabiola C R; Dombroski, Thaís C D; Costa, Edmar T; Guethe, Liliane M; Oliveira, Alina O; Donatti, Ana L F; Neder, Luciano; Chimelli, Leila; De Nucci, Gilberto; Lee-Ho, Paulo; Murad, Ferid

    2011-05-15

    Nitric oxide (NO) exerts important physiological and pathological roles in humans. The study of NO requires the immunolocalization of its synthesizing enzymes, neuronal, endothelial and inducible NO synthases (NOS). NOS are labile to formalin-fixation and paraffin-embedding, which are used to prepare human archival tissues. This lability has made NOS immunohistochemical studies difficult, and a detailed protocol is not yet available. We describe here a protocol for the immunolocalization of NOS isoforms in human archival cerebellum and non-nervous tissues, and in rat tissues and cultured cells. Neuronal NOS antigenicity in human archival and rat nervous tissue sections was microwave-retrieved in 50 mM Tris-HCl buffer, pH 9.5, for 20 min at 900 W. Neuronal NOS was expressed in stellate, basket, Purkinje and granule cells in human and rat cerebellum. Archival and frozen human cerebellar sections showed the same neuronal NOS staining pattern. Archival cerebellar sections not subjected to antigen retrieval stained weakly. Antigenicity of inducible NOS in human lung was best retrieved in 10 mM sodium citrate buffer, pH 6.0, for 15 min at 900 W. Inflammatory cells in a human lung tuberculoma were strongly stained by anti-inducible NOS antibody. Anti-endothelial NOS strongly stained kidney glomeruli. Cultured PC12 cells were strongly stained by anti-neuronal NOS without antigen retrieving. The present immunohistochemistry protocol is easy to perform, timeless, and suitable for the localization of NOS isoforms in nervous and non-nervous tissues, in human archival and rat tissues. It has been extensively used in our laboratory, and is also appropriate for other antigens.

  1. Effect of decellularized tissue powders on a rat model of acute myocardial infarction.

    PubMed

    Tabuchi, Masaki; Negishi, Jun; Yamashita, Akitatsu; Higami, Tetsuya; Kishida, Akio; Funamoto, Seiichi

    2015-11-01

    Many research groups are currently investigating new treatment modalities for myocardial infarction. Numerous aspects need to be considered for the clinical application of these therapies, such as low cell integration and engraftment rates of cell injection techniques. Decellularized tissues are considered good materials for promoting regeneration of traumatic tissues. The properties of the decellularized tissues are sustained after processing to powder form. In this study, we examined the use of decellularized tissue powder in a rat model of acute myocardial infarction. The decellularized tissue powders, especially liver powder, promoted cell integration and neovascularization both in vitro and in vivo. Decellularized liver powder induced neovascularization in the infarct area, resulting in the suppression of myocardial necrosis. The results of this study suggest that decellularized liver powder has good potential for application as a blood supply material for the treatment of myocardial infarction.

  2. 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.

  3. Characterization of acute renal allograft rejection by proteomic analysis of renal tissue in rat.

    PubMed

    Chen, Gang; Huang, Jing-Bin; Mi, Jie; He, Yun-Feng; Wu, Xiao-Hou; Luo, Chun-Li; Liang, Si-Min; Li, Jia-Bing; Tang, Ya-Xiong; Li, Jie

    2012-02-01

    Rapid and reliable biomarkers of renal allograft rejection have not been available. This study aimed to investigate biomarkers in renal allograft tissue using proteomic analysis. Orthotopic kidney transplantations were performed using Fisher (F344) or Lewis rats as donors and Lewis rats as recipients. Syngenic control group (Group I) constituted F344-to-F344 orthotopic kidney allo-transplantations (n = 8); and allogenic group (Group II) consisted of F344-to-Lewis orthotopic kidney allo-transplantations (n = 8). Renal tissues were harvested 7 days after transplantation. Samples were analyzed using 2-D electrophoresis and matrix assisted laser desorption ionization-time of flight mass spectrometry. 6 differentially expressed proteins were identified between allogenic group and syngenic control group. A rat model of acute renal allograft rejection was successfully set up. Differentially expressed proteins in renal allograft tissue of rat were detected using proteomic analysis and might serve as novel diagnostic and therapeutic targets in human. Quantitative proteomics, using MALDL-TOF-MS methodology has the potential to provide a profiling and a deeper understanding of acute renal rejection.

  4. 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

  5. 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

  6. 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.

  7. 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

  8. Resveratrol attenuates visfatin and vaspin genes expression in adipose tissue of rats with type 2 diabetes

    PubMed Central

    Asadi, Soheila; Goodarzi, Mohammad Taghi; Saidijam, Massoud; Karimi, Jamshid; Azari, Reza Yadgar; Farimani, Azam Rezaei; Salehi, Iraj

    2015-01-01

    Objective(s): Visfatin and vaspin are secreted by adipose tissue and play key roles in glucose homeostasis and subsequently are potential targets for diabetes treatment. Resveratrol (RVS) corrects insulin secretion and improves insulin sensitivity. We investigated the RVS effects on serum antioxidants, insulin and glucose levels, also visfatin and vaspin genes expression in adipose tissue of streptozotocin-nicotinamide (STZ-NA) induced type 2 diabetic rats. Materials and Methods: Diabetes was induced in Wistar rats (n=32) using STZ (60 mg/kg body weight) and NA (120 mg/kg body weight); rats were divided into 4 groups (n=8). Eight untreated normal rats were used as control group; four diabetic rat groups (2–5) were treated with 0, 1, 5 and 10 mg/kg body weight of RVS, respectively for 30 days. After treatment blood and adipose tissue were prepared from all animals. Serum glucose, insulin, HOMA index, total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured. Visfatin and vaspin genes expression in adipose tissue were evaluated using real-time PCR. Results: RVS reduced blood glucose significantly and increased insulin level, resulting in insulin sensitivity improvement. Furthermore RVS increased weight and TAC, while reducing serum MDA in the diabetic groups. Visfatin gene expression increased in the diabetic group, and RVS treatment reduced it. Vaspin gene expression was reduced in RVS receiving diabetic groups. Conclusion: The results indicated that RVS has potential hypoglycemic effect, probably by increasing insulin level and changing gene expression of visfatin and vaspin. Moreover RVS showed antioxidant effects through reduction in peroxidiation products and augmented antioxidant capacity. PMID:26221476

  9. 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

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

    PubMed

    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

    2013-02-01

    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.

  11. Schisandrin B protects against solar irradiation-induced oxidative stress in rat skin tissue.

    PubMed

    Lam, Philip Y; Yan, Chung Wai; Chiu, Po Yee; Leung, Hoi Yan; Ko, Kam Ming

    2011-04-01

    Schisandrin B (Sch B) and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate, protected rat skin tissue against solar irradiation-induced oxidative injury, as evidenced by a reversal of solar irradiation-induced changes in cellular reduced glutathione and α-tocopherol levels, as well as antioxidant enzyme activities and malondialdehyde production. The cytochrome P-450-mediated metabolism of Sch B or Sch C caused ROS production in rat skin microsomes. Taken together, Sch B or Sch C, by virtue of its pro-oxidant action and the subsequent eliciting of a glutathione antioxidant response, may prevent photo-aging of skin.

  12. A quantitative bioassay to measure the rate of respiration of isolated rat tooth pulp tissue.

    PubMed

    Levine, L S; Marcus, F; de Kooker, M

    1987-01-01

    The formation of carbon dioxide, expressed as milligrammes of carbon dioxide per gramme wet weight, was used to determine the rate of succinate-induced respiration in rat incisal dental pulp, after incubation in a phosphate buffer. Seven experimental parameters: (a) physical nature of the tissue; (b) mass of the rat; (c) pre-incubation time; (d) incubation time; (e) substrate concentration; (f) effect of pH; and (g) effects of technique on pH, were analysed; pH was a critical determinant for success with this assay.

  13. Expression of retinoic acid nuclear receptors and tissue transglutaminase is altered in various tissues of rats fed a vitamin A-deficient diet.

    PubMed

    Verma, A K; Shoemaker, A; Simsiman, R; Denning, M; Zachman, R D

    1992-11-01

    The effects of vitamin A nutritional status on the levels of expression of retinoic acid nuclear receptors (RAR), and the retinoic acid-responsive gene, tissue transglutaminase, were determined in rats. Weanling male Sprague-Dawley rats fed a vitamin A-deficient diet for approximately 7 wk developed vitamin A deficiency, as confirmed by the depletion of liver retinol and retinyl palmitate. Controls were fed the same diet supplemented with 24 mg/kg retinyl acetate. The levels of expression of RAR beta mRNA were approximately 80% lower in bladder, brain, liver, lung and trachea and those of RAR gamma mRNA were approximately 50% lower in bladder, lung and trachea of rats fed the vitamin A-deficient diet than in controls. The levels of expression of RAR alpha mRNA were approximately 90% lower in brain and approximately 30% greater in liver, kidney, intestine and lung of rats fed the vitamin A-deficient diet. Vitamin A deficiency also resulted in reduced expression of tissue transglutaminase in the bladder, lungs and trachea, which paralleled the effects observed for RAR beta and RAR gamma. When vitamin A-deficient rats were subsequently fed a retinol-deficient diet supplemented with retinoic acid for 4 wk, the expression of RAR (beta and gamma) and tissue transglutaminase returned to the control levels. These results indicate that vitamin A nutritional status in rats influences the expression of both RAR and tissue transglutaminase in certain tissues. PMID:1279143

  14. 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

  15. 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

  16. 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.

  17. Norepinephrine uptake by hypothalamic tissue from the rat related to feeding.

    PubMed

    Van Der Gugten, J; Slangen, J L

    1975-01-01

    Norepinephrine (NE) uptake by rat hypothalamus in vitro was studied in relation to food intake. Significant daily variations in NE uptake were observed in caudal hypothalamus from freely feeding rats. A maximal elevation occurred at the beginning of the night when food intake is also increasing to a maximum. NE uptake by caudal hypothalamus from relatively hungry rats previously adjusted to restricted feeding during the daytime was enhanced in afternoon and evening when compared with uptake by tissue from ad lib feeding animals. Determination of NE uptake by caudal hypothalamus from freely feeding individual rats and registration of individual meals taken by these rats revealed a relation between hypothalamic neuronal activity and the feeding pattern of the rat. A positive correlation was observed between NE uptake in vitro and feeding rate during a 2- to 4-hr interval. It also appeared that NE uptake by caudal hypothalamus is dependent on the time elapsed after the last meal. The data were evaluated in view of physiological studies concerning the onset of feeding and the hypothesis of hypothalamic adrenergic control of food intake.

  18. Effect of Urtica dioica L. (Urticaceae) on testicular tissue in STZ-induced diabetic rats.

    PubMed

    Ghafari, S; Balajadeh, B Kabiri; Golalipour, M J

    2011-08-15

    Urtica dioica L. (Stinging nettle) has already been known for a long time as a medicinal plant in the world. This histopathological and morphometrical study was conducted to determine the effects of the hydroalcoholic extract of Urtica dioica leaves on testis of streptozotocin-induced diabetic rats. Eighteen male Wistar rats were allocated to equally normal, diabetic and treatment groups. Hyperglycemia was induced by Streptozotocin (80 mg kg(-1)) in animals of diabetic and treatment groups. One week after STZ injection (80 mg kg(-1)), the rats of treatment group received the extract of U. dioica (100 mg/kg/day) IP for 28 days. After 5 weeks of study, all the rats were sacrificed and testes were removed and fixed in bouin and after tissue processing stained with H and E technique. Tubular cell disintegration, sertoli and spermatogonia cell vacuolization and decrease in sperm concentration in seminiferous tubules were seen in diabetic and treatment groups group in comparison with control. External Seminiferous Tubular Diameter (STD) and Seminiferous Epithelial Height (SEH) significantly reduced (p < 0.05) in the diabetic rats compared with controls and these parameters in the treatment group were similar to diabetics animals. This study showed that hydroalcoholic extract of Urtica dioica leaves, after induction of diabetes; has no treatment effect on seminiferous tubules alterations in streptozotocin-induced diabetic rats. PMID:22545354

  19. Regulation of lypolysis in white adipose tissues of lean and obese Zucker rats.

    PubMed

    Bairras, C; Mauriege, P; Bukowiecki, L; Atgie, C

    2007-12-01

    Obese Zucker rat is often used as a model of genetic obesity to understand the mechanism of the development of obesity. In the present work, in order to better understand the regulation of lipolysis in the Zucker rat, the lipolytic activities of adipocytes isolated from different adipose depots of lean and obese Zucker rats, in the basal state or after catecholamine stimulation have been measured. The obese Zucker rat presents hyperinsulinemia without hyperglycemia and with elevated plasma free fatty acids, suggesting a dyslipidemia. Morphological studies of three adipose deposits show a marked hypertrophic and hyperplastic type of obesity, much pronounced in the subcutaneous depot. In the current study we show that the basal lipolytic rate is higher in adipocytes from each deposit of obese rats (when results are corrected for cell surface area). This finding, associated with the increase of all deposits, could contribute to the elevated plasma FFA observed. Investigation of the responsiveness of dibutyril cAMP (DBcAMP) points out that the defect in the NE responsiveness is essentially located at post-receptor level. Nevertheless, a receptor defect could not be excluded as suggested by a decrease of the beta-ARs observed in all deposits. Our study points out that the lipolytic resistance to catecholamines in adipose tissue of obese Zucker rats appears to counteract the increase in the lipolytic rate, in order to moderate the increase in plasma FFA levels that may contribute to the hyperinsulinemia observed, characteristic of an insulino-resistant state.

  20. Characteristics of ionic binding by rat renal tissue in vitro.

    PubMed Central

    Law, R O

    1984-01-01

    A study has been made of Na+ and Cl- binding in metabolically inhibited slices of rat renal cortex and outer medulla incubated in modified Krebs phosphate-bicarbonate Ringer solution. At pH 7.35 in control media (cortex, 147 mmol Na+/l, 105 mmol Cl-/l; outer medulla, 187 mmol Na+/l, 145 mmol Cl-/l) cortical slices bound (mean) 171 nmol Na+ and 56.7 nmol Cl-/mg solute-free dry weight; outer medullary slices bound 188 nmol Na+/mg and negligible amounts of Cl-. In both regions, Na+ was exchangeable on a 1:1 basis for K+ or Li+ in media containing equal concentrations of each cation: Na+ was completely displaced by La3+. In cortical slices in media containing equimolar Cl- and other monovalent anions, binding occurred according to the sequence acetate less than or equal to salicylate less than or equal to Cl- less than SCN-; Cl- was completely displaced by PO4(3-). When medium pH was lowered, Na+ binding was markedly reduced in both regions, whereas Cl- binding increased (and became significant in outer medulla). In NaCl solutions, Na+ binding capacity was saturated at control Na+ concentrations. When [Na+] was progressively reduced (iso-osmolality being maintained by addition of urea), bound Na+ in both regions was nearly linearly related to log medium [Na+]. Raising medium osmolality with urea caused decreased Na+ binding and increased Cl- binding in both regions. Na+ binding in both regions was significantly reduced by pre-treatment with chondroitinase ABC. Binding of both ions was independent of temperature within the range 2-37 degrees C. The possibility is raised that renal ionic binding might influence vectorial ion transport by affecting free ion activity in the region of the transporting cells. PMID:6481630

  1. Histopathological Effects of Tissue Adhesives on Experimental Peripheral Nerve Transection Model in Rats

    PubMed Central

    Çıralık, Harun

    2015-01-01

    Objective Our aim was to evaluate the histopathological effects of tissue adhesives on peripheral nerve regeneration after experimental sciatic nerve transection in rats and to search whether these tissue adhesives may possess a therapeutic potential in peripheral nerve injuries. Methods This experimental study was performed using 42 female Wistar-Albino rats distributed in 6 groups subsequent to transection of right sciatic nerves. Group I underwent external circumferential neurolysis; Group II received suture repair; Group III had local polymeric hydrogel based tissue adhesive administration; Group IV received suture repair and polymeric hydrogel based tissue adhesive application together; Group V had gelatin based tissue adhesive application and Group VI had suture repair and gelatin based tissue adhesive together. After a 6-week follow-up period, biopsies were obtained from site of neural injury and groups were compared with respect to histopathological scoring based on inflammatory, degenerative, necrotic and fibrotic changes. Results There were remarkable differences between control group and study groups with respect to inflammation (p=0.001), degeneration (p=0.002), necrosis (p=0.007), fibrosis (p<0.001) and vascularity (p=0.001). Histopathological scores were similar between study groups and the only noteworthy difference was that Group V displayed a lower score for necrosis and higher score in terms of vascularization. Conclusion Our results imply that tissue adhesives can be useful in repair of peripheral nerve injuries by decreasing the surgical trauma and shortening the duration of intervention. Results with gelatin based tissue adhesive are especially promising since more intense vascularity was observed in tissue after application. However, trials on larger series with longer durations of follow-up are essential for reaching more reliable conclusions. PMID:26819683

  2. Incidental pathologic extracardiac uptake of (99m)Tc-tetrofosmin in myocardial perfusion imaging: Importance of patient background evaluation.

    PubMed

    González García, B; García Vicente, A M; Palomar Muñoz, A; Poblete García, V M; Jiménez Londoño, G A; Soriano Castrejón, A M

    2015-01-01

    (99m)Tc-tetrofosmin single photon emission computed tomography ((99m)Tc-tetrofosmin SPECT) has an important role in the assessment of coronary artery disease. Despite being its main indication, this study does not only evaluate myocardial perfusion, but much more. Moreover, during the SPECT acquisition, the field area covered includes many important organs of the thorax and abdomen, so extracardiac abnormalities can be observed. The correct etiologic diagnosis of them is only possible if we understand how (99m)Tc-tetrofosmin works and make a comprehensive investigation of the clinical history of the patient. PMID:25937520

  3. Changes in white adipose tissue metabolism induced by resveratrol in rats

    PubMed Central

    2011-01-01

    Background A remarkable range of biological functions have been ascribed to resveratrol. Recently, this polyphenol has been shown to have body fat lowering effects. The aim of the present study was to assess some of the potential underlying mechanisms of action which take place in adipose tissue. Methods Sixteen male Sprague-Dawley rats were randomly divided into two groups: control and treated with 30 mg resveratrol/kg body weight/d. All rats were fed an obesogenic diet and after six weeks of treatment white adipose tissues were dissected. Lipoprotein lipase activity was assessed by fluorimetry, acetyl-CoA carboxylase by radiometry, and malic enzyme, glucose-6P-dehydrogenase and fatty acid synthase by spectrophotometry. Gene expression levels of acetyl-CoA carboxylase, fatty acid synthase, lipoprotein lipase, hormone-sensitive lipase, adipose triglyceride lipase, PPAR-gamma, SREBP-1c and perilipin were assessed by Real time RT-PCR. The amount of resveratrol metabolites in adipose tissue was measured by chromatography. Results There was no difference in the final body weight of the rats; however, adipose tissues were significantly decreased in the resveratrol-treated group. Resveratrol reduced the activity of lipogenic enzymes, as well as that of heparin-releasable lipoprotein lipase. Moreover, a significant reduction was induced by this polyphenol in hormone-sensitive lipase mRNA levels. No significant changes were observed in other genes. Total amount of resveratrol metabolites in adipose tissue was 2.66 ± 0.55 nmol/g tissue. Conclusions It can be proposed that the body fat-lowering effect of resveratrol is mediated, at least in part, by a reduction in fatty acid uptake from circulating triacylglycerols and also in de novo lipogenesis. PMID:21569266

  4. 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.

  5. A comparative study of artificial ceroid/lipofuscin from different tissue materials of rats.

    PubMed

    Wang, Xinhui; Liao, Yanyang; Li, Guolin; Yin, Dazhong; Sheng, Shuli

    2008-01-01

    The artificial ceroid/lipofuscin pigments originated from different organ tissues, including liver, brain, heart, and kidney of rats, and biomaterials were studied with improved fluorometric techniques. With all tissue materials exposed under ultraviolet (UV) light, a series of similar fluorescent colors were observed under microfluorometer. Analogous fluorescence spectra were also demonstrated with a three-dimensional (3-D) front-surface fluorometric technique despite of the tissue differences. Measured with 3-D fluorometry, relatively simple lipofuscin-like fluorophores were observed from the reactions of malondialdehyde (MDA) with critical biological macromolecules, such as bovine serum albumin (BSA) and DNA. Our results demonstrated that the biomaterials from different tissues have a similar fate under accelerated oxidative/carbonyl stresses but may be differentiated by a fluorescence intensity ratio.

  6. [POLYPEPTIDES INFLUENCE ON TISSUE CELL CULTURES REGENERATION OF VARIOUS AGE RATS].

    PubMed

    Ryzhak, A P; Chalisova, N I; Lin'kova, N S; Khalimov, R I; Ryzhak, G A; Zhekalov, A N

    2015-01-01

    A comparative study of polypeptides extracted from the tissues of calves: Cortexin (from brain cortex), Epinorm (from pineal gland), Ventvil (from liver), Prostatilen (from prostate), Thymalin (from thymus), Chelohart (from heart), Chondrolux (from cartilage) on the relevant organotypic tissue cultures of young and old rats, in concentration 0,01-100 ng/ml was performed. Polypeptides specifically stimulated "young" and "old" cell cultures growth in concentration 20-50 ng/ml. This effect correlates with increasing of PCNA and decreasing of p53 expression in brain cortex, pineal gland, liver, prostate, heart, cartilage. Moreover, Thymalin activated CD5, CD20 expression--markers of B-cells differentiation. These data show that polypeptides isolated from different tissues have selective molecular activity on the regeneration of suitable tissues in aging.

  7. 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

  8. Androgen Withdrawal Fails to Induce Detectable Tissue Hypoxia in the Rat Prostate

    PubMed Central

    Regter, Sietze; Hedayati, Mohammad; Zhang, Yonggang; Zhou, Haoming; Dalrymple, Susan; Koch, Cameron J.; Isaacs, John T.; DeWeese, Theodore L.

    2015-01-01

    BACKGROUND It has been reported that significant hypoxia may occur in the rat prostate following androgen deprivation (AD). It is well known that hypoxia substantially reduces radiation sensitivity of cells both in vitro and in vivo. Given that contemporary management of men with intermediate and high-risk prostate cancer includes the use of neoadjuvant androgen suppression and radiation, AD-induced hypoxia in the prostate could result in suboptimal therapeutic results. Given this concern, we fully investigate possible AD-induced hypoxia in the ventral prostate (VP) of adult rats by two independent methods. METHODS Tissue pO2 levels in the VP of adult Spraque-Dawley rats were evaluated prior to and at various time points following castration by two independent techniques. First, an Oxylab tissue oxygen monitor with a 240 μm probe was used for quantitative monitoring of global VP oxygenation. Second, fluorescence immunohistochemistry using the hypoxia marker EF5, known to be metabolically activated by hypoxic cells, was used to evaluate cell-to-cell variation in hypoxia at various days post-castration. RESULTS Neither the oxygen probe nor EF5 method demonstrate any substantive change in pO2 levels in the rat VP at any time point post-castration. CONCLUSIONS We find no evidence that the rat VP becomes hypoxic at any point following castration using an animal model that closely mimics the human prostate. These data are in contrast to previous reports suggesting prostatic hypoxia occurs following AD and provide assurance that our present therapeutic strategy of neoadjuvant AD followed by radiation is not compromised by AD-induced tissue hypoxia. PMID:24677180

  9. Effect of Nrf2 on rat ovarian tissues against atrazine-induced anti-oxidative response.

    PubMed

    Zhao, Fan; Li, Kun; Zhao, Lijing; Liu, Jian; Suo, Qi; Zhao, Jing; Wang, Hebin; Zhao, Shuhua

    2014-01-01

    The environmental persistence and bioaccumulation of herbicide atrazine may pose a significant threat to human health. In this experiment, Wistar rats were treated by 5, 25 and 125 mg·kg(-1) atrazine respectively for 28 days, and the oxidative stress responses as well as the activations of Nrf2 signaling pathway in ovarian tissues induced by atrazine were observed. The results showed that after be treated by atrazine, the proportion of atretic follicles in the rat ovary were increased, the contents of NO and MDA in the tissue homogenates were increased, the over-expressed Nrf2 transferred into the nuclei and played an antioxidant role by up-regulated the expression of II phase detoxifying enzymes such as HO1 and NQO1 and the expression of antioxidant enzymes such as CAT, SOD and GSH-PX.

  10. [Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

    PubMed

    Titov, E A; Sosedova, L M; Novikov, M A

    2015-01-01

    The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum. PMID:27116877

  11. [Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix].

    PubMed

    Titov, E A; Sosedova, L M; Novikov, M A

    2015-01-01

    The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum.

  12. In vitro effects of toxaphene on mitochondrial calcium ATPase and calcium uptake in selected rat tissues

    SciTech Connect

    Trottman, C.H.; Rao, K.S.P.; Morrow, W.; Uzodinma, J.E.; Desaiah, D.

    1985-02-04

    In vitro effects of toxaphene on Ca/sup 2 +/-ATPase activity and /sup 45/Ca/sup 2 +/-uptake were studied in mitochondrial fractions of heart, kidney and liver tissues of rat. Mitochondrial fractions were prepared by the conventional centrifugation method. Ca/sup 2 +/-ATPase activity was determined by measuring the inorganic phosphate liberated during ATP hydrolysis. Toxaphene inhibited Ca/sup 2 +/-ATPase in a concentration dependent manner in all the three tissues. Substrate activation kinetics, with heart, kidney and liver tissue fractions, revealed that toxaphene inhibited Ca/sup 2 +/-ATPase activity non-competetively by decreasing the maximum velocity of the enzyme without affecting the enzyme-substrate affinity. Toxaphene also inhibited mitochondrial /sup 45/Ca/sup 2 +/-uptake in the three selected tissues in a concentration dependent manner. These results indicate that toxaphene is an inhibitor of mitochondrial Ca/sup 2 +/-ATPase and calcium transport in heart, kidney and liver tissues of rat. 19 references, 5 figures.

  13. 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.

  14. 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

  15. 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

  16. 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.

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

    PubMed Central

    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

  18. Measurement of the optical properties of rat brain tissue using contact spatially resolved spectroscopy

    NASA Astrophysics Data System (ADS)

    Gysbrechts, Barbara; Nguyen Do Trong, Nghia; Wang, Ling; Cabral, Henrique; Navratilova, Zaneta; Battaglia, Francesco P.; Saeys, Wouter; Bartic, Carmen

    2014-05-01

    Nowadays, biophotonics is widely used in neuroscience. The effectiveness of biophotonic techniques, such as fluorescence imaging and optogenetics, is affected by the optical properties of the examined tissue. Therefore, knowledge of these properties is essential to carefully plan experiments. Mice and rats are widely used in neuroscience studies. However, reports about optical properties of their brains are very rare. We measured optical absorption μa and reduced scattering μ's coefficients of native rat brain in the visible and near-infrared wavelength region, using contact spatially resolved spectroscopy (SRS). In this study, we estimate μa and μ's for the rat cortex and discuss their stability in time. Additionally, variations in optical properties within and between samples were characterized. The results extend the range of known optical properties for the rat cortex, especially in the visible range, relevant to optogenetics. μa and μ's are stable within a time span of four hours, and show low variation in and between brain samples. This indicates that a suitable protocol was used to estimate optical properties of rodent brain tissue. Since contact SRS is a non-destructive method, this technique could be used also to measure μa and μ's in living animals. Moreover, the probe has small dimensions, allowing the characterization of optical properties in different structures of the brain.

  19. Tissue-specific PAI-1 gene expression and glycosylation pattern in insulin-resistant old rats.

    PubMed

    Serrano, R; Barrenetxe, J; Orbe, J; Rodríguez, J A; Gallardo, N; Martínez, C; Andrés, A; Páramo, J A

    2009-11-01

    Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with obesity, aging, insulin resistance, and type 2 diabetes, conditions that contribute to increased cardiovascular risk. PAI-1 is expressed in a variety of tissues, but the cellular origin of plasma PAI-1 is unknown. To link insulin resistance, aging, and cardiovascular disease, we examined the expression and glycosylation pattern of PAI-1 in liver and white adipose tissue (WAT) from adult (3 mo) and insulin-resistant old (24 mo) Wistar rats. Glycosylated PAI-1 protein was also purified by affinity chromatography from endothelial culture supernatans to analyze its inhibitory activity. We also analyzed the contribution of adipocytes and stromal vascular cells from WAT to PAI-1 levels with aging. Aging caused a significant increase of PAI-1 mRNA (P < 0.001) in WAT that was predominantly due to the adipocytes and not to stroma-vascular cells, while there was no modification in liver from aged rats. Moreover, PAI-1 expression increased during preadipocyte differentiation (P < 0.001). Furthermore, we found a tissue-dependent PAI-1 glycosylation pattern: adipose tissue only expresses the glycosylated PAI-1 form, whereas the liver mainly expresses the nonglycosylated form. Finally, we also found evidences suggesting that the glycosylated PAI-1 form shows higher inhibitory activity than the nonglycosylated. Our data suggest that WAT may be a major source of the elevated plasma levels of PAI-1 in insulin-resistant old rats. Additionally, the high degree of PAI-1 glycosylation and activity, together with the significant increase in visceral fat in old rats, may well contribute to an increased cardiovascular risk associated with insulin-resistant states.

  20. 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

  1. 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

  2. Hormonal regulation of prolactin receptors in male rat target tissues: the effect of hypothyroidism and adrenalectomy.

    PubMed

    Kharroubi, A T; Slaunwhite, W R

    1984-10-01

    The effects of hypothyroidism and adrenalectomy (ADX) on PRL receptors as well as the subcellular distribution of PRL-binding sites in adult male rat target tissues were investigated. In ventral prostate, kidney, and adrenal, PRL-binding activity was enriched in the 15,000 X g pellet (mitochondrial/Golgi fraction). The zona fasiculata/reticularis plus medulla of the adrenal had higher PRL-binding activity than the zona glomerulosa (plus capsule). Propylthiouracil-induced hypothyroidism significantly decreased PRL binding to kidney (65%) and testis (50%), and 16-h replacement with T4 restored PRL binding to control levels. T4 was, however, without effect on renal PRL binding in hypothyroid castrated rats, indicating that androgen may be required for this response. The increase in PRL binding to ventral prostate and adrenal due to hypothyroidism was not reversed within 16 h of T4 injection, whereas T3 injection decreased PRL binding to ventral prostate within 12 h. ADX increased PRL binding to rat testis (38%) and kidney (18%), and 5-day replacement with dexamethasone decreased PRL binding to levels lower than those in control rats. ADX had no effect, and dexamethasone treatment decreased (16-20%) PRL binding to ventral prostate and hCG binding to rat testis. The modulation of PRL receptors by hypothyroidism and ADX suggests that thyroid and adrenal hormones play a role in the regulation of PRL receptors. PMID:6090097

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. Duodenal Absorption and Tissue Utilization of Dietary Heme and Nonheme Iron Differ in Rats123

    PubMed Central

    Cao, Chang; Thomas, Carrie E.; Insogna, Karl L.; O'Brien, Kimberly O.

    2014-01-01

    Background: Dietary heme contributes to iron intake, yet regulation of heme absorption and tissue utilization of absorbed heme remains undefined. Objectives: In a rat model of iron overload, we used stable iron isotopes to examine heme- and nonheme-iron absorption in relation to liver hepcidin and to compare relative utilization of absorbed heme and nonheme iron by erythroid (RBC) and iron storage tissues (liver and spleen). Methods: Twelve male Sprague-Dawley rats were randomly assigned to groups for injections of either saline or iron dextran (16 or 48 mg Fe over 2 wk). After iron loading, rats were administered oral stable iron in the forms of 57Fe-ferrous sulfate and 58Fe-labeled hemoglobin. Expression of liver hepcidin and duodenal iron transporters and tissue stable iron enrichment was determined 10 d postdosing. Results: High iron loading increased hepatic hepcidin by 3-fold and reduced duodenal expression of divalent metal transporter 1 (DMT1) by 76%. Nonheme-iron absorption was 2.5 times higher than heme-iron absorption (P = 0.0008). Absorption of both forms of iron was inversely correlated with hepatic hepcidin expression (heme-iron absorption: r = −0.77, P = 0.003; nonheme-iron absorption: r = −0.80, P = 0.002), but hepcidin had a stronger impact on nonheme-iron absorption (P = 0.04). Significantly more 57Fe was recovered in RBCs (P = 0.02), and more 58Fe was recovered in the spleen (P = 0.01). Conclusions: Elevated hepcidin significantly decreased heme- and nonheme-iron absorption but had a greater impact on nonheme-iron absorption. Differential tissue utilization of heme vs. nonheme iron was evident between erythroid and iron storage tissues, suggesting that some heme may be exported into the circulation in a form different from that of nonheme iron. PMID:25332470

  9. 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.

  10. 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.

  11. Melatonin improves mitochondrial function in inguinal white adipose tissue of Zücker diabetic fatty rats.

    PubMed

    Jimenéz-Aranda, Aroa; Fernández-Vázquez, Gumersindo; Mohammad A-Serrano, María; Reiter, Russel J; Agil, Ahmad

    2014-08-01

    Mitochondrial dysfunction in adipose tissue may contribute to obesity-related metabolic derangements such as type 2 diabetes mellitus (T2DM). Because mitochondria are a target for melatonin action, the goal of this study was to investigate the effects of melatonin on mitochondrial function in white (WAT) and beige inguinal adipose tissue of Zücker diabetic fatty (ZDF) rats, a model of obesity-related T2DM. In this experimental model, melatonin reduces obesity and improves the metabolic profile. At 6 wk of age, ZDF rats and lean littermates (ZL) were subdivided into two groups, each composed of four rats: control (C-ZDF and C-ZL) and treated with oral melatonin in the drinking water (10 mg/kg/day) for 6 wk (M-ZDF and M-ZL). After the treatment period, animals were sacrificed, tissues dissected, and mitochondrial function assessed in isolated organelles. Melatonin increased the respiratory control ratio (RCR) in mitochondria from white fat of both lean (by 26.5%, P < 0.01) and obese (by 34.5%, P < 0.01) rats mainly through a reduction of proton leaking component of respiration (state 4) (28% decrease in ZL, P < 0.01 and 35% in ZDF, P < 0.01). However, melatonin treatment lowered the RCR in beige mitochondria of both lean (by 7%, P < 0.05) and obese (by 13%, P < 0.05) rats by maintaining high rates of uncoupled respiration. Melatonin also lowered mitochondrial oxidative status by reducing nitrite levels and by increasing superoxide dismutase activity. Moreover, melatonin treatment also caused a profound inhibition of Ca-induced opening of mPTP in isolated mitochondria from both types of fat, white and beige, in both lean and obese rats. These results demonstrate that chronic oral melatonin improves mitochondrial respiration and reduces the oxidative status and susceptibility to apoptosis in white and beige adipocytes. These melatonin effects help to prevent mitochondrial dysfunction and thereby to improve obesity-related metabolic disorders such as

  12. Pharmacokinetics, tissue distribution and mass balance of radiolabeled dihydroartemisinin in male rats

    PubMed Central

    Xie, Lisa H; Li, Qigui; Zhang, Jing; Weina, Peter J

    2009-01-01

    Background Dihydroartemisinin (DHA), a powerful anti-malarial drug, has been used as monotherapy and artemisinin-based combination therapy (ACT) for more than decades. So far, however, the tissue distribution and metabolic profile of DHA data are not available from animal and humans. Methods Pharmacokinetics, tissue distribution, mass balance, and elimination of [14C] DHA have been studieded in rats following a single intravenous administration. Protein binding was performed with rat and human plasma. Drug concentrations were obtained up to 192 hr from measurements of total radioactivity and drug concentration to determine the contribution by the parent and metabolites to the total dose of drug injected from whole blood, plasma, urine and faecal samples. Results Drug was widely distributed after 1 hr and rapidly declined at 24 hr in all tissues except spleen until 96 hrs. Only 0.81% of the total radioactivity was detected in rat brain tissue. DHA revealed a high binding capacity with both rat and human plasma proteins (76–82%). The concentration of total radioactivity in the plasma fraction was less than 25% of that in blood total. Metabolism of DHA was observed with high excretion via bile into intestines and approximately 89–95% dose of all conjugations were accounted for in blood, urine and faeces. However, the majority of elimination of [14C] DHA was through urinary excretion (52% dose). The mean terminal half-lives of plasma and blood radioactivity (75.57–122.13 h) were significantly prolonged compared with that of unchanged DHA (1.03 h). Conclusion In rat brain, the total concentration of [14C] was 2-fold higher than that in plasma, indicating the radioactivity could easily penetrate the brain-blood barrier. Total radioactivity distributed in RBC was about three- to four-fold higher than that in plasma, suggesting that the powerful anti-malarial potency of DHA in the treatment of blood stage malaria may relate to the high RBC binding. Biliary excretion

  13. 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.

  14. 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

  15. Measurement of plasma and tissue triiodothyronine concentration in the rat by radioimmunoassay.

    PubMed

    Nejad, I; Bollinger, J; Mitnick, M A; Sullivan, P; Reichlin, S

    1975-03-01

    This paper reports a radioimmunoassay method for triiodothyronine (T3) and the application of this assay to the study of plasma and tissue T3 concentration in the rat. Several antisera formed to a T3-bovine fibrogen complex in guinea pigs and T3-thyroglobulin complex in rabbits are shown to have low or no cross reactivity with T4, monoiodotyrosine, diiodotyrosine, tetraiodothyroacetic acid (TETRAC) and reverse T3. Cross reactivity with T3 derivatives, triiodothyroacetic acid (TRIAC), and triiodothyropropionic (TRIPROP) was variable, some antisera differentiating moderately well and others not at all. An extraction method is described which removes approximately 85% of added 125I-T3 or unlabelled T3 from tissues and in the final step represents 57% of total tissue T3. Mean plasma T3 in 5 normal male rats was 58 plus or minus 6.0 ng/100 ml (SEM), in liver 769 plus or minus 56 ng/100 g, and kidney 627 plus or minus 39 ng/100 g. Tissue to plasma concentration gradients for liver and kidney were 13.3 and 10.8, respectively.

  16. 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.

  17. Effects of Tannic Acid on the Ischemic Brain Tissue of Rats.

    PubMed

    Sen, Halil Murat; Ozkan, Adile; Guven, Mustafa; Akman, Tarık; Aras, Adem Bozkurt; Sehitoglu, Ibrahim; Alacam, Hasan; Silan, Coskun; Cosar, Murat; Ozisik Karaman, Handan Isın

    2015-08-01

    Many studies of brain ischemia have shown the role played by massive ischemia-induced production of reactive oxygen species, the main mechanism of neuronal death. However, currently, there is no treatment choice to prevent cell death triggered by reactive oxygen species. In our study, we researched the effects of tannic acid, an antioxidant, on the ischemic tissue of rats with induced middle cerebral artery occlusion. The animals were divided into three groups of eight animals. The sham group were only administered 10 % ethanol intraperitoneally, the second group had middle cerebral artery occlusion induced and were given 10 % ethanol intraperitoneally, while the third group had middle cerebral artery occlusion with 10 mg/kg dose tannic acid dissolved in 10 % ethanol administered within half an hour intraperitoneally. The rats were sacrificed 24 h later, and brain tissue was examined biochemically and histopathologically. Biochemical evaluation of brain tissue found that comparing the ischemic group with no treatment with the tannic acid-treated ischemia group; the superoxide dismutase (SOD) levels were higher, malondialdehyde (MDA) levels were lower, and nuclear respiratory factor-1 (NRF-1) was higher in the tannic acid-treated group. Histopathological examination showed that the histopathological results of the tannic acid group were better than the group not given tannic acid. Biochemical and histopathological results showed that tannic acid administration had an antioxidant effect on the negative effects of ischemia in brain tissue.

  18. 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

  19. 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

  20. Comparison of Microdialysis Sampling Perfusion Fluid Components on the Foreign Body Reaction in Rat Subcutaneous Tissue

    PubMed Central

    Keeler, Geoffrey D.; Durdik, Jeannine M.; Stenken, Julie A.

    2013-01-01

    Microdialysis sampling is a commonly used technique for collecting solutes from the extracellular space of tissues in laboratory animals and humans. Large molecular weight solutes can be collected using high molecular weight cutoff (MWCO) membranes (100 kDa or greater). High MWCO membranes require addition of high molecular weight dextrans or albumin to the perfusion fluid to prevent fluid loss via ultrafiltration. While these perfusion fluid additives are commonly used during microdialysis sampling, the tissue response to the loss of these compounds across the membrane is poorly understood. Tissue reactions to implanted microdialysis sampling probes containing different microdialysis perfusion fluids were compared over a 7-day time period in rats. The base perfusion fluid was Ringer’s solution supplemented with either bovine serum albumin (BSA), rat serum albumin (RSA), Dextran-70, or Dextran-500. A significant inflammatory response to Dextran-70 was observed. No differences in the tissue response between BSA and RSA were observed. Among these agents, the BSA, RSA, and Dextran-500 produced a significantly reduced inflammatory response compared to the Dextran-70. This work demonstrates that use of Dextran-70 in microdialysis sampling perfusion fluids should be eliminated and replaced with Dextran-500 or other alternatives. PMID:24239995

  1. 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.

  2. 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

  3. Connective tissue reaction of rats to a new zinc-oxide-eugenol endodontic sealer.

    PubMed

    Trichês, Karen Melina; Júnior, Jacy Simi; Calixto, João Batista; Machado, Ricardo; Rosa, Tiago Pereira; Silva, Emmanuel João Nogueira Leal; Vansan, Luiz Pascoal

    2013-12-01

    The aim of this study was to evaluate the biocompatibility in rat subcutaneous connective tissue of a new zinc oxide endodontic sealer (Endomethasone N) compared to those provided by Endofill and Sealer 26. Polyethylene tubes containing the test materials were implanted into dorsal subcutaneous connective tissue of Wistar albino rats. After 7 and 42 days, the implants with the surrounding tissue were collected, fixed, and processed for histologic evaluation. Sections were evaluated for the presence of inflammatory cells (poly or monomorfonuclear), blood vessels, necrosis area, and thickness of fibrous capsule. Comparisons between groups and time-periods were performed with Kruskal-Wallis and Mann-Whitney U non-parametric tests for 5% significance level. No differences in the biocompatibility patterns among the materials for the 2 experimental periods were observed. Independently of the sealer, the tissue behavior showed a tendency to decrease the irritation effect over time. It can be concluded that all sealers are irritant, but its toxicity decreased with time. Endomethásone N showed biocompatible characteristics comparable with those provided by Endofill and Sealer 26.

  4. 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

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

    PubMed Central

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

    2014-01-01

    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

  6. 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.

  7. 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

  8. Expression of beta 3-adrenoceptor mRNA in rat tissues.

    PubMed Central

    Evans, B. A.; Papaioannou, M.; Bonazzi, V. R.; Summers, R. J.

    1996-01-01

    1. This study examines the expression of beta 3-adrenoceptor messenger RNA (beta 3-AR mRNA) in rat tissues to allow comparison with atypical beta-adrenoceptors determined by functional and radioligand binding techniques. 2. A reverse transcription/polymerase chain reaction protocol has been developed for determining the relative amounts of beta 3-AR mRNA in rat tissues. 3. Measurement of adipsin and uncoupling protein (UCP) mRNA was used to examine all tissues for the presence of white and brown adipose tissue which may contribute beta 3-AR mRNA. 4. The beta 3-AR mRNA is expressed at high levels in brown and white adipose tissue, stomach fundus, the longitudinal/circular smooth muscle of both colon and ileum, and colon submucosa. There was substantial expression of adipsin in colon submucosa and moderate expression in fundus, suggesting that in these regions at least some of the beta 3-AR signal may be contributed by fat. Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin. Ileum mucosa and submucosa showed low but readily detectable levels of beta 3-AR. 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver. These results raise the possibility that the atypical beta-AR demonstrated by functional and/or binding studies in muscle and in heart is not the beta 3-AR. 6. By use of two different sets of primers for amplification of beta 3-AR cDNA, no evidence was found for differential splicing of the mRNA in any of the tissues examined. 7. The detection of beta 3-AR mRNA in the gut mucosa and submucosa suggests that in addition to its established roles in lipolysis, thermogenesis and regulation of gut motility beta 3-AR may subserve other functions in the gastrointestinal tract. The absence of beta 3-AR mRNA in rat heart or its presence with

  9. Pulpal and periapical tissue reactions after experimental pulpal exposure in rats.

    PubMed

    Yamasaki, M; Kumazawa, M; Kohsaka, T; Nakamura, H; Kameyama, Y

    1994-01-01

    The purpose of this study was to investigate histologically and histometrically the changes in pulpal and periapical tissues after pulpal exposure in rats. All animals received a pulpal exposure in the left mandibular first molar. Animals were killed at 1 to 56 days after pulpal exposure, and their mandibles were evaluated histologically and histometrically. Histologically, pulpal necrosis extended gradually from the upper part of the pulpal tissue to the apex, with inflammation starting in the periapical tissue at an early stage. As the periapical lesion developed, alveolar bone and cementum resorption was also found. Histometrically, the length of pulpal necrosis increased gradually from 1 to 28 days. The vertical length of the periapical lesion after 14 days was significantly increased, while the horizontal length and the overall area after 7 days were also significantly increased. The periapical lesion extended in a mesiodistal direction at first and then in a vertical direction before expansion ceased. PMID:8182380

  10. 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.

  11. Temporal and topographic profiles of tissue hypoxia following transient focal cerebral ischemia in rats.

    PubMed

    Noto, Takahisa; Furuichi, Yasuhisa; Ishiye, Masayuki; Matsuoka, Nobuya; Aramori, Ichiro; Mutoh, Seitaro; Yanagihara, Takehiko; Manabe, Noboru

    2006-08-01

    Intravascular accumulation of blood cells after brain ischemia-reperfusion can cause obstruction of cerebral blood flow and tissue hypoxia/ischemia as a consequence. In the present study, we examined temporal and topographic changes of tissue hypoxia/ischemia after occlusion of the middle cerebral artery (MCA) for 60 min in rats with immunohistochemical staining for hypoxia (2-nitroimidazole hypoxia marker: hypoxyprobe-1 adducts). Our results showed that tissue hypoxia expressed as positive staining for hypoxyprobe-1 adducts preceded neuronal degeneration. Platelets and granulocytes were detected close to the hypoxyprobe-1 adducts positive area. These results suggested that the hypoxic environment could persist even after reperfusion of MCA, because of vascular obstruction with accumulation of platelets and granulocytes.

  12. Rat subcutaneous tissue response to MTA Fillapex® and Portland cement.

    PubMed

    Marques, Nádia Carolina Teixeira; Lourenço Neto, Natalino; Fernandes, Ana Paula; Rodini, Camila de Oliveira; Duarte, Marco Antônio Hungaro; Oliveira, Thais Marchini

    2013-01-01

    The aim of this study was to evaluate the response of rat subcutaneous tissue to MTA Fillapex® (Angelus), an experimental root canal filling material based on Portland cement and propylene glycol (PCPG), and a zinc oxide, eugenol and iodoform (ZOEI) paste. These materials were placed in polyethylene tubes and implanted into the dorsal connective tissue of Wistar rats for 7 and 15 days. The specimens were stained with hematoxylin and eosin, and evaluated regarding inflammatory reaction parameters by optical microscopy. The intensity of inflammatory response against the sealers was analyzed by two blinded and previously calibrated examiners for all experimental periods (kappa=0.96). The histological evaluation showed that all materials caused a moderate inflammatory reaction at 7 days, which subsided with time. A greater inflammatory reaction was observed at 7 days in the tubes filled with ZOEI paste. Tubes filled with MTA Fillapex presented some giant cells, macrophages and lymphocytes after 7 days. At 15 days, the presence of fibroblasts and collagen fibers was observed indicating normal tissue healing. The tubes filled with PCPG showed similar results to those observed in MTA Fillapex. At 15 days, the inflammatory reaction was almost absent at the tissue, with several collagen fibers indicating normal tissue healing. Data were analyzed by the nonparametric Kruskal-Wallis test (α=0.05). Statistically significant difference (p<0.05) was found only between PCPG at 15 days and ZOEI at 7 days groups. No significant differences were observed among the other groups/periods (p>0.05). MTA Fillapex and Portland cement added with propylene glycol had greater tissue compatibility than the PCPG paste.

  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. Tissue specificity of N-nitrosomorpholine metabolism in Sprague-Dawley rats.

    PubMed

    Löfberg, B; Tjälve, H

    1985-07-01

    The distribution and metabolism of N-nitroso[14C]morpholine ([14C]NMOR) in Sprague-Dawley rats were studied by autoradiographic and in vitro techniques. Low-temperature whole-body autoradiography indicated that the non-metabolized compound is able to pass freely through the cellular membranes and distribute evenly in most tissues of the body. Experiments in vitro showed that, in addition to the liver, the nasal mucosa had a high capacity to degrade the [14C]NMOR and a localization of metabolites was also observed in this tissue in vivo. Microautoradiography of the nasal olfactory mucosa showed the highest labelling over the subepithelial glands in the lamina propria mucosae. The nasal mucosa is, apart from the liver, the most prevalent site of NMOR carcinogenesis in the rat and the results indicate that a local bioactivation occurs in this tissue. Further experiments showed that NMOR metabolism in the nasal mucosa and the liver was inhibited by metyrapone and by a carbon monoxide atmosphere, indicating that the metabolism is cytochrome P-450 dependent. In addition to the nasal mucosa and the liver, a localization of metabolites was demonstrated in the oesophageal mucosa in vivo, while in vitro this tissue showed a capacity to degrade the [14C]NMOR. A low incidence of tumours of the oesophagus has been reported in rats treated with NMOR. It is concluded that NMOR is metabolized in the nasal and oesophageal mucosa as well as in the liver, and that local bioactivation at these sites may give rise to tumours.

  15. Prolonged oral administration of potassium upon aldosterone biosynthesis by rat glomerulosa tissue in vitro.

    PubMed

    Regöly-Mérei, J; Sólyom, J

    1975-01-01

    Steroid production rate of adrenals derived from rats drinking a 0.3 M KC1 + 5% glucose solution for 7 days was compared to that of control rats drinking a 5% glucose solution in order to investigate the effect of potassium loading upon the early and late step of aldosterone biosynthesis. Following potassium loading the quartered adrenals produced more aldosterone but less corticosterone as compared to the control. Potassium loading resulted in an increased aldosterone production rate by capsular adrenals (z. glomerulosa) provided that the corticosterone concentration in the incubation medium was elevated either by incubating it together with the decapsulated adrenal or adding exogenous corticosterone (4--16 mug/ml) to the medium. The corticosterone to aldosterone converting capacity of capsular adrenals is markedly higher in the potassium-loaded rats than in the controls. In the first 15 minutes of incubation the corticosterone production rate of the two groups was equal, aldosterone production rate by capsular adrenals of potassium-loaded rats, being higher than that of control animals. Corticosterone output of capsular adrenals from potassium-loaded rats decreased more rapidly in course of the incubation than it did in control tissue. These results suggest that the increase in aldosterone secretion in vivo following potassium loading is due to the stimulation of conversion of corticosterone to aldosterone in the glomerulosa cells. However, the endogenous corticosterone production during the incubation of glomerulosa cells from pottasium-loaded rats decreases so rapidly that the cells are not capable of producing more aldosterone than the control ones in spite of activated 18-hydroxylase.

  16. Sinusoidal electromagnetic fields promote bone formation and inhibit bone resorption in rat femoral tissues in vitro.

    PubMed

    Zhou, Jian; Ma, Xiao-Ni; Gao, Yu-Hai; Yan, Juan-Li; Shi, Wen-Gui; Xian, Cory J; Chen, Ke-Ming

    2016-01-01

    Effects of sinusoidal electromagnetic fields (SEMFs) on bone metabolism have not yet been well defined. The present study investigated SEMF effects on bone formation and resorption in rat femur bone tissues in vitro. Cultured femur diaphyseal (cortical bone) and metaphyseal (trabecular bone) tissues were treated with 50 Hz 1.8 mT SEMFs 1.5 h per day for up to 12 days and treatment effects on bone formation and resorption markers and associated gene expression were examined. Treatment with SEMFs caused a significant increase in alkaline phosphatase (ALP) activity and inhibited the tartrate-resistant acid phosphatase (TRACP) activity in the femoral diaphyseal or metaphyseal tissues. SEMFs also significantly increased levels of mRNA expression of osterix (OSX), insulin-like growth factor (IGF-1) and ALP in the bone tissues. SEMF treatment decreased glucose content and increased lactic acid contents in the culture conditioned medium. In addition, treatment with SEMFs decreased mRNA expression levels of bone resorption-related genes TRACP, macrophage colony stimulating factor (M-CSF) and cathepsin K (CTSK) in the cultured bone tissues. In conclusion, the current study demonstrated that treatment with 1.8 mT SEMFs at 1.5 h per day promoted bone formation, increased metabolism and inhibited resorption in both metaphyseal and diaphyseal bone tissues in vitro.

  17. 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

  18. 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.

  19. Tissue distribution and vitamin D dependence of IMCAL in the rat

    SciTech Connect

    Kowarski, S.; Cowen, L.A.; Takahashi, M.T.; Schachter, D.

    1987-09-01

    Integral membrane calcium-binding protein (IMCAL) is a vitamin D-dependent integral membrane protein that binds calcium with relatively high affinity. Specific immunoassays for IMCAL utilizing rabbit polyclonal and mouse monoclonal antibodies were developed and applied to studies of its tissue distribution and regulation by vitamin D/sub 3/ and dietary calcium in the rat. The results indicate that vitamin D-dependent, cross-reactive protein is present in small intestinal mucosa, cecal mucosa, bone, kidney, brain, testis, heart, lung, spleen, and skin. Rats maintained on a low- (0.02%) compared with a high- (2.0%) calcium diet had significantly higher content of IMCAL in duodenal mucosa, cecal mucosa, bone, kidney, brain, testis, and heart. Treatment of rats on the high-calcium diet with 1,25-dihydroxyvitamin D/sub 3/ increased the IMCAL content of the duodenal mucosa, cecal mucosa, and kidney. The widespread tissue distribution of vitamin D-dependent IMCAL, its close correlation in intestinal mucosa with the calcium transport mechanism, and its occurrence in isolated preparations of enterocyte plasma membranes (microvillus and basolateral membranes) suggest that the protein is involved in the regulation of calcium flux in a number of cell types.

  20. 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).

  1. Consumption of resistant starch decreases postprandial lipogenesis in white adipose tissue of the rat

    PubMed Central

    Higgins, Janine A; Brown, Marc A; Storlien, Leonard H

    2006-01-01

    Chronic consumption of diets high in resistant starch (RS) leads to reduced fat cell size compared to diets high in digestible starch (DS) in rats and increases total and meal fat oxidation in humans. The aim of the present study was to examine the rate of lipogenesis in key lipogenic organs following a high RS or DS meal. Following an overnight fast, male Wistar rats ingested a meal with an RS content of 2% or 30% of total carbohydrate and were then administered an i.p bolus of 50 μCi 3H2O either immediately or 1 hour post-meal. One hour following tracer administration, rats were sacrificed, a blood sample collected, and the liver, white adipose tissue (WAT), and gastrocnemius muscle excised and frozen until assayed for total 3H-lipid and 3H-glycogen content. Plasma triglyceride and NEFA concentrations and 3H-glycogen content did not differ between groups. In all tissues, except the liver, there was a trend for the rate of lipogenesis to be higher in the DS group than the RS group which reached significance only in WAT at 1 h (p < 0.01). On a whole body level, this attenuation of fat deposition in WAT in response to a RS diet could be significant for the prevention of weight gain in the long-term. PMID:16987425

  2. 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

  3. 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

  4. 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

  5. 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

  6. Extraction of optical properties and prediction of light distribution in rat brain tissue

    NASA Astrophysics Data System (ADS)

    Azimipour, Mehdi; Baumgartner, Ryan; Liu, Yuming; Jacques, Steven L.; Eliceiri, Kevin; Pashaie, Ramin

    2014-07-01

    Predicting the distribution of light inside any turbid media, such as biological tissue, requires detailed information about the optical properties of the medium, including the absorption and scattering coefficients and the anisotropy factor. Particularly, in biophotonic applications where photons directly interact with the tissue, this information translates to system design optimization, precision in light delivery, and minimization of unintended consequences, such as phototoxicity or photobleaching. In recent years, optogenetics has opened up a new area in deep brain stimulation with light and the method is widely adapted by researchers for the study of the brain circuitries and the dynamics of neurological disorders. A key factor for a successful optogenetic stimulation is delivering an adequate amount of light to the targeted brain objects. The adequate amount of light needed to stimulate each brain object is identified by the tissue optical properties as well as the type of opsin expressed in the tissue, wavelength of the light, and the physical dimensions of the targeted area. Therefore, to implement a precise light delivery system for optogenetics, detailed information about the optical properties of the brain tissue and a mathematical model that incorporates all determining factors is needed to find a good estimation of light distribution in the brain. In general, three measurements are required to obtain the optical properties of any tissue, namely diffuse transmitted light, diffuse reflected light, and transmitted ballistic beam. In this report, these parameters were measured in vitro using intact rat brain slices of 500 μm thickness via a two-integrating spheres optical setup. Then, an inverse adding doubling method was used to extract the optical properties of the tissue from the collected data. These experiments were repeated to cover the whole brain tissue with high spatial resolution for the three different cuts (transverse, sagittal, and coronal

  7. Detection and characterization of chemical-induced abnormal tissue and rat tumors at different stages using fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Chen, Wei R.; Jassemnejad, Baha; Crull, Jason; Knobbe, Edward T.; Nordquist, Robert E.

    1996-04-01

    Fluorescence spectroscopy of diseased tissues, including chemical-induced rat liver, kidney and testis lesions, as well as murine mammary tumor, was studied. The rat liver, kidney and testis tissues were excited by radiation of 350 and 366 nm, which appeared to provide the optimal differentiation between normal and lesion tissues; the tumor tissues were excited by both 350 nm and 775 nm wavelengths. In comparison with normal liver tissue, at (lambda) ex equals 366 nm, the fluorescent spectrum of liver lesion showed a clear red shift around the emission peak of 470 nm, the major native fluorescent peak of organized tissue. When excited by 350 nm wavelength, all the chemically induced lesion tissues (liver, kidney and testis) appeared to cause a significant reduction of emission intensity at the 470 nm peak. While the 775 nm excitation did not reveal any significant difference among tumor, muscle and skin tissues, the 350 nm excitation did provide some interesting features among the tumor tissues at different stages. Compared with muscle tissue, the viable tumor showed an overall reduction of emission intensity around 470 nm. In addition, the viable tumor tissue showed a secondary emission peak at 390 nm with necrotic tumor tissue having a reduced intensity. The histology of both viable and necrotic tumor tissue was examined and appeared to correlate with the results of the fluorescent spectroscopy observation.

  8. Effects of carnosine plus vitamin E and betaine treatments on oxidative stress in some tissues of aged rats.

    PubMed

    Çoban, Jale; Bingül, Ilknur; Yesil-Mizrak, Kubra; Dogru-Abbasoglu, Semra; Oztezcan, Serdar; Uysal, Mujdat

    2013-07-01

    Oxidative stress plays an important role in aging. Effects of several antioxidants on age-related oxidative stress have been investigated. Carnosine (CAR) and betaine have antioxidant actions. The combination of CAR with vitamin E(CAR+E) increases its antioxidant efficiency. We investigated the effects of CAR+E and betaine treatments on oxidative and antioxidative status in liver, heart and brain tissues of aged rats. Experiments were carried out on young (5 months)and aged (22 months) male Wistar rats. Aged rats were given CAR (250 mg/kg; i.p.; 5 days per week) and vitamin E (200mg/kg; i.m.; twice per week) or betaine (1% w/v) for two months. Malondialdehyde (MDA) and diene conjugate (DC)levels and antioxidants were measured. MDA and DC levels were higher in tissues of aged rats than young rats. Glutathione(GSH) levels decreased in liver, but not heart and brain. There were no changes in vitamin E and vitamin C levels and superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione transferase (GST) activities in tissues of aged rats. CAR+E treatment was observed to decrease MDA and DC levels in tissues of aged rats. However, betaine decreased only hepatic MDA and DC levels. Both CAR+E and betaine increased hepatic GSH and vitamin E levels, but these treatments did not affect antioxidant enzyme activities. These results suggest that CAR+E treatment seems to be useful to decrease oxidative stress in liver, heart and brain tissues, but betaine is only effective in liver tissue of aged rats. PMID:23701646

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. Smoking affects the self-healing capacity of periodontal tissues. A histological study in the rat.

    PubMed

    Benatti, Bruno Braga; César-Neto, João Batista; Gonçalves, Patrícia Furtado; Sallum, Enílson Antônio; Nociti, Francisco Humberto

    2005-10-01

    This study aimed to evaluate in rats the impact of cigarette smoke inhalation (CSI) and nicotine administration (NA) on a periodontal healing model in the absence of a plaque biofilm. Wistar rats (n = 42) were assigned to three groups: Group 1, control (n = 14); Group 2, NA (3 mg kg(-1)) (n = 14); and Group 3, CSI (n = 14). Thirty days after CSI and NA exposure, fenestration defects were created buccally to the distal root of the first mandibular molar. The animals were killed 21 d later and their mandibles were processed for histological examination. The percentage of bone fill and the density of newly formed bone were assessed histometrically. Intergroup analysis demonstrated that compared to the control and NA groups, CSI was associated with a reduced rate of bone repair. No new cementum had been formed along the root surface in any of the three groups. It is concluded that cigarette smoke reduces the self-healing capacity of periodontal tissues.

  14. Syzigium cumini seed extracts reduce tissue damage in diabetic rat brain.

    PubMed

    Stanely Mainzen Prince, P; Kamalakkannan, N; Menon, Venugopal P

    2003-02-01

    Syzigium cumini commonly known as Jamun, is widely used in different parts of India for the treatment of diabetes mellitus. Oral administration of an aqueous Jamun seed extract (JSEt) for 6 weeks caused a significant decrease in lipids, thiobarbituric acid reactive substances (TBARS) and an increase in catalase and superoxide dismutase in the brain of alloxan induced diabetic rats. Oral administration of an alcoholic JSEt for 6 weeks brought back all the parameters to near normal. The effect of alcoholic JSEt (100 mg/kg) was better than aqueous JSEt (5 g/kg). The effect of both these extracts was better than glibenclamide (600 microg/kg). Thus, our study shows that S. cumini seed extracts reduce tissue damage in diabetic rat brain. PMID:12648817

  15. 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

  16. [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

  17. 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

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

    PubMed

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

    2014-07-01

    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.

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

    PubMed

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

    2014-07-01

    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

  20. 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.

  1. 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

  2. Effectiveness of Aloe vera on the antioxidant status of different tissues in irradiated rats.

    PubMed

    Saada, H N; Ussama, Z S; Mahdy, A M

    2003-12-01

    This study was performed to evaluate the role of Aloe vera (Aloe barbadensis Miller) on the antioxidant status in different tissues of animals whole body exposed to 7 Gy gamma radiations, delivered as a shot dose. Aloe vera (leaf juice filtrate) was supplemented daily to rats (0.25 ml/kg body weight/day), by gavage, 5 days before irradiation and 10 days after irradiation. Experimental investigations performed 3, 7 and 10 days after exposure to radiation showed that Aloe vera treatment has significantly minimized the radiation-induced increase in the amount of malondialdehyde in liver, lungs, and kidney tissues of irradiated rats. Significant amelioration in superoxide dismutase (SOD) and catalase activities was observed from the 3rd up to the 10th days for lungs, on the 7th and 10th days for kidneys and at 10 days for liver. Data obtained showed that for the different tissues, improvement in the decrease of reduced glutathione (GSH) contents was obvious on the 10th day after irradiation. Treatment with Aloe vera was also effective in minimizing the radiation-induced increase in plasma glucose levels throughout the experimental period, while it has not ameliorated the increase in plasma insulin levels. It could be concluded that the synergistic relationship between the elements found in the leaf of Aloe vera could be a useful adjunct for maintaining the integrity of the antioxidant status.

  3. 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

  4. [Comparative analysis of tissue reaction to acrylic resin materials in studies on Wistar strain rats].

    PubMed

    Sobolewska, E

    1999-01-01

    The study takes up the issue of assessing rat tissue reaction to operatively inserted implants of different acrylic resin materials used in prosthetic dentistry. The materials subjected to analysis were polyacrylics: Vertex Soft, Vertex R.S., Vertex S.C., Superacryl and silicone material Molloplast B. The prolongation of life and the dynamic development of prosthetic treatment have caused removable dentures to be used longer and among more people. Polymerised acrylic resin material of these dentures is a potential pathogenic factor to the oral cavity mucosa which is in contact with it. As many as 20 to 70% of patients using removable acrylic dentures suffer from prosthetic stomatopathy. It is considered that the mucosa irritation may be caused by denture trauma, a mycotic infection or toxic action of some components of acrylic materials. Therefore the use of new generation acrylic materials in producing prosthetic dentures needs a precise assessment of undesirable local and systemic effects. A comparative analysis of the effect of correctly polymerised acrylic material on rat mucosa, parotid glands and lymphatic nodes was carried out. Systemic toxicity of these materials was assessed. Acrylic plates were prepared from the most often used acrylic resin materials in the Department of Prosthetic Dentistry PAM and a silicone material (these materials were polymerised precisely according to the producers instruction). Before implantation the plates underwent a thermodynamic analysis in order to ensure that the polymerisation process was carried out correctly and to determine thermal resistance of particular materials. Next sterile acrylic plates were implanted in rats under general anaesthesia. The animals were divided into 6 groups, 10 rats each. In four groups acrylic plates were implanted, in one group silicone material plates were implanted and it represented the comparative group, in one control group an incision of the buccal mucosa was made. The rats were

  5. [Comparative analysis of tissue reaction to acrylic resin materials in studies on Wistar strain rats].

    PubMed

    Sobolewska, E

    1999-01-01

    The study takes up the issue of assessing rat tissue reaction to operatively inserted implants of different acrylic resin materials used in prosthetic dentistry. The materials subjected to analysis were polyacrylics: Vertex Soft, Vertex R.S., Vertex S.C., Superacryl and silicone material Molloplast B. The prolongation of life and the dynamic development of prosthetic treatment have caused removable dentures to be used longer and among more people. Polymerised acrylic resin material of these dentures is a potential pathogenic factor to the oral cavity mucosa which is in contact with it. As many as 20 to 70% of patients using removable acrylic dentures suffer from prosthetic stomatopathy. It is considered that the mucosa irritation may be caused by denture trauma, a mycotic infection or toxic action of some components of acrylic materials. Therefore the use of new generation acrylic materials in producing prosthetic dentures needs a precise assessment of undesirable local and systemic effects. A comparative analysis of the effect of correctly polymerised acrylic material on rat mucosa, parotid glands and lymphatic nodes was carried out. Systemic toxicity of these materials was assessed. Acrylic plates were prepared from the most often used acrylic resin materials in the Department of Prosthetic Dentistry PAM and a silicone material (these materials were polymerised precisely according to the producers instruction). Before implantation the plates underwent a thermodynamic analysis in order to ensure that the polymerisation process was carried out correctly and to determine thermal resistance of particular materials. Next sterile acrylic plates were implanted in rats under general anaesthesia. The animals were divided into 6 groups, 10 rats each. In four groups acrylic plates were implanted, in one group silicone material plates were implanted and it represented the comparative group, in one control group an incision of the buccal mucosa was made. The rats were

  6. Rat nasal tissue activation of benzo(a)pyrene and 2-aminoanthracene to mutagens in Salmonella typhimurium

    SciTech Connect

    Bond, J.A.; Li, A.P.

    1983-01-01

    Cytochrome P-450-dependent monooxygenase activity has been measured in the nasal turbinates of dogs and rats. The capacity of male Fischer-344 rat nasal tissue to bioactiviate benzo(a)pyrene (BaP) and 2-aminoanthracene (2-AA) to mutagens in Salmonella typhimurium was investigated. 2-AA was mutagenic in strains TA98 and TA100 when nasal tissue S-9 was utilized as the activation enzyme system and BaP was mutagenic in strain TA100. At all doses and protein concentrations tested, 2-AA displayed nearly 500-1000 times greater bacterial mutagenicity than BaP. In strain TA-100, nasal tissue S-9 was approximately twice as active toward 2-AA as lung S-9 and 75% as active as liver S-9. Aryl hydrocarbon hydroxylase activity was detected in rat nasal tissue when /sup 14/C-BaP was used as a substrate. Rat nasal tissue metabolized BaP to several oxidized metabolites which included dihydrodiols, quinones, and phenols. 3-Hydroxybenzo(a)pyrene and BaP-3,6-quinone were the major metabolites detected (150 pmoles/mg protein/30 min). These results indicate that rat nasal tissue can metabolize promutagens to reactive species which may play an important role in xenobiotic-induced nasal tumors.

  7. 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

  8. 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.

  9. Optically based-indentation technique for acute rat brain tissue slices and thin biomaterials

    PubMed Central

    Lee, S. J.; Sun, J.; Flint, J. J.; Guo, S.; Xie, H. K.; King, M. A.; Sarntinoranont, M.

    2011-01-01

    Currently, micro-indentation testing of soft biological materials is limited in its capability to test over long time scales due to accumulated instrumental drift errors. As a result, there is a paucity of measures for mechanical properties such as the equilibrium modulus. In this study, indentation combined with optical coherence tomography (OCT) was used for mechanical testing of thin tissue slices. OCT was used to measure the surface deformation profiles by placing spherical beads onto submerged test samples. Agarose-based hydrogels at low-concentrations (w/v, 0.3–0.6 %) and acute rat brain tissue slices were tested using this technique over a 30 min time window. To establish that tissue slices maintained cell viability, allowable testing times were determined by measuring neuronal death or degeneration as a function of incubation time with Fluor-Jade C (FJC) staining. Since large deformations at equilibrium were measured, displacements of surface beads were compared with finite element elastic contact simulations to predict the equilibrium modulus, μ∞. Values of μ∞ for the low- concentration hydrogels ranged from 0.07–1.8 kPa, and μ∞ for acute rat brain tissue slices was 0.13 ± 0.04 kPa for the cortex and 0.09 ± 0.015 kPa for the hippocampus (for Poisson ratio=0.35). This indentation technique offers a localized, real-time, and high resolution method for long-time scale mechanical testing of very soft materials. This test method may also be adapted for viscoelasticity, for testing of different tissues and biomaterials, and for analyzing changes in internal structures with loading. PMID:21290586

  10. 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

  11. Distribution and accumulation of caffeine in rat tissues and its inhibition on semicarbazide-sensitive amine oxidase.

    PubMed

    Che, Baoquan; Wang, Lin; Zhang, Zhe; Zhang, Yongqian; Deng, Yulin

    2012-10-01

    Wistar rats were treated with caffeine or 2-bromoethylamine, the effect of caffeine on the activity of semicarbazide-sensitive amine oxidase (SSAO) in rat serum and tissues was studied using various LC-MS methods. Caffeine was found to present in all tissues after administration for 10 days and accumulated for 25 days. The level of caffeine was high in brain and liver, and the SSAO activity in all tissues was found to be inhibited by caffeine. As the concentration of caffeine increased, the SSAO activity decreased. The inhibition ratio was correlated to the levels of caffeine present. We presume that caffeine may treat with SSAO activity associated diseases.

  12. Chronic ethanol and nicotine interaction on rat tissue antioxidant defense system.

    PubMed

    Husain, K; Scott, B R; Reddy, S K; Somani, S M

    2001-10-01

    Ethanol consumption and cigarette smoking are common in societies worldwide and have been identified as injurious to human health. This study was undertaken to examine the interactive effects of chronic ethanol and nicotine consumption on the antioxidant defense system in different tissues of rat. Male Fisher-344 rats were divided into four groups of five animals each and treated for 6.5 weeks as follows: (1) Control rats were administered normal saline orally; (2) ethanol (20% [wt./vol.]) was given orally at a dose of 2 g/kg; (3) nicotine was administered subcutaneously at a dose of 0.1 mg/kg; and (4) a combination of ethanol plus nicotine was administered by the route and at the dose described above. The animals were killed 20 h after the last treatment, and liver, lung, kidney, and testes were isolated and analyzed. Chronic ingestion of ethanol resulted in a significant depletion of glutathione (GSH) content in liver, lung, and testes, whereas chronic administration of nicotine significantly depleted GSH content in liver and testes. The combination of ethanol plus nicotine resulted in a significant depletion of GSH content in liver, lung, and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased superoxide dismutase (SOD) activity in liver and decreased SOD activity in kidney. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly decreased catalase (CAT) activity in liver and increased CAT activity in kidney and testes. Chronic ingestion of ethanol resulted in a significant decrease in glutathione peroxidase (GSH-Px) activity in liver and kidney, whereas a combination of ethanol plus nicotine increased GSH-Px activity in liver and decreased GSH-Px activity in kidney and testes. Ethanol, nicotine, or a combination of ethanol plus nicotine significantly increased lipid peroxidation, respectively, in liver. It is suggested that prolonged exposure to ethanol and nicotine produce similar, and in some cases

  13. 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

  14. Changes in the antioxidant defence and in selenium concentration in tissues of vanadium exposed rats.

    PubMed

    Sanchez-Gonzalez, Cristina; Bermudez-Peña, Carmen; Trenzado, Cristina E; Goenaga-Infante, Heidi; Montes-Bayon, María; Sanz-Medel, Alfredo; Llopis, Juan

    2012-08-01

    Vanadium is an element whose role as a micronutrient for humans is not yet completely established, but which has been shown to possess hypoglycaemic properties in diabetes. In an earlier study, we showed that in STZ-diabetic rats, exposure to 1 mg V per day has no effect on glycaemia or on antioxidant status. When the exposure was raised to 3 mg V per day there was a hypoglycaemic effect, together with reduced Se in the tissues, which reduced antioxidant defences. The aim of the present study was to examine whether exposure to 1 mg V per day modifies Se nutritional status and/or antioxidant defences in healthy rats. Two groups of rats were examined: control and vanadium-treated. Vanadium, as bis(maltolato)oxovanadium(iv), was supplied in the drinking water. The experiment had a duration of five weeks. Selenium was measured in excreta, serum, skeletal muscle, kidneys, liver, heart, femur and adipose tissue. Number of red (RBC) and white (WBC) blood cells and haemoglobin (Hb) were determined in samples of whole blood. Glutathione peroxidase (GPx), glutathione transferase (GST), catalase (CAT) and NAD(P)H:quinine-oxidoreductase1 (NQO1) activity, and malondialdehyde (MDA) in the liver were evaluated. Treatment significantly reduced food intake, produced an anaemic state, and decreased Se absorption and Se content in serum, kidneys and the liver. GPx, GST and NQO1 activity were decreased in the liver, while MDA levels rose. We conclude that healthy rats are more sensitive than diabetic ones to the effects of V. This should be taken into account for populations that are particularly exposed to V for environmental reasons, and/or that consume V as a nutritional supplement.

  15. Bioavailability, tissue distribution and hypoglycaemic effect of vanadium in magnesium-deficient rats.

    PubMed

    Sánchez, Cristina; Torres, Miguel; Bermúdez-Peña, María C; Aranda, Pilar; Montes-Bayón, María; Sanz-Medel, Alfredo; Llopis, Juan

    2011-12-01

    Vanadium is an element whose role as a micronutrient and hypoglycaemic drug has yet to be fully clarified. The present study was undertaken to investigate the bioavailability and tissue distribution of vanadium and its interactions with magnesium in healthy and in magnesium-deficient rats, in order to determine its role as a micronutrient and antidiabetic agent. Four groups were used: control (456.4 mg magnesium and 0.06 mg vanadium/kg food); control treated with 1mg vanadium/day; magnesium-deficient (164.4 mg magnesium/kg food and 0.06 mg vanadium/kg food); and magnesium-deficient treated with 1 mg vanadium/day. The vanadium was supplied in the drinking water as bis(maltolato)oxovanadium (IV). The experiment had a duration of five weeks. We measured vanadium and magnesium in excreta, serum, skeletal muscle, kidney, liver, adipose tissue and femur. Fasting glucose, insulin and total antioxidant status (TAS) in serum were studied. The vanadium treatment applied to the control rats reduced the absorption, retention, serum level and femur content of magnesium. Magnesium deficiency increased the retention and serum level of vanadium, the content of vanadium in the kidney, liver and femur (organs where magnesium had been depleted), serum glycaemia and insulin, and reduced TAS. V treatment given to magnesium-deficient rats corrected magnesium content in muscle, kidney and liver and levels of serum glucose, insulin and TAS. In conclusion, our results show interactions between magnesium and vanadium in the digestive and renal systems. Treatment with vanadium to magnesium-deficient rats corrected many of the alterations that had been generated by the magnesium deficiency.

  16. The neuroprotective effect of cornus MAS on brain tissue of Wistar rats.

    PubMed

    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.

  17. Intrinsic optical signals of brains in rats during loss of tissue viability: effect of brain temperature

    NASA Astrophysics Data System (ADS)

    Kawauchi, Satoko; Sato, Shunichi; Ooigawa, Hidetoshi; Nawashiro, Hiroshi; Kikuchi, Makoto

    2007-07-01

    Noninvasive, real-time monitoring of brain tissue viability is crucial for the patients with stroke, traumatic brain injury, etc. For this purpose, measurement of intrinsic optical signal (IOS) is attractive because it can provide direct information about the viability of brain tissue noninvasively. We performed simultaneous measurements of IOSs that are related to morphological characteristics, i.e., light scattering, and energy metabolism for rat brains during saline infusion as a model with temporal loss of brain tissue viability. The results showed that the scattering signal was steady in an initial phase but showed a drastic, triphasic change in a certain range of infusion time, during which the reduction of CuA in cytochrome c oxidase started and proceeded rapidly. The start time of triphasic scattering change was delayed for about 100 s by lowering brain temperature from 29°C to 24°C, demonstrating the optical detection of cerebroprotection effect by brain cooling. Electron microscopic observation showed morphological changes of dendrite and mitochondria in the cortical surface tissue after the triphasic scattering change, which was thought to be associated with the change in light scattering we observed. These findings suggest that the simultaneous measurement of the intrinsic optical signals related to morphological characteristics and energy metabolism is useful for monitoring tissue viability in brain.

  18. Optical assessment of tissue anisotropy in ex vivo distended rat bladders

    NASA Astrophysics Data System (ADS)

    Alali, Sanaz; Aitken, Karen J.; Shröder, Annette; Bagli, Darius J.; Alex Vitkin, I.

    2012-08-01

    Microstructural remodelling in epithelial layers of various hollow organs, including changes in tissue anisotropy, are known to occur under mechanical distension and during disease processes. In this paper, we analyze how bladder distension alters wall anisotropy using polarized light imaging (followed by Mueller matrix decomposition). Optical retardance values of different regions of normal rat bladders under different distension pressures are derived. Then optical coherence tomography is used to measure local bladder wall thicknesses, enabling the calculation of the tissue birefringence maps as a measure of the tissue anisotropy. Selected two-photon microscopy is also performed to better understand the compositional origins of the obtained anisotropy results. The dome region of the bladder shows maximum birefringence when the bladder is distended to high pressures, whereas the ventral remains roughly isotropic during distension. In addition, the average anisotropy direction is longitudinal, along the urethra to dome. The derived wall anisotropy trends are based on birefringence as an intrinsic property of the tissue organization independent of its thickness, to aid in understanding the structure-functions relation in healthy bladders. These new insights into the wall microstructure of ex vivo distending bladders may help improve the functionality of the artificially engineered bladder tissues.

  19. 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

  20. 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

  1. The neuroprotective effect of cornus MAS on brain tissue of Wistar rats.

    PubMed

    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

  2. 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.

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

    PubMed Central

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

    2012-01-01

    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

  4. 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

  5. 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.

  6. Dermal exposure to pesticides modifies antioxidant enzymes in tissues of rats.

    PubMed

    Panemangalore, M; Bebe, F N

    2000-07-01

    Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities were determined in rat tissues after dermal exposure to pesticides. Two experiments were conducted in male SD rats, 190-210 g body weight. Acephate (ACP), methamidophos (MAP) and nicotine (NIC) were dissolved either individually or together in 0.25 mL of 50% ethanol, which contained: AP = 12.6 or MAP 1.3 or NIC = 9.6 mg; EXP 1--individual pesticide exposure; 64 rats, 16/group; EXP 2--mixture of AP + MAP + NIC at levels of 1X, 2X, 3X; 48 rats, 12/group; 0.25 mL of solution or ethanol (Controls) was applied to 25 mm2 area of shaved skin 3 times a week. Half the rats were terminated after 4 weeks and the rest after 4 weeks of stopping exposure. Single pesticides decreased erythrocyte (RBC) SOD by 17% after exposure and in the NIC group after post exposure (P#0.05). Increasing concentrations of AP + MAP + NIC mixture elevated RBC SOD by 22% in the 2X and 3X groups and CAT by 13% in the 3X group (P#0.05); post exposure increased RBC SOD by 2-3 fold and CAT activity by 13% in all 3 groups. Liver GPX increased by 30-40% and CAT decreased by 12% in all exposed and post exposed groups (P#0.05). The results suggest that dermal exposure to mixtures of pesticides can selectively induce SOD, CAT and GPX activities in RBC and liver. PMID:10874619

  7. Dermal exposure to pesticides modifies antioxidant enzymes in tissues of rats.

    PubMed

    Panemangalore, M; Bebe, F N

    2000-07-01

    Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX) activities were determined in rat tissues after dermal exposure to pesticides. Two experiments were conducted in male SD rats, 190-210 g body weight. Acephate (ACP), methamidophos (MAP) and nicotine (NIC) were dissolved either individually or together in 0.25 mL of 50% ethanol, which contained: AP = 12.6 or MAP 1.3 or NIC = 9.6 mg; EXP 1--individual pesticide exposure; 64 rats, 16/group; EXP 2--mixture of AP + MAP + NIC at levels of 1X, 2X, 3X; 48 rats, 12/group; 0.25 mL of solution or ethanol (Controls) was applied to 25 mm2 area of shaved skin 3 times a week. Half the rats were terminated after 4 weeks and the rest after 4 weeks of stopping exposure. Single pesticides decreased erythrocyte (RBC) SOD by 17% after exposure and in the NIC group after post exposure (P#0.05). Increasing concentrations of AP + MAP + NIC mixture elevated RBC SOD by 22% in the 2X and 3X groups and CAT by 13% in the 3X group (P#0.05); post exposure increased RBC SOD by 2-3 fold and CAT activity by 13% in all 3 groups. Liver GPX increased by 30-40% and CAT decreased by 12% in all exposed and post exposed groups (P#0.05). The results suggest that dermal exposure to mixtures of pesticides can selectively induce SOD, CAT and GPX activities in RBC and liver.

  8. Oxidative status and citrate concentration in rat tissues during experimental hyperthyroidism and melatonin treatment.

    PubMed

    Popov, S S; Pashkov, A N; Popova, T N; Zoloedov, V I; Semenikhina, A V; Rakhmanova, T I

    2007-08-01

    Biochemiluminescence increased, while aconitate hydratase activity and citrate accumulation in tissues of the liver and heart and blood decreased in rats with experimental hyperthyroidism. These changes reflect activation of free radical oxidation, damage to enzyme molecules with reactive oxygen species, and impaired utilization of citrate under pathological conditions. Melatonin treatment during hyperthyroidism normalized aconitate hydratase activity and citrate concentration. Biochemiluminescence study showed that the effect of melatonin is related to antioxidant activity of this hormone, inhibition of free radical oxidation, and suppression of reactive oxygen species generation.

  9. [Endogenous ethanol in the blood and tissues of rats with hypobaric hypoxia].

    PubMed

    Tarasov, Iu A; Ostrovskiĭ, Iu M; Satanovskaia, V I; Liopo, A V; Velichko, M G; Abakumov, G Z

    1989-01-01

    Albino male rats weighing 160-180 g were used to study the effect of short-term hypobaric hypoxia (ascent in an altitude chamber to 2500 m and 5000 m for 1 hr) on endogenous ethanol measured in blood, brain and liver; simultaneously enzymes responsible for ethanol and acetaldehyde metabolism were determined. Endogenous ethanol in blood and tissues was found to be a very sensitive marker of hypoxia which was not correlated with lactate, pyruvate, lipid peroxidation or 11-hydroxycorticosteroids. The latter parameters varied in response to severe hypoxia.

  10. 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.

  11. 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.

  12. Chronic Tissue Response to Untethered Microelectrode Implants in the Rat Brain and Spinal Cord

    PubMed Central

    ERSEN, Ali; ELKABES, Stella; FREEDMAN, David S.; SAHIN, Mesut

    2015-01-01

    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. PMID:25605679

  13. 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.

  14. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

  15. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats

    PubMed Central

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  16. Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats.

    PubMed

    Moriya, Chihiro; Satoh, Hiroaki

    2016-01-01

    We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects. PMID:27652270

  17. Tissue response of defined collagen-elastin scaffolds in young and adult rats with special attention to calcification.

    PubMed

    Daamen, W F; Nillesen, S T M; Hafmans, T; Veerkamp, J H; van Luyn, M J A; van Kuppevelt, T H

    2005-01-01

    Collagen-elastin scaffolds may be valuable biomaterials for tissue engineering because they combine tensile strength with elasticity. In this study, the tissue response to and the calcification of these scaffolds were evaluated. In particular, the hypothesis was tested that calcification, a common phenomenon in biomaterials, may be due to microfibrils within the elastic fibre, and that these microfibrils might generate a tissue response. Four scaffolds were subcutaneously implanted, viz. collagen, collagen + pure elastin, collagen+microfibril-containing, and collagen + pulverised elastic ligament (the source for elastin). Explants were evaluated at day 3, 7 and 21. In young Sprague Dawley rats, collagen + ligament calcified substantially, whereas collagen + elastin (with and without microfibrils) calcified less, and collagen did not. Calcification started at elastic fibres. In both Sprague Dawley and Wistar adult rats, however, none of the scaffolds calcified. Mononuclear cell infiltration was prominent in young and adult Sprague Dawley rats. In adult Wistar rats, this infiltration was associated with the presence of microfibrils. Degradation of scaffolds and new matrix formation were related with cellular influx and degree of vascularisation. In conclusion, absence of microfibrils from the elastic fibre does not prevent calcification in young Sprague Dawley rats, but does reduce the tissue response in adult Wistar rats. Cellular response and calcification differs with age and strain and therefore the choice of animal model is of key importance in biomaterial evaluation.

  18. Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

    PubMed Central

    Li, Zhenyu; Li, Aiping; Gao, Jining; Li, Hong; Qin, Xuemei

    2016-01-01

    Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF.

  19. Kidney Tissue Targeted Metabolic Profiling of Unilateral Ureteral Obstruction Rats by NMR

    PubMed Central

    Li, Zhenyu; Li, Aiping; Gao, Jining; Li, Hong; Qin, Xuemei

    2016-01-01

    Renal interstitial fibrosis is a common pathological process in the progression of kidney disease. A nuclear magnetic resonance (NMR) based metabolomic approach was used to analyze the kidney tissues of rats with renal interstitial fibrosis (RIF), induced by unilateral ureteral obstruction (UUO). The combination of a variety of statistical methods were used to screen out 14 significantly changed potential metabolites, which are related with multiple biochemical processes including amino acid metabolism, adenine metabolism, energy metabolism, osmolyte change and induced oxidative stress. The exploration of the contralateral kidneys enhanced the understanding of the disease, which was also supported by serum biochemistry and kidney histopathology results. In addition, the pathological parameters (clinical chemistry, histological and immunohistochemistry results) were correlated with the significantly changed differential metabolites related with RIF. This study showed that targeted tissue metabolomic analysis can be used as a useful tool to understand the mechanism of the disease and provide a novel insight in the pathogenesis of RIF. PMID:27695416

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. Application of coenzyme Q10 for accelerating soft tissue wound healing after tooth extraction in rats.

    PubMed

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

    2014-12-10

    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.

  7. Transmission electron microscopy of heart and liver tissues from rats fed with gums arabic and tragacanth.

    PubMed

    Anderson, D M; Ashby, P; Busuttil, A; Kempson, S A; Lawson, M E

    1984-04-01

    Transmission electron microscopy has been used to examine the ultrastructure of rat hearts and livers after diet supplementation with (a) 0, 0.5, 1.5, 2.5 and 3.5% (w/w) gum tragacanth (GT) for 91 days, (b) 0 and 1% GT for 5 days (c) 0, 1, 4 and 8% (w/w) gum arabic (GA) for 28 days. The preparation and scrutiny of the electron micrographs was undertaken by two independent teams of specialists. There were no detectable abnormalities in any of the organelles in the heart and liver specimens from any of the test animals and no inclusions nor other pathological changes were observed. All micrographs showed normal, healthy tissues; particular attention was given to the mitochondria in hepatocytes as they serve as sensitive indicators of the health and state of activity of cells. In addition, the data obtained from assays of the microsomal protein and cytochrome P-450 content of the livers showed that GA and GT did not cause inductive effects. These results do not support earlier suggestions, based on in vitro assays, that GA and GT cause changes in the function of rat heart and liver mitochondria and liver microsomes; however, they confirm a report by Zbinden that the ingestion of GT does not produce abnormalities in the cardiac function of rats.

  8. Effects of subchronic digestive exposure to organic or inorganic cadmium on biomarkers in rat tissues.

    PubMed

    Hispard, F; de Vaufleury, A; Martin, H; Devaux, S; Cosson, R P; Scheifler, R; Richert, L; Berthelot, A; Badot, P-M

    2008-07-01

    In an experimental food chain, Wistar rats were fed cadmium (Cd) in an inorganic (CdCl(2)) or organic (mainly associated with metallothionein from Helix aspersa snail viscera) form. After 1 month of exposure to 100 microg inorganic Cd g(-1) in food, an induction of metallothionein was observed in all target tissues. In liver, glutathione peroxidase (GSH-Px) activity decreased and alanine aminotransferase (ALAT) activity increased, suggesting that Cd causes hepatotoxicity. However, lipid peroxidation as well as catalase and caspase 3 (a marker of apoptosis) activities were not modified. At a rather low exposure (2.5 microg Cd g(-1)), metallothionein level in the kidney was found to be the most sensitive biomarker of exposure for both Cd forms. In the small intestine of rats ingesting inorganic Cd, metallothionein expression was significantly higher than that observed for rats fed organic Cd. Present results allowed proposing a simple design to assess the effect of a chemical in a trophic transfer approach.

  9. 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.

  10. Hyperplasia of brown adipose tissue after chronic stimulation of beta 3-adrenergic receptor in rats.

    PubMed

    Nagase, I; Sasaki, N; Tsukazaki, K; Yoshida, T; Morimatsu, M; Saito, M

    1994-12-01

    When mammals are exposed to a cold environment for a long time, the capacity of nonshivering thermogenesis by brown adipose tissue (BAT) increases in association with the increased expression of some specific proteins and tissue hyperplasia, which are totally dependent on sympathetic innervation to this tissue. To clarify roles of the beta-adrenergic mechanism in BAT hyperplasia, the effects of chronic administration of various beta-adrenergic agonists on BAT were examined in rats, especially focusing on some agonists to the beta 3-adrenoceptor which is present specifically in adipocytes. Chronic administration of noradrenaline or isoproterenol for 7-10 days produced a marked increase in the tissue contents of DNA, total protein, mitochondrial uncoupling protein, and insulin-regulatable glucose transporter protein. The trophic effects of noradrenaline and isoproterenol were mimicked by chronic administration of beta 3-adrenergic agonists, such as CL316,243, BRL 26830A, and ICI D7114. These results suggest that the beta 3-adrenoceptor plays important roles for hyperplasia of BAT, and thereby increasing in the capacity of thermogenesis. PMID:7745877

  11. 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

  12. Distribution of prenyltransferases in rat tissues. Evidence for a cytosolic all-trans-geranylgeranyl diphosphate synthase.

    PubMed

    Ericsson, J; Runquist, M; Thelin, A; Andersson, M; Chojnacki, T; Dallner, G

    1993-01-15

    The present study describes the presence of two different geranylgeranyl diphosphate (GGPP) synthase activities, one cytosolic and one membrane-associated, in a number of rat tissues. Both enzymes utilize farnesyl diphosphate (FPP) and isopentenyl diphosphate (IPP) as substrates, but they give rise to different products. The membrane-associated activity produces trans,trans,cis-(E,E,Z)-GGPP, involved in the biosynthesis of long-chain polyprenols. The cytosolic activity produces only the all-trans-(E,E,E) isomer of GGPP, which is utilized as substrate in cytosolic protein prenylation reactions. All-trans-GGPP synthase activity was recovered in the cytosolic fraction from all tissues investigated, but the specific activities varied. The highest specific activities were found in brain, spleen, and testis, followed by kidney and liver. The enzyme activity in rat brain cytosol was further characterized and found to exhibit a narrow pH optimum around 5.0-6.0 and to be highly stimulated by Zn2+. Maximal stimulation was attained with 1 mM Zn2+, whereas Mg2+ had no effect on the enzyme activity. The all-trans-GGPP synthase activity exhibited high affinities for its substrates, i.e. the apparent Km values for FPP and IPP were found to be 0.6 and 3.5 microM, respectively. When rats were fed mevinolin (lovastatin), FPP and all-trans-GGPP synthase activities were affected differently in certain tissues. Mevinolin treatment resulted in an increase in FPP but a decrease in all-trans-GGPP synthase activity in rat liver and kidney. In spleen mevinolin treatment caused a greater than 70% decrease in all-trans-GGPP synthase activity, while FPP synthase was almost unaffected. The presence of two different GGPP synthase activities in the cell, together with the fact that FPP and all-trans-GGPP synthesis in the cytosol are regulated independently, may be of significance in the regulation of isoprenoid biosynthesis, as well as of protein isoprenylation.

  13. Tissue ACE inhibition improves microcirculation in remote myocardium after coronary stenosis: MR imaging study in rats.

    PubMed

    Hiller, Karl-Heinz; Ruile, Philipp; Kraus, Günter; Bauer, Wolfgang R; Waller, Christiane

    2010-12-01

    ACE inhibition has been shown to improve left ventricular (LV) and myocardial blood flow. Previous data regarding changes in capillary density and angiogenesis during ACE inhibition are controversial. The aim of the following study was to determine myocardial microcirculation and heart function in the rat after coronary stenosis using non invasive MR imaging techniques. MR spin labeling and cine techniques have been performed in female Wistar rats 2weeks after coronary artery stenosis. In one group, animals were treated with quinapril in a dose of 6mg/kg/day. Perfusion, relative blood volume (RBV), LV mass and function were determined non-invasively 2weeks after treatment. Finally, fibrosis and capillary density were analyzed histologically. Additionally, hemodynamic measurements were realized in a further group in order to calculate systemic vascular resistance (SVR). Quinapril resulted in a significant increase in perfusion at rest in the remote and the poststenotic myocardium with improved systolic function and a decrease in SVR compared to the non treated control group. Additionally, maximum perfusion and RBV were slightly elevated whereas capillary density was unchanged among the groups. MRI allows for non-invasive quantification of functional microcirculation and heart function. In addition to the well known effect of ACE inhibition on systolic function, treatment with the tissue specific ACE inhibitor quinapril revealed an important microvascular improvement, especially at arteriolar level. These findings may support the use of tissue ACE inhibitors to improve cardiac microcirculation after ischemia.

  14. Rat adipose tissue amino acid metabolism in vivo as assessed by microdialysis and arteriovenous techniques.

    PubMed

    Kowalski, T J; Wu, G; Watford, M

    1997-09-01

    In fed, anesthetized rats, microdialysis demonstrated a net release of glycerol, glutamine, serine, tyrosine, and taurine and a net uptake of glutamate, aspartate, glycine, and arginine across the inguinal adipose depot. However, the results also indicated excessive proteolysis associated with implantation of the microdialysis probe, and a novel arteriovenous difference technique was developed. Arteriovenous difference across the inguinal fat pat demonstrated a net uptake of glucose and a net release of lactate and glycerol. Starvation (48 h) resulted in higher rates of glycerol and lactate release with lower rates of glucose uptake. A net uptake of triacylglycerol was seen in starved-refed animals. Net glutamine, tyrosine, and taurine release was seen in fed and starved animals, but in starved-refed animals taurine and serine were the only amino acids showing significant release. No significant net uptake or release of ammonia, pyruvate, or alanine was observed. These experiments confirm that adipose tissue is a site of glutamine synthesis and suggest that the principal substrates are derived from intracellular proteolysis. The results also demonstrate the viability of an arteriovenous difference technique for the study of adipose tissue in the rat.

  15. Variations in lead isotopic abundances in Sprague-Dawley rat tissues: possible reason of formation.

    PubMed

    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 ((206)Pb, (207)Pb and (208)Pb) 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.

  16. Sodium metabisulfite induces lipid peroxidation and apoptosis in rat gastric tissue.

    PubMed

    Ercan, Sevim; Oztürk, Nihal; Celik-Ozenci, Ciler; Gungor, Nazli Ece; Yargicoglu, Piraye

    2010-08-01

    Sodium metabisulfite (Na( 2)S(2)O(5)) is used as an antioxidant and antimicrobial agent in a variety of drugs and functions as a preservative in many food preparations. This study was performed to elucidate the dose-dependent effects of sodium metabisulfite ingestion on rat gastric tissue apoptotic changes and lipid peroxidation. Forty male wistar rats, aged 3 months were used. They were randomly divided into four groups: control (C), the group treated with Na(2)S(2)O(5) (10 mg/kg; S1), the group treated with Na(2)S(2)O(5) (100 mg/kg; S2), the group treated with Na(2)S(2)O(5) (260 mg/kg; S3). Na( 2)S(2)O(5) was given by intragastric intubation for 35 days. In the S2 and S3 groups, malondialdehyde (MDA) levels increased markedly when compared with the control group. High doses of sulfite administration elevated number of apoptotic cells both in mucosa and submucosa layers of stomach in parallel with increased MDA levels. These results suggest that sodium metabisulfite increased lipid peroxidation and thus number of apoptotic cells on gastric tissue in dose-dependent manner.

  17. 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.

  18. 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

  19. Tissue-specific processing of cocaine- and amphetamine-regulated transcript peptides in the rat

    PubMed Central

    Thim, Lars; Kristensen, Peter; Nielsen, Per F.; Wulff, Birgitte S.; Clausen, Jes T.

    1999-01-01

    Cocaine- and amphetamine-regulated transcript (CART) is a recently discovered hypothalamic peptide regulated by leptin and with a potent appetite-suppressing activity. In the rat, the CART gene encodes a peptide of 116 amino acid residues (or a splice variant 13 residues longer). The predicted signal sequence is 27 amino acid residues, resulting in a prohormone of 89 residues. The CART prohormone contains several potential posttranslational processing sites in the form of mono- and dibasic sequences. In the present study we have purified CART peptides from extracts of adrenal gland, hypothalamus, nucleus accumbens, and pituitary gland (anterior and neurointermediate lobe) of the rat and determined the peptide structures by using microsequencing and mass spectrometry. In none of the tissues examined the long splice variant was found. From the adrenal gland, the CART(1–89) and CART(10–89) peptides were isolated, in contrast to the hypothalamus and nucleus accumbens, from which the shorter form peptides CART(42–89) and CART(49–89) were purified. From the anterior lobe of the pituitary gland, CART(42–89) was isolated, in contrast to the neurointermediate lobe, which contains only CART(49–89). This tissue-specific processing indicates that CART peptides may have different biological functions in the periphery and in the central nervous system. PMID:10077578

  20. Dose-dependent immunohistochemical and ultrastructural changes after oral methylphenidate administration in rat heart tissue.

    PubMed

    Take, G; Bahcelioglu, M; Oktem, H; Tunc, E; Gözil, R; Erdogan, D; Calguner, E; Helvacioglu, F; Giray, S G; Elmas, C

    2008-08-01

    Methylphenidate, more commonly known as Ritalin, is a piperidine derivative and is the drug most often used to treat attention deficit/hyperactivity disorder, one of the most common behavioural disorders of children and young adults. Our aims were to investigate dose-dependent immunohistochemical D2 expression and ultrastructural changes of the rat heart tissue, and to demonstrate possible toxicity of the long-term and high dose use of the methylphenidate. In this study, 27 female pre-pubertal Wistar albino rats, divided into three different dose groups (5, 10 and 20 mg/kg) and their control groups, were used. They were treated orally with methylphenidate dissolved in saline solution for 5 days/week during 3 months. At the end of the third month, after perfusion fixation, left ventricle of cardiac tissue was removed. Paraffin, semi-thin and thin sections were collected and immunohistochemical, terminal deoxynucleotidyl transferase-mediated Dig-dUTP nick end labelling assay and ultrastructural studies were performed. In conclusion, we believe that Ritalin is dose-related affecting dopaminergic system to increase heart rhythm and contraction. Thus, this drug may cause degenerative ultrastructural changes in mitochondrial path.

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. 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

  7. High mitomycin C concentration in tumour tissue can be achieved by isolated liver perfusion in rats.

    PubMed

    Marinelli, A; Pons, D H; Vreeken, J A; Nagesser, S K; Kuppen, P J; Tjaden, U R; van de Velde, C J

    1991-01-01

    To enable the treatment of hepatic metastasis with higher, theoretically more effective, doses of systemically toxic anticancer drugs, an isolated liver perfusion (ILP) technique was developed in WAG/Ola rats. First, in a toxicity study the maximally tolerated dose (MTD) of mitomycin C (MMC) was determined for a 25-min ILP and for hepatic artery infusion (HAI) after the administration of a bolus dose. The MTD in the ILP setting (4.8 mg/kg) was 4 times that using HAI (1.2 mg/kg). Subsequently, in a rat colorectal hepatic-metastasis model, concentrations of MMC in tumour, liver, plasma and perfusate were measured during a 25-min ILP to investigate the expected pharmacokinetic advantage of ILP. The mean plasma level determined after ILP (1.2 as well as 4.8 mg/kg MMC) was significantly lower (P less than 0.001) than that obtained following HAI. This may explain both the absence of severe systemic toxicity and the higher MTD in ILP-treated groups. No significant difference in mean tumour and liver tissue concentrations of MMC were found when the groups treated with 1.2 mg/kg drug via HAI vs ILP were compared. The mean MMC concentration in tumour tissue was significantly higher (almost 5 times; P less than 0.05) in rats treated by ILP with the MTD (4.8 mg/kg) than in those treated via HAI with the MTD (1.2 mg/kg). ILP of MMC can be safely performed using a dose 4 times higher than the MTD in the HAI setting, leading to an almost 5-fold concentration of MMC in hepatic metastasis. ILP of MMC may therefore represent a promising therapy for metastasis confined to the liver. PMID:1905590

  8. Altered gene expression in rat mesenteric tissue following in vivo exposure to a phosphodiesterase 4 inhibitor

    SciTech Connect

    Dagues, Nicolas . E-mail: nicolas.dagues@pfizer.com; Pawlowski, Valerie; Guigon, Ghislaine; Ledieu, David; Sobry, Cecile; Hanton, Gilles; Freslon, Jean-Louis; Chevalier, Stephan

    2007-01-01

    Vascular injury is a relatively common finding during the pre-clinical toxicity testing of drugs. The mechanisms of the injury are poorly understood and in turn, sensitive and specific biomarkers for pre-clinical and clinical monitoring do not exist. The present study was undertaken to investigate the molecular mechanisms of drug-induced vascular injury in mesenteric tissue of rats treated with the selective phosphodiesterase 4 (PDE4) inhibitor CI-1044. In a time-course study, male Sprague Dawley rats were given daily doses of 40 or 80 mg/kg for 1, 2 or 3 successive days and were euthanized the following day. Gene expression profiles in mesenteric tissue were determined using Affymetrix RG{sub U}34A microarrays and fibrinogen and cytokine measurements were performed in blood samples. Hierarchical clustering analysis produced a clear pattern separation of the animals with inflammation, animal with inflammation and necrosis and animals without any lesion. Genes associated with inflammation, procoagulation, extracellular matrix remodeling were up-regulated. An altered expression of genes involved in vascular tone regulation, lipid and glucose metabolism was also observed. Selected genes expression changes were confirmed by TaqMan real-time RT-PCR. The inflammatory process was also detected in the bloodstream at the protein level since fibrinogen, IL6 and IL1{beta} concentrations were increased in treated animals. Overall, the present study reveals several molecular changes supporting the hypothesis by which PDE4 inhibitor-induced vascular lesions in rats are triggered by an inflammatory mechanism and/or a vascular tone dysregulation.

  9. Pharmacokinetics and tissue distribution study of PA-824 in rats by LC-MS/MS.

    PubMed

    Wang, Libin; Ma, Yetao; Duan, Hongtao; Yao, Jiahui; Liang, Li; Zhang, Ruitao; Zhou, Xuejiao; Liu, Xueying; Wang, Qingwei; Zhang, Shengyong

    2015-12-01

    A simple, sensitive and rapid LC-MS/MS method has been developed and validated for determination of PA-824 in rat biological samples using darunavir as internal standard. Chromatographic separation was achieved on an Inertsil(®)ODS3 C18 column (150mm×4.6mm, 5μm) using gradient elution of methanol-0.1% ammonia in water (90:10, v/v) with fast gradient elution at a flow rate of 0.6mL/min and run time of 5min. The mass spectrometer was run in positive electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The optimized ion transition pairs for quantitation were m/z360.1→m/z175.0 for PA-824, m/z548.5→m/z504.2 for IS. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, matrix effect and robustness. All validation parameters met the acceptance criteria according to regulatory guidelines. The LLOQ was 0.05μg/mL. The calibration curves showed a good linearity over the concentration range of 0.05-50μg/mL. The calibration curves for all biological samples showed good linearity (r(2)>0.9978) over the concentration ranges tested. The recoveries obtained for PA-824 were ≥88.8%. The developed method was successfully applied to investigate the pharmacokinetics and tissue distribution of PA-824 in rats following oral administration. It was also the first study to investigate the tissue distribution of PA-824 in rats following oral administration.

  10. 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

  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. 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

  13. 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

  14. Protective Effects of Green Tea Extract against Hepatic Tissue Injury in Streptozotocin-Induced Diabetic Rats

    PubMed Central

    Abolfathi, Ali Akbar; Mohajeri, Daryoush; Rezaie, Ali; Nazeri, Mehrdad

    2012-01-01

    Although diabetic hepatopathy is potentially less common, it may be appropriate for addition to the list of target organ conditions related to diabetes. This study was designed to evaluate the hepatoprotective properties of green tea extract (GTE) in STZ-induced diabetes in rats. Wistar rats were made diabetic through single injection of STZ (75 mg/kg i.p.). The rats were randomly divided into four groups of 10 animals each: Group 1, healthy control; Group 2, nondiabetics treated with GTE administered orally (1.5%, w/v); Group 3, diabetics; Group 4, diabetics treated with GTE (1.5%, w/v) for 8 weeks. Serum biomarkers were assessed to determine hepatic injury. Malondialdehyde (MDA) and reduced glutathione (GSH) contents were measured to assess free radical activity in the liver tissue. Hepatic antioxidant activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) were also determined. The biochemical findings were matched with histopathological verifications. Liver MDA content and serum levels of ALT, AST, ALP, and bilirubin in Group 3 significantly increased compared to Group 1 (P < 0.05) and significantly decreased in Group 4 compared to Group 3 (P < 0.05). Serum albumin level and GSH, SOD, CAT, and GSH-Px contents of the liver in Group 3 were significantly decreased compared to Group 1 (P < 0.05) and were significantly increased in Group 4 compared to Group 3 (P < 0.05). Histopathologically, the changes were in the same direction with biochemical findings. This study proved the hepatoprotective activity of GTE in experimentally induced diabetic rats. PMID:22956978

  15. 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

  16. Effect of afobazole on genotoxic effects of tobacco smoke in the placenta and embryonic tissues of rats.

    PubMed

    Durnev, A D; Solomina, A S; Zhanataev, A K; Zhukov, V N; Seredenin, S B

    2010-09-01

    The DNA comet assay was used to evaluate the severity of genotoxic changes in embryonic tissues and placenta of rats daily exposed to tobacco smoke per se or in combination with an anxiolytic agent afobazole. The exposure to tobacco smoke (4 cigarettes containing 13 mg tar and 1 mg nicotine per 72 dm(3)) for 20 min on days 1-13 of pregnancy increased the degree of DNA damage and elevation of apoptotic DNA comets in cells of the placenta and embryo from pregnant rats. Afobazole (1 and 10 mg/kg orally) reduced the genotoxic effect of tobacco smoke and decreased the amount of apoptotic DNA comets in placental tissue and embryonic tissue from rats. PMID:21246089

  17. 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.

  18. 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

  19. 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

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

    PubMed

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

    2015-09-01

    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.

  1. Effects of zinc supplementation on the element distribution in kidney tissue of diabetic rats subjected to acute swimming.

    PubMed

    Sivrikaya, Abdullah; Bicer, Mursel; Akil, Mustafa; Baltaci, Abdulkerim Kasim; Mogulkoc, Rasim

    2012-06-01

    In this study, we report the effect of zinc supplementation on the distribution of elements in kidney tissue of diabetic rats subjected to acute swimming exercise. Diabetes was induced by two subcutaneous injections of 40 mg/kg of streptozotocin within a 24-h period. Zinc was given intraperitoneally at a dose of 6 mg/kg per day for a period of 4 weeks. The rats (n = 80) were equally divided into eight study groups: controls, zinc-supplemented, swimming, diabetic, zinc-supplemented diabetic, zinc-supplemented swimming, diabetic swimming, and zinc-supplemented diabetic swimming. The levels of lead, cobalt, molybdenum, chromium, boron, magnesium, iron, copper, calcium, zinc, and selenium were determined in the kidney tissue samples by ICP-AES. Higher molybdenum, calcium, zinc, and selenium values were found in both swimming and nonswimming diabetic rats. Significantly higher iron values were found in swimming, diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats (p < 0.001). Diabetic, zinc-supplemented diabetic, diabetic swimming, and zinc-supplemented diabetic swimming rats had the highest copper values. These results show that zinc supplementation normalized the higher levels of molybdenum, calcium, selenium, and iron levels seen in diabetic rats, indicating that zinc may have a regulatory effect on element metabolism in kidney tissue. PMID:22161314

  2. Effect of urinary alkalinisation and acidification on the tissue distribution of hexachlorophene in rats.

    PubMed

    Flanagan, R J; Ruprah, M; Strutt, A V; Malarkey, P; Cockburn, A

    1995-10-01

    1. Urinary alkalinisation may be helpful in treating acute poisoning with uncouplers of oxidative phosphorylation containing a phenolic hydroxyl (pKa 4-6) or other acidic moiety. 2. We studied the effects of urine alkalinisation and acidification on the tissue distribution of hexachlorophene (HCP, pKa 5.7) in male Sprague Dawley rats (10 rats/group). 3. Ammonium chloride (10 mL kg-1, 2% m/v) or sodium bicarbonate (10 mL kg-1, 2% m/v) were administered by gavage on three occasions over 24 h, prior to a single gavage dose of HCP (180 mg kg-1). Controls received aqueous sodium chloride (10 mL kg-1, 0.9% m/v) followed by either HCP (180 mg kg-1) or vehicle alone. 4. Urine pH, body mass and body temperature were monitored during the study and, at the conclusion of the experiment (12 h post-HCP dose), organ mass (liver, kidney, brain), and plasma, urine and tissue HCP concentrations were measured. 5. No clinical features of toxicity were observed in any group. However, sodium bicarbonate significantly reduced median HCP in liver--median plasma and kidney HCP concentrations were also reduced but not significantly. Conversely, ammonium chloride significantly increased median HCP concentrations in liver and kidney--median plasma HCP was also increased but not significantly. 6. The results provide some support for the hypothesis that blood pH influences the tissue distribution of uncouplers of oxidative phosphorylation containing an acidic moiety. Urinary alkalinisation may be useful in treating acute poisoning with these compounds.

  3. 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.

  4. Effects of Berberine on Adipose Tissues and Kidney Function in 3T3-L1 Cells and Spontaneously Hypertensive Rats.

    PubMed

    Kishimoto, Aya; Dong, Shi-Fen; Negishi, Hiroko; Yasui, Naomi; Sun, Jian-Ning; Ikeda, Katsumi

    2015-09-01

    We aimed to investigate the effect of berberine on adipose tissues, as well as its effect on renal injury in 3T3-L1 cells and spontaneously hypertensive rats. 3T3-L1 cells were cultured and treated with berberine (5-20 pM) from days 3 to 8. Berberine added to the cultured medium could significantly down-regulate transcription factors, including CCAAT/enhancer binding protein β, CCAAT/enhancer binding protein a, and peroxisome pro liferator-activated receptor y, and suppress peroxisome proliferator-activated receptor target genes, such as adipocyte fatty acid binding protein and fatty acid synthase, and inhibit 3T3-Ll fibroblast differentiation to adipocytes. Male spontaneously hypertensive rats received either 150 mg/day of berberine or saline orally for 8 weeks. Compared with the control, berberine-treated rats exhibited significant reductions in body weight gain (p < 0.05), as well as retroperitoneal and mesenteric adipose tissues (p < 0.05). Berberine-treated rats significantly decreased urinary albumin excretion, a marker of renal injury (p < 0.05). Long-term treatment with berberine decreased the adipose tissues weight and attenuated renal injury in spontaneously hypertensive rats. Based on these results, berberine has an important role in regulating adipose tissues. These results suggest the protective effect of berberine on metabolic syndrome related diseases, such as renal injury.

  5. Vitamin D-dependent rat renal calcium-binding protein: development of a radioimmunoassay, tissue distribution, and immunologic identification

    SciTech Connect

    Sonnenberg, J.; Pansini, A.R.; Christakos, S.

    1984-08-01

    A sensitive double antibody RIA has been developed for the 28,000 mol wt rat renal vitamin D-dependent calcium-binding protein. Using this assay, concentrations of calcium-binding protein (CaBP) as low as 30 ng can be measured. The assay is precise (intraassay variability, 5.0%) and reproductible (interassay variability, 8.2%). Measurements of renal CaBP by RIA showed a good correlation with measurements of CaBP by the chelex resin assay and by polyacrylamide gel analysis by densitometric tracing using a purified CaBP marker. The concentration of CaBP in the vitamin D-replete rat kidney is 7.3 +/- 1.0 (mean +/- SEM) micrograms/mg protein. In vitamin D-deficient rats the level of renal CaBP is 2.6 +/- 0.3 micrograms/mg protein. Tissue distribution of immunoreactive rat renal CaBP showed the highest concentration of CaBP in the rat cerebellum (38.3 +/- 5.1 micrograms/mg protein). Lower concentrations of immunoreactive CaBP were detected in several other rat tissues. No immunoreactive CaBP was detected in rat or human serum. In necropsy human kidney and cerebellum, high levels of immunoreactive CaBP were also detected (1.5 +/- 0.1 and 27.3 +/- 2.1 micrograms/mg protein, respectively). When extracts of rat kidney and brain and human cerebellum and kidney were assayed at several dilutions, immunodisplacement curves parallel to that of pure renal CaBP were observed, indicating immunochemical similarity. Fractionation of extracts of rat cerebellum, human kidney, and human cerebellum on Sephadex G-100 revealed immunoreactivity and calcium-binding activity in the 28,000 mol wt region similar to rat kidney.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Circadian variations in gene expression in rat abdominal adipose tissue and relationship to physiology

    PubMed Central

    Sukumaran, Siddharth; Xue, Bai; Jusko, William J.; DuBois, Debra C.

    2010-01-01

    Circadian rhythms occur in all levels of organization from expression of genes to complex physiological processes. Although much is known about the mechanism of the central clock in the suprachiasmatic nucleus, the regulation of clocks present in peripheral tissues as well as the genes regulated by those clocks is still unclear. In this study, the circadian regulation of gene expression was examined in rat adipose tissue. A rich time series involving 54 animals euthanized at 18 time points within the 24-h cycle (12:12 h light-dark) was performed. mRNA expression was examined with Affymetrix gene array chips and quantitative real-time PCR, along with selected physiological measurements. Transcription factors involved in the regulation of central rhythms were examined, and 13 showed circadian oscillations. Mining of microarray data identified 190 probe sets that showed robust circadian oscillations. Circadian regulated probe sets were further parsed into seven distinct temporal clusters, with >70% of the genes showing maximum expression during the active/dark period. These genes were grouped into eight functional categories, which were examined within the context of their temporal expression. Circadian oscillations were also observed in plasma leptin, corticosterone, insulin, glucose, triglycerides, free fatty acids, and LDL cholesterol. Circadian oscillation in these physiological measurements along with the functional categorization of these genes suggests an important role for circadian rhythms in controlling various functions in white adipose tissue including adipogenesis, energy metabolism, and immune regulation. PMID:20682845

  13. 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.

  14. 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.

  15. Subacute Tissue Response to 3D Graphene Oxide Scaffolds Implanted in the Injured Rat Spinal Cord.

    PubMed

    López-Dolado, Elisa; González-Mayorga, Ankor; Portolés, María Teresa; Feito, María José; Ferrer, María Luisa; Del Monte, Francisco; Gutiérrez, María Concepción; Serrano, María Concepción

    2015-08-26

    The increasing prevalence and high sanitary costs of lesions affecting the central nervous system (CNS) at the spinal cord are encouraging experts in different fields to explore new avenues for neural repair. In this context, graphene and its derivatives are attracting significant attention, although their toxicity and performance in the CNS in vivo remains unclear. Here, the subacute tissue response to 3D flexible and porous scaffolds composed of partially reduced graphene oxide is investigated when implanted in the injured rat spinal cord. The interest of these structures as potentially useful platforms for CNS regeneration mainly relies on their mechanical compliance with neural tissues, adequate biocompatibility with neural cells in vitro and versatility to carry topographical and biological guidance cues. Early tissue responses are thoroughly investigated locally (spinal cord at C6 level) and in the major organs (i.e., kidney, liver, lung, and spleen). The absence of local and systemic toxic responses, along with the positive signs found at the lesion site (e.g., filler effect, soft interface for no additional scaring, preservation of cell populations at the perilesional area, presence of M2 macrophages), encourages further investigation of these materials as promising components of more efficient material-based platforms for CNS repair.

  16. 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.

  17. 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

  18. Detection of Angiostrongylus cantonensis in the Blood and Peripheral Tissues of Wild Hawaiian Rats (Rattus rattus) by a Quantitative PCR (qPCR) Assay

    PubMed Central

    2015-01-01

    The nematode Angiostrongylus cantonensis is a rat lungworm, a zoonotic pathogen that causes human eosinophilic meningitis and ocular angiostrongyliasis characteristic of rat lungworm (RLW) disease. Definitive diagnosis is made by finding and identifying A. cantonensis larvae in the cerebral spinal fluid or by using a custom immunological or molecular test. This study was conducted to determine if genomic DNA from A. cantonensis is detectable by qPCR in the blood or tissues of experimentally infected rats. F1 offspring from wild rats were subjected to experimental infection with RLW larvae isolated from slugs, then blood or tissue samples were collected over multiple time points. Blood samples were collected from 21 rats throughout the course of two trials (15 rats in Trial I, and 6 rats in Trial II). In addition to a control group, each trial had two treatment groups: the rats in the low dose (LD) group were infected by approximately 10 larvae and the rats in the high dose (HD) group were infected with approximately 50 larvae. In Trial I, parasite DNA was detected in cardiac bleed samples from five of five LD rats and five of five HD rats at six weeks post-infection (PI), and three of five LD rats and five of five HD rats from tail tissue. In Trial II, parasite DNA was detected in peripheral blood samples from one of two HD rats at 53 minutes PI, one of two LD rats at 1.5 hours PI, one of two HD rats at 18 hours PI, one of two LD rats at five weeks PI and two of two at six weeks PI, and two of two HD rats at weeks five and six PI. These data demonstrate that parasite DNA can be detected in peripheral blood at various time points throughout RLW infection in rats. PMID:25910229

  19. 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

  20. Therapeutic efficacy of amniotic membrane stem cells and adipose tissue stem cells in rats with chemically induced ovarian failure

    PubMed Central

    Fouad, Hanan; Sabry, Dina; Elsetohy, Khaled; Fathy, Naglaa

    2015-01-01

    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

  1. Metabolism of chrysene, 5-methylchrysene, 6-methylchrysene and 5,6-dimethylchrysene in rat liver cytosol, in vitro, and in rat subcutaneous tissue, in vivo.

    PubMed

    Myers, S R; Flesher, J W

    1991-01-01

    The polynuclear aromatic hydrocarbon chrysene undergoes a bioalkylation substitution reaction in vitro, in rat liver cytosol preparations, and in vivo, in rat dorsal subcutaneous tissue to yield 6-methylchrysene as a metabolite. In addition, both 5-methyl- and 6-methylchrysene were found to undergo a dealkylation reaction in these tissues to yield chrysene as well as both a biooxidation reaction to yield the corresponding hydroxyalkyl substituted chrysene and a bioalkylation reaction to give a dimethyl substituted chrysene. 5-Methylchrysene enzymatically cyclized to the 4,5-methylenechrysene derivative, an analog of benzo[a]pyrene in these tissues. 5,6-Dimethylchrysene was metabolized to monomethyl chrysenes, chrysene, and the hydroxyalkyl substituted chrysenes. The results suggest that chemical or biochemical substitution of a methyl group at the center of highest biochemical reactivity may be a necessary step in the metabolic activation and carcinogenicity of these compounds and their methylene bridged metabolites.

  2. An LC-MS/MS method for determination of novel fungicide pyraoxystrobin in rat plasma and tissues: Toxicokinetics and tissue distribution study.

    PubMed

    Lin, Li H; Duan, Ming Y; Chen, Guang; You, Xiao H; Liu, Chang L; Guo, Xing J

    2015-05-01

    A simple, specific and reproducible liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the determination of pyraoxystrobin in rat plasma and tissues. Chromatographic separation was achieved on a Zorbax Extend-C18 column (50×2.1mm I. D., 3.5µm), using a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid (v/v) at a flow rate of 0.5mL min(-1). Pyraoxystrobin and picoxystrobin (internal standard) were detected without interference in the selected reaction monitoring (SRM) mode with positive electrospray ionization. Further, the method was validated following FDA guideline. The calibration curves for plasma and tissues were linear over a concentration range of 1.00-200ng mL(-1), with lower limits of quantitation of 1.00ng mL(-1). Mean extraction recoveries in plasma and tissues ranged from 101.4% to 108.2% and from 49.1% to 59.4%, respectively. The intra-day and inter-day precision in plasma and tissues were within 9.9% and 8.9%, and the intra-day and inter-day accuracy ranged from 88.7% to 110.7% and 93.2% to 108.7%, respectively. Finally, the validated method was successfully applied to toxicokinetics and tissue distribution studies after oral administration of pyraoxystrobin to rats.

  3. White adipose tissue genome wide-expression profiling and adipocyte metabolic functions after soy protein consumption in rats.

    PubMed

    Frigolet, Maria E; Torres, Nimbe; Uribe-Figueroa, Laura; Rangel, Claudia; Jimenez-Sanchez, Gerardo; Tovar, Armando R

    2011-02-01

    Obesity is associated with an increase in adipose tissue mass due to an imbalance between high dietary energy intake and low physical activity; however, the type of dietary protein may contribute to its development. The aim of the present work was to study the effect of soy protein versus casein on white adipose tissue genome profiling, and the metabolic functions of adipocytes in rats with diet-induced obesity. The results showed that rats fed a Soy Protein High-Fat (Soy HF) diet gained less weight and had lower serum leptin concentration than rats fed a Casein High-Fat (Cas HF) diet, despite similar energy intake. Histological studies indicated that rats fed the Soy HF diet had significantly smaller adipocytes than those fed the Cas HF diet, and this was associated with a lower triglyceride/DNA content. Fatty acid synthesis in isolated adipocytes was reduced by the amount of fat consumed but not by the type of protein ingested. Expression of genes of fatty acid oxidation increased in adipose tissue of rats fed Soy diets; microarray analysis revealed that Soy protein consumption modified the expression of 90 genes involved in metabolic functions and inflammatory response in adipose tissue. Network analysis showed that the expression of leptin was regulated by the type of dietary protein and it was identified as a central regulator of the expression of lipid metabolism genes in adipose tissue. Thus, soy maintains the size and metabolic functions of adipose tissue through biochemical adaptations, adipokine secretion, and global changes in gene expression.

  4. Rapid elongation of arteries and veins in rats with a tissue expander.

    PubMed

    Stark, G B; Hong, C; Futrell, J W

    1987-10-01

    The saphenous arteries and veins of 40 rats were elongated with 20-cc tissue expanders underlying the leg adductor muscles. The mean rate of successful elongation of the vessels was 84 +/- 47 percent SD, with a maximum gain of 140 percent. The fastest mean elongation velocity reached 45 percent per day. Thrombosis occurred only with stretching velocities of more than 10 percent per day, which seemed to be a safe margin. Distribution of the volume into many intervals was safer than infrequent high-volume injections. Histology showed no reduction in vessel wall diameter or loss intimal integrity. Subendothelial cellular proliferation was an indicator of this rapid regeneration. Microvascular anastomoses performed in elongated arteries and veins had the same patency rate (90 percent) as in controls.

  5. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats.

    PubMed

    Gajdosechova, L; Krskova, K; Olszanecki, R; Zorad, S

    2015-07-01

    Multifunctional peptide oxytocin currently undergoes intensive research due to its proposed anti-obesity properties. Until now, little is known about regulation of oxytocin receptor in metabolically active tissues in obesity. The aim of the present study was to measure expression of oxytocin receptor upon obese phenotype with respect to the variety among adipose tissue and skeletal muscles with distinct anatomical localisation. Total homogenates were prepared from epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was determined by immunoblot. Interestingly, elevated oxytocin receptor was observed in epididymal adipose tissue of obese rats in contrast to its downregulation in subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin receptor protein was expressed at similar levels in all adipose depots. This uniformity was not observed in the case of skeletal muscle in which fibre type composition seems to be determinant of oxytocin receptor expression. Quadriceps muscle with the predominance of glycolytic fibres exhibits higher oxytocin receptor expression than almost exclusively oxidative soleus muscle. Oxytocin receptor protein levels were decreased in both skeletal muscles analysed upon obese phenotype. The present work demonstrates that even under identical endocrine circumstances, oxytocin receptor is differentially regulated in adipose tissue of obese rats depending on fat depot localisation. These results also imply which tissues may be preferentially targeted by oxytocin treatment in metabolic disease.

  6. Effects of alcohol inhalation on the fatty acid composition of rat tissues

    SciTech Connect

    Melville, D.M.; Karanian, J.W.; Salem, N. Jr.

    1986-05-01

    The objective of this study was to determine if polyunsaturated fatty acid levels in rat tissues are altered by alcohol exposure. Therefore, rats were exposed to ethanol vapor using an inhalation system designed in their laboratory and capable of producing rats with blood ethanol concentrations (BEC) of 50-400 mg%, as desired. Mean BEC were determined after 7 or 14 days of exposure and the lipids were extracted from brains, hearts, livers and aortas by the method of Bligh and Dyer. These total lipid extracts were transmethylated with BF/sub 3/ in methanol and analyzed using a fused silica capillary column. The largest compositional changes were observed in the liver after 14 days of exposure; 18:0, 18:2w6 and 20:4w6 decreased by 7, 18, and 20%, respectively, whereas 16:1w7, 18:1w9, 18:3w3 and 22:6w3 increased by 42, 19, 9, and 11%, respectively. A similar, although quantitatively smaller, effect was observed after only 7 days of alcohol inhalation. Little change was observed in the total lipid extract fatty acyl distribution in the brain or heart, however, the aorta showed losses in the polyunsaturates 20:4w6 and 22:6w3. More detailed data will be presented for the fatty acid distributional changes in individual phospholipid classes. It appears that the direction and magnitude of compositional changes depend upon both the duration of exposure and the blood concentration of alcohol.

  7. 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.

  8. Evaluation of an attenuated Trypanosoma cruzi strain in rats. Analysis of survival, parasitemia and tissue damage.

    PubMed

    Revelli, S; Basombrío, M A; Valenti, J L; Moreno, H; Poli, H; Morini, J C

    1993-01-01

    Infection and tissue damage induced by parasites of an attenuated Trypanosoma cruzi culture strain (TCC) were studied in "I" line of inbred rats. Suckling rats (S), 3-5 day old were inoculated i.p. with 10(6) TCC (S1), 10(7) TCC (S2) and 10(8) TCC (S3). Weaned rats (W), 21-25 day old were inoculated s.c. with 10(6) TCC (W1), 10(7) TCC (W2) and 10(8) TCC (W3). The cultures yielded up to 2% of trypomastigotes. Controls inoculated either i.p. or s.c. with 10(6) blood form trypomastigotes (SC and WC) as well as normal controls (NC) were included. Survival was 100% in S1, S2 and S3, and 0% in SC on day 13 post-infection (p.i.). The latter animals died with acute Chagas disease signs. Survival was 100% in the W groups. In the first 30 days p.i. parasites were detected in S1, S2 and S3 and W1, W2, W3 groups after exhaustive examination. Parasites were easily found in WC and SC until day 13. Xeno-diagnoses were positive (5/5) at 2 months p.i. and negative at 6 months p.i. (W1, W2, W3, 0/23; WC, 0/5). Only cardiac lesions were slightly increased. The frequency of focal chronic myocarditis seemed to be increased in a dose-independent manner (S1, S2, S3, 26%; W1, W2, W3, 46%) but was not significant in comparison with NC, and even was lower than usually found in WC (61.3%). The reduced virulence and pathogenicity suggest that the TCC strain suffered a remarkable attenuation after long term in vitro culture. PMID:8246729

  9. 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

  10. 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.

  11. Testing an aflatoxin B1 gene signature in rat archival tissues.

    PubMed

    Merrick, B Alex; Auerbach, Scott S; Stockton, Patricia S; Foley, Julie F; Malarkey, David E; Sills, Robert C; Irwin, Richard D; Tice, Raymond R

    2012-05-21

    Archival tissues from laboratory studies represent a unique opportunity to explore the relationship between genomic changes and agent-induced disease. In this study, we evaluated the applicability of qPCR for detecting genomic changes in formalin-fixed, paraffin-embedded (FFPE) tissues by determining if a subset of 14 genes from a 90-gene signature derived from microarray data and associated with eventual tumor development could be detected in archival liver, kidney, and lung of rats exposed to aflatoxin B1 (AFB1) for 90 days in feed at 1 ppm. These tissues originated from the same rats used in the microarray study. The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue. The qPCR FFPE liver results were compared to the original liver microarray data and to qPCR results using RNA from fresh frozen liver. Archival liver paraffin blocks yielded 30 to 50 μg of degraded RNA that ranged in size from 0.1 to 4 kB. qPCR results from FFPE and fresh frozen liver samples were positively correlated (p ≤ 0.05) by regression analysis and showed good agreement in direction and proportion of change with microarray data for 11 of 14 genes. All 14 transcripts could be amplified from FFPE kidney RNA except the glutamate receptor gene Grin2c; however, only Abcb1b was significantly upregulated from control. Abundant constitutive transcripts, S18 and β-actin, could be amplified from lung FFPE samples, but the narrow RNA size range (25-500 bp length) prevented consistent detection of target transcripts. Overall, a discrete gene signature derived from prior transcript profiling and representing cell cycle progression, DNA damage response, and xenosensor and detoxication pathways was successfully applied to archival liver and kidney by qPCR and indicated that gene expression changes in response to subchronic AFB1 exposure occurred predominantly in the liver, the primary target for AFB1-induced

  12. Tissue stiffness induced by prolonged immobilization of the rat knee joint and relevance of AGEs (pentosidine).

    PubMed

    Lee, Sachiko; Sakurai, Takashi; Ohsako, Masafumi; Saura, Ryuichi; Hatta, Hideo; Atomi, Yoriko

    2010-12-01

    Joints, connective tissues consisting of extracellular matrix (ECM) with few blood vessels, transfer tension to the skeleton in response to environmental demand. Therefore, joint immobilization decreases active and passive mechanical stress, resulting in increased joint stiffness and tissue degeneration; however, the cause of joint stiffness is obscure. Using a rat knee immobilization model, we examined the relationship between range of motion (ROM) and cell numbers and ECM cross-links by accumulation of advanced glycation end products, pentosidine, in the posterior joint capsule of immobilized joints during 16 weeks of immobilization. The left knee joint was immobilized by internal fixation and compared with the non-immobilized right leg. As early as 2 weeks of immobilization, joint ROM and torque significantly decreased and in parallel, disordered alignment of collagen fiber bundles significantly increased, compared with non-immobilized joints. Those changes continued until 16 weeks of immobilization. Significant increases in pentosidine-positive areas after 8 weeks and significantly decreased cell numbers after 16 weeks of immobilization were also observed compared to the contralateral side. A significant negative correlation between tissue stiffness measured by restriction of ROM and accumulation of pentosidine was observed. This study is the first to show that immobilization of knee joints induces articular contracture associated with sequential changes of ECM alignment, influencing ROM and later pentosidine accumulation and decreased cell numbers during the 16-week immobilization period. Pentosidine appears to be an indicator toward a chronic tissue stiffness leading to decreased cell number rather than a cause of ROM restriction induced by joint immobilization.

  13. Gonadotropin releasing hormone stimulates the formation of inositol phosphates in rat anterior pituitary tissue.

    PubMed Central

    Schrey, M P

    1985-01-01

    The production of inositol phosphates in response to gonadotropin releasing hormone (GnRH) was studied in rat anterior pituitary tissue preincubated with [3H]inositol. Prelabelled paired hemipituitaries from prepubertal female rats were incubated in the presence or absence of GnRH in medium containing 10 mM-Li+ X Li+, which inhibits myo-inositol-1-phosphatase, greatly amplified the stimulation of inositol phosphate production by GnRH (10(-7) M) to 159, 198 and 313% of paired control values for inositol 1-phosphate, inositol bisphosphate and inositol trisphosphate respectively after 20 min. The percentage distribution of [3H]inositol within the phosphoinositides was 91.3, 6.3 and 2.4 for phosphatidylinositol, phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate respectively and was unaffected by GnRH. The stimulation of inositol trisphosphate production by GnRH was evident after 5 min incubation, was dose-dependent with a half-maximal effect around 11 nM, and was not inhibited by removal of extracellular Ca2+. Elevation of cytosolic Ca2+ by membrane depolarization with 50 mM-K+ had no significant effect on inositol phosphate production. These findings are consistent with the hypothesis that GnRH action in the anterior pituitary involves the hydrolysis of phosphatidylinositol 4,5-bisphosphate. The resulting elevation of inositol trisphosphate may in turn lead to intracellular Ca2+ mobilization and subsequent stimulation of gonadotropin secretion. PMID:2986599

  14. Tissue distribution, intracellular localization and proteolytic processing of rat 4-hydroxyphenylpyruvate dioxygenase.

    PubMed

    Neve, Søren; Aarenstrup, Lene; Tornehave, Ditte; Rahbek-Nielsen, Henrik; Corydon, Thomas Juhl; Roepstorff, Peter; Kristiansen, Karsten

    2003-01-01

    4-hydroxyphenylpyruvate dioxygenase (HPD) is an important enzyme involved in tyrosine catabolism. HPD was shown to be identical to a protein named the F-antigen, exploited by immunologists because of its unique immunological properties. Congenital HPD deficiency is a rare, relatively benign condition known as hereditary type III tyrosinemia. Decreased expression of HPD is often observed in association with the severe type I tyrosinemia, and interestingly, inhibition of HPD activity seems to ameliorate the clinical symptoms of type I tyrosinemia. In this study we present a comprehensive analysis of tissue specific expression and intracellular localization of HPD in the rat. By combined use of in situ hybridization and immunohistochemistry we confirm previously known sites of expression in liver and kidney. In addition, we show that HPD is abundantly expressed in neurons in the cortex, cerebellum and hippocampus. By using immunoelectron microscopy and confocal laser scanning microscopy, we provide evidence that HPD contrary to earlier assumptions specifically localizes to membranes of the endoplasmic reticulum and the Golgi apparatus. Detailed mass spectrometric analyses of HPD purified from rat liver revealed N-terminal and C-terminal processing of HPD, and expression of recombinant HPD suggested that C-terminal processing enhances the enzymatic activity.

  15. 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

  16. Histomorphometric analysis of tissue responses to bioactive glass implants in critical defects in rat calvaria.

    PubMed

    Cardoso, Ana Karina M V; Barbosa, Aryon de Almeida; Miguel, Fúlvio Borges; Marcantonio, Elcio; Farina, Marcos; Soares, Glória Dulce de Almeida; Rosa, Fabiana Paim

    2006-01-01

    The aim of this study was to evaluate the osteogenic behavior of two chemically similar bioactive glass products (Biogranand Perioglas) implanted in critical bone defects in rat calvaria. Thirty-six transfixed bone defects of 8 mm diameter were made surgically in adult male Wistar rats. The animals were distributed equally into three groups: Biogran (GI), Perioglas (GII) and without implant material (control; GIII). The morphology and composition of both bioactive glasses were analyzed by scanning electron microscopy and energy-dispersive spectrometry. Tissue specimens were analyzed at the biological time points of 15, 30 and 60 days by optical microscopy and morphometry, demonstrating biocompatibility for the tested materials with moderate chronic inflammation involving their particles. Bone neoformation resulted only as a reparative reaction to an intentionally produced defect and was limited to the defect's edges. No statistically significant differences among the groups were observed. At the scar interstice, abundant deposits of collagenous fibers enveloping the particles were noted. The present results indicated that the bioactive glasses, under the experimental conditions analyzed, did not show osteogenic behavior.

  17. 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.

  18. 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

  19. Measurement of rat heart fatty acid binding protein by ELISA. Tissue distribution, developmental changes and subcellular distribution.

    PubMed

    Crisman, T S; Claffey, K P; Saouaf, R; Hanspal, J; Brecher, P

    1987-05-01

    A class of soluble, low molecular weight proteins collectively called fatty acid binding proteins (FABP) are thought to function in the intracellular movement of fatty acids. To understand more clearly the role of FABP in cardiac metabolism, we used ELISA and immunoblotting techniques to study the distribution of heart FABP in several rat tissues, compare male and female rat heart content, quantitate developmental changes, and determine its subcellular distribution. Immunoreactive protein was found in appreciable amounts in rat heart, red skeletal muscle and kidney. Adult rat heart contained about 1.5 mg FABP/g tissue wet weight with the atrial content being approximately 50% of the ventricular concentration. No significant difference was detected between the sexes. The amount of FABP increased progressively during development from fetal to adult animals, and measureable amounts were found in 17-day-old fetal tissue. Comparisons between myoglobin and FABP showed that FABP appeared earlier than myoglobin in development, but myoglobin was more abundant than FABP at birth. Using immunoblots it was determined that rat heart FABP was localized in the cytosol with no detectable intramitochondrial material. PMID:3625779

  20. 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

  1. Ameliorating effects of CAPE on oxidative damage caused by pneumoperitoneum in rat lung tissue

    PubMed Central

    Davarci, Isil; Alp, Harun; Ozgur, Tumay; Karcioglu, Murat; Tuzcu, Kasim; Evliyaoglu, Osman; Motor, Sedat; Durgun Yetim, Tulin

    2014-01-01

    We investigated the biochemical and histopathological effects of caffeic acid phenethyl ester (CAPE) against oxidative stress causing lung injury induced by pneumoperitoneum. Twenty-eight rats were selected at random and seven rats were assigned to each of the following groups. The control group (S) was subjected to a sham operation without pneumoperitoneum. The other groups were subjected to CO2 pneumoperitoneum 15 mmHg for 60 min. The laparoscopy group (L) had no additional drugs administered, the laparoscopy + alcohol (LA) group had 1 ml of 70% ethyl alcohol administered 1 h before the desufflation period, and the laparoscopy + CAPE (LC) group had CAPE administered at 10 μmol/kg 1 h before the desufflation period. The total oxidative status levels of lung and plasma were significantly increased in the LA group as compared with the LC and S group. When the LC group was compared with the L group, there was a decrease in the level of total oxidant status and increase in the levels of total antioxidant status and paraoxonase in lung tissue. The level of total antioxidative status in the S group was increased compared with the L group in lung tissue and bronchoalveolar lavage fluid. TNF-α and IL-6 were found significantly elevated in the L group compared with the LC and S groups in bronchoalveolar lavage fluid. There was a similar increase in plasma levels of IL-6. These results were supported by histopathological examination. CAPE was found to considerably reduce oxidative stress and inflammation induced by pneumoperitoneum. PMID:25126167

  2. 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

  3. Cerebral tissue repair and atrophy after embolic stroke in rat: an MRI study of Erythropoietin therapy

    PubMed Central

    Ding, Guangliang; Jiang, Quan; Li, Lian; Zhang, Li; Wang, Ying; Zhang, Zheng Gang; Lu, Mei; Panda, Swayamprava; Li, Qingjiang; Ewing, James R.; Chopp, Michael

    2010-01-01

    Using magnetic resonance imaging (MRI) protocols of T2-, T2*-, diffusion- and susceptibility-weighted imaging (T2WI, T2*WI, DWI and SWI) with a 7T system, we tested the hypothesis that treatment of embolic stroke with Erythropoietin (EPO) initiated at 24 hours and administered daily for 7 days after stroke onset has benefit on repairing ischemic cerebral tissue. Adult Wistar rats were subjected to embolic stroke by means of middle cerebral artery occlusion (MCAO) and were randomly assigned to a treatment (n=11) or a control group (n=11). The treated group was given EPO intraperitoneally at a dose of 5,000 IU/kg daily for 7 days starting 24h after MCAO. Controls were given an equal volume of saline. MRI was performed at 24h and then weekly for 6 weeks. MRI and histological measurements were compared between groups. Serial T2WI images demonstrated that expansion of the ipsilateral ventricle was significantly reduced in the EPO treated rats. The volume ratio of ipsilateral parenchymal tissue relative to the contralateral hemisphere was significantly increased after EPO treatment compared with control animals, indicating that EPO significantly reduces atrophy of the ipsilateral hemisphere, although no significant differences in ischemic lesion volume were observed between the two groups. Angiogenesis and white matter remodeling were significantly increased and occurred earlier in EPO treated animals than in the controls, as evident from T2*WI and diffusion anisotropy maps, respectively. These data indicate that EPO treatment initiated 24h post stroke promotes angiogenesis and axonal remodeling in the ischemic boundary, which may potentially reduce atrophy of the ipsilateral hemisphere. PMID:20722071

  4. Adenosine triphosphate hydrolysis in rat dental tissues. A histochemical study to differentiate the enzymes involved.

    PubMed

    Mörnstad, H; Sundström, B

    1976-07-19

    The purpose of this study was to try to differentiate histochemically between the various enzymes which may catalyze the hydrolysis of ATP in developing rat dental tissues. Freeze cut and freeze dried sections of molar and incisor teeth were incubated in lead capture-based media at pH 5.0, 7.2 or 9.4 with one of the following substrates: beta-glycerophosphate, AMP, ADP, ATP, AMP-PNP and tetrasodium pyrophosphate. To establish the enzymatic nature of the hydrolysis parallel sections were incubated after prior fixation in either formaldehyde or glutaraldehyde. By comparing the enzymatic stainings obtained with the various substrates and at the different pH:s, it was concluded that ATP can be visibly hydrolyzed in rat dental tissues by alkaline phosphatase (stratum intermedium, apical part of maturation ameloblasts, basal part of all ameloblasts, odontoblasts and subodontoblastic layer), specific ATPase (apical and basal parts of secretory ameloblasts) and ATP pyrophosphatase and/or adenylate cyclase (stratum intermedium, odontoblasts). Acid phosphatase, specific ADPase, 5'-nucleotidase, inorganic pyrophosphatase, 3':5'-cyclic-AMP-phosphodiesterase and adenylate kinase on the other hand, seem not to be engaged in the ATP hydrolysis to such a degree as to complicate the interpretation of the histochemical staining. The alkaline phosphatase part of the ATP hydrolysis appeared to be rather insensitive to aldehyde fixation, while the hydrolysis effected by specific ATPase and ATP pyrophosphatase and/or adenylate cyclase was extinguished after fixation with formaldehyde for 4 h or glutaraldehyde for 10 min.

  5. A novel pungency biosensor prepared with fixing taste-bud tissue of rats.

    PubMed

    Qiao, Lixin; Jiao, Lihua; Pang, Guangchang; Xie, Junbo

    2015-06-15

    A novel taste biosensor based on ligand-receptor interaction was developed through fixing taste-bud tissues of SD rats to a glassy carbon electrode. Using the sodium alginate-starch gel as a fixing agent, taste-bud tissues of SD rats were fixed between two nuclear microporous membranes to make a sandwich-type sensing membrane. With the taste biosensor, the response current induced by capsaicin and gingerol stimulating the corresponding receptors was measured. The results showed that the lowest limit of detection of this biosensor to capsaicin was 1×10(-13) mol/L and the change rate of response current was the highest at the concentration of 9×10(-13) mol/L, indicating that the capsaicin receptor was saturated at this point. The lowest limit of detection of this biosensor to gingerol was 1×10(-12) mol/L, and the gingerol receptor was saturated when the concentration of gingerol was 3×10(-11) mol/L. It was demonstrated that the interaction curves of capsaicin and gingerol with their respective receptors exhibited high correlation (R(2): 0.9841 and 0.9904). The binding constant and dissociation constant of gingerol with its receptor were 1.564×10(-11) and 1.815×10(-11) respectively, which were all higher than those of capsaicin with its receptor (1.249×10(-12) and 2.078×10(-12)). This study, for the first time, made it possible to quantitatively determine the interaction of the taste receptor and pungent substances with a new biosensor, thus providing a simple approach for monitoring pungent substances and investigating the mechanism of ligand-receptor interaction.

  6. Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells.

    PubMed

    Babij, P; Zhao, J; White, S; Woodcock-Mitchell, J; Mitchell, J; Absher, M; Baldor, L; Periasamy, M; Low, R B

    1993-08-01

    RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha-actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions.

  7. 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

  8. Expression and activity of ovarian tissue inhibitors of metalloproteinases during pseudopregnancy in the rat.

    PubMed

    Nothnick, W B; Edwards, D R; Leco, K J; Curry, T E

    1995-09-01

    The present study examined the role of tissue inhibitors of metalloproteinases (TIMPs) in tissue remodeling that occurs during luteal development and regression throughout pseudopregnancy in the rat. Pseudopregnancy was induced in immature female rats by eCG/hCG priming. Animals (n = 4 per time point) were killed on Days 1, 2, 4, 8, 12, 14, and 16 of pseudopregnancy (post hCG administration), and ovaries were removed and analyzed for metalloproteinase inhibitor activity or TIMP-1, TIMP-2, and TIMP-3 mRNA expression. Inhibitory activity was highest in Day-1 samples (41.35 +/- 6.50 inhibitory units), and inhibitor activity significantly decreased (p < 0.05) thereafter to minimal values at Day 12 (8.14 +/- 2.71 inhibitory units). Methylamine hydrochloride treatment, which inactivates macroglobulin-type inhibitors, revealed that the majority of the inhibitor activity in the Day-1 samples (82.6%) and the Day-16 samples (77.3%) could be attributed to TIMPs. To further distinguish the contribution of each TIMP to this activity, Northern analysis for TIMP-1, -2, and -3 was performed. Analysis of TIMP mRNA expression revealed that TIMP-1 transcript expression was highest (p = 0.00009) at Day 1, decreased approximately 3- to 20-fold from Days 2 to 12, respectively, and again increased at Days 14-16. However, TIMP-2 expression did not change (p > 0.05) over any of the time points studied. In contrast to TIMP-1 and TIMP-2 expression, TIMP-3 mRNA expression was lowest during Days 1 and 2 of pseudopregnancy, increased approximately 4-fold at Day 4, peaked at Day 8, and remained elevated throughout the remainder of pseudopregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Exposure to low doses of endosulfan and chlorpyrifos modifies endogenous antioxidants in tissues of rats.

    PubMed

    Bebe, Frederick N; Panemangalore, Myna

    2003-05-01

    Two experiments were conducted in male SD rats (225-250 g) to determine changes in the activities of endogenous antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX) and concentrations of glutathione (GSH) in tissues after exposure to low doses of endosulfan and chlorpyrifos using a whole body exposure technique. In both experiments, 6 rats/group were exposed 3 hr/day, 5 days/week for 30 days to: 0 (control), 5, 10, 20, 40 and 60% of LD50 of either pesticide in 50% ethanol; actual concentrations were: endosulfan = 0, 0.5, 1.0, 2.0, 4.0, 6.0 mg/250 g body weight; chlorpyrifos = 0, 1.9, 3.8, 7.6, 15.2, and 22.8 mg/250 g body weight. Endosulfan decreased erythrocyte SOD by 21% in all groups and chlorpyrifos increased SOD by 18% in groups 40 and 60. Liver SOD was 12%-20% lower after endosulfan exposure; lung SOD was altered: endosulfan decreased activity by 21% and 51% and chlorpyrifos by 58 and 75% in the 40 and 60 groups, respectively (P < or = 0.05). Both pesticides increased plasma GPX activity at lower levels and reduced it by 26% and 19% in groups 40 and 60, respectively (P < or = 0.05). Liver GPX increased in the 60 group and lung GPX declined between 20% and 38% after endosulfan exposure. GSH in the liver and lung: endosulfan reduced GSH by about 30% at lower levels and increased by 41% or 70% at higher levels; chlorpyrifos decreased GSH by 28-40% in 20 and 60 groups, respectively (P < or = 0.05). Exposure to low, increasing levels of endosulfan and chlorpyrifos can differentially modify endogenous antioxidants SOD, GPX and GSH, which may lead to the development of oxidative stress in some tissues.

  10. 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

  11. In vivo isolated liver perfusion technique in a rat hepatic metastasis model: 5-fluorouracil concentrations in tumor tissue.

    PubMed

    de Brauw, L M; van de Velde, C J; Tjaden, U R; de Bruijn, E A; Bell, A V; Hermans, J; Zwaveling, A

    1988-02-01

    An in vivo method of isolated rat liver perfusion was developed with true vascular isolation and recirculating perfusate. This new surgical technique to temporarily isolate the liver vascularly, and the perfusion procedure are described in depth. Twelve inbred WAG/RIJ rats were subjected to 25 min of normothermic liver perfusion without chemotherapy, and all rats survived the procedure. Hepatic functional and histological integrity were not significantly altered during perfusion. To determine the role of isolated liver perfusion (ILP) as a means of improved targeting of antitumor agents, 5-fluorouracil (5-FU) concentrations were monitored in hepatic tumor and liver tissues and in systemic plasma using high-performance liquid chromatography. Fifty-one rats with hepatic tumors of colonic origin were randomly assigned to one of three dosage groups (20, 40, or 80 mg/kg) receiving 5-FU by ILP, hepatic artery infusion (HAI), or jugular vein infusion (JVI). ILP resulted in significantly increased 5-FU concentrations in liver tissue. However, no significant differences were found in tumor tissue concentrations of 5-FU between the three treatment modalities. 5-FU concentrations in tumor tissue increased as a function of the dose with ILP, HAI, and JVI. ILP was associated with the lowest systemic drug concentrations. The low systemic 5-FU concentrations with ILP suggest a higher maximum tolerable dose. This mode of treatment deserves to be studied further in our model before conclusions can be drawn regarding its therapeutic potential. PMID:3339874

  12. 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...

  13. 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...

  14. INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS

    EPA Science Inventory

    Title: INVESTIGATION OF THE ABILITY OF DIISONONYL PHTHALATE (DINP) TO ALTER ANDROGEN-DEPENDENT TISSUE DEVELOPMENT IN SPRAGUE-DAWLEY RATS.
    Authors: J S Ostby 1 , A K Hotchkiss 2 , J R Furr 1 and L E Gray Jr. 1
    Sponsor: L Gray Jr.
    Institutions: 1. USEPA, NH...

  15. Tissue-transplant fusion and vascularization of myocardial microtissues and macrotissues implanted into chicken embryos and rats.

    PubMed

    Kelm, Jens M; Djonov, Valentin; Hoerstrup, Simon P; Guenter, Christina I; Ittner, Lars M; Greve, Frauke; Hierlemann, Andreas; Sanchez-Bustamante, Carlota Diaz; Perriard, Jean-Claude; Ehler, Elisabeth; Fussenegger, Martin

    2006-09-01

    Cell-based therapies and tissue engineering initiatives are gathering clinical momentum for next-generation treatment of tissue deficiencies. By using gravity-enforced self-assembly of monodispersed primary cells, we have produced adult and neonatal rat cardiomyocyte-based myocardial microtissues that could optionally be vascularized following coating with human umbilical vein endothelial cells (HUVECs). Within myocardial microtissues, individual cardiomyocytes showed native-like cell shape and structure, and established electrochemical coupling via intercalated disks. This resulted in the coordinated beating of microtissues, which was recorded by means of a multi-electrode complementary metal-oxide-semiconductor microchip. Myocardial microtissues (microm3 scale), coated with HUVECs and cast in a custom-shaped agarose mold, assembled to coherent macrotissues (mm3 scale), characterized by an extensive capillary network with typical vessel ultrastructures. Following implantation into chicken embryos, myocardial microtissues recruited the embryo's capillaries to functionally vascularize the rat-derived tissue implant. Similarly, transplantation of rat myocardial microtissues into the pericardium of adult rats resulted in time-dependent integration of myocardial microtissues and co-alignment of implanted and host cardiomyocytes within 7 days. Myocardial microtissues and custom-shaped macrotissues produced by cellular self-assembly exemplify the potential of artificial tissue implants for regenerative medicine.

  16. Protective effect of green tea on lead-induced oxidative damage in rat's blood and brain tissue homogenates.

    PubMed

    Hamed, Enas A; Meki, Abdel-Raheim M A; Abd El-Mottaleb, Nashwa A

    2010-06-01

    Recent studies have shown that lead (Pb) could disrupt tissue prooxidant/antioxidant balance which lead to physiological dysfunction. Natural antioxidants are particularly useful in such situation. Current study was designed to investigate efficacy of green tea extract (GTE), on oxidative status in brain tissue and blood caused by chronic oral Pb administration in rats. Four groups of adult male rats (each 15 rats) were utilized: control group; GTE-group (oral 1.5% w/v GTE for 6 weeks); Pb-group (oral 0.4% lead acetate for 6 weeks), and Pb+GTE-group (1.5% GTE and 0.4% lead acetate for 6 weeks). Levels of prooxidant/antioxidant parameters [lipid peroxides (LPO), nitric oxides (NO), total antioxidant capacity (TAC), glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD)] in plasma, erythrocytes, and brain tissue homogenate were measured using colorimetric methods. Pb concentrations in whole blood and brain tissue homogenate were measured by atomic absorption. In Pb-group, levels of LPO were higher while NO and GSH were lower in plasma, erythrocytes, and brain tissue than controls. TAC in plasma, SOD in erythrocytes, and GST in brain tissue homogenate were lower in Pb-group versus control. GTE co-administrated with Pb-reduced Pb contents, increased antioxidant status than Pb-group. In erythrocytes, Pb correlated positively with LPO and negatively with NO, GSH, SOD, and Hb. In brain tissue homogenate, Pb correlated positively with LPO and negatively with GSH. This study suggests that lead induce toxicity by interfering balance between prooxidant/antioxidant. Treatment of rats with GTE combined with Pb enhances antioxidant/ detoxification system which reduced oxidative stress. These observations suggest that GTE is a potential complementary agent in treatment of chronic lead intoxication.

  17. 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

  18. Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats.

    PubMed

    Vogel, H G

    1980-01-01

    The influence of maturation and age on the physical and chemical properties of various organs of connective tissue has been studied in rats at ages of 4 weeks, 8 weeks, 4 monhs, 1 year and 2 years. The changes between young (4 weeks old) and adult (4 months to 1 year old) animals were considered as the effects of maturation, whereas the changes between adult and senescent (2 years old) rats were regarded as the effects of aging. Ultimate values, such as ultimate load, tensile strength and breaking strength, or ultimate modulus of elasticity, showed a sharp rise during maturation and a smaller but significant decrease during aging in all organs, such as skin strips, tail tendons, shaft bones, epiphyseal cartilage and aorta rings. Ultimate strain showed a similar pattern, but the maximum occurred earlier. These changes were parallel with the content of insoluble collagen. Other chemical parameters such as soluble collagen or glycosaminoglycans, showed a continuous decrease during the life span, whereas elastin rose continuously. More detailed analysis of mechanical properties in rat skin gave insight into the viscoelastic behaviour of skin. In creep experiments time until break under constant load rose continuously during the life span, whereas ultimate extension rate showed a sharp fall during maturation and a slow decrease during senescence. Stress at low extension degree and moduli of elasticity at low extension degree were decreased by maturation and increased by senescence, exactly the opposite of the changes at high extension degrees. The so-called step phenomenon was increased due to maturation and decreased due to aging. Relaxation and mechanical recovery were changed in the same direction by maturation and aging. Relative viscoelastic parameters, such as the hysteresis phenomenon and relative decrease of stress under cyclic strain, were barely influenced by the aging process. Changes of most of the mechanical parameters at high extension degrees during

  19. Evaluation of 2-year-old intrasplenic fetal liver tissue transplants in rats.

    PubMed

    Lupp, Amelie; Danz, Manfred; Müller, Dieter

    2003-01-01

    Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with beta-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class alpha and mu isoform expression. No immunostaining for P450 1A1 was visible. At both sites, beta-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class pi isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST pi-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class alpha and mu isoforms and a stronger inducibility of the P450 1A

  20. Steroid balance and tissue cholesterol accumulation in germfree and conventional rats fed diets containing saturated and polyunsaturated fats.

    PubMed

    Kellogg, T F

    1974-11-01

    Steroid balance studies were conducted on 24 conventional and 12 germfree male rats, 90-120 days old, fed diets containing either 20% safflower or 20% coconut oil. Both germfree and conventional rats fed the safflower oil diets had significantly lower serum cholesterol levels and significantly higher liver cholesterol levels than did the rats fed coconut oil. No significant differences in total fecal neutral sterols, coprostanol, Delta(7)-cholestenol, or total fecal bile acid excretion were seen between dietary groups of rats of either status. There was no evidence of qualitative differences in fecal bile acid excretion as a function of diet. The increased liver cholesterol was in the ester form, with cholesteryl linoleate the largest single component. There was no significant difference in the cholesterol content of the skin, muscle, adipose tissue, or gastrointestinal tract. The significance of a large increase in liver cholesteryl ester, lowered serum cholesterol, and no change in steroid excretion is discussed.

  1. Dietary Salt Restriction Improves Cardiac and Adipose Tissue Pathology Independently of Obesity in a Rat Model of Metabolic Syndrome

    PubMed Central

    Hattori, Takuya; Murase, Tamayo; Takatsu, Miwa; Nagasawa, Kai; Matsuura, Natsumi; Watanabe, Shogo; Murohara, Toyoaki; Nagata, Kohzo

    2014-01-01

    Background Metabolic syndrome (MetS) enhances salt sensitivity of blood pressure and is an important risk factor for cardiovascular disease. The effects of dietary salt restriction on cardiac pathology associated with metabolic syndrome remain unclear. Methods and Results We investigated whether dietary salt restriction might ameliorate cardiac injury in DahlS.Z‐Leprfa/Leprfa (DS/obese) rats, which are derived from a cross between Dahl salt‐sensitive and Zucker rats and represent a model of metabolic syndrome. DS/obese rats were fed a normal‐salt (0.36% NaCl in chow) or low‐salt (0.0466% NaCl in chow) diet from 9 weeks of age and were compared with similarly treated homozygous lean littermates (DahlS.Z‐Lepr+/Lepr+, or DS/lean rats). DS/obese rats fed the normal‐salt diet progressively developed hypertension and showed left ventricular hypertrophy, fibrosis, and diastolic dysfunction at 15 weeks. Dietary salt restriction attenuated all of these changes in DS/obese rats. The levels of cardiac oxidative stress and inflammation and the expression of cardiac renin–angiotensin–aldosterone system genes were increased in DS/obese rats fed the normal‐salt diet, and dietary salt restriction downregulated these parameters in both DS/obese and DS/lean rats. In addition, dietary salt restriction attenuated the increase in visceral adipose tissue inflammation and the decrease in insulin signaling apparent in DS/obese rats without reducing body weight or visceral adipocyte size. Dietary salt restriction did not alter fasting serum glucose levels but it markedly decreased the fasting serum insulin concentration in DS/obese rats. Conclusions Dietary salt restriction not only prevents hypertension and cardiac injury but also ameliorates insulin resistance, without reducing obesity, in this model of metabolic syndrome. PMID:25468654

  2. 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.

  3. 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.

  4. Morphological and biochemical examination of Cosmos 1887 rat heart tissue: Part I--Ultrastructure.

    PubMed

    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 (1). 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 (2-4).

  5. 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

  6. 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.

  7. 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.

  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. 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.

  10. Dietary borage oil alters plasma, hepatic and vascular tissue fatty acid composition in spontaneously hypertensive rats.

    PubMed

    Engler, M M; Engler, M B

    1998-07-01

    Dietary borage oil rich in gamma-linolenic acid (GLA) has been shown to lower blood pressure in Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). A potential mechanism for this effect may be attributed to changes in metabolism of GLA to dihomogamma-linolenic (DGLA) and arachidonic acids (AA). We investigated the effects of dietary borage oil on fatty acid composition in the plasma, liver and vascular tissue in WKY and SHR. The diet significantly increased the levels of omega-6 polyunsaturated fatty acids. GLA and DGLA levels in the plasma, liver, aorta and renal artery tissues increased in SHR (P < 0.001) and WKY (P < 0.001). AA levels were also increased in both plasma and liver of SHR (P < 0.05) and WKY (P < 0.05) fed the borage oil enriched diet. The results demonstrate that dietary borage oil produces marked changes in the metabolism of GLA which may contribute to its blood pressure lowering effect in WKY and SHR.

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. Dose-response efficacy of caraway (Carum carvi L.) on tissue lipid peroxidation and antioxidant profile in rat colon carcinogenesis.

    PubMed

    Kamaleeswari, Muthaiyan; Nalini, Namasivayam

    2006-08-01

    Colon cancer is a leading cause of cancer death and its prevention is of great interest throughout the world. This study was conducted to examine the efficacy of different doses of dietary caraway (Carum carvi L.) on tissue lipid peroxidation (LPO) and antioxidant profile in rat colon carcinogenesis. Wistar male rats were divided into 6 groups and were fed a modified pellet diet for the whole of 30 weeks. To induce colon cancer, rats were given a weekly subcutaneous injection of 1,2-dimethylhydrazine (DMH) at a dose of 20 mg kg(-1) (based on body weight) for the first 15 weeks. Caraway was supplemented every day orally at doses of 30, 60 and 90 mg kg(-1) for different groups of rats for the total period of 30 weeks. All rats were sacrificed at the end of 30 weeks, the colons were examined visually for masses and were subsequently evaluated histologically. The results showed diminished levels of intestinal, colonic and caecal LPO products, such as conjugated dienes (CD), lipid hydroperoxides (LOOH) and thiobarbituric acid reactive substances (TBARS) and also the antioxidants superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH) and glutathione reductase (GR) in DMH treated rats, which were significantly reversed (P<0.05) on caraway supplementation. Moreover, enhanced activity of intestinal, colonic and caecal glutathione peroxidase (GPx), glutathione S-transferase (GST) and colonic ascorbic acid and alpha-tocopherol levels were observed in carcinogen-treated rats, which were significantly (P<0.05) reduced on caraway supplementation. Thus, our study showed that caraway supplementation at a dose of 60 mg kg(-1) had a modulatory role on tissue LPO, antioxidant profile and prevented DMH-induced histopathological lesions in colon cancer rats.

  16. 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

  17. Effect of higher frequency components and duration of vibration on bone tissue alterations in the rat-tail model

    PubMed Central

    PEELUKHANA, Srikara V.; GOENKA, Shilpi; KIM, Brian; KIM, Jay; BHATTACHARYA, Amit; STRINGER, Keith F.; BANERJEE, Rupak K.

    2015-01-01

    To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s2, for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at p<0.05 level of significance was used for analysis. In the cortical bone, structural damage quantified through empty lacunae count was significant (p<0.05) at 250 Hz (10.82 ± 0.66) in comparison to the control group (7.41 ± 0.76). The biochemical damage was significant (p<0.05) at both the 125 Hz and 250 Hz vibration frequencies. The structural damage was significant (p<0.05) at 5D for cortical bone while the trabecular bone showed significant (p<0.05) damage at 20D time point. Further, the biochemical damage increased with increase in the duration of vibration with a significant (p<0.05) damage observed at 20D time point and a near significant change (p=0.08) observed at 5D time point. Structural and biochemical changes in bone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D). PMID:25843564

  18. Effect of higher frequency components and duration of vibration on bone tissue alterations in the rat-tail model.

    PubMed

    Peelukhana, Srikara V; Goenka, Shilpi; Kim, Brian; Kim, Jay; Bhattacharya, Amit; Stringer, Keith F; Banerjee, Rupak K

    2015-01-01

    To formulate more accurate guidelines for musculoskeletal disorders (MSD) linked to Hand-Arm Vibration Syndrome (HAVS), delineation of the response of bone tissue under different frequencies and duration of vibration needs elucidation. Rat-tails were vibrated at 125 Hz (9 rats) and 250 Hz (9 rats), at 49 m/s(2), for 1D (6 rats), 5D (6 rats) and 20D (6 rats); D=days (4 h/d). Rats in the control group (6 rats for the vibration groups; 2 each for 1D, 5D, and 20D) were left in their cages, without being subjected to any vibration. Structural and biochemical damages were quantified using empty lacunae count and nitrotyrosine signal-intensity, respectively. One-way repeated-measure mixed-model ANOVA at p<0.05 level of significance was used for analysis. In the cortical bone, structural damage quantified through empty lacunae count was significant (p<0.05) at 250 Hz (10.82 ± 0.66) in comparison to the control group (7.41 ± 0.76). The biochemical damage was significant (p<0.05) at both the 125 Hz and 250 Hz vibration frequencies. The structural damage was significant (p<0.05) at 5D for cortical bone while the trabecular bone showed significant (p<0.05) damage at 20D time point. Further, the biochemical damage increased with increase in the duration of vibration with a significant (p<0.05) damage observed at 20D time point and a near significant change (p=0.08) observed at 5D time point. Structural and biochemical changes in bone tissue are dependent upon higher vibration frequencies of 125 Hz, 250 Hz and the duration of vibration (5D, 20D).

  19. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  20. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats.

    PubMed

    Kelly, Karen B; Kennelly, John P; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J; Jacobs, René L

    2016-09-23

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet.

  1. Excess Folic Acid Increases Lipid Storage, Weight Gain, and Adipose Tissue Inflammation in High Fat Diet-Fed Rats

    PubMed Central

    Kelly, Karen B.; Kennelly, John P.; Ordonez, Marta; Nelson, Randal; Leonard, Kelly; Stabler, Sally; Gomez-Muñoz, Antonio; Field, Catherine J.; Jacobs, René L.

    2016-01-01

    Folic acid intake has increased to high levels in many countries, raising concerns about possible adverse effects, including disturbances to energy and lipid metabolism. Our aim was to investigate the effects of excess folic acid (EFA) intake compared to adequate folic acid (AFA) intake on metabolic health in a rodent model. We conducted these investigations in the setting of either a 15% energy low fat (LF) diet or 60% energy high fat (HF) diet. There was no difference in weight gain, fat mass, or glucose tolerance in EFA-fed rats compared to AFA-fed rats when they were fed a LF diet. However, rats fed EFA in combination with a HF diet had significantly greater weight gain and fat mass compared to rats fed AFA (p < 0.05). Gene expression analysis showed increased mRNA levels of peroxisome proliferator-activated receptor γ (PPARγ) and some of its target genes in adipose tissue of high fat-excess folic acid (HF-EFA) fed rats. Inflammation was increased in HF-EFA fed rats, associated with impaired glucose tolerance compared to high fat-adequate folic acid (HF-AFA) fed rats (p < 0.05). In addition, folic acid induced PPARγ expression and triglyceride accumulation in 3T3-L1 cells. Our results suggest that excess folic acid may exacerbate weight gain, fat accumulation, and inflammation caused by consumption of a HF diet. PMID:27669293

  2. Comparison of labeled acetate and glucose incorporations into lipids in the liver and adipose tissue after intravenous injection in rats.

    PubMed

    Iritani, Nobuko; Hirakawa, Tomoe; Fukuda, Hitomi; Katsukawa, Michiko; Kouno, Mika

    2014-01-01

    To compare incorporations of acetate and glucose in tissue total lipids and triacylglycerols (TAG), incorporations of labeled acetate and glucose in livers and epididymal adipose tissues (adipose tissue) were followed after their intravenous injection in the tail vein of individual rat fed a fat-free or 10% corn oil diet. The incorporation of acetate into total lipids (mostly TAG) in the liver reached maximum 2 h after the injection, while the incorporation of glucose decreased more quickly. Incorporation of glucose into total lipids and TAG was more greatly suppressed by dietary corn oil than that of acetate in the liver. In the adipose tissues, the incorporation of labeled acetate or glucose into total lipids was maximum 2-8 h after the injection, while the incorporation of glucose was very low, especially in rats fed the corn oil diet. Moreover, the time courses for labeled acetate and glucose incorporations into total lipids in the liver were parallel to those in plasma, but opposite to those in adipose tissue. TAG synthesized from acetate and glucose in the liver appeared to be mostly transported to adipose tissue. Thus, it is suggested that as the labeled glucose rapidly decreased in the liver, plasma and adipose tissue, TAG should be less derived from dietary carbohydrate than from dietary fat.

  3. Destruction of rat mammary tumor and normal tissue microcirculation by hematoporphyrin derivative photoradiation observed in vivo in sandwich observation chambers.

    PubMed

    Star, W M; Marijnissen, H P; van den Berg-Blok, A E; Versteeg, J A; Franken, K A; Reinhold, H S

    1986-05-01

    The effect of hematoporphyrin derivative photoradiation on tumor and normal tissue microcirculation was studied microscopically in vivo on rats with mammary carcinomas transplanted into subcutis in transparent observation chambers. One day after i.p. injection of hematoporphyrin derivative (15 mg/kg), chambers were exposed to red light (632 +/- 2 nm, eight light dose values, 0 to 270 J/cm2). After an initial blanching (ischemia) of the tumor accompanied by apparent vasoconstriction, reperfusion was observed with a slowing down of the tumor circulation, vasodilatation, and eventually a complete stasis, together with diffuse hemorrhages and subsequent necrosis. Besides, in large normal tissue vessels, platelet aggregates were observed, but no hemorrhage. Tumor regrowth occurred unless the tumor circulation and the adjacent normal tissue circulation were both destroyed. Tumor cell viability after treatment was assessed by transplanting the tumor from the chamber into the flank of the same animal. Even after a combined porphyrin and light dose 4 times the lethal dose for all tissues in the chamber, five of five transplanted tumors did regrow. This leads to the conclusion that, in our model system, tumor cell death after photoradiation occurs secondary to destruction of the microcirculation. In order to obtain additional information on normal tissue damage, rat ears were also irradiated. For the same light dose, the biological effect was only slightly larger than that of the normal tissue in the observation chambers, even though the measured ratio of porphyrin concentrations in ears and normal tissue in the chambers (subcutis) was about six.

  4. Influence of ammonium chloride on the tissue distribution of anticholinergic drugs in rats.

    PubMed

    Ishizaki, J; Yokogawa, K; Nakashima, E; Ohkuma, S; Ichimura, F

    1998-07-01

    Ammonium chloride (NH4Cl) increases lysosomal pH and thereby abolishes intralysosomal accumulation of drugs. Its effect on the tissue distribution of biperiden and trihexyphenidyl in rats has been investigated. The tissue-plasma concentration ratios (Kp) of these drugs in various tissues were determined by infusion studies at steady-state in the presence or absence of NH4Cl. Treatment with NH4Cl reduced the Kp values for both drugs, causing the largest reduction in Kp in the lung (52.1 to 11.8 for biperiden and 59.5 to 18.9 for trihexyphenidyl; ratios of decrease 0.77 and 0.68, respectively), followed by the heart and kidneys, with relatively small reductions in the brain, gut, muscle and fat. Subcellular fractionation studies in the lung indicated that the subcellular fraction-plasma concentration ratio of each drug at the steady state (K(p,sf)) was reduced by treatment with NH4Cl, with the largest decrease in the post-nuclear fraction (ratio of decrease 0.82 for biperiden and 0.74 for trihexyphenidyl), followed by the nucleus, microsomes and supernatant, in that order. A strong correlation was found between the ratio of decrease in K(p,sf) after NH4Cl treatment and the specific activity of acid phosphatases, a marker of lysosomes, in each fraction (biperiden, r = 0.948; trihexyphenidyl, r = 0.945). These results suggest that acidic organelles contribute significantly to the distribution kinetics of anticholinergic drugs.

  5. 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

  6. Identification of an enhancer involved in tissue-specific regulation of the rat fibronectin gene.

    PubMed Central

    Sporn, S A; Schwarzbauer, J E

    1995-01-01

    Fibronectin (FN) is a widely distributed extracellular matrix protein that is essential for cell adhesion in a variety of biological processes such as wound healing, tissue development and remodeling and oncogenic transformation. Appropriate FN levels are obtained by induction or repression of the FN gene in response to specific factors or circumstances in vivo. In order to identify regulatory regions involved in tissue-specific expression of FN, we have examined the transcriptional activity of overlapping fragments, within 4 kb upstream of the rat FN gene, following transfection into different cell types. Two regions conferred increases in transcription. The region between -1.08 and -2.6 displayed tissue-specificity and was active in fibroblasts but not hepatoma cells. The second region, between -3.2 and -3.9, was active in both cell types. Further characterization of the -1.08 to -2.6 segment demonstrated that it acts as an enhancer. Exonuclease III deletions of the 3' and 5' ends of the enhancer localized essential sequences between -1.5 and -1.7 and indicate that this fragment acts in concert with other sites between -1.08 and -2.6 to provide maximum enhancer activity. Gel mobility shift assays demonstrated fibroblast-specific binding of nuclear protein(s) to a 65 bp fragment within the essential region and DNase I footprinting localized this binding to a 27 bp sequence. Deletion of the sequence abolished the activity of the 1.5 kb enhancer. These studies show that a novel DNA sequence at -1688 is involved in regulating transcription of the FN gene in fibroblasts. Images PMID:7667111

  7. 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).

  8. Effects of low-energy shockwave therapy on the erectile function and tissue of a diabetic rat model.

    PubMed

    Qiu, Xuefeng; Lin, Guiting; Xin, Zhongcheng; Ferretti, Ludovic; Zhang, Haiyang; Lue, Tom F; Lin, Ching-Shwun

    2013-03-01

    Introduction.  Low-energy shockwave therapy (LESWT) has been shown to improve erectile function in patients suffering from diabetes mellitus (DM)-associated erectile dysfunction (ED). However, the underlying mechanism remains unknown. Aim.  The aim of this study is to investigate whether LESWT can ameliorate DM-associated ED in a rat model and examine the associated changes in the erectile tissues. Methods.  Newborn male rats were intraperitoneally injected with 5-ethynyl-2-deoxyuridine (EdU; 50 mg/kg) for the purpose of tracking endogenous mesenchymal stem cells (MSCs). Eight weeks later, eight of these rats were randomly chosen to serve as normal control (N group). The remaining rats were injected intraperitoneally with 60 mg/kg of streptozotocin (STZ) to induce DM. Eight of these rats were randomly chosen to serve as DM control (DM group), whereas another eight rats were subject to shockwave (SW) treatment (DM+SW group). Each rat in the DM+SW group received 300 shocks at energy level of 0.1 mJ/mm(2) and frequency of 120/minute. This procedure was repeated three times a week for 2 weeks. Another 2 weeks later, all 24 rats were evaluated for erectile function by intracavernous pressure (ICP) measurement. Afterward, their penile tissues were examined by histology. Main Outcome Measures.  Erectile function was measured by ICP. Neuronal nitric oxide synthase (nNOS)-positive nerves and the endothelium were examined by immunofluorescence staining. Smooth muscle and MSCs were examined by phalloidin and EdU staining, respectively. Results.  STZ treatment caused a significant decrease in erectile function and in the number of nNOS-positive nerves and in endothelial and smooth muscle contents. These DM-associated deficits were all partially but significantly reversed by LESWT. MSCs (EdU-positive cells) were significantly more numerous in DM+SW than in DM rats. Conclusion.  LESWT can partially ameliorate DM-associated ED by promoting regeneration of n

  9. 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

  10. Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host Disease in the Rat

    PubMed Central

    Jalapothu, Dasaradha; Boieri, Margherita; Crossland, Rachel E.; Shah, Pranali; Butt, Isha A.; Norden, Jean; Dressel, Ralf; Dickinson, Anne M.; Inngjerdingen, Marit

    2016-01-01

    MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate

  11. Tissue-Specific Expression Patterns of MicroRNA during Acute Graft-versus-Host Disease in the Rat

    PubMed Central

    Jalapothu, Dasaradha; Boieri, Margherita; Crossland, Rachel E.; Shah, Pranali; Butt, Isha A.; Norden, Jean; Dressel, Ralf; Dickinson, Anne M.; Inngjerdingen, Marit

    2016-01-01

    MicroRNAs (miRNA) have emerged as central regulators of diverse biological processes and contribute to driving pathology in several diseases. Acute graft-versus-host disease (aGvHD) represents a major complication after allogeneic hematopoietic stem cell transplantation, caused by alloreactive donor T cells attacking host tissues leading to inflammation and tissue destruction. Changes in miRNA expression patterns occur during aGvHD, and we hypothesized that we could identify miRNA signatures in target tissues of aGvHD that may potentially help understand the underlying molecular pathology of the disease. We utilized a rat model of aGvHD with transplantation of fully MHC-mismatched T cell depleted bone marrow, followed by infusion of donor T cells. The expression pattern of 423 rat miRNAs was investigated in skin, gut, and lung tissues and intestinal T cells with the NanoString hybridization platform, in combination with validation by quantitative PCR. MHC-matched transplanted rats were included as controls. In the skin, upregulation of miR-34b and downregulation of miR-326 was observed, while in the intestines, we detected downregulation of miR-743b and a trend toward downregulation of miR-345-5p. Thus, tissue-specific expression patterns of miRNAs were observed. Neither miR-326 nor miR-743b has previously been associated with aGvHD. Moreover, we identified upregulation of miR-146a and miR-155 in skin tissue of rats suffering from aGvHD. Analysis of intestinal T cells indicated 23 miRNAs differentially regulated between aGvHD and controls. Two of these miRNAs were differentially expressed either in skin (miR-326) or in intestinal (miR-345-5p) tissue. Comparison of intestinal and peripheral blood T cells indicated common dysregulated expression of miR-99a, miR-223, miR-326, and miR-345-5p. Analysis of predicted gene targets for these miRNAs indicated potential targeting of an inflammatory network both in skin and in the intestines that may further regulate

  12. 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

  13. Pathologic changes of wound tissue in rats with stage III pressure ulcers treated by transplantation of human amniotic epithelial cells.

    PubMed

    Zheng, Xilan; Jiang, Zhixia; Zhou, Aiting; Yu, Limei; Quan, Mingtao; Cheng, Huagang

    2015-01-01

    This study aims to determine the impact of orthotopic transplantation of human amniotic epithelial cells (hAECs) on the pathologic changes of wound tissues in a self-prepared rat stage III pressure ulcer model. Ninety-six SD rats were randomly divided into the model group (group M), hAEC transplantation group (group H), traditional treatment group (group T), and the control group (group C), with 24 rats in each group. The wound healing time was observed in 6 rats from each group, and 6 rats of each group were selected for post-modeling on day(s) (D) 1, 3, and 7 for HE staining to compare the pathological changes. The healing time of group H was significantly shorter than the other three groups. Moreover, pathological observations revealed that group H exhibited significant proliferation of fibrous tissues and vessels in the dermal layer, and the appearance time and degree of skin appendages were significantly greater than that observed in the other three groups. Pathological observations showed that hAEC transplantation could significantly speed up the healing of stage III pressure ulcer.

  14. Expression and location of HSP60 and HSP10 in the heart tissue of heat-stressed rats

    PubMed Central

    Cheng, Yanfen; Sun, Jiarui; Chen, Hongbo; Adam, Abdelnasir; Tang, Shu; Kemper, Nicole; Hartung, Jörg; Bao, Endong

    2016-01-01

    The present study aimed to analyze the expression levels and localizations of heat shock protein (HSP) 60 and HSP10 in the heart tissue of rats subjected to heat stress (42°C) for 0, 20, 80 and 100 min. Histopathological injuries and increased serum activities of serum lactate dehydrogenase and creatine kinase isoenzyme MB were detected in the heated rat myocardial cells. These results suggested that heat stress-induced acute degeneration may be sufficient to cause sudden death in animals by disrupting the function and permeability of the myocardial cell membrane. In addition, the expression levels of HSP60 were significantly increased following 20 min heat stress, whereas the expression levels of its cofactor HSP10 were not. Furthermore, the location of HSP60, but not of HSP10, was significantly altered during periods of heat stress. These results suggested that HSP60 in myocardial tissue may be more susceptive to the effects of heat stress as compared with HSP10, and that HSP10 is constitutively expressed in the heart of rats. The expression levels and localizations of HSP60 and HSP10 at the different time points of heat stress were not similar, which suggested that HSP60 and HSP10 may not form a complex in the heart tissue of heat-stressed rats.

  15. 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

  16. Expression and location of HSP60 and HSP10 in the heart tissue of heat-stressed rats

    PubMed Central

    Cheng, Yanfen; Sun, Jiarui; Chen, Hongbo; Adam, Abdelnasir; Tang, Shu; Kemper, Nicole; Hartung, Jörg; Bao, Endong

    2016-01-01

    The present study aimed to analyze the expression levels and localizations of heat shock protein (HSP) 60 and HSP10 in the heart tissue of rats subjected to heat stress (42°C) for 0, 20, 80 and 100 min. Histopathological injuries and increased serum activities of serum lactate dehydrogenase and creatine kinase isoenzyme MB were detected in the heated rat myocardial cells. These results suggested that heat stress-induced acute degeneration may be sufficient to cause sudden death in animals by disrupting the function and permeability of the myocardial cell membrane. In addition, the expression levels of HSP60 were significantly increased following 20 min heat stress, whereas the expression levels of its cofactor HSP10 were not. Furthermore, the location of HSP60, but not of HSP10, was significantly altered during periods of heat stress. These results suggested that HSP60 in myocardial tissue may be more susceptive to the effects of heat stress as compared with HSP10, and that HSP10 is constitutively expressed in the heart of rats. The expression levels and localizations of HSP60 and HSP10 at the different time points of heat stress were not similar, which suggested that HSP60 and HSP10 may not form a complex in the heart tissue of heat-stressed rats. PMID:27698781

  17. Regulation of lipid flux between liver and adipose tissue during transient hepatic steatosis in carnitine-depleted rats.

    PubMed

    Degrace, Pascal; Demizieux, Laurent; Du, Zhen-Yu; Gresti, Joseph; Caverot, Laurent; Djaouti, Louiza; Jourdan, Tony; Moindrot, Bastien; Guilland, Jean-Claude; Hocquette, Jean-François; Clouet, Pierre

    2007-07-20

    Rats with carnitine deficiency due to trimethylhydrazinium propionate (mildronate) administered at 80 mg/100 g body weight per day for 10 days developed liver steatosis only upon fasting. This study aimed to determine whether the transient steatosis resulted from triglyceride accumulation due to the amount of fatty acids preserved through impaired fatty acid oxidation and/or from up-regulation of lipid exchange between liver and adipose tissue. In liver, mildronate decreased the carnitine content by approximately 13-fold and, in fasted rats, lowered the palmitate oxidation rate by 50% in the perfused organ, increased 9-fold the triglyceride content, and doubled the hepatic very low density lipoprotein secretion rate. Concomitantly, triglyceridemia was 13-fold greater than in controls. Hepatic carnitine palmitoyltransferase I activity and palmitate oxidation capacities measured in vitro were increased after treatment. Gene expression of hepatic proteins involved in fatty acid oxidation, triglyceride formation, and lipid uptake were all increased and were associated with increased hepatic free fatty acid content in treated rats. In periepididymal adipose tissue, mildronate markedly increased lipoprotein lipase and hormone-sensitive lipase activities in fed and fasted rats, respectively. On refeeding, carnitine-depleted rats exhibited a rapid decrease in blood triglycerides and free fatty acids, then after approximately 2 h, a marked drop of liver triglycerides and a progressive decrease in liver free fatty acids. Data show that up-regulation of liver activities, peripheral lipolysis, and lipoprotein lipase activity were likely essential factors for excess fat deposit and release alternately occurring in liver and adipose tissue of carnitine-depleted rats during the fed/fasted transition.

  18. Effect of tumor necrosis factor administration in vivo on lipoprotein lipase activity in various tissues of the rat.

    PubMed

    Grunfeld, C; Gulli, R; Moser, A H; Gavin, L A; Feingold, K R

    1989-04-01

    When added to murine adipocytes in culture, tumor necrosis factor (TNF) decreases the levels of lipoprotein lipase (LPL). Semb et al (1987. J. Biol Chem. 262: 8390-8394) have shown that administration of murine TNF to rats decreases lipoprotein lipase (LPL) in the epididymal fat pad with maximal inhibition requiring several hours. We have now tested the effects of treatment of rats with TNF on LPL activity in a variety of tissues and find that few show decreases in LPL under conditions that acutely increase serum triglycerides. Ninety minutes after treatment of male rats with human TNF (25 micrograms/200 g, i.v.), serum triglycerides rose 2.2-fold but there was no decrease in LPL activity in epididymal fat. Sixteen hours after TNF treatment LPL activity had decreased by 44% in epididymal fat, consistent with the previously reported data. In contrast, in female rats, no significant decrease was seen in LPL activity in parametrial adipose tissue at either 90 min or 16 hr after TNF administration despite increases in serum triglycerides (1.8-fold and 1.5-fold, respectively). There was little change in LPL activity in most other adipose tissue sites of male or female rats at either time after TNF treatment. No effect of TNF was seen on heart or diaphragm muscle LPL at any time. TNF treatment of both male and female rats produces consistent increases in de novo hepatic lipogenesis in vivo under conditions that increase serum triglycerides. It is unlikely that the limited effects of TNF on LPL in vivo can account for the rapid and sustained increase in serum triglycerides.

  19. The effects of lifelong ubiquinone Q10 supplementation on the Q9 and Q10 tissue concentrations and life span of male rats and mice.

    PubMed

    Lönnrot, K; Holm, P; Lagerstedt, A; Huhtala, H; Alho, H

    1998-04-01

    The effect of lifelong oral supplementation with ubiquinone Q10 (10 mg/kg/day) was examined in Sprague-Dawley rats and C57/B17 mice. There were no significant differences in survival or life-span found in either rats or mice. Histopathologic examination of different rat tissues showed no differences between the groups. In Q10 supplemented rats, plasma and liver Q10 levels were 2.6 to 8.4 times higher at all age points than in control rats. Interestingly, in supplemented rats the Q9 levels also were significantly higher (p<0.05) in plasma and liver at ages 18 and 24 months. Neither Q9 nor Q10 levels were affected by supplementation in kidney, heart, or brain tissues. In spite of the significant changes in plasma and liver ubiquinone concentrations, lifelong Q10 supplementation did not prolong or shorten the lifespan of either rats or mice.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. Study of sodium tanshinone II A sulfonate tissue distribution in rat by liquid chromatography/tandem mass spectrometry.

    PubMed

    He, Tingting; Zou, Qiaogen; Feng, Zhenbin; Zhang, Zunjian

    2010-01-01

    A rapid and sensitive method based on liquid chromatography/tandem mass spectrometry (LC-MS/MS) has been developed and fully validated for the quantitative determination of sodium tanshinone IIA sulfonate (STS, sodium (1,6,6-trimethyl-10,11-dioxo-7,8,9-trihydrophenanthro[1,2-b]furan)-yl-2-sulfonate) in rat biosamples including plasma and different tissues using sodium tanshinone I sulfonate (sodium (1,6-dimethyl-10,11-dioxo-phenanthro[1,2-b]furan)-yl-2-sulfonate) as internal standard. Simple protein precipitation by acetonitrile was utilized for extracting STS from the rat biosamples. Chromatographic separation of the sample matrix from the analyte and the internal standard was performed using a commercially available analytical column with a mobile phase consisting of methanol-5 mmoL/L ammonia acetate (70:30, v/v) at a flow rate of 0.2 mL/min. Detection was performed on a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization source and operated in the negative-ion mode. The intra- and inter-day precisions (RSD%) and deviations of the assay accuracies were within 10.0% for STS. The extraction recovery of STS was more than 86.5%. The limit of detection (LOD) of STS was 1.0 ng/mL. The method was successfully applied to the tissue distribution study of STS intravenously administered to healthy Sprague-Dawley rats. The tissue distribution results showed that liver, kidney, lung, small intestine and duodenum were the major distribution tissues of STS in rats, and that STS had difficulty in crossing the blood-brain barrier. After 24 h, STS could be detected only in the kidney, stomach and small intestine, indicating that there was no long-term accumulation of STS in rat. PMID:21175038

  5. Angiotensin II and 1-7 during aging in Metabolic Syndrome rats. Expression of AT1, AT2 and Mas receptors in abdominal white adipose tissue.

    PubMed

    Rubio-Ruíz, M E; Del Valle-Mondragón, L; Castrejón-Tellez, V; Carreón-Torres, E; Díaz-Díaz, E; Guarner-Lans, V

    2014-07-01

    Renin-Angiotensin System (RAS) plays an important role in the development of Metabolic Syndrome (MS) and in aging. Angiotensin 1-7 (Ang 1-7) has opposite effects to Ang II. All of the components of RAS are expressed locally in adipose tissue and there is over-activation of adipose RAS in obesity and hypertension. We determined serum and abdominal adipose tissue Ang II and Ang 1-7 in control and MS rats during aging and the expression of AT1, AT2 and Mas in white adipose tissue. MS was induced by sucrose ingestion during 6, 12 and 18 months. During aging, an increase in body weight, abdominal fat and dyslipidemia were found but increases in aging MS rats were higher. Control and MS concentrations of serum Ang II from 6-month old rats were similar. Aging did not modify Ang II seric concentration in control rats but decreased it in MS rats. Ang II levels increased in WAT from both groups of rats. Serum and adipose tissue Ang 1-7 increased during aging in MS rats. Western blot analysis revealed that AT1 expression increased in the control group during aging while AT2 and Mas remained unchanged. In MS rats, AT1 and AT2 expression decreased significantly in aged rats. The high concentration of Ang 1-7 and adiponectin in old MS rats might be associated to an increased expression of PPAR-γ. PPAR-γ was increased in adipose tissue from MS rats. It decreased with aging in control rats and showed no changes during aging in MS rats. Ang 1-7/Mas axis was the predominant pathway in WAT from old MS animals and could represent a potential target for therapeutical strategies in the treatment of MS during aging.

  6. A Low-Protein, High-Carbohydrate Diet Stimulates Thermogenesis in the Brown Adipose Tissue of Rats via ATF-2.

    PubMed

    de França, Suélem A; dos Santos, Maísa P; Przygodda, Franciele; Garófalo, Maria Antonieta R; Kettelhut, Isis C; Magalhães, Diego A; Bezerra, Kalinne S; Colodel, Edson M; Flouris, Andreas D; Andrade, Cláudia M B; Kawashita, Nair H

    2016-03-01

    The aim of this study was to evaluate thermogenesis in the interscapular brown adipose tissue (IBAT) of rats submitted to low-protein, high-carbohydrate (LPHC) diet and the involvement of adrenergic stimulation in this process. Male rats (~100 g) were submitted to LPHC (6%-protein; 74%-carbohydrate) or control (C; 17%-protein; 63%-carbohydrate) isocaloric diets for 15 days. The IBAT temperature was evaluated in the rats before and after the administration of noradrenaline (NA) (20 µg 100 g b w(-1) min(-1)). The expression levels of uncoupling protein 1 (UCP1) and other proteins involved in the regulation of UCP1 expression were determined by Western blot (Student's t test, P ≤ 0.05). The LPHC diet promoted a 1.1 °C increase in the basal temperature of IBAT when compared with the basal temperature in the IBAT of the C group. NA administration promoted a 0.3 °C increase in basal temperature in the IBAT of the C rats and a 0.5 °C increase in the IBAT of the LPHC group. The level of UCP1 increased 60% in the IBAT of LPHC-fed rats, and among the proteins involved in its expression, such as β3-AR and α1-AR, there was a 40% increase in the levels of p38-MAPK and a 30% decrease in CREB when compared to the C rats. The higher sympathetic flux to IBAT, which is a consequence of the administration of the LPHC diet to rats, activates thermogenesis and increases the expression of UCP1 in the tissue. Our results suggest that the increase in UCP1 content may occur via p38 MAPK and ATF2.

  7. Rat Cytomegalovirus Gene Expression in Cardiac Allograft Recipients Is Tissue Specific and Does Not Parallel the Profiles Detected In Vitro▿

    PubMed Central

    Streblow, Daniel N.; van Cleef, Koen W. R.; Kreklywich, Craig N.; Meyer, Christine; Smith, Patricia; Defilippis, Victor; Grey, Finn; Früh, Klaus; Searles, Robert; Bruggeman, Cathrien; Vink, Cornelis; Nelson, Jay A.; Orloff, Susan L.

    2007-01-01

    Rat cytomegalovirus (RCMV) is a β-herpesvirus with a 230-kbp genome containing over 167 open reading frames (ORFs). RCMV gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early, and late). However, the extent of viral-gene expression in vivo and its relationship to the in vitro expression are unknown. In this study, we used RCMV-specific DNA microarrays to investigate the viral transcriptional profiles in cultured, RCMV-infected endothelial cells, fibroblasts, and aortic smooth muscle cells and to compare these profiles to those found in tissues from RCMV-infected rat heart transplant recipients. In cultured cells, RCMV expresses approximately 95% of the known viral ORFs with few differences between cell types. By contrast, in vivo viral-gene expression in tissues from rat heart allograft recipients is highly restricted. In the tissues studied, a total of 80 viral genes expressing levels twice above background (5,000 to 10,000 copies per μg total RNA) were detected. In each tissue type, there were a number of genes expressed exclusively in that tissue. Although viral mRNA and genomic DNA levels were lower in the spleen than in submandibular glands, the number of individual viral genes expressed was higher in the spleen (60 versus 41). This finding suggests that the number of viral genes expressed is specific to a given tissue and is not dependent upon the viral load or viral mRNA levels. Our results demonstrate that the profiles, as well as the amplitude, of viral-gene expression are tissue specific and are dramatically different from those in infected cultured cells, indicating that RCMV gene expression in vitro does not reflect viral-gene expression in vivo. PMID:17251289

  8. 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

  9. The effect of rapamycin on DNA synthesis in multiple tissues from late gestation fetal and postnatal rats.

    PubMed

    Sanders, Jennifer A; Lakhani, Alisha; Phornphutkul, Chanika; Wu, Ke-Ying; Gruppuso, Philip A

    2008-08-01

    Rapamycin is a potent antiproliferative agent that arrests cells in the G1 phase of the cell cycle through a variety of mechanisms involving the inhibition of the mammalian target of rapamycin (mTOR) pathway. The majority of normal cells in culture are sensitive to the cytostatic effects of rapamycin, whereas the growth of many malignant cells and tumors is rapamycin resistant. We had shown previously that hepatic DNA synthesis in the late gestation rat fetus is rapamycin resistant even though signaling through the mTOR/S6 kinase (S6K) pathway is attenuated. On the basis of this finding, we went on to characterize the response to rapamycin in a spectrum of tissues during late gestation and the early postnatal period in the rat. We found that rapamycin had no effect on DNA synthesis in major organs such as heart, intestine, and kidney in the fetal and early postnatal rat despite a marked attenuation in the phosphorylation of ribosomal protein S6. In contrast, the proliferation of mature hepatocytes during liver regeneration was highly sensitive to rapamycin. These data indicate that basal cellular proliferation in a wide variety of tissues is rapamycin resistant and occurs independently of mTOR/S6K signaling. Furthermore, the well-characterized effects of rapamycin in tissue culture systems are not recapitulated in the asynchronous cell proliferation that accompanies normal growth and tissue remodeling.

  10. 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

  11. 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.

  12. Simultaneous tissue profiling of eicosanoid and endocannabinoid lipid families in a rat model of osteoarthritis[S

    PubMed Central

    Wong, Amy; Sagar, Devi R.; Ortori, Catharine A.; Kendall, David A.; Chapman, Victoria; Barrett, David A.

    2014-01-01

    We describe a novel LC method for the simultaneous and quantitative profiling of 43 oxylipins including eicosanoids, endocannabinoids, and structurally related bioactive lipids with modified acyl groups. The LC-MS/MS method uses switching at a defined time between negative and positive electrospray ionization modes to achieve optimal detection sensitivity for all the lipids. The validated method is linear over a range of 0.01–5 nmol/g (0.1–50 nmol/g for 2-arachidonoyl glycerol) with intra- and interday precision and accuracy between 1.38 and 26.76% and 85.22 and 114.3%, respectively. The method successfully quantified bioactive lipids in different tissue types in the rat, including spinal cord, dorsal root ganglia (DRGs), knee joint, brain, and plasma. Distinct regional differences in the pattern of lipid measured between tissue types were observed using principle component analysis. The method was applied to analyze tissue samples from an established preclinical rat model of osteoarthritis (OA) pain and showed that levels of 12-hydroxyeicosatetraenoic acid were significantly increased in the OA rat knee joint compared with controls, and that 15-hydroxyeicosatetraenoic acid was significantly increased in the DRGs in the model of OA compared with controls. The developed LC-MS/MS method has the potential to provide detailed pathway profiling in tissues and biofluids where the disruption of bioactive oxylipins may be involved in disease states. PMID:25062663

  13. Cardiac physiologic and tissue metabolic changes following chronic low-level cadmium and cadmium plus lead ingestion in the rat.

    PubMed

    Kopp, S J; Perry, H M; Perry, E F; Erlanger, M

    1983-06-15

    Female Long-Evans hooded rats received Schroeder's rye-based diet and 0 or 1 microgram/ml cadmium, or cadmium plus lead in mineral fortified drinking water from weaning to 18 months. The heavy metal-fed rats were normal with respect to control, including growth rates and final body weights. Rats receiving added cadmium and cadmium plus lead in the diet were characterized by a persistent hypertension which was evident after 2 months. Cardiac conduction system excitability was depressed preferentially in cadmium-(atrioventricular nodal region) and cadmium plus lead-(His-Purkinje system) fed rats. Although heart rates were comparable to control, myocardial contractile activity (peak active tension and dT/dt) was significantly decreased in intact perfused heart preparations from both heavy metal-treated groups. In conjunction with the observed physiologic changes, various tissue-specific metabolic alterations were detected in heart, kidney, and liver. Generally, prolonged heavy-metal ingestion at these levels resulted in impaired energy metabolism (e.g., decreased ATP, PCr; increased Pj, ADP concentrations) and altered essential mineral composition (e.g., calcium, magnesium, zinc, and to a lesser extent, sodium and potassium; copper levels were unaffected) that varied in severity according to the tissue. The addition of lead to the cadmium diet had little additive effect on the cardiovascular system; however, renal and hepatic tissues did exhibit apparent additive effects further suggesting that cadmium and lead actions and interactions may be tissue dependent. These experimental findings and the biologic inferences derived are consonant with the hypothesis that chronic, life-long cadmium exposure approximating environmental levels may have significant adverse effects on mammalian systems, that include effects on cardiovascular tissues.

  14. Differential methylation of the gene encoding myo-inositol 3-phosphate synthase (Isyna1) in rat tissues

    PubMed Central

    Seelan, Ratnam S; Pisano, M Michele; Greene, Robert M; Casanova, Manuel F; Parthasarathy, Ranga N

    2011-01-01

    Aims Myo-inositol levels are frequently altered in several brain disorders. Myo-inositol 3-phosphate synthase, encoded by the Isyna1 gene, catalyzes the synthesis of myo-inositol in cells. Very little is known about the mechanisms regulating Isyna1 expression in brain and other tissues. In this study, we have examined the role of DNA methylation in regulating Isyna1 expression in rat tissues. Materials & methods Transfection analysis using in vitro methylated promoter constructs, Southern blot analysis of genomic DNA from various tissues digested with a methylation-sensitive enzyme and CpG methylation profiling of genomic DNA from different tissues were used to determine differential methylation of Isyna1 in tissues. Transfection analysis using plasmids harboring mutated CpG residues in the 5’-upstream region of Isyna1 was used to identify critical residues mediating promoter activity. Results The −700 bp to −500 bp region (region 1) of Isyna1 exhibited increased methylation in brain cortex compared with other tissues; it also exhibited sex-specific methylation differences between matched male and female brain cortices. Mutation analysis identified one CpG residue in region 1 necessary for promoter activity in neuronal cells. A tissue-specific differentially methylated region (T-DMR) was found to be localized between +450 bp and +650 bp (region 3). This DMR was comparatively highly methylated in spleen, moderately methylated in brain cortex and poorly methylated in testis, consistent with mRNA levels observed in these tissues. Conclusion Rat Isyna1 exhibits tissue-specific DNA methylation. Brain DNA was uniquely methylated in the 5’-upstream region and displayed gender specificity. A T-DMR was identified within the gene body of Isyna1. These findings suggest that Isyna1 is regulated, in part, by DNA methylation and that significant alterations in methylation patterns during development could have a major impact on inositol phosphate synthase expression in

  15. Through metal binding, curcumin protects against lead- and cadmium-induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain.

    PubMed

    Daniel, Sheril; Limson, Janice L; Dairam, Amichand; Watkins, Gareth M; Daya, Santy

    2004-02-01

    Curcumin, the major constituent of turmeric is a known, naturally occurring antioxidant. The present study examined the ability of this compound to protect against lead-induced damage to hippocampal cells of male Wistar rats, as well as lipid peroxidation induced by lead and cadmium in rat brain homogenate. The thiobarbituric assay (TBA) was used to measure the extent of lipid peroxidation induced by lead and cadmium in rat brain homogenate. The results show that curcumin significantly protects against lipid peroxidation induced by both these toxic metals. Coronal brain sections of rats injected intraperitoneally with lead acetate (20 mg/kg) in the presence and absence of curcumin (30 mg/kg) were compared microscopically to determine the extent of lead-induced damage to the cells in the hippocampal CA1 and CA3 regions, and to establish the capacity of curcumin to prevent such damage. Lead-induced damage to the neurons was significantly curtailed in the rats injected with curcumin. Possible chelation of lead and cadmium by curcumin as its mechanism of neuroprotection against such heavy metal insult to the brain was investigated using electrochemical, ultraviolet spectrophotometric and infrared spectroscopic analyses. The results of the study show that there is an interaction between curcumin and both cadmium and lead, with the possible formation of a complex between the metal and this ligand. These results imply that curcumin could be used therapeutically to chelate these toxic metals, thus potentially reducing their neurotoxicity and tissue damage.

  16. 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

  17. 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.

  18. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    PubMed

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  19. Metabolomic Analysis of Rat Brain by High Resolution Nuclear Magnetic Resonance Spectroscopy of Tissue Extracts

    PubMed Central

    Lutz, Norbert W.; Béraud, Evelyne; Cozzone, Patrick J.

    2014-01-01

    Studies of gene expression on the RNA and protein levels have long been used to explore biological processes underlying disease. More recently, genomics and proteomics have been complemented by comprehensive quantitative analysis of the metabolite pool present in biological systems. This strategy, termed metabolomics, strives to provide a global characterization of the small-molecule complement involved in metabolism. While the genome and the proteome define the tasks cells can perform, the metabolome is part of the actual phenotype. Among the methods currently used in metabolomics, spectroscopic techniques are of special interest because they allow one to simultaneously analyze a large number of metabolites without prior selection for specific biochemical pathways, thus enabling a broad unbiased approach. Here, an optimized experimental protocol for metabolomic analysis by high-resolution NMR spectroscopy is presented, which is the method of choice for efficient quantification of tissue metabolites. Important strengths of this method are (i) the use of crude extracts, without the need to purify the sample and/or separate metabolites; (ii) the intrinsically quantitative nature of NMR, permitting quantitation of all metabolites represented by an NMR spectrum with one reference compound only; and (iii) the nondestructive nature of NMR enabling repeated use of the same sample for multiple measurements. The dynamic range of metabolite concentrations that can be covered is considerable due to the linear response of NMR signals, although metabolites occurring at extremely low concentrations may be difficult to detect. For the least abundant compounds, the highly sensitive mass spectrometry method may be advantageous although this technique requires more intricate sample preparation and quantification procedures than NMR spectroscopy. We present here an NMR protocol adjusted to rat brain analysis; however, the same protocol can be applied to other tissues with minor

  20. 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.

  1. The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics.

    PubMed

    Liu, Yue-tao; Jia, Hong-mei; Chang, Xing; Ding, Gang; Zhang, Hong-wu; Zou, Zhong-Mei

    2013-11-01

    Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

  2. 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

  3. Investigating the recovery period of rat brain tissue after electrolytic and 980-nm laser induced lesions

    NASA Astrophysics Data System (ADS)

    Bozkulak, Ozguncem; Tabakoglu, H. Ozgur; Aksoy, Ayla; Canbeyli, Resit; Bilgin, Nes'e.; Kurtkaya, Ozlem; Sav, Aydin; Gulsoy, Murat

    2003-10-01

    The effects of 980-nm diode laser and electrolytic lesions in Wistar rat brain tissue were observed by immunohistochemical staining for CD68 marker and Hematoxylin-Eosin (H&E). Bilateral lesions; laser lesions (2W/2sec) in the right hemispheres, and electrolytic lesions (1.5mA/20sec) in the left hemispheres were done through in vivo stereotaxic neurosurgical procedure. Subjects were classified into three groups due to the recovery period. Subjects in Group I, II, and III were sacrificed after 0, 2 and 7 days of recovery period respectively. After saline perfusion their brains were dislocated, and paraffin embedded sections were taken. One section for H&E and one for CD68 were cut consecutively in 3μm thickness by examining the lesion in every 30-μm thickness. CD68 was found more efficient marker than H&E in observing the after-effects of both types of lesions. The total damage of laser was smaller than that of electrosurgical unit. The shape of the ablated area in laser induced lesions was more spherical than that of electrosurgical unit. The number of macrophages increased as the recovery period increased for all subjects. Group III showed the highest number of macrophages in three, and the number of macrophages around electrolytic lesion is nearly 1.5 times higher than that of laser lesion. The remarkable ablating ability, the damage zone created and the healing of nearby tissue clearly showed that the 980-nm diode laser is an effective and useful alternative to electrosurgical unit in neurosurgery.

  4. 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

  5. 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

  6. 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.

  7. The presence of acyl-CoA hydrolase in rat brown-adipose-tissue peroxisomes.

    PubMed

    Alexson, S E; Osmundsen, H; Berge, R K

    1989-08-15

    The subcellular distribution of acyl-CoA hydrolase was studied in rat brown adipose tissue, with special emphasis on possible peroxisomal localization. Subcellular fractionation by sucrose-density-gradient centrifugation, followed by measurement of short-chain (propionyl-CoA) acyl-CoA hydrolase in the presence of NADH, resulted in two peaks of activity in the gradient: one peak corresponded to the distribution of cytochrome oxidase (mitochondrial marker enzyme), and another peak of activity coincided with the peroxisomal marker enzyme catalase. The distribution of the NADH-inhibited short-chain hydrolase activity fully resembled that of cytochrome oxidase. The substrate-specificity curve of the peroxisomal acyl-CoA hydrolase activity indicated the presence of a single enzyme exhibiting a broad substrate specificity, with maximal activity towards fatty acids with chain lengths of 3-12 carbon atoms. The mitochondrial acyl-CoA hydrolase substrate specificity, in contrast, indicated the presence of at least two acyl-CoA hydrolases (of short- and medium-chain-length specificity). The peroxisomal acyl-CoA hydrolase activity was inhibited by CoA at low (microM) concentrations and by ATP at high concentrations (greater than 0.8 mM). In contrast with the mitochondrial short-chain hydrolase, the peroxisomal acyl-CoA hydrolase activity was not inhibited by NADH. PMID:2573347

  8. 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 (tran