Preliminary phytochemical, acute oral toxicity and antihepatotoxic study of roots of Paeonia officinalis Linn.

PubMed Central

Ahmad, Feroz; Tabassum, Nahida

2013-01-01

Objective To carry out a preliminary phytochemical, acute oral toxicity and antihepatotoxic study of the roots of Paeonia officinalis (P. officinalis) L. Methods Preliminary phytochemical investigation was done as per standard procedures. Acute oral toxicity study was conducted as per OECD 425 guidelines. The antihepatotoxic activity of aqueous extract of root of P. officinalis was evaluated against carbon tetrachloride (CCl4) induced hepatic damage in rats. Aqueous extract of P. officinalis at the dose levels of 100 and 200 mg/kg body weight was administered daily for 14 d in experimental animals. Liver injury was induced chemically, by CCl4 administration (1 mL/kg i.p.). The hepatoprotective activity was assessed using various biochemical parameters like aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum alkaline phosphatase (SALP), total bilirubin and total protein (TP) along with histopathological studies. Result Phytochemical screening revealed that the roots of P. officinalis contain alkaloids, tannins, saponins, glycosides, carbohydrates, flavonoids, terpenes, steroids and proteins. The aqueous extract did not cause any mortality up to 2 000 mg/kg. In rats that had received the root extract at the dose of 100 and 200 mg/kg, the substantially elevated AST, ALT, SALP, total bilirubin levels were significantly lowered, respectively, in a dose dependent manner, along with CCl4 while TP levels were elevated in these groups. Histopathology revealed regeneration of the livers in extract treated groups while Silymarin treated rats were almost normal. Conclusions The aqueous extract of P. officinalis is safe and possesses antihepatotoxic potential. PMID:23570019

Development and full validation of an UPLC-MS/MS method for the determination of an anti-allergic indolinone derivative in rat plasma, and application to a preliminary pharmacokinetic study.

PubMed

Oufir, Mouhssin; Sampath, Chethan; Butterweck, Veronika; Hamburger, Matthias

2012-08-01

The natural product (E,Z)-3-(4-hydroxy-3,5-dimethoxybenzylidene)indolin-2-one (indolinone) was identified some years ago as a nanomolar inhibitor of FcɛRI-receptor dependent mast cell degranulation. To further explore the potential of the compound, we established an UPLC-MS/MS assay for dosage in rat plasma. The method was fully validated according to FDA Guidance for industry. Results of this validation and long term stability study demonstrate that the method in lithium heparinized rat plasma is specific, accurate, precise and capable of producing reliable results according to recommendations of international guidelines. The method was validated with a LLOQ of 30.0 ng/mL and an ULOQ of 3000 ng/mL. The response versus concentration data were fitted with a first order polynomial with 1/X(2) weighting. No matrix effect was observed when using three independent sources of rat plasma. The average extraction recovery was consistent over the investigated range. This validation in rat plasma demonstrated that indolinone was stable for 190 days when stored below -65 °C; for 4 days at 10 °C in the autosampler; for 4h at RT, and during three successive freeze/thaw cycles at -65 °C. Preliminary pharmacokinetic data were obtained in male Sprague-Dawley rats (2 mg/kg BW i.v.). Blood samples taken from 0 to 12 h after injection were collected, and data analyzed with WinNonlin. A short half-life (4.30±0.14 min) and a relatively high clearance (3.83±1.46 L/h/kg) were found. Copyright © 2012 Elsevier B.V. All rights reserved.

Feasibility Study of Pharmacological Treatment to Reduce Morbidity and Mortality after Brain Injury.

DTIC Science & Technology

1987-05-01

preliminary study of human stroke patients with hemiparesis showed an acceleration of recovery cumpared to placebo controls (15). The most frequent...cause of permanent disability is cerebral trauma (61) and a model of cortical cotusion producing hemiparesis in rats has been developed (21). The purpose

Rosiglitazone attenuates liver inflammation in a rat model of nonalcoholic steatohepatitis.

PubMed

Tahan, Veysel; Eren, Fatih; Avsar, Erol; Yavuz, Dilek; Yuksel, Meral; Emekli, Ebru; Imeryuz, Nese; Celikel, Cigdem; Uzun, Hafize; Haklar, Goncagul; Tozun, Nurdan

2007-12-01

Rosiglitazone is an insulin-sensitizing agent. We aimed to assess the effects of rosiglitazone on a methionine- and choline-deficient diet (MCDD) model of nonalcoholic steatohepatitis (NASH) in rats. Wistar rats were fed either MCDD or a control diet in the 4-week induction study; they were given saline or 4 mg/kg/day rosiglitazone. After the induction study period, the rats were divided into four groups and fed MCDD or given a control diet for an additional 8 weeks and received saline or rosiglitazone. Serum and tissue samples were obtained. Rosiglitazone improved inflammation in NASH and improved ALT, alkaline phosphatase, and interleukin-6 levels in the induction study and interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha levels in the treatment study. Our preliminary study is the first to show the anti-inflammatory effects of rosiglitazone in NASH. Rosiglitazone's effect on cytokines may be a key mechanism of its anti-inflammatory effect in NASH.

A preliminary 13-week oral toxicity study of ginger oil in male and female Wistar rats.

PubMed

Jeena, Kottarapat; Liju, Vijayastelter B; Kuttan, Ramadasan

2011-12-01

Zingiber officinale Roscoe, ginger, is a major spice extensively used in traditional medicine. The toxicity profile of ginger oil was studied by subchronic oral administration for 13 weeks at doses of 100, 250, and 500 mg/kg per day to 6 groups of Wistar rats (5/sex per dose). Separate groups of rats (5/sex per group) received either paraffin oil (vehicle) or were untreated and served as comparative control groups. There was no mortality and no decrease in body weight or food consumption as well as selective organ weights during the study period. Administration of ginger oil to rats did not produce any treatment-related changes in hematological parameters, hepatic, renal functions, serum electrolytes, or in histopathology of selected organs. The major component of ginger oil was found to be zingiberene (31.08%), and initial studies indicated the presence of zingiberene in the serum after oral dosing. These results confirmed that ginger oil is not toxic to male and female rats following subchronic oral administrations of up to 500 mg/kg per day (no observed adverse effect level [NOAEL]).

Breeding, husbandry, veterinary care, and hematology of marsh rice rats (Oryzomys palustris), a small animal model for periodontitis.

PubMed

Aguirre, J Ignacio; Edmonds, Kent; Zamora, Bernadette; Pingel, Jennifer; Thomas, Linda; Cancel, Denisse; Schneider, Laura; Reinhard, Mary K; Battles, August H; Akhter, Mohammed P; Kimmel, Donald B; Wronski, Thomas J

2015-01-01

Rice rats (Oryzomys palustris) are a recognized animal model for studying periodontal disease and the photoperiodic regulation of reproduction. Here we share information regarding the breeding, husbandry, veterinary care, and hematologic findings about this animal species to facilitate its use in studies at other research institutions. Rice rats initially were quarantined and monitored for excluded pathogens by using microbiologic, parasitologic, and serologic methods with adult female Mus musculus and Rattus norvegicus sentinel animals. Breeders were paired in a monogamous, continuous-breeding system. Rats were housed in static filter-top cages, maintained on commercial chow under 14:10-h light:dark cycles at 68 to 79 °F (20.0 to 26.1 °C) and 30% to 70% humidity. Rice rats apparently adapt relatively well to standard laboratory conditions, despite their aggressive behavior toward conspecifics and humans. Our analysis of 97 litters revealed that dams gave birth to an average of 5.2 pups per dam and weaned 4.2 pups per dam. Several procedures and biologic reagents normally used in standard laboratory rodents (mice and rats) can be used with rice rats. In addition, we present hematologic and serum chemistry values that can be used as preliminary reference values for future studies involving rice rats.

Breeding, Husbandry, Veterinary Care, and Hematology of Marsh Rice Rats (Oryzomys palustris), a Small Animal Model for Periodontitis

PubMed Central

Aguirre, J Ignacio; Edmonds, Kent; Zamora, Bernadette; Pingel, Jennifer; Thomas, Linda; Cancel, Denisse; Schneider, Laura; Reinhard, Mary K; Battles, August H; Akhter, Mohammed P; Kimmel, Donald B; Wronski, Thomas J

2015-01-01

Rice rats (Oryzomys palustris) are a recognized animal model for studying periodontal disease and the photoperiodic regulation of reproduction. Here we share information regarding the breeding, husbandry, veterinary care, and hematologic findings about this animal species to facilitate its use in studies at other research institutions. Rice rats initially were quarantined and monitored for excluded pathogens by using microbiologic, parasitologic, and serologic methods with adult female Mus musculus and Rattus norvegicus sentinel animals. Breeders were paired in a monogamous, continuous-breeding system. Rats were housed in static filter-top cages, maintained on commercial chow under 14:10-h light:dark cycles at 68 to 79 °F (20.0 to 26.1 °C) and 30% to 70% humidity. Rice rats apparently adapt relatively well to standard laboratory conditions, despite their aggressive behavior toward conspecifics and humans. Our analysis of 97 litters revealed that dams gave birth to an average of 5.2 pups per dam and weaned 4.2 pups per dam. Several procedures and biologic reagents normally used in standard laboratory rodents (mice and rats) can be used with rice rats. In addition, we present hematologic and serum chemistry values that can be used as preliminary reference values for future studies involving rice rats. PMID:25651091

A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies.

PubMed

Besch-Williford, Cynthia; Pesavento, Patricia; Hamilton, Shari; Bauer, Beth; Kapusinszky, Beatrix; Phan, Tung; Delwart, Eric; Livingston, Robert; Cushing, Susan; Watanabe, Rie; Levin, Stephen; Berger, Diana; Myles, Matthew

2017-07-01

We report the identification, pathogenesis, and transmission of a novel polyomavirus in severe combined immunodeficient F344 rats with null Prkdc and interleukin 2 receptor gamma genes. Infected rats experienced weight loss, decreased fecundity, and mortality. Large basophilic intranuclear inclusions were observed in epithelium of the respiratory tract, salivary and lacrimal glands, uterus, and prostate gland. Unbiased viral metagenomic sequencing of lesioned tissues identified a novel polyomavirus, provisionally named Rattus norvegicus polyomavirus 2 (RatPyV2), which clustered with Washington University (WU) polyomavirus in the Wuki clade of the Betapolyomavirus genus. In situ hybridization analyses and quantitative polymerase chain reaction (PCR) results demonstrated viral nucleic acids in epithelium of respiratory, glandular, and reproductive tissues. Polyomaviral disease was reproduced in Foxn1 rnu nude rats cohoused with infected rats or experimentally inoculated with virus. After development of RatPyV2-specific diagnostic assays, a survey of immune-competent rats from North American research institutions revealed detection of RatPyV2 in 7 of 1,000 fecal samples by PCR and anti-RatPyV2 antibodies in 480 of 1,500 serum samples. These findings suggest widespread infection in laboratory rat populations, which may have profound implications for established models of respiratory injury. Additionally, RatPyV2 infection studies may provide an important system to investigate the pathogenesis of WU polyomavirus diseases of man.

Synthesis of [{sup 125}I]iodoDPA-713: A new probe for imaging inflammation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Haofan; Pullambhatla, Mrudula; Guilarte, Tomas R.

2009-11-06

[{sup 125}I]IodoDPA-713 [{sup 125}I]1, which targets the translocator protein (TSPO, 18 kDa), was synthesized in seven steps from methyl-4-methoxybenzoate as a tool for quantification of inflammation in preclinical models. Preliminary in vitro autoradiography and in vivo small animal imaging were performed using [{sup 125}I]1 in a neurotoxicant-treated rat and in a murine model of lung inflammation, respectively. The radiochemical yield of [{sup 125}I]1 was 44 {+-} 6% with a specific radioactivity of 51.8 GBq/{mu}mol (1400 mCi/{mu}mol) and >99% radiochemical purity. Preliminary studies showed that [{sup 125}I]1 demonstrated increased specific binding to TSPO in a neurotoxicant-treated rat and increased radiopharmaceutical uptakemore » in the lungs of an experimental inflammation model of lung inflammation. Compound [{sup 125}I]1 is a new, convenient probe for preclinical studies of TSPO activity.« less

Effect of unbalanced diets on the long-term metabolism of a toxicant. 1. Lead in rats: preliminary note.

PubMed

Baldini, M; Coni, E; Mantovani, A; Stacchini, A; Zanasi, F

1989-01-01

The aim of this study was the evaluation of the effect of dietary imbalances on absorption and distribution of lead in the female Sprague-Dawley rat. In this note preliminary results on the relationship between blood concentrations of lead and unbalanced diets are presented. Hyperproteic, hyperglycidic, hyperlipidic and balanced diets were prepared, and most of them included 15 mg/kg lead. Blood samples were collected at day 0, 21, 36, and 95 of the diets and analyzed by anodic stripping voltammetry (ASV). Lead uptake as a function of feed consumption was found to decrease in the order: balanced, hyperproteic and hyperglycidic, hyperlipidic diet. On the other hand lead blood levels were as follows (decreasing order): hyperlipidic, hyperproteic, hyperglycidic, balanced. Further research is being carried out on the influences of dietary imbalances on whole-body distribution of lead.

System Performance Simulations of the RatCAP Awake Rat Brain Scanner

NASA Astrophysics Data System (ADS)

Shokouhi, S.; Vaska, P.; Schlyer, D. J.; Stoll, S. P.; Villanueva, A.; Kriplani, A.; Woody, C. L.

2005-10-01

The capability to create high quality images from data acquired by the Rat Conscious Animal PET tomograph (RatCAP) has been evaluated using modified versions of the PET Monte Carlo code Simulation System for Emission Tomography (SimSET). The proposed tomograph consists of lutetium oxyorthosilicate (LSO) crystals arranged in 12 4 /spl times/ 8 blocks. The effects of the RatCAPs small ring diameter (/spl sim/40 mm) and its block detector geometry on image quality for small animal studies have been investigated. Since the field of view will be almost as large as the ring diameter, radial elongation artifacts due to parallax error are expected to degrade the spatial resolution and thus the image quality at the edge of the field of view. In addition to Monte Carlo simulations, some preliminary results of experimentally acquired images in both two-dimensional (2-D) and 3-D modes are presented.

Initial studies using the RatCAP conscious animal PET tomograph

NASA Astrophysics Data System (ADS)

Woody, C.; Vaska, P.; Schlyer, D.; Pratte, J.-F.; Junnarkar, S.; Park, S.-J.; Stoll, S.; Purschke, M.; Southekal, S.; Kriplani, A.; Krishnamoorthy, S.; Maramraju, S.; Lee, D.; Schiffer, W.; Dewey, S.; Neill, J.; Kandasamy, A.; O'Connor, P.; Radeka, V.; Fontaine, R.; Lecomte, R.

2007-02-01

The RatCAP is a small, head-mounted PET tomograph designed to image the brain of a conscious rat without the use of anesthesia. The detector is a complete, high-performance 3D tomograph consisting of a 3.8 cm inside-diameter ring containing 12 block detectors, each of which is comprised of a 4×8 array of 2.2×2.2×5 mm 3 LSO crystals readout with a matching APD array and custom ASIC, and has a 1.8 cm axial field of view. Construction of the first working prototype detector has been completed and its performance characteristics have been measured. The results show an intrinsic spatial resolution of 2.1 mm, a time resolution of ˜14 ns FWHM, and a sensitivity of 0.7% at an energy threshold of 150 keV. First preliminary images have been obtained using 18F-FDG and 11C-methamphetamine, which show comparable image quality to those obtained from a commercial MicroPET R4 scanner. Initial studies have also been carried out to study stress levels in rats wearing the RatCAP.

Mechanisms of PCBS-Induced Breast Cancer

DTIC Science & Technology

1998-09-01

oxidative stress in the livers of treated rats. 3) Mammary tissue levels of oxided DNA bases suggest a differential response of oxidative stress in PCB...in several systems including MCF-7 human breast cancer cells). 6) Preliminary studies have been undertaken to react PCB metabolites with DNA bases and

Preliminary Study on Intrasplenic Implantation of Artificial Cell Bioencapsulated Stem Cells to Increase the Survival of 90% Hepatectomized Rats

PubMed Central

Liu, Zun Chang; Chang, Thomas M.S.

2012-01-01

We implanted artificial cell bioencapsulated bone marrow mesenchymal stem cells into the spleens of 90% hepatectomized (PH) rats. The resulting 14 days survival rate was 91%. This is compared to a survival rate of 21% in 90% hepatectomized rats and 25% for those receiving free MSCs transplanted the same way. Unlike free MSCs, the bioencapsulated MSCs are retained in the spleens and their hepatotrophic factors can continue to drain directly into the liver without dilution resulting in improved hepatic regeneration. In addition, with time the transdifferentiation of MSCs into hepatocyte-like cells in the spleen renders the spleen as a ectopic liver support. PMID:19132579

Sensor integration of multiple tripolar concentric ring electrodes improves pentylenetetrazole-induced seizure onset detection in rats.

PubMed

Makeyev, Oleksandr; Ding, Quan; Kay, Steven M; Besio, Walter G

2012-01-01

As epilepsy affects approximately one percent of the world population, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via tripolar concentric ring electrodes on the scalp of rats after inducing seizures with pentylenetetrazole. We developed a system to detect seizures and automatically trigger the stimulation and evaluated the system on the electrographic activity from rats. In this preliminary study we propose and validate a novel seizure onset detection algorithm based on exponentially embedded family. Unlike the previously proposed approach it integrates the data from multiple electrodes allowing an improvement of the detector performance.

Flow Cytometric Analysis of Hepatocytes from Normal, PFDA, and PH/DEN/ PB-Treated Rats

DTIC Science & Technology

1989-12-31

SUB-GROUP’ Perfluorodecanoic acid ( PFDA ); hepatocarcinogenesis; preneoplastic lesions; flow cytometry; imunotoxicitYyc3 1%&STRACT (Continue on...effects of perfluorodecanoic acid ( PFDA ). Flow cytometric evaluation of hepatocytes from PEDA-treated rats revealed an increase in size and granularity...was designed to generate preliminary information regarding the toxic and potential carcinogenic effects of perfluorodecanoic acid ( PFDA ) on rat

The Characterization of Deqi during Moxibustion in Stroke Rats

PubMed Central

Lv, Zhimai; Liu, Zhongyong; Huang, Dandan; Chen, Rixin; Xie, Dingyi

2013-01-01

The efficacy of acupuncture and moxibustion is closely related to Deqi phenomenons, which are some subjective feelings. However, no one has reported the objective characterization of Deqi. Our preliminary research has found a phenomenon of tail temperature increasing (TTI) obviously in some stroke rats by suspended moxibustion at the acupoint dà zhuī (DU 14), which is similar to one characterization of Deqi during moxibustion that moxibustion heat is transferred from the original moxibustion acupoint to the other areas of the body. We wonder whether TTI is the objective indicator of Deqi characterization in animals. The present study showed that the stroke rat's recovery was also associated with TTI phenomenon. This suggests that TTI phenomenon is one objective characterization of the Deqi in stroke rats. Application of the TTI phenomenon contributes to explore the physiological mechanism of Deqi. PMID:24194777

The Characterization of Deqi during Moxibustion in Stroke Rats.

PubMed

Lv, Zhimai; Liu, Zhongyong; Huang, Dandan; Chen, Rixin; Xie, Dingyi

2013-01-01

The efficacy of acupuncture and moxibustion is closely related to Deqi phenomenons, which are some subjective feelings. However, no one has reported the objective characterization of Deqi. Our preliminary research has found a phenomenon of tail temperature increasing (TTI) obviously in some stroke rats by suspended moxibustion at the acupoint dà zhuī (DU 14), which is similar to one characterization of Deqi during moxibustion that moxibustion heat is transferred from the original moxibustion acupoint to the other areas of the body. We wonder whether TTI is the objective indicator of Deqi characterization in animals. The present study showed that the stroke rat's recovery was also associated with TTI phenomenon. This suggests that TTI phenomenon is one objective characterization of the Deqi in stroke rats. Application of the TTI phenomenon contributes to explore the physiological mechanism of Deqi.

Comparing Apollo and Mars Exploration Rover (MER) Operations Paradigms for Human Exploration During NASA Desert-Rats Science Operations

NASA Technical Reports Server (NTRS)

Yingst, R. A.; Cohen, B. A.; Ming, D. W.; Eppler, D. B.

2011-01-01

NASA's Desert Research and Technology Studies (D-RATS) field test is one of several analog tests that NASA conducts each year to combine operations development, technology advances and science under planetary surface conditions. The D-RATS focus is testing preliminary operational concepts for extravehicular activity (EVA) systems in the field using simulated surface operations and EVA hardware and procedures. For 2010 hardware included the Space Exploration Vehicles, Habitat Demonstration Units, Tri-ATHLETE, and a suite of new geology sample collection tools, including a self-contained GeoLab glove box for conducting in-field analysis of various collected rock samples. The D-RATS activities develop technical skills and experience for the mission planners, engineers, scientists, technicians, and astronauts responsible for realizing the goals of exploring planetary surfaces.

Rat reaction to hypokinesia after prior adaptation to hypoxia

NASA Technical Reports Server (NTRS)

Barashova, Z. I.; Tarakanova, O. I.

1980-01-01

The effect of prior hypoxia adaptation on body tolerance to hypokinesia was investigated. Rats trained to a 50 day period of hypokinesia and hypoxia with a preliminary month of adaptation to hypoxia showed less weight loss, higher indices for red blood content, heightened reactivity of the overall organism and the central nervous system to acute hypoxia, and decreased modification of the skeletal muscles compared to rats subjected to hypokinesia alone.

Investigation of irradiated rats DNA in the presence of Cu(II) chelates of amino acids Schiff bases.

PubMed

Karapetyan, N H; Torosyan, A L; Malakyan, M; Bajinyan, S A; Haroutiunian, S G

2016-01-01

The new synthesized Cu(II) chelates of amino acids Schiff bases were studied as a potential radioprotectors. Male albino rats of Wistar strain were exposed to X-ray whole-body irradiation at 4.8 Gy. This dose caused 30% mortality of the animals (LD30). The survival of animals exposed to radiation after preliminary administration of 10 mg/kg Cu(II)(Nicotinyl-L-Tyrosinate)2 or Cu(II)(Nicotinyl-L-Tryptophanate)2 prior to irradiation was registered about 80 and 100% correspondingly. Using spectrophotometric melting and agarose gel electrophoresis methods, the differences between the DNA isolated from irradiated rats and rats pretreated with Cu(II) chelates were studied. The fragments of DNA with different breaks were revealed in DNA samples isolated from irradiated animals. While, the repair of the DNA structure was observed for animals pretreated with the Cu(II) chelates. The results suggested that pretreatment of the irradiated rats with Cu(II)(Nicotinyl-L-Tyrosinate)2 and Cu(II)(Nicotinyl-L-Tryptophanate)2 compounds improves the liver DNA characteristics.

Simultaneous quantification of flavonoids in blood plasma by a high-performance liquid chromatography method after oral administration of Blumea balsamifera leaf extracts in rats.

PubMed

Nessa, Fazilatun; Ismail, Zhari; Mohamed, Nornisah; Karupiah, Sundram

2013-03-01

The leaves of Blumea balsamifera are used as a folk medicine in kidney stone diseases in South-East Asia. Phytochemical investigation revealed leaves contained a number of flavonoids. In view of these, the present work was aimed to quantify and preliminary pharmacokinetic investigation of five flavonoids viz. dihydroquercetin-7,4¢-dimethyl ether (I), dihydroquercetin-4¢-methyl ether (II), 5,7,3¢,5¢-tetrahydroxyflavanone (III), blumeatin (IV) and quercetin (V) in rat plasma following oral administration (0.5g/Kg) of B. balsamifera leaf extract in rats. Quantification was achieved by using a validated, reproducible high-performance liquid chromatographic method. The mean recoveries of I, II, III, IV and V were 90.6, 93.4, 93.5, 91.2 and 90.3% respectively. The limit of quantification was 25 ng/mL for I and IV, 10 ng/mL for II and III and 100 ng/mL for V respectively. The within day and day-to-day precision for all the compounds were < 10%. The validated HPLC method herein was applied for pharmacokinetic studies and the main pharmacokinetic parameters were: t1/2 (hr) 5.8, 4.3, 2.9, 5.7 and 7.3, Cmax (ng/mL) 594.9, 1542.9 1659.9, 208.9 and 3040.4; Tmax (hr) 4.7, 1.0, 1.0, 3.5 and 2.3; AUC0-oo (ng hr/mL) 5040, 5893, 9260, 1064 and 27233 for I, II, III, IV and V respectively. The developed method was suitable for pharmacokinetic studies and this preliminary study also revealed significant absorption after oral dosing in rats.

Evidence of glycemia-lowering effect by a Cynara scolymus L. extract in normal and obese rats.

PubMed

Fantini, Noemi; Colombo, Giancarlo; Giori, Andrea; Riva, Antonella; Morazzoni, Paolo; Bombardelli, Ezio; Carai, Mauro A M

2011-03-01

Several recent preliminary clinical studies have suggested that artichoke (Cynara scolymus L., Asteraceae family) preparations may be capable of lowering post-prandial glycemia. The present study was designed to test this hypothesis in laboratory rats. To this aim, non-selected Wistar and genetically obese Zucker rats were treated acutely with a purified extract of Cynara scolymus flowering heads (500-1500 mg/kg by gavage) immediately prior to 1 h access to a fixed amount of food. Glycemia was recorded 60, 120 and 360 min after food presentation. Treatment with Cynara scolymus flowering head extract resulted in a significant decrease of post-prandial glycemia in both rat strains. The lack of any fiber content in this Cynara scolymus flowering head extract excludes the involvement of dietary fibers in glycemia reduction. The results obtained constitute the first evidence of a hypoglycemic effect of an artichoke preparation in laboratory rodents and confirm previous observations made in humans. Copyright © 2010 John Wiley & Sons, Ltd.

2-Butoxyethanol model of haemolysis and disseminated thrombosis in female rats: a preliminary study of the vascular mechanism of osteoarthritis in the temporomandibular joint.

PubMed

Amir, G; Goldfarb, A W; Nyska, M; Redlich, M; Nyska, A; Nitzan, D W

2011-01-01

Female rats develop haemolytic anaemia and disseminated thrombosis and infarction in multiple organs, including bone, when exposed to 2-butoxyethanol (BE). There is growing evidence that vascular occlusion of the subchondral bone may play a part in some cases of osteoarthritis. The subchondral bone is the main weight bearer as well as the source of the blood supply to the mandibular articular cartilage. Vascular occlusion is thought to be linked to sclerosis of the subchondral bone associated with disintegration of the articular cartilage. The aim of this study was to find out whether this model of haemolysis and disseminated thrombosis supports the vascular hypothesis of osteoarthritis. Six female rats were given BE orally for 4 consecutive days and the two control rats were given tap water alone. The rats were killed 26 days after the final dose. The mandibular condyles showed histological and radiological features consistent with osteoarthritis in three of the four experimental rats and in neither of the control rats. These results may support the need to explore the vascular mechanism of osteoarthritis further. Copyright © 2009 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Persistent Elongated Particle Total Surface Area Dose to Rat Pleura is Optimum Predictor of Mesothelioma Incidence

EPA Science Inventory

Based on preliminary statistical analyses of 29 reanalyzed (quantitative TEM) diverse elongated particle (EP) test samples from the well known and often cited study of Stanton et al. 1981, total surface area (TSA) of biodurable EPs was reported at the 2008 Johnson Conference to b...

Hippocampal gene expression in a rat model of depression after electroacupuncture at the Baihui and Yintang acupoints

PubMed Central

Duan, Dongmei; Yang, Xiuyan; Ya, Tu; Chen, Liping

2014-01-01

Preliminary basic research and clinical findings have demonstrated that electroacupuncture therapy exhibits positive effects in ameliorating depression. However, most studies of the underlying mechanism are at the single gene level; there are few reports regarding the mechanism at the whole-genome level. Using a rat genomic gene-chip, we profiled hippocampal gene expression changes in rats after electroacupuncture therapy. Electroacupuncture therapy alleviated depression-related manifestations in the model rats. Using gene-chip analysis, we demonstrated that electroacupuncture at Baihui (DU20) and Yintang (EX-HN3) regulates the expression of 21 genes. Real-time PCR showed that the genes Vgf, Igf2, Tmp32, Loc500373, Hif1a, Folr1, Nmb, and Rtn were upregulated or downregulated in depression and that their expression tended to normalize after electroacupuncture therapy. These results indicate that electroacupuncture at Baihui and Yintang modulates depression by regulating the expression of particular genes. PMID:25206746

A Preliminary Model for the Protective Role of the Endocannabinoid 2-Arachydonylglycerol in Neuroinflammation

DTIC Science & Technology

2015-09-30

example, Liu et al. (2013) measured the effect of chlorpyrifos (280 mg/kg via subcutaneous (sc) injection) and parathion (27 mg/kg sc) in rats on 2...rats to the organophosphates (OPs) chlorpyrifos (280 mg/kg, sc) and parathion (27 mg/kg, sc), and correspond to 53 and 20 percent predicted inhibition...Effects of Parathion and Chlorpyrifos on Extracellular Endocannabinoid Levels in Rat Hippocampus: Influence on Cholinergic Toxicity. Toxicol Appl

Biodistribution and Stability Studies of [18F]Fluoroethylrhodamine B, a Potential PET Myocardial Perfusion Agent

PubMed Central

Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederick H; Treves, S. Ted; Packard, Alan B.

2010-01-01

Introduction Fluorine-18-labeled rhodamine B was developed as a potential PET tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was, therefore, undertaken to further evaluate this hypothesis. Methods [18F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 °C in human, rat and mouse serum and in PBS. Samples were removed periodically and assayed by HPLC. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results In vitro stability studies demonstrated that [18F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but <30% intact in mouse serum. The microPET imaging and biodistribution studies in rats confirmed this result showing high and persistent tracer accumulation in the myocardium compared with the absence of uptake by the myocardium in mice thereby validating our original hypothesis that 18F-labeled rhodamines should accumulate in the heart. Conclusions [18F]Fluoroethyl rhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion. PMID:20346876

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats.

PubMed

Petchi, Ramesh R; Parasuraman, S; Vijaya, C

2013-09-01

To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats.

Antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Linn.) in streptozotocin-induced diabetic rats

PubMed Central

Petchi, Ramesh R.; Parasuraman, S.; Vijaya, C.

2013-01-01

Objective: To study the antidiabetic and antihyperlipidemic effects of an ethanolic extract of the whole plant of Tridax procumbens (Asteraceae) in streptozotocin-induced diabetic rats. Materials and Methods: The whole plant of T. procumbens was collected in different regions of Madurai districts, Tamil Nadu. The air dried whole plant of T. procumbens was extracted with ethanol (95%) in a Soxhlet apparatus for 72 h. Diabetes was induced in male Wistar rats by streptozotocin (50 mg/jk, i.p.) and nicotinamide (120 mg/kg, i.p) injection. The dry mass of the extract was used for preliminary phytochemical and pharmacological analysis. Diabetic rats were treated with glibenclamide (0.25 mg/kg, p.o.) or T. procumbens extract (250 and 500 mg/k, p.o.) for 21 consecutive days. The blood samples were collected at regular intervals to access hypoglycemic effect of an ethanolic extract of the whole plant of T. procumbens. At the end of the experiment, serum lipid profile and liver enzymes levels were analyzed for all the experimental animals and compared with diabetic control. Results: The preliminary phytochemical analysis of an ethanolic extract of the whole plant of T. procumbens indicated the presence of alkaloids, tannins, flavonoids, saponins, and phenolic compounds. The ethanolic extract of the whole plant of T. procumbens at 250 and 500 mg/kg has significant antidiabetic and antihyperlipidemic activities. The diabetic control animals exhibited a significant decrease in body weight compared with control animals. T. procumbens inhibited streptozotocin-induced weight loss and significantly alter the lipid levels. Conclusion: The ethanolic extract of the whole plant of T. procumbens showed significant antidiabetic and antihyperlipidemic activities against streptozotocin-induced diabetes in rats. PMID:24808679

Beneficial effects of gradual intense exercise in tissues of rats fed with a diet deficient in vitamins and minerals: a pilot study.

PubMed

Teixeira, Angélica; Müller, Liz; dos Santos, Alessandra A; Reckziegel, Patrícia; Emanuelli, Tatiana; Rocha, João Batista T; Bürger, Marilise E

2009-05-01

This study evaluated the preliminary effects of intense physical training (swimming) on oxidative stress in rats with nutritional deficiencies. Rats were fed with a standard diet or a diet deficient in vitamins and minerals for 4 months. The deficient diet contained one-fourth of the recommended vitamin and mineral levels for rats. From the second month, half of the animals were subjected to a swimming exercise in a plastic container with water maintained at 34 +/- 1 degrees C for 1 h/d, five times per week, for 11 wk. The rats were subjected to swimming exercise with loads attached to the dorsal region, which were progressively increased according to their body weight (1% to 7%). Sedentary rats were transported to the experimental room and handled as often in a similar way as the exercise group, except that they were not put in water. In the exercised group, blood lactate levels were significantly lower and the heart weight/body weight ratio was significantly higher than in the sedentary group (P < 0.05). Increased lipid peroxidation was observed in the liver, heart, and skeletal muscle of rats fed with the deficient diet, but it was completely reversed by exercise. Exercise also decreased lipid peroxidation levels in the heart and skeletal muscle of rats fed with the standard diet (P < 0.05). This pilot study leads to the continuity of the studies, because the partial results observed suggest that inadequate nutrition may enhance oxidative stress, and that intense chronic physical training may activate antioxidant defenses, possibly by hormesis.

Neuroprotective effect of Lycium barbarum on retina of Royal College of Surgeons (RCS) rats: a preliminary study.

PubMed

Ni, Tongshang; Wei, Guangwei; Yin, Xuntao; Liu, Xianghe; Liu, Dianwei

2013-01-01

Hereditary retinal dystrophy usually leads to blindness. Using Royal College of Surgeons (RCS) rats as a hereditary retinal dystrophy model, we investigated the possible neuroprotective effects of the aqueous extract of dried Lycium barbarum (LBA). Sixty postnatal RCS rats were selected and randomly divided into a control group (CG, thirty rats) and an experimental group (EG). Ten days after birth, EG rats were treated by 1 mg/kg of LBA per day, and CG rats were normally fed. These rats were killed at postnatal day (P) 25, P35 and P50, and retinal tissue was prepared for analysis. Photoreceptor cells were assessed by hematoxylin and eosin (HE) staining, TUNEL detection and Caspase-2 protein expression. We found that in rats at P25, the outer nuclear layer (ONL) of EG was thicker and more photoreceptor cells survived. Meanwhile, the TUNEL expression in EG was obviously reduced compared with CG. The Caspase-2 positive cells were found in the ganglion cell layer and inner nuclear layer in both CG and EG at 25-50 postnatal days, but the expression in EG rats was significantly lower than in CG at P25. The results demonstrated that LBA might have a neuroprotective role on the retinal tissue of RCS rats at the early stage by protecting photoreceptors and inhibiting apoptosis involving Caspase-2 protein.

Antidiabetic Effect of Young and Old Ethanolic Leaf Extracts of Vernonia amygdalina: A Comparative Study

PubMed Central

Asante, Du-Bois; Effah-Yeboah, Emmanuel; Barnes, Precious; Abban, Heckel Amoabeng; Ameyaw, Elvis Ofori; Boampong, Johnson Nyarko; Ofori, Eric Gyamerah; Dadzie, Joseph Budu

2016-01-01

The young leaves of Vernonia amygdalina are often utilized as vegetable and for medicinal purpose compared to the old leaves. This study was designed to evaluate and compare the antidiabetic effects between ethanolic leaf extracts of old and young V. amygdalina on streptozotocin (STZ) induced diabetic rat for four weeks. Preliminary screening of both young and old ethanolic extracts revealed the presence of the same phytochemicals except flavonoids which was only present in the old V. amygdalina. Difference in antioxidant power between the young and old leaf extracts was statistically significant (p < 0.05). Both leaf extracts produced a significant (p < 0.05) antihyperglycaemic effect. Also results from treated rats revealed increasing effect in some haematological parameters. Similarly, the higher dose (300 mg/kg) of both extracts significantly (p < 0.05) reduced serum ALT, AST, and ALP levels as compared to the diabetic control rats. Results also showed significant (p < 0.05) decrease in LDL-C and VLDL-C in the extract-treated rats with a corresponding increase in HDL-C, as compared to the diabetic control rats. Moreover histopathological analysis revealed ameliorative effect of pathological insults induced by the STZ in the pancreas, liver, and spleen, most significantly the regeneration of the beta cells of the islets of Langerhans in treated rats. PMID:27294153

Developmental toxicity evaluation of unleaded gasoline vapor in the rat.

PubMed

Roberts, L; White, R; Bui, Q; Daughtrey, W; Koschier, F; Rodney, S; Schreiner, C; Steup, D; Breglia, R; Rhoden, R; Schroeder, R; Newton, P

2001-01-01

To evaluate the potential of unleaded gasoline vapor for developmental toxicity, a sample was prepared by slowly heating API 94-02 (1990 industry average gasoline) and condensing the vapor. The composition of this vapor condensate, which comprises 10.4% by volume of the starting gasoline, is representative of real-world exposure to gasoline vapor encountered at service stations and other occupational settings and consists primarily of volatile short chain (C4-C6) aliphatic hydrocarbons (i.e. paraffins) with small amounts of cycloparaffins and aromatic hydrocarbons. A preliminary study in rats and mice resulted in no developmental toxicity in either species. However, a slight reduction in maternal body weight gain in rats led to the selection of rats for this guideline study. Groups of pregnant rats (n = 24/group) were exposed to unleaded gasoline vapor at concentrations of 0, 1000, 3000, or 9000 (75% lower explosive limit) ppm equivalent to 0, 2653, 7960, or 23,900 mg/m3, for 6 h/day on gestation days 6-19. All rats were sacrificed on gestation day 20. No maternal toxicity was observed. Developmentally, there were no differences between treated and control groups in malformations, total variations, resorptions, fetal body weight, or viability. The maternal and developmental NOAEL is 9000 ppm. Under conditions of this study, unleaded gasoline vapors did not produce evidence of developmental toxicity.

Contraceptive effect and potential side-effects of deslorelin acetate implants in rats (Rattus norvegicus): Preliminary observations

PubMed Central

Grosset, Claire; Peters, Stijn; Peron, Franck; Figuéra, Joëlle; Navarro, Christelle

2012-01-01

During the last ten years, numerous species have been treated with deslorelin implants to induce contraception. The aims of the study were 1) to assess contraceptive efficacy of 4.7 mg subcutaneous deslorelin implants in rats, 2) to determine the latency of contraceptive effect, and 3) to determine potential side effects. Three experimental females were implanted and their estrous cycle was studied by vaginal smear. Two weeks after implantation, a male whose fertility was previously assessed with a control female, was introduced into their cage. No female conceived during the 4 mo following implantation. Additionally, 38 pet rats were recruited from clients in practice to test for potential side effects, including 6 males and 32 females with a mean age of 14 mo. Local reaction and transient weight gain during the first 2 wk, as well as behavioral changes were recorded. According to this pilot study, deslorelin implant could be used as a contraceptive method in female rats. The latency period is about 2 wk. Nevertheless, it might be possible to refine the treatment further using hormonal measurements. The duration of contraceptive effect is to be determined in an upcoming study. PMID:23277700

Preliminary dosimetric evaluation of (166)Ho-TTHMP for human based on biodistribution data in rats.

PubMed

Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza; Tajik, Mojtaba; Ghannadi-Maragheh, Mohammad

2014-12-01

In this work, the absorbed dose to each organ of human for (166)Ho-TTHMP was evaluated based on biodistribution studies in rats by a RADAR method and was compared with (166)Ho-DOTMP as the only clinically used Ho-166 bone marrow ablative agent. The highest absorbed dose for this complex is observed in red marrow with 0.922mGy/MBq. The results show that (166)Ho-TTHMP has considerable characteristics compared to (166)Ho-DOTMP and can be a good candidate for bone marrow ablation in patients with multiple myeloma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Shiga toxin type 2 (Stx2), a potential agent of bioterrorism, has a short distribution and a long elimination half-life, and induces kidney and thymus lesions in rats.

PubMed

Liu, Yue-Nan; Wang, Sheng-Han; Li, Tao; Wang, Qin; Tu, Wei; Cai, Kun; Hou, Xiao-Jun; Tian, Ren-Mao; Gao, Xiang; Liu, Hao; Xiao, Le; Shi, Jing; Cheng, Yuan-Guo; Li, Jian-Chun; Wang, Hui

2011-09-01

Shiga toxin type 2, a major virulence factor produced by the Shiga toxin-producing Escherichia coli, is a potential toxin agent of bioterrorism. In this study, iodine-125 (125I) was used as an indicator to describe the in vivo Stx2 biodistribution profile. The rats were injected intravenously (i.v.) with 125I-Stx2 at three doses of 5.1-127.5 μg/kg body weight. Stx2 had a short distribution half-life (t (1/2)α, less than 6 min) and a long elimination half-life in rat. The toxicokinetics of Stx2 in rats was dose dependent and nonlinear. Stx2 concentrations in various tissues were detected at 5-min, 0.5-h, and 72-h postinjection. High radioactivity was found in the lungs, kidneys, nasal turbinates, and sometimes in the eyes, which has never been reported in previous studies. In a preliminary assessment, lesions were found in the kidney and thymus.

Studies on the antihyperlipidemic properties of Averrhoa bilimbi fruit in rats.

PubMed

Ambili, Savithri; Subramoniam, Appian; Nagarajan, Natesan Shanmugam

2009-01-01

Averrhoa bilimbi Linn. fruit and its extracts were screened for antihypercholesterolemic activity using Triton-induced hypercholesterolemia in rats as a model. The fruit and its water extract, but not alcohol and hexane extracts, showed remarkable antihypercholesterolemic activity. An active fraction, which showed activity at a low dose of 0.8 mg/kg, was purified from the water extract. An active component was isolated from the active fraction, which showed optimum activity at a dose of 0.3 mg/kg. The efficacy of the fruit was tested in chronic high-fat diet fed hyperlipidemic rats. The fruit (125 mg/kg) as well as its water extract (50 mg/kg) were found to be effective in lowering lipids in the high-fat diet fed rats. The fruit was subjected to preliminary general toxicity evaluation in mice. Oral administration of the fruit homogenate daily for 15 days did not result in any toxic symptoms up to a dose of 1 g/kg studied. Thus, this fruit can be used as a dietary ingredient to prevent as well as treat hyperlipidemia.

A preliminary report of percutaneous craniofacial osteoplasty in a rat calvarium.

PubMed

Parkes, William J; Greywoode, Jewel; O'Hara, Brian J; Heffelfinger, Ryan N; Krein, Howard

2014-07-01

To evaluate the potential for injectable, permanent bone augmentation by assessing the biocompatability and bioactivity of subperiosteal hydroxylapatite (Radiesse) deposition in a rat model. Randomized controlled animal model. Fourteen adult Sprague Dawley rats were injected in the parietal skull with 0.2 ml of hydroxylapatite (10 animals) or 0.2 ml of a carrier gel control (4 animals), using a subperiosteal injection technique on the right and a subcutaneous injection technique on the left. At 1, 3, and 6 months, three rats (1 negative control, 2 variables) were sacrificed and the calvaria were harvested. At 12 months, the remaining five rats were sacrificed. After each harvest, the specimens were processed and then examined under both light and polarized microscopy for new bone growth at the injection sites. The inflammatory response was limited with both hydroxylapatite and carrier injections. Injectables were still present 12 months after the injection. New bone formation was only observed when the injection was located deep to a disrupted periosteum The odds of new bone formation was 48.949 times higher (95% confidence intervals CI [2.637, 3759.961]; P=0.002) with subperiosteal hydroxylapatite injections compared to all other combinations of injection plane and injectable. This preliminary report of subperiosteal hydroxylapatite (Radiesse) injection in a rat model has verified the biocompatibility of injectable hydroxylapatite at the bony interface and suggests the potential for new bone formation. N/A. © 2013 The American Laryngological, Rhinological and Otological Society, Inc.

Antidyslipidemic effect and antioxidant activity of anthraquinone derivatives from Rheum emodi rhizomes in dyslipidemic rats.

PubMed

Mishra, Sunil K; Tiwari, Shashi; Shrivastava, Atul; Srivastava, Shishir; Boudh, Goutam K; Chourasia, Shivendra K; Chaturvedi, Upma; Mir, Snober S; Saxena, Anil K; Bhatia, Gitika; Lakshmi, Vijai

2014-04-01

The aim of the present study was to evaluate the antidyslipidemic effect of ethanolic extract of Rheum emodi rhizomes and its constituents in Triton-WR-1339 and high-fat diet (HFD)-induced dyslipidemic rats. In preliminary screening, the ethanolic extract showed significant activity in Triton-treated rats. Bioassay-guided fractionation of the ethanolic extract resulted in the identification of four anthraquinone derivatives, viz. chrysophanol, emodin, chrysophanol 8-O-β-D-glucopyranoside and emodin 8-O-β-D-glucopyranoside as active constituents. All these compounds significantly reduced plasma lipid levels. The most active compound emodin showed significant lipid-lowering activity in the HFD-fed model. In addition, these compounds showed significant antioxidant activity. The effect of emodin on enzymes modulating lipid metabolism confirms and supports the efficiency of emodin as a potent antidyslipidemic agent.

Qualitative changes in ultrasonic vocalization in rats after unilateral dopamine depletion or haloperidol: A preliminary study

PubMed Central

Ciucci, Michelle; Ma, Teh-Sheng; Fox, Cynthia; Kane, Jacqueline; Ramig, Lorraine; Schallert, Timothy

2007-01-01

The sensorimotor speech/voice deficits associated with Parkinson Disease have been well-documented in humans. They are largely resistant to pharmacological and surgical treatment, but respond to intensive speech treatment. The mechanisms underlying this phenomenon are not well understood and are difficult to systematically test in humans. Thus we turn to the rat as a model. The purpose of this study is to compare the ultrasonic vocalization (USV) of rats in three conditions: control, haloperidol-induced transient dopamine depletion, and unilateral 6-hydroxydopamine (6-OHDA) induced moderately-severe degeneration of dopamine neurons. It was hypothesized that both dopamine-altered conditions would lead to a change in the features of the USV acoustic signal. Results demonstrated that bandwidth decreased in the dopamine-altered rats. This is the first study to document a degradation of the acoustic signal of frequency-modulated 50-kHz calls as a result of interfering with dopamine synaptic transmission in rats. The data suggest that mild transient dopamine depletion with haloperidol or even unilateral degeneration of dopamine neurons is associated with changes in the USV acoustic signal. Thus, dopaminergic dysfunction appears to influence USV production. This study provides a foundation to examine the role of dopamine in sensorimotor processes underlying USV production and potentially to explore treatments for dopamine deficiency-related impaired vocal outcome. PMID:17397940

Noninvasive Ultrasound Transdermal Insulin Delivery and Glucose Monitoring Using a Low-Profile Cymbal Array

NASA Astrophysics Data System (ADS)

Park, E.-J.; Luis, J.; Meyer, R. J.; Pishko, M. V.; Smith, N. B.

2006-05-01

Recent studies have shown that ultrasound mediated transdermal drug delivery offers promising results for noninvasive drug administration. The purpose of this study was to demonstrate ultrasonic transdermal insulin delivery and in vivo sensing glucose with a novel, low-profile ultrasound array based on the cymbal transducer. As a practical device, the array composed of circular cymbal transducers was thin (< 7mm) and weighed less than 22g. Using this array on hyperglycemic rats, our previous experiments demonstrated that blood glucose would decrease by 296.7 mg/dL from 60 minutes of ultrasound exposure. With a similar intensity, our goal was to evaluate the feasibility of insulin delivery with large animals (rabbits and pigs) and noninvasively determine the glucose level of hyperglycemic rats with the array system. Ultrasound was exposed for 60 minutes at Isptp=100 mW/cm2. With the same procedure, a preliminary experiment of large animal was performed on a pig (12 kg) at Isptp=50 mW/cm2. For the control experiments in insulin delivery, the blood glucose level varied little from the initial baseline. However, for the ultrasound and insulin exposure experiment, the glucose level was found to decrease by 132.6 mg/dL in 60 minutes and continued to decrease by 208.1 mg/dL in 90 minutes. From the preliminary pig experiment, the blood glucose level decreased by 120 mg/dL in 90 minutes. To noninvasively determine the glucose level, ultrasound exposure experiments with an electrochemical glucose biosensor were performed on hyperglycemic rats. After 20 minutes ultrasound exposure, the biosensor was placed at the exposure area to determine the concentration of glucose diffused through the skin. The glucose level of rats determined by the biosensor was 408 mg/dL which was very similar to the results of conventional glucose meter reading 396.7 mg/dL. Recently, a rectangular cymbal transducer was developed to obtain a larger sonication area without an increase in array size. Preliminary experiments were performed on hyperglycemic rabbits to evaluate the new transducer design. The results showed that the rectangular array has enhanced performance compared to the circular array. All results of ultrasound application indicate the feasibility of using a low-cost, light-weight cymbal array for enhanced noninvasive transdermal insulin delivery and glucose monitoring.

Simultaneous delivery of antibiotics neomycin and ampicillin in drinking water inhibits fermentation of resistant starch in rats.

PubMed

Carvajal-Aldaz, Diana G; Guice, Justin L; Page, Ryan C; Raggio, Anne M; Martin, Roy J; Husseneder, Claudia; Durham, Holiday A; Geaghan, James; Janes, Marlene; Gauthier, Ted; Coulon, Diana; Keenan, Michael J

2017-03-01

Antibiotics ampicillin 1 g/L and neomycin 0.5 g/L were added to drinking water before or during feeding of resistant starch (RS) to rats to inhibit fermentation. In a preliminary study, antibiotics and no RS were given prior to rats receiving a transplant of cecal contents via gavage from donor rats fed RS (without antibiotics) or a water gavage before feeding resistant starch to both groups. Antibiotics given prior to feeding RS did not prevent later fermentation of RS regardless of either type of gavage. In the second study, antibiotics were given simultaneously with feeding of RS. This resulted in inhibition of fermentation of RS with cecal contents pH >8 and low amounts of acetate and butyrate. Rats treated with antibiotics had reduced Bifidobacteria spp., but similar Bacteroides spp. to control groups to reduce acetate and butyrate and preserve the production of propionate. Despite reduced fermentation, rats given antibiotics had increased glucagon-like peptide 1 (GLP-1) and cecum size, measures that are usually associated with fermentation. A simultaneous delivery of antibiotics inhibited fermentation of RS. However, increased GLP-1 and cecum size would be confounding effects in assessing the mechanism for beneficial effects of dietary RS by knocking out fermentation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electrochemical treatment of mouse and rat fibrosarcomas with direct current

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chou, C.K.; McDougall, J.A.; Ahn, C.

1997-03-01

Electrochemical treatment (ECT) of cancer utilizes direct current to produce chemical changes in tumors. ECT has been suggested as an effective alternative local cancer therapy. However, a methodology is not established, and mechanisms are not well studied. In vivo studies were conducted to evaluate the effectiveness of ECT on animal tumor models. Radiation-induced fibrosarcomas were implanted subcutaneously in 157 female C3H/HeJ mice. Larger rat fibrosarcomas were implanted on 34 female Fisher 344 rats. When the spheroidal tumors reached 10 mm in the mice, two to five platinum electrodes were inserted into the tumors at various spacings and orientations. Ten ratsmore » in a pilot group were treated when their ellipsoidal tumors were about 25 mm long; electrode insertion was similar to the later part of the mouse study; i.e., two at the base and two at the center. A second group of 24 rats was treated with six or seven electrodes when their tumors were about 20 mm long; all electrodes were inserted at the tumor base. Of the 24 rats, 12 of these were treated once, 10 were treated twice, and 2 were treated thrice. All treated tumors showed necrosis and regression for both mice and rats; however, later tumor recurrence reduced long-term survival. When multiple treatments were implemented, the best 3 month mouse tumor cure rate was 59.3%, and the best 6 month rat tumor cure rate was 75.0%. These preliminary results indicate that ECT is effective on the radiation-induced fibrosarcoma (RIF-1) mouse tumor and rat fibrosarcoma. The effectiveness is dependent on electrode placement and dosage.« less

Distinct effects of ovarian transplantation and exogenous 17 beta-oestradiol on cancellous bone of osteopenic ovariectomized rats.

PubMed

Gallagher, A C; Chambers, T J; Tobias, J H

1995-10-01

Although 17 beta-oestradiol (E2) is known to prevent bone loss, prolonged administration of E2 is unable to reverse this in female rats rendered osteopenic by ovariectomy. To determine whether this reflects a failure to replace other components of ovarian function involved in bone metabolism, we compared the effects of administering E2 to osteopenic ovariectomized (ovx) rats with those of ovarian transplantation. Ovariectomy was performed in female rats. After 13 weeks, by which time marked bone loss had occurred, one group of ovx animals received ovaries from donor rats, and, after a delay of 2 weeks to allow oestrus cycles to return, a further group received E2 5 micrograms.kg-1.day-1 for 9 weeks. The dose of E2 was chosen as that which in preliminary studies restored mean serum E2 levels to that of intact female rats. The study was terminated 24 weeks after ovariectomy. Both E2 and ovarian transplantation largely restored indices of oestrogenic exposure in ovx rats to those of sham-ovx animals. Animals receiving ovarian transplants also showed a small increase in serum progesterone and full restoration of serum testosterone. However, while ovarian transplantation also returned indices of cancellous bone metabolism to those of sham-ovx animals, there was little increase in bone volume. Interestingly, exogenous E2 caused a greater increase in cancellous bone volume than ovarian transplantation but also caused more marked suppression of bone formation, as assessed at the end of the study. In conclusion, exogenous E2 and ovarian transplantation exerted distinct effects on skeletal metabolism in osteopenic ovx rats, although the basis for this difference is currently unclear.

Influence of simulated weightlessness on maximal oxygen uptake of untrained rats

NASA Technical Reports Server (NTRS)

Overton, J. Michael; Tipton, Charles M.

1987-01-01

The purpose of this study was to determine the effect of hindlimb suspension on maximal oxygen uptake of rodents. Male Sprague-Dawley rats were assigned to head-down (HD) suspension, horizontal (HOZ) suspension, or cage (C) control for 6-9 days. Rats were tested for maximal oxygen uptake before and after surgical instrumentation (Doppler flow probes, carotid and jugular cannulae), and after suspension. Body weight was significantly decreased after suspension in both HD and HOZ groups, but was significantly increased in the C group. Absolute maximal O2 uptake (ml/min) was not different in the C group. However, because of their increased weight, relative maximal O2 uptake (ml/min per kg) was significantly reduced. In contrast, both relative and absolute maximal O2 uptake were significantly lower, following suspension, for the HD and HOZ groups. These preliminary results support the use of hindlimb suspension as an effective model to study the mechanism(s) of cardiovascular deconditioning.

Role of Neurotrophins in Mediating the Effect of Altered Gravity on the Developing Rat Cerebellum.

NASA Astrophysics Data System (ADS)

Sajdel-Sulkowska, Elizabeth

We previously reported that perinatal exposure to hypergravity resulted in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. However, the increase in oxidative stress markers was not uniformly observed in males and females. In the present study we explored the possibility that exposure to hypergravity may result in altered level of neurotrophins, which have been recognized as mediators of both neurodegenerative and neuroprotective mechanisms in the central nervous system. An elevation of neurotrophin-3 (NT-3) has been observed in animal models of hypoxia. To test this hypothesis we compared cerebellar levels of NT-3 between stationary control (SC) and rat neonates exposed perinatally to 1.65 G on a 24-ft centrifuge. The levels of NT-3 were determined by specific ELISA. Preliminary data suggests a 123

Preliminary studies on Campomanesia xanthocarpa (Berg.) and Cuphea carthagenensis (Jacq.) J.F. Macbr. aqueous extract: weight control and biochemical parameters.

PubMed

Biavatti, M W; Farias, C; Curtius, F; Brasil, L M; Hort, S; Schuster, L; Leite, S N; Prado, S R T

2004-08-01

An infusion of Campomanesia xanthocarpa Berg. (Myrtaceae) leaves (Guabiroba) and the herb Cuphea carthagenensis (Jacq.) J.F. Macbr. (Lythraceae) (Sete-sangrias) is traditionally used in the South of Brazil to treat high levels of cholesterol and triglycerides. The effects of the aqueous extracts of these herbs were investigated in rats fed on a high calorie diet. Chronic treatment with the Guabiroba aqueous extract induced a significant reduction in weight gain in the rats, compared to the control group. Also, biochemical analysis showed that this treatment reduced the glycemia, while no effects on lipidic levels were observed. The biochemical analysis of the animals treated with Sete-sangrias aqueous extract showed no effect on glucose and triglyceride levels, while chronic treatment with the Sete-sangrias aqueous extract induced a significant reduction in plasma cholesterol in rats.

Neuronal Tracing with Magnetic Labels: NMR Imaging Methods, Preliminary Results, and New Optimized Coils.

NASA Astrophysics Data System (ADS)

Ghosh, Pratik

1992-01-01

The investigations focussed on in vivo NMR imaging studies of magnetic particles with and within neural cells. NMR imaging methods, both Fourier transform and projection reconstruction, were implemented and new protocols were developed to perform "Neuronal Tracing with Magnetic Labels" on small animal brains. Having performed the preliminary experiments with neuronal tracing, new optimized coils and experimental set-up were devised. A novel gradient coil technology along with new rf-coils were implemented, and optimized for future use with small animals in them. A new magnetic labelling procedure was developed that allowed labelling of billions of cells with ultra -small magnetite particles in a short time. The relationships among the viability of such cells, the amount of label and the contrast in the images were studied as quantitatively as possible. Intracerebral grafting of magnetite labelled fetal rat brain cells made it possible for the first time to attempt monitoring in vivo the survival, differentiation, and possible migration of both host and grafted cells in the host rat brain. This constituted the early steps toward future experiments that may lead to the monitoring of human brain grafts of fetal brain cells. Preliminary experiments with direct injection of horse radish peroxidase-conjugated magnetite particles into neurons, followed by NMR imaging, revealed a possible non-invasive alternative, allowing serial study of the dynamic transport pattern of tracers in single living animals. New gradient coils were built by using parallel solid-conductor ribbon cables that could be wrapped easily and quickly. Rapid rise times provided by these coils allowed implementation of fast imaging methods. Optimized rf-coil circuit development made it possible to understand better the sample-coil properties and the associated trade -offs in cases of small but conducting samples.

PIEX and neurological diseases

NASA Astrophysics Data System (ADS)

Van Rinsvelt, H. A.; Hurd, R. W.; Kondoro, J. W. A.; Andres, J. M.; Mickle, J. P.; Wilder, B. J.; Maenhaut, W.; De Reu, L.

1984-04-01

Preliminary studies in our laboratories indicated alterations of specific trace metals in humans and animals treated with valproic acid (VPA), an anticonvulsant, and in animals treated with 4-pentenoic acid (4-PA), a fatty acid which produces a Reyes Syndrome-like condition. In this study, we report the results of PIXE analysis of plasma, liver, and brain of rats treated with VPA and 4-PA. Tissue specific changes in selenium, zinc and calcium may underly the pathophysiological changes produced by these chemicals.

Sildenafil Attenuates Hepatocellular Injury after Liver Ischemia Reperfusion in Rats: A Preliminary Study

PubMed Central

Savvanis, Spyridon; Nastos, Constantinos; Tasoulis, Marios-Konstantinos; Papoutsidakis, Nikolaos; Demonakou, Maria; Karmaniolou, Iosifina; Arkadopoulos, Nikolaos; Smyrniotis, Vassilios; Theodoraki, Kassiani

2014-01-01

We evaluated the role of sildenafil in a rat liver ischemia-reperfusion model. Forty male rats were randomly allocated in four groups. The sham group underwent midline laparotomy only. In the sildenafil group, sildenafil was administered intraperitoneally 60 minutes before sham laparotomy. In the ischemia-reperfusion (I/R) group, rats were subjected to 45 minutes of hepatic ischemia followed by 120 minutes of reperfusion, while in the sild+I/R group rats were subjected to a similar pattern of I/R after the administration of sildenafil, 60 minutes before ischemia. Two hours after reperfusion, serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured and histopathological examination of the lobes subjected to ischemia as well as TUNEL staining for apoptotic bodies was performed. Additionally, myeloperoxidase (MPO) activity and the expression of intercellular adhesion molecule-1 (ICAM-1) were analyzed. Serum markers of hepatocellular injury were significantly lower in the sild+I/R group, which also exhibited lower severity of histopathological lesions and fewer apoptotic bodies, as compared to the I/R group. The I/R group showed significantly higher MPO activity and higher expression of ICAM-1, as compared to the sild+I/R group. Use of sildenafil as a preconditioning agent in a rat model of liver I/R exerted a protective effect. PMID:24999378

LncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG.

PubMed

Wu, Bing; Zhang, Chunping; Zou, Lifang; Ma, Yucheng; Huang, Kangyu; Lv, Qiulan; Zhang, Xi; Wang, Shouyu; Xue, Yun; Yi, Zhihua; Jia, Tianyu; Zhao, Shanhong; Liu, Shuangmei; Xu, Hong; Li, Guilin; Liang, Shangdong

2016-05-01

Diabetic autonomic neuropathy includes the sympathetic ganglionic dysfunction. P2X7 receptor in superior cervical ganglia (SCG) participated in the pathological changes of cardiac dysfunction. Abnormal expression of long noncoding RNAs (lncRNAs) was reported to be involved in nervous system diseases. Our preliminary results obtained from rat lncRNA array profiling revealed that the expression of the uc.48+ was significantly increased in the rat SCG in response to diabetic sympathetic pathology. In this study, we found that lncRNAuc.48+ and P2X7 receptor in the SCG were increased in type 2 diabetic rats and were associated with the cardiac dysfunction. The uc.48+ small interference RNA (siRNA) improved the cardiac autonomic dysfunction and decreased the up-regulation P2X7 and the ratio of phosphorylated extracellular regulated protein kinases1/2 (p-ERK1/2) to ERK1/2 in SCG of type 2 diabetic rats. In conclusion, lncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats through regulating the expression of P2X7 and ERK signaling in SCG. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic potential of spinal cord stimulation for gastrointestinal motility disorders: a preliminary rodent study.

PubMed

Song, G-Q; Sun, Y; Foreman, R D; Chen, J D Z

2014-03-01

Spinal cord electrical stimulation (SCS) has been applied for the management of chronic pain. Most of studies have revealed a decrease in sympathetic activity with SCS. The aim of this study was to investigate the effects and mechanisms of SCS on gastrointestinal (GI) motility in healthy and diabetic rats. Male rats chronically implanted with a unipolar electrode at T9/T10 were studied. The study included four experiments to assess the effects of SCS on (1) gastric tone; (2) gastric emptying of liquids and intestinal transit; (3) gastric emptying of solids; and (4) sympathovagal balance in healthy rats and/or in Streptozotocin (STZ)-induced diabetic rat. (1) Spinal cord stimulation intensity dependently increased gastric tone in healthy rats. The gastric volume was 0.97 ± 0.15 mL at baseline, and decreased to 0.92 ± 0.16 mL with SCS of the 30% motor threshold (MT; p = 0.13 vs baseline), 0.86 ± 0.14 mL with 60% MT (p = 0.045 vs baseline), and 0.46 ± 0.19 mL with 90% MT (p = 0.0050 vs baseline). (2) Spinal cord stimulation increased gastric emptying of liquids by about 17% and accelerated small intestinal transit by about 20% in healthy rats (p < 0.001). (3) Spinal cord stimulation accelerated gastric emptying of solids by about 24% in healthy rats and by about 78% in diabetic rats. (4) Spinal cord stimulation decreased sympathetic activity (1.13 ± 0.18 vs 0.68 ± 0.09, p < 0.04) and sympathovagal balance (0.51 ± 0.036 vs 0.40 ± 0.029, p = 0.028). Spinal cord stimulation accelerates gastric emptying of liquids and solids, and intestinal transit, probably by inhibiting the sympathetic activity. Spinal cord stimulation may have a therapeutic potential for treating GI motility disorders. © 2013 John Wiley & Sons Ltd.

Vapor Inhalation Exposure to Soman in Conscious Untreated Rats: Preliminary Assessment of Neurotoxicity

DTIC Science & Technology

2015-12-22

study, which did not survive until the 24 h post-exposure endpoint, experienced severe signs of cholin- ergic intoxication , resulting in mortality...following vapor inhalation exposure, to aid in the development of potential treatment strategies. Gross clinical signs of soman intoxication were...consistent with typical cholinergic-induced intoxication . The observed CWNA-induced cholinergic crises and clinical signs of toxicity such as straub tail

Rehabilitative Soft Exoskeleton for Rodents.

PubMed

Florez, Juan Manuel; Shah, Manan; Moraud, Eduardo Martin; Wurth, Sophie; Baud, Laetitia; Von Zitzewitz, Joachim; van den Brand, Rubia; Micera, Silvestro; Courtine, Gregoire; Paik, Jamie

2017-02-01

Robotic exoskeletons provide programmable, consistent and controllable active therapeutic assistance to patients with neurological disorders. Here we introduce a prototype and preliminary experimental evaluation of a rehabilitative gait exoskeleton that enables compliant yet effective manipulation of the fragile limbs of rats. To assist the displacements of the lower limbs without impeding natural gait movements, we designed and fabricated soft pneumatic actuators (SPAs). The exoskeleton integrates two customizable SPAs that are attached to a limb. This configuration enables a 1 N force load, a range of motion exceeding 80 mm in the major axis, and speed of actuation reaching two gait cycles/s. Preliminary experiments in rats with spinal cord injury validated the basic features of the exoskeleton. We propose strategies to improve the performance of the robot and discuss the potential of SPAs for the design of other wearable interfaces.

Esophageal incisions repair by CO2 laser soldering.

PubMed

Nageris, Ben I; Zilker, Zeev; Zilker, Maya; Kariv, Noam; Feinmesser, Rafael; Katzir, Abraham

2004-12-01

This study evaluated the feasibility of fiberoptic CO2 laser soldering for the repair of esophageal injuries under tight temperature feedback control in an animal model. Healing was compared to conventional suture closure. A CO2 soldering system equipped with infrared transmitting silver halide fibers was used. The soldered tissue temperature was monitored continuously, and laser power was adjusted to provide constant temperature. The procedure was done with 50% bovine serum albumin solder. Longitudinal incisions measuring 8 to 10 mm were made under general anesthesia in the cervical esophagus of 25 rats. Twenty rats (group I) underwent laser tissue bonding; 8 of which were tested in a preliminary study to determine optimal laser parameters. In the remaining 5 rats (group II, controls), closure was performed with 1 layer of 6/0 Vicryl sutures. The rats were sacrificed 2, 3, 4, and 6 weeks postoperatively, and the esophagus was examined histologically. Optimal temperature was found to be 65 to 70 degrees C and optimal exposure time, 150 to 200 seconds. Laser soldering was successful in 9 of the 12 rats (75%) treated under optimal settings; suturing was successful in 4 of the 5 control rats (80%). There were no significant differences between the groups in healing or complication rates. These results indicate that the CO2 laser soldering technique is a valid option for the correction of esophageal tears or incisions in rats. The confirmation and extension of these findings in further studies with larger animals may ultimately lead to the routine in vivo use of temperature-controlled laser repair for the esophagus and other organs. This method lends itself to endoscopic bonding of tissues.

Bitter taste and nicotine preference: evidence for sex differences in rats.

PubMed

Nesil, Tanseli; Kanit, Lutfiye; Pogun, Sakire

2015-01-01

Nicotine affects sensory pathways and an interaction between taste and nicotine preference is likely. In addition to pharmacologic effects, orosensory factors are important in nicotine dependence. Recent evidence suggests a link between taste (notably bitter) receptor genes and nicotine addiction. To explore the possible interaction between taste and nicotine preference in rats, including sex as a factor. Adult male and female Sprague Dawley rats (n = 82) were used in free choice oral intake experiments. In Experiment 1 rats received water from one bottle and one of the taste substances (quinine, sucrose, or saccharine) from the other bottle for 12 days. Following a wash-out period, Experiment 2a was initiated in the same rats. Rats received water from one bottle and nicotine (10 and 20 mg/l) from the other for 12 days. In Experiment 2b, nicotine exposure was continued for four more weeks. Liquid intake and weight were measured at four-day (Experiments 1 and 2a) and one week (Experiment 2b) periods. In female rats, quinine and subsequent nicotine intake were positively correlated and quinine intake and weight gain were negatively correlated. No association was depicted between nicotine consumption and sweet tastants in either female or male animals. The results suggest that bitter taste and nicotine preference are related, but only in female rats. This finding is parallel to observations in human smokers. Our study may be a preliminary step in the search for common genes that underlie nicotine dependence and taste preference.

Recognition of the Species of Origin of Cells in Culture by Mixed Agglutination

PubMed Central

Coombs, R. R. A.; Daniel, Mary R.; Gurner, B. W.; Kelus, A.

1961-01-01

Preliminary experiment on the mixed agglutination reaction suggests that this reaction will afford a useful method for identifying the species of origin of cells maintained in culture. The reaction depends on the presence of antigens characteristic of the species, common to both tissue cells and red cells. Culture cells derived from man, ox, pig and rat could be distinguished one from the other. Fibroblasts of the mouse may be differentiated from those of the rat by means of a rat anti-mouse red-cell serum or a mouse anti-rat red-cell serum. Experiments are reported on trial absorption procedures to render the sera completely species-specific in their reactions. ImagesFIG. 1 PMID:13695283

Antidiabetic activity and phytochemical screening of crude extract of Stevia rebaudiana in alloxan-induced diabetic rats

PubMed Central

Kujur, R. S.; Singh, Vishakha; Ram, Mahendra; Yadava, Harlokesh Narayan; Singh, K. K.; Kumari, Suruchi; Roy, B. K.

2010-01-01

Background: Stevia rebaudiana regulates blood sugar, prevents hypertension and tooth decay. Other studies have shown that it has antibacterial as well as antiviral property. Methods: Preliminary phytochemical screening of aqueous, ether and methanolic extracts of S. rebaudiana was done. Acute and sub-acute toxicity were conducted on twenty four Albino rats, divided into one control (Group I) and three treatment groups viz. aqueous extract (Group II), ether extract (Group III) and methanolic extract (Group IV). For the study of antidiabetic effect of S. rebaudiana rats were divided into seven groups (n=6). Diabetes was induced by a single dose of 5% alloxan monohydrate (125 mg/kg, i.p.) after 24 hour fasting.Blood samples were analysed on day 0, 1, 5, 7, 14 and 28. Results: Phytochemical tests showed presence of different kinds of phyto-constituents in aqueous, ether and methanol extract of Stevia rebaudiana leaves. Daily single dose (2.0 g/kg) administration of aqueous extract (A.E.) , ether extract (E.E.) and methanol extract (M.E.) for 28 days of S. rebaudiana could not show any significant change in ALT and AST levels in rats. Blood sugar level was found to be decreased on day 28 in groups of rats treated with A.E., E.E. and M.E. of S. rebaudiana. Conclusion: The extracts of Stevioside rebaudiana could decrease the blood glucose level in diabetic rats in time dependent manner. PMID:21808578

Functional significance of muscarinic receptor expression within the proximal and distal rat vagina.

PubMed

Basha, Maureen; Labelle, Edward F; Northington, Gina M; Wang, Tanchun; Wein, Alan J; Chacko, Samuel

2009-11-01

Information regarding the role of cholinergic nerves in mediating vaginal smooth muscle contraction is sparse, and in vitro studies of the effects of muscarinic agonists on vaginal smooth muscle are discrepant. The goal of this study was to determine the expression of muscarinic receptors in the vaginal wall of the rat. In addition, we sought to determine the effect of the muscarinic receptor agonist carbachol on contractility and inositol phosphate production of the proximal and distal rat vaginal muscularis. RT-PCR analysis indicated that both M(2) and M(3) receptor transcripts were expressed within the proximal and distal rat vagina. Carbachol dose-dependently (10(-7)-10(-4) M) contracted the rat vaginal muscularis with a greater maximal contractile response in the proximal vagina (P < 0.01) compared with the distal vagina. The contractile responses of the rat vaginal muscularis to carbachol were dose dependently inhibited by the M(3) antagonist para-fluoro-hexahydrosiladefenidol, and a pK(B) of 7.78 and 7.95 was calculated for the proximal and distal vagina, respectively. Inositol phosphate production was significantly increased in both regions of the vagina following 20-min exposure to 50 muM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M(2) and M(3) receptors in the human vaginal muscularis as well as contraction of human vaginal muscularis to carbachol, indicating that our animal studies are relevant to human tissue. Our results provide strong evidence for the functional significance of M(3) receptor expression in the vaginal muscularis.

Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer.

PubMed

Hotkar, Mukesh S; Avachat, Amelia M; Bhosale, Sagar S; Oswal, Yogesh M

2015-04-01

Nitroglycerin (NTG) is an organic nitrate rapidly denitrated by enzymes to release free radical nitric oxide and shows improved wound healing and tissue protection from oxidative damage. The purpose of this study was to evaluate whether topical application of NTG in the form of gel/ointment along with a natural wound healing agent, aloe vera, would bring about wound healing by using diabetes-induced foot ulcer model and rat excision wound model. All these formulations were evaluated for pH, viscosity, drug content and ex vivo diffusion studies using rat skin. Based on ex vivo permeation studies, the formulation consisting of carbopol 974p as a gelling agent and aloe vera was found to be suitable. The in vivo study used streptozotocin-induced diabetic foot ulcer and rat excision wound models to analyse wound healing activity. The wound size in animals of all treated groups was significantly reduced compared with that of the diabetic control and marketed treated animals. This study showed that the gel formed with carbopol 974p (1%) and aloe vera promotes significant wound healing and closure in diabetic rats compared with the commercial product and provides a promising product to be used in diabetes-induced foot ulcer. © 2013 The Authors. International Wound Journal © 2013 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Morphological and functional manifestations of rat adrenal-cortex response to sodium bromide administration under hypodynamic stress

NASA Technical Reports Server (NTRS)

Kirichek, L. T.; Zholudeva, V. I.

1979-01-01

Functional and morphological manifestations of adrenal cortex response to hypodynamia (2-hr immobilization on an operating table) under the influence of bromine preparations were studied. The sodium bromide was administered intraperitoneally in 100, 250, and 500 mg/kg doses once and repeatedly during ten days. The adrenal gland was evaluated functionally by ascorbic acid and cholesterol content and morphologically by coloring it with hematoxylin-eosin and Sudans for lipid revealing at freezing. Results are displayed in two tables and microphotographs. They are summarized as follows: the bromine weakens the functional state of the adrenal cortex in intact rats, causing changes similar to those under stress. During immobilization combined with preliminary bromine administration, a less pronounced stress reaction is noticeable.

Dietary modulation of the effects of exposure to 56Fe particles

NASA Astrophysics Data System (ADS)

Rabin, B. M.; Joseph, J. A.; Shukitt-Hale, B.; Carey, A. N.

On exploratory missions to other planets, astronauts will be exposed to galactic cosmic rays composed of protons and heavy particles, such as 56Fe. Long-term exposure to these particles can cause cancer. However, there are significant uncertainties in the risk estimates for the probability of developing heavy particle-induced cancer, and in the amount of shielding needed to provide an adequate level of radiation protection. The results of this preliminary study, using a ground-based model for exposure to cosmic rays, show reduced tumorigenesis in rats maintained on diets containing blueberry or strawberry extract prior to exposure to 56Fe particles. Because the study was not initially designed to evaluate tumorigenesis following exposure to 56Fe particles, additional research is needed to evaluate the effectiveness of strawberry and blueberry supplementation. However, the preliminary results presented in this study suggest that diets containing antioxidant phytochemicals can provide additional radiation protection on interplanetary voyages.

Use of ultrasonography in the diagnosis of osteomalacia: preliminary results on experimental osteomalacia in the rat.

PubMed

Luisetto, G; Camozzi, V; De Terlizzi, F; Moschini, G; Ballanti, P

1999-03-01

This study was performed to investigate the ability of ultrasonographic technique to distinguish osteomalacia from normal bone with the same mineral content. Ten rats with experimentally induced osteomalacia (group A) and 12 control rats having similar body size and weight (group B) were studied. Histomorphometric analysis confirmed the presence of osteomalacia in two rats from group A and showed normally mineralized bone in two rats from group B. Whole body bone mineral density, measured by dual-energy x-ray absorptiometry, was similar in the two groups (86 +/- 6 mg/cm2 in group A and 89 +/- 4 mg/cm2 in group B). The velocity of the ultrasound beam in bone was measured by densitometer at the first caudal vertebra of each rat. The velocity was measured when the first peak of the waveform reached a predetermined minimum amplitude value (amplitude-dependent speed of sound) as well as at the lowest point of this curve before it reaches the predetermined minimum amplitude (first minimum speed of sound). Although the amplitude-dependent speed of sound was similar in the two groups (1381.9 +/- 11.8 m/s in group A and 1390.9 +/- 17.8 m/s in group B), the first minimum speed of sound was clearly different (1446.1 +/- 8.9 m/s in group A and 1503.3 +/- 10.9 m/s in group B; P < 0.001). This study shows that ultrasonography could be used to identify alterations in bone quality, such as osteomalacia, but further studies need to be carried out before this method can be introduced into clinical practice.

Cassava starch fermentation wastewater: characterization and preliminary toxicological studies.

PubMed

Avancini, S R P; Faccin, G L; Vieira, M A; Rovaris, A A; Podestá, R; Tramonte, R; de Souza, N M A; Amante, E R

2007-11-01

Cassava starch fermentation wastewater is an industrial residue composed mainly of lactic acid bacteria with predominance of the genera Lactobacillus, and organic acids. To evaluate the safety of this residue for possible production of probiotic beverages, acute in mice and sub-chronic (28-day repeated dose) toxicity studies in rats were carried. The administration of a single dose of 5 g/kg/body weight did not produce mortality in mice. Rats treated with water containing 0 (control), 25%, 50%, and 100% of the residue for 28 days, did not present alterations in behaviour or in food and water consumption. There were no treatment-related changes of toxicological significance in the relative weight of the organs neither in the haematological nor in the biochemical parameters. Histopathologic alterations observed in the small intestine did not seem to be associated with the treatment.

Hyperpolarized ketone body metabolism in the rat heart.

PubMed

Miller, Jack J; Ball, Daniel R; Lau, Angus Z; Tyler, Damian J

2018-06-01

The aim of this work was to investigate the use of 13 C-labelled acetoacetate and β-hydroxybutyrate as novel hyperpolarized substrates in the study of cardiac metabolism. [1- 13 C]Acetoacetate was synthesized by catalysed hydrolysis, and both it and [1- 13 C]β-hydroxybutyrate were hyperpolarized by dissolution dynamic nuclear polarization (DNP). Their metabolism was studied in isolated, perfused rat hearts. Hyperpolarized [1- 13 C]acetoacetate metabolism was also studied in the in vivo rat heart in the fed and fasted states. Hyperpolarization of [1- 13 C]acetoacetate and [1- 13 C]β-hydroxybutyrate provided liquid state polarizations of 8 ± 2% and 3 ± 1%, respectively. The hyperpolarized T 1 values for the two substrates were 28 ± 3 s (acetoacetate) and 20 ± 1 s (β-hydroxybutyrate). Multiple downstream metabolites were observed within the perfused heart, including acetylcarnitine, citrate and glutamate. In the in vivo heart, an increase in acetylcarnitine production from acetoacetate was observed in the fed state, as well as a potential reduction in glutamate. In this work, methods for the generation of hyperpolarized [1- 13 C]acetoacetate and [1- 13 C]β-hydroxybutyrate were investigated, and their metabolism was assessed in both isolated, perfused rat hearts and in the in vivo rat heart. These preliminary investigations show that DNP can be used as an effective in vivo probe of ketone body metabolism in the heart. © 2018 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.

PCR Conditions for 16S Primers for Analysis of Microbes in the Colon of Rats.

PubMed

Guillen, I A; Camacho, H; Tuero, A D; Bacardí, D; Palenzuela, D O; Aguilera, A; Silva, J A; Estrada, R; Gell, O; Suárez, J; Ancizar, J; Brown, E; Colarte, A B; Castro, J; Novoa, L I

2016-09-01

The study of the composition of the intestinal flora is important to the health of the host, playing a key role in maintaining intestinal homeostasis and the evolution of the immune system. For these studies, various universal primers of the 16S rDNA gene are used in microbial taxonomy. Here, we report an evaluation of 5 universal primers to explore the presence of microbial DNA in colon biopsies preserved in RNAlater solution. The DNA extracted was used for the amplification of PCR products containing the variable (V) regions of the microbial 16S rDNA gene. The PCR products were studied by restriction fragment length polymorphism (RFLP) analysis and DNA sequence, whose percent of homology with microbial sequences reported in GenBank was verified using bioinformatics tools. The presence of microbes in the colon of rats was quantified by the quantitative PCR (qPCR) technique. We obtained microbial DNA from rat, useful for PCR analysis with the universal primers for the bacteria 16S rDNA. The sequences of PCR products obtained from a colon biopsy of the animal showed homology with the classes bacilli (Lactobacillus spp) and proteobacteria, normally represented in the colon of rats. The proposed methodology allowed the attainment of DNA of bacteria with the quality and integrity for use in qPCR, sequencing, and PCR-RFLP analysis. The selected universal primers provided knowledge of the abundance of microorganisms and the formation of a preliminary test of bacterial diversity in rat colon biopsies.

In Vitro Studies and Preliminary Mathematical Model for Jet Fuel and Noise Induced Auditory Impairment

DTIC Science & Technology

2015-06-01

K.C. and Hu, B.H. 2006. The role of oxidative stress in noise-induced hearing loss. Ear Hear 27(1): 1-19. Hillerdal, M. 1987. Cochlear blood flow ...Larsen, H.C., Angelborg, C. and Slepecky, N. 1984. Determination of the regional cochlear blood flow in the rat cochlea using non-radioactive...24-Hour JP-8 Exposure using a Cochlear Cell Model and Cellular Pathway Modulation

Protective effects on vascular endothelial cell in N'-nitro-L-arginine (L-NNA)-induced hypertensive rats from the combination of effective components of Uncaria rhynchophylla and Semen Raphani.

PubMed

Li, Yunlun; Yang, Wenqing; Zhu, Qingjun; Yang, Jinguo; Wang, Zhen

2015-08-01

Endothelial dysfunction is closely associated with hypertension. Protection of vascular endothelial cell is the key to prevention and treatment of hypertension. Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid, isolated from traditional Chinese medicine Uncaria rbyncbopbylla and Semen Raphani respectively, exhibit properties of anti-hypertension and protection of blood vessels. In the present study, we observed the protective effect of the combined use of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid to the vascular endothelial cell in N'-nitro-L-arginine-induced hypertensive rats and investigate the preliminary mechanism. Blood pressure was detected by non-invasive rats tail method to observe the anti-hypertension effect of drugs. Scanning electron microscopy was used to observe the integrity or shedding state of vascular endothelial cell. The amount of circulating endothelial cells and CD54 and CD62P expression on circulating endothelial cells were tested to evaluate the endothelium function. In this study, we found that the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility can effectively lower the blood pressure, improve the structural integrity of vascular endothelium, and significantly reduce the number of circulating endothelial cells. Furthermore, the mean fluorescence intensity of CD54 and CD62P expressed showed decrease after the intervention of Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid compatibility. In conclusion, the combination of effective components of the Uncaria rhynchophylla total alkaloids and Semen Raphani soluble alkaloid demonstrated good antihypertension effect and vascular endothelium protective effect. The preliminary mechanism of the protective effect may attribute to relieve the overall low-grade inflammation.

Noninvasive quantification of cerebral metabolic rate for glucose in rats using 18F-FDG PET and standard input function

PubMed Central

Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

2015-01-01

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed 18F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIFNS) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF1S). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIFNS-, and EIF1S-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIFNS was highly correlated with those derived from AIF and EIF1S. Preliminary comparison between AIF and EIFNS in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIFNS method might serve as a noninvasive substitute for individual AIF measurement. PMID:25966947

Noninvasive quantification of cerebral metabolic rate for glucose in rats using (18)F-FDG PET and standard input function.

PubMed

Hori, Yuki; Ihara, Naoki; Teramoto, Noboru; Kunimi, Masako; Honda, Manabu; Kato, Koichi; Hanakawa, Takashi

2015-10-01

Measurement of arterial input function (AIF) for quantitative positron emission tomography (PET) studies is technically challenging. The present study aimed to develop a method based on a standard arterial input function (SIF) to estimate input function without blood sampling. We performed (18)F-fluolodeoxyglucose studies accompanied by continuous blood sampling for measurement of AIF in 11 rats. Standard arterial input function was calculated by averaging AIFs from eight anesthetized rats, after normalization with body mass (BM) and injected dose (ID). Then, the individual input function was estimated using two types of SIF: (1) SIF calibrated by the individual's BM and ID (estimated individual input function, EIF(NS)) and (2) SIF calibrated by a single blood sampling as proposed previously (EIF(1S)). No significant differences in area under the curve (AUC) or cerebral metabolic rate for glucose (CMRGlc) were found across the AIF-, EIF(NS)-, and EIF(1S)-based methods using repeated measures analysis of variance. In the correlation analysis, AUC or CMRGlc derived from EIF(NS) was highly correlated with those derived from AIF and EIF(1S). Preliminary comparison between AIF and EIF(NS) in three awake rats supported an idea that the method might be applicable to behaving animals. The present study suggests that EIF(NS) method might serve as a noninvasive substitute for individual AIF measurement.

A preliminary survey of Trichinella spp. in pigs raised under controlled housing conditions in Colombia: 2014–2016

PubMed Central

Chaparro-Gutiérrez, Jenny J.; Pozio, Edoardo; Gómez-Morales, María A.; López, Anderson; Mejia, Jaime; Zambrano, Corina; Piedrahita, Diego; Villar, David

2018-01-01

A preliminary survey of Trichinella spp. infection was conducted in Colombian swine herds between 2014 and 2016. A total of 1,773 pigs reared on farms under controlled housing conditions and processed in 34 slaughterhouses were tested either by the artificial digestion of pooled muscle samples (n = 1,173) or by serology (n = 600). In addition, 550 rats trapped on 29 swine farm premises were also tested by artificial digestion. No positive pig samples were detected. Similarly, no Trichinella spp. muscle larvae were detected in rats. These results are in agreement with the lack of historical Trichinella infection reports in domestic and wild animals and humans in Colombia. However, a more extensive epidemiological investigation and a continuous surveillance program are needed to continue declaring swine herds in Colombia free of Trichinella infection. PMID:29633706

Hormone synthesis and secretion by rat parathyroid glands in tissue culture.

PubMed

Au, W Y; Poland, A P; Stern, P H; Raisz, L G

1970-09-01

Rat parathyroid glands maintained in organ culture secrete biologically active parathyroid hormone (PTH) and synthesize and secrete labeled proteins from (3)H- or (14)C-labeled amino acids added to the medium. The amounts of biological activity and labeled protein in the medium are both inversely proportional to the calcium concentration. Some of the labeled low molecular weight protein was identified as PTH which had been synthesized and secreted in culture by preliminary isolation on Sephadex G-100 columns and further purification using an antibody to bovine PTH which cross-reacted with rat PTH. The cross-reacting antibody inhibited the biological effects of rat PTH and caused hypocalcemia in intact rats. The antibody bound some of the labeled low molecular weight protein of the medium at neutral pH so that it migrated as a large molecular weight complex on Sephadex. Biologically active, labeled PTH was recovered by dissociation of this complex in acid and rechromatography.

A two-hit model: behavioural investigation of the effect of combined neonatal MK-801 administration and isolation rearing in the rat.

PubMed

Lim, Ann Li; Taylor, David Alan; Malone, Daniel Thomas

2012-09-01

This study combined two neurodevelopmental manipulations, neonatal MK-801 treatment and isolation rearing, to produce a 'two-hit' model and determine whether two hits induce a more robust behavioural phenotype of an animal model of aspects of schizophrenia compared with individual manipulations alone. The effect of clozapine was also assessed. Male Sprague-Dawley rats received 0.2 mg/kg MK-801 or saline intraperitoneally (i.p.) once daily on postnatal days (PNDs) 7-10 and were assigned to group or isolation rearing at weaning (PND 21). From PND 77, they received a vehicle or 5 mg/kg clozapine (i.p.) treatment regimen and were subjected to three prepulse inhibition (PPI) tests, a locomotor activity assessment and a novel object recognition task. MK-801-treated rats reared in isolation displayed robust PPI disruptions which were consistently manifested in all three tests. PPI deficits were also detected in saline-treated rats reared in isolation but not in all tests. Only the two-hit rats demonstrated hyperlocomotion and impaired object recognition memory. Clozapine restored PPI anomalies in the two-hit rats. The two-hit model showed greater psychotic-like effects than either neonatal MK-801 or isolation rearing alone. The preliminary predictive validity shown with clozapine suggests this model may be useful for predicting the efficacy of putative antipsychotics.

Role of the rat in the transmission of porcine parvovirus.

PubMed

Cutler, R; Molitor, T W; Sauber, T E; Leman, A D

1982-03-01

Rats experimentally inoculated with porcine parvovirus (PPV) shed virus in excreta from 3 to 21 days. Rats inoculated subcutaneously with PPV responded serologically with hemagglutination-inhibition titers (512-1,024). The PPV antigen was readily detected in lung and spleen 2 and 3 days after rats were inoculated and in liver and intestine, 4 days. The rats remained clinically healthy. Rats given PPV orally or in drinking water either with PPV-infected cell culture fluid or swine fetal homogenate failed to respond serologically to PPV, the exception being 2 of 4 rats exposed to swine fetal homogenate over a 5-day span. Pigs exposed to PPV-contaminated rat excreta, either by direct oral dosing or by contaminating the feed, failed to seroconvert. Pigs given (IM) PPV which had been isolated on cell culture from rat excreta did seroconvert. Results of these experiments indicated that rats became infected with PPV, but did so after systemic challenge exposure or prolonged oral exposure to highly infective swine fetal homogenate. Insufficient virus was shed by rats to cause susceptible pigs to seroconvert upon oral feeding--thus indicating that a minimal dose is necessary to ensure oral challenge. In a preliminary experiment, seronegative pigs given different doses of PPV orally showed a gradient level of serologic response and different rates of shedding.

Photoacoustic tomography of joints aided by an Etanercept-conjugated gold nanoparticle contrast agent—an ex vivo preliminary rat study

NASA Astrophysics Data System (ADS)

Chamberland, David L.; Agarwal, Ashish; Kotov, Nicholas; Fowlkes, J. Brian; Carson, Paul L.; Wang, Xueding

2008-03-01

Monitoring of anti-rheumatic drug delivery in experimental models and in human diseases would undoubtedly be very helpful for both basic research and clinical management of inflammatory diseases. In this study, we have investigated the potential of an emerging hybrid imaging technology—photoacoustic tomography—in noninvasive monitoring of anti-TNF drug delivery. After the contrast agent composed of gold nanorods conjugated with Etanercept molecules was produced, ELISA experiments were performed to prove the conjugation and to show that the conjugated anti-TNF-α drug was biologically active. PAT of ex vivo rat tail joints with the joint connective tissue enhanced by intra-articularly injected contrast agent was conducted to examine the performance of PAT in visualizing the distribution of the gold-nanorod-conjugated drug in articular tissues. By using the described system, gold nanorods with a concentration down to 1 pM in phantoms or 10 pM in biological tissues can be imaged with good signal-to-noise ratio and high spatial resolution. This study demonstrates the feasibility of conjugating TNF antagonist pharmaceutical preparations with gold nanorods, preservation of the mechanism of action of TNF antagonist along with preliminary evaluation of novel PAT technology in imaging optical contrast agents conjugated with anti-rheumatic drugs. Further in vivo studies on animals are warranted to test the specific binding between such conjugates and targeted antigen in joint tissues affected by inflammation.

Anti-inflammatory effects of aqueous extract of Mangifera indica in Wistar rats.

PubMed

Oluwole, Oluwafemi Gabriel; Esume, Celestine

2015-05-01

Recent studies in standard laboratories have indicated that a typical mango stem bark aqueous extract (Magnifera indica Linn) possess anti-malaria and anti-fever properties. Recent information also exists in the literature, suggesting its potency as a very effective anti-inflammatory plant extract. This study will therefore contribute immensely to the systemic search for a useful, less toxic and natural bioactive medicinal compound. This study investigated the anti-inflammatory effects of the aqueous extract of Mangifera indica (MI) in a carrageenin-induced rat paw oedema model of acute inflammation. Rats (n=5) were treated orally with MI (50, 100 and 200 mg/kg), acetylsalicylic acid (100 mg/kg) or distilled water (3 mL). Thirty minutes later, acute inflammation was induced with a sub-plantar injection of 0.1 mL of 1% carrageenin solution into the right hind paw of the rats. The paw oedema sizes were measured with the aid of a Vernier calliper over a period of 3 hours. The aqueous extract of MI (50-200 mg/kg, p.o.) produced a dose-dependent and significant inhibition of the acute inflammation induced by the carrageenin in rats when compared with controls. The percentage inhibition of oedema formation produced by MI (200 mg/kg, p.o.) was similar to that elicited by acetylsalicylic acid (100 mg/kg, p.o.). The results of this preliminary investigation suggest that MI contains active compounds with an anti-inflammatory activity. However, more detailed studies using additional models are necessary to further characterise the effects of MI in inflammatory disorders.

An integrated bioanalytical method development and validation approach: case studies.

PubMed

Xue, Y-J; Melo, Brian; Vallejo, Martha; Zhao, Yuwen; Tang, Lina; Chen, Yuan-Shek; Keller, Karin M

2012-10-01

We proposed an integrated bioanalytical method development and validation approach: (1) method screening based on analyte's physicochemical properties and metabolism information to determine the most appropriate extraction/analysis conditions; (2) preliminary stability evaluation using both quality control and incurred samples to establish sample collection, storage and processing conditions; (3) mock validation to examine method accuracy and precision and incurred sample reproducibility; and (4) method validation to confirm the results obtained during method development. This integrated approach was applied to the determination of compound I in rat plasma and compound II in rat and dog plasma. The effectiveness of the approach was demonstrated by the superior quality of three method validations: (1) a zero run failure rate; (2) >93% of quality control results within 10% of nominal values; and (3) 99% incurred sample within 9.2% of the original values. In addition, rat and dog plasma methods for compound II were successfully applied to analyze more than 900 plasma samples obtained from Investigational New Drug (IND) toxicology studies in rats and dogs with near perfect results: (1) a zero run failure rate; (2) excellent accuracy and precision for standards and quality controls; and (3) 98% incurred samples within 15% of the original values. Copyright © 2011 John Wiley & Sons, Ltd.

Contribution of collagen stable isotope biogeochemistry to the paleobiology of extinct endemic vertebrates from Tenerife (Canary Islands, Spain).

PubMed

Bocherens, H; Michaux, J; Billiou, D; Castanet, J; Garcìa-Talavera, F

2003-09-01

The paleodiet and paleoenvironmental context of two extinct species from Tenerife island, one giant rat Canariomys bravoi and one giant lizard Gallotia goliath, have been investigated using carbon and nitrogen isotopic compositions of fossil bone collagen. Preliminary to this study, a calibration of the isotopic variations of bone collagen from modern Rat Rattus rattus, Rabbit Oryctolagus cuniculus and Lizard Gallotia galotti relative to environmental conditions on Tenerife Islands has been attempted. No clear relationship could be found between collagen delta13C and delta15N values and aridity; the only relevant factors seem to be seashore proximity for rat, and the relative amount of C3 and CAM plants. It seems that anthropic activities have interfered with the expected relationships between collagen isotopic compositions and environmental conditions. Most fossil specimens yielded well preserved collagen. The isotopic composition of giant rat and giant lizard collagen suggest a purely C3 environment, possibly more humid than today on Tenerife. Large ranges of nitrogen isotopic compositions, especially within giant rats, may be due to local environmental conditions. Further work is needed in order to provide more valuable paleobiological information in order to better understand the role of environmental factors in the evolution and extinction of insular endemic species on Tenerife.

An alternative treatment modality in closing bladder exstrophy: use of rectus abdominus muscle flap--preliminary results in a rat model.

PubMed

Büyükünal, S N; Kaner, G; Celayir, S

1989-06-01

The aim of this study was to find a new alternate method for bladder exstrophies with small capacity and inelasticity, and to resolve complications of other bladder augmentation techniques. In 50 Wistar albino rats, a large bladder defect was created excising at least one half of their original bladder, keeping the peritrigonal zone intact. In each rat, a 2.5 x 1-cm inferiorly based rectus abdominus muscle flap was prepared from the lower abdominal quadrant. This flap was then rotated to cover the bladder defect. The inner layer formed by the peritoneum was sutured to the edges of the bladder defect by 6-0 separate sutures. The post-operative radiologic and scintigraphic examination of the urinary system done at different intervals showed no difference from that of normal rats. The only observed disadvantage of this technique was the formation of calculi in the bladder in 8/50 rats in the late post-operative period. Post-mortem histopathologic investigations performed at different intervals showed the inner layer of the flap to be completely covered by the transitional urinary epithelium of the bladder. We think this technique is easy to perform, non-time-consuming, and has a low complication rate. It may be useful in infants with small, noncompliant, inelastic bladder exstrophies.

Development and full validation of an UPLC-MS/MS method for the quantification of the plant-derived alkaloid indirubin in rat plasma.

PubMed

Jähne, Evelyn A; Sampath, Chethan; Butterweck, Veronika; Hamburger, Matthias; Oufir, Mouhssin

2016-09-05

An UPLC-MS/MS method for the quantification of indirubin in lithium heparinized rat plasma was developed and validated according to current international guidelines. Indirubin was extracted from rat plasma by using Waters Ostro™ pass-through sample preparation plates. The method was validated with a LLOQ of 5.00ng/mL and an ULOQ of 500ng/mL. The calibration curve was fitted by least-square quadratic regression, and a weighting factor of 1/X was applied. Recoveries of indirubin and I.S. were consistent and ≥75.5%. Stability studies demonstrated that indirubin was stable in lithium heparinized rat plasma for at least 3 freeze/thaw cycles, for 3h at RT, for 96h in the autosampler at 10°C, and for 84days when stored below -65°C. Preliminary pharmacokinetic (PK) data were obtained from Sprague Dawley rats after intravenous administration of indirubin (2mg/kg b.w.) and blood sampling up to 12h after injection. PK parameters were determined by non-compartmental analysis. Indirubin had a half-life (t1/2) of 35min, and a relatively high clearance (CL) of 2.71L/h/kg. Copyright © 2016 Elsevier B.V. All rights reserved.

Experimental study of brachial plexus and vessel compression: evaluation of combined central and peripheral electrodiagnostic approach.

PubMed

Yang, Chaoqun; Xu, Jianguang; Chen, Jie; Li, Shulin; Cao, Yu; Zhu, Yi; Xu, Lei

2017-08-01

We sought to investigate the reliability of a new electrodiagnostic method for identifying Electrodiagnosis of Brachial Plexus & Vessel Compression Syndrome (BPVCS) in rats that involves the application of transcranial electrical stimulation motor evoked potentials (TES-MEPs) combined with peripheral nerve stimulation compound muscle action potentials (PNS-CMAPs). The latencies of the TES-MEP and PNS-CMAP were initially elongated in the 8-week group. The amplitudes of TES-MEP and PNS-CMAP were initially attenuated in the 16-week group. The isolateral amplitude ratio of the TES-MEP to the PNS-CMAP was apparently decreased, and spontaneous activities emerged at 16 weeks postoperatively. Superior and inferior trunk models of BPVCS were created in 72 male Sprague Dawley (SD) rats that were divided into six experimental groups. The latencies, amplitudes and isolateral amplitude ratios of the TES-MEPs and PNS-CMAPs were recorded at different postoperative intervals. Electrophysiological and histological examinations of the rats' compressed brachial plexus nerves were utilized to establish preliminary electrodiagnostic criteria for BPVCS.

Anatomo-radiological correlation using 18-FDG-PET in abdominal sepsis model in rats. A preliminary study.

PubMed

Azevedo, Ítalo Medeiros; Carvalho, Marília Daniela Ferreira; Nascimento, Rafael Pereira; Macedo, Robson; Aquino, Mônica Raquel de Souza; Medeiros, Aldo Cunha

2017-03-01

To examine a correlation of micro-PET images with photographic images of the digestive organs in abdominal sepsis model. Male Wistar rats weighing 265±18g were used. Abdominal sepsis was induced by ligature and cecal puncture. Micro-PET Images from abdominal cavity septic foci were obtained using 18-Fluoro-deoxyglucose, looking for a correlation with photographic images of abdominal cavity organs. Pearson's correlation test was used. The mean standard uptake values (SUV) and lesion areas were 2.58±0.63SUVbwg/ml and 546.87±300.95mm2, respectively. There was a strong positive correlation between the two variables (r=0.863, p=0.137), which resulted in a coefficient of determination r2?0.75, meaning that 75% of SUV variation is explained by the lesion areas of digestive organs. Micro-PET allows high throughput assessment of lesion count and volume in pre-clinical rat model of CPL abdominal sepsis.

Metabolism of adiphenine. I. Absorption, distribution and excretion in rats and mice.

PubMed

Michelot, J; Madelmont, J C; Jordan, D; Mornex, R; Meyniel, G

1981-02-01

1. The disposition of adiphenine labelled with 14C in two positions has been investigated in rats and mice after i.v. administration, and has been compared with that of the [14C]diethylethanolamine HCl and of the [14C]diphenylacetic acid. 2. Radioactivity in the blood declined in a biphasic manner. Biliary elimination depended upon the 14C-labelled compound administered: less than 5% dose for the diethylethanolamine moiety, 100% dose for the carboxylic moiety. Of the radioactivity appearing in rat bile, less than 1% is associated with unchanged adiphenine. 3. In preliminary metabolic studies, three major metabolites have been identified: diphenylacetic acid, diethylethanolamine and a diphenylacetic acid glucuronide. 4. Uptake by the brain of [14C]adiphenine shortly after dosing is 15 times greater than that of blood. Radioactivity is also found in the hypophysis, the adrenals and melanoid pigments, with a concn. up to 30 times greater than that found in the blood.

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology.

PubMed

Romeo, Stefania; Viaggi, Cristina; Di Camillo, Daniela; Willis, Allison W; Lozzi, Luca; Rocchi, Cristina; Capannolo, Marta; Aloisi, Gabriella; Vaglini, Francesca; Maccarone, Rita; Caleo, Matteo; Missale, Cristina; Racette, Brad A; Corsini, Giovanni U; Maggio, Roberto

2013-01-01

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague-Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution.

Bright light exposure reduces TH-positive dopamine neurons: implications of light pollution in Parkinson's disease epidemiology

PubMed Central

Romeo, Stefania; Viaggi, Cristina; Di Camillo, Daniela; Willis, Allison W.; Lozzi, Luca; Rocchi, Cristina; Capannolo, Marta; Aloisi, Gabriella; Vaglini, Francesca; Maccarone, Rita; Caleo, Matteo; Missale, Cristina; Racette, Brad A.; Corsini, Giovanni U.; Maggio, Roberto

2013-01-01

This study explores the effect of continuous exposure to bright light on neuromelanin formation and dopamine neuron survival in the substantia nigra. Twenty-one days after birth, Sprague–Dawley albino rats were divided into groups and raised under different conditions of light exposure. At the end of the irradiation period, rats were sacrificed and assayed for neuromelanin formation and number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra. The rats exposed to bright light for 20 days or 90 days showed a relatively greater number of neuromelanin-positive neurons. Surprisingly, TH-positive neurons decreased progressively in the substantia nigra reaching a significant 29% reduction after 90 days of continuous bright light exposure. This decrease was paralleled by a diminution of dopamine and its metabolite in the striatum. Remarkably, in preliminary analysis that accounted for population density, the age and race adjusted Parkinson's disease prevalence significantly correlated with average satellite-observed sky light pollution. PMID:23462874

Effect of recombinant human granulocyte colony-stimulating factor on efficacy of radiation therapy in tumor-bearing rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koji Kabaya; Masahiko Watanabe; Masaru Kusaka

The effect of recombinant human granulocyte colony-stimulating factor on radiation-induced neutropenia and on growth of transplanted tumors treated by irradiation was investigated using tumor-bearing rats as a model for radiation therapy. In a preliminary study using normal rats, neutropenia induced by upper hemi-body irradiation at 3 Gy/day 5 times a week for 3 weeks was prevented by consecutive subcutaneous injections of rhG-CSF at 100 {mu}g/kg/day. Rats bearing Walker-256, a mammary tumor, were scheduled to receive upper hemibody irradiation at 3 Gy/day for 15 times in 3 weeks if white blood cell (WBC) counts were maintained above 3,000/{mu}l. In control tumor-bearingmore » rats not receiving rhG-CSF, irradiation was often withheld because of the decrease in WBC counts below 3,000/{mu}l. In contrast, a decrease in WBC counts below 3,000/{mu}l was rarely found in tumor-bearing rats injected daily with rhG-CSF. The average number of radiation treatments in control rats and rats treated with rhG-CSF was about 8 and 14, respectively, out of the scheduled 15 treatments in 3 weeks. Treatment with rgG-CSF made it possible to complete the radiation therapy regimen and thus inhibit the growth of the transplanted tumor more effectively. These results suggest that rgG-CSF may be useful to ensure radiation therapy on schedule in cancer patients. 20 refs., 4 figs., 1 tab.« less

Reduction in plasma vasopressin levels of dehydrated rats following acute stress

NASA Technical Reports Server (NTRS)

Keil, L. C.; Severs, W. B.

1977-01-01

Results are presented for an investigation directed to substantiate and extend preliminary findings of stress-induced reduction in plasma arginine vasopressin (pAVP). Since normally hydrated rats have very low levels of pAVP, it is difficult to measure reliably any decrease in pAVP that may result from stress. To overcome this problem, the pAVP levels of the tested rats were raised by dehydration prior to application of stress. A radioimmunoassay for pAVP is described and used to determine the levels of vasopressin in the plasma of nondehydrated and dehydrated rats after exposure to ether or acceleration stress. Plasma pAVP is also determined in rats following nicotine administration. It is shown that exposure of nondehydrated rats to ether or acceleration stress does not elicit any significant alterations in circulating pAVP levels while nicotine injections stimulate a marked increase. In particular, ether and acceleration stress produce a rapid reduction in the pAVP level of dehydrated rats, the decrease being observed in both large and small animals. The mechanism for this reduction in pAVP level following stress is yet unknown.

Functional significance of muscarinic receptor expression within the proximal and distal rat vagina

PubMed Central

Basha, Maureen; LaBelle, Edward F.; Northington, Gina M.; Wang, Tanchun; Wein, Alan J.

2009-01-01

Information regarding the role of cholinergic nerves in mediating vaginal smooth muscle contraction is sparse, and in vitro studies of the effects of muscarinic agonists on vaginal smooth muscle are discrepant. The goal of this study was to determine the expression of muscarinic receptors in the vaginal wall of the rat. In addition, we sought to determine the effect of the muscarinic receptor agonist carbachol on contractility and inositol phosphate production of the proximal and distal rat vaginal muscularis. RT-PCR analysis indicated that both M2 and M3 receptor transcripts were expressed within the proximal and distal rat vagina. Carbachol dose-dependently (10−7–10−4 M) contracted the rat vaginal muscularis with a greater maximal contractile response in the proximal vagina (P < 0.01) compared with the distal vagina. The contractile responses of the rat vaginal muscularis to carbachol were dose dependently inhibited by the M3 antagonist para-fluoro-hexahydrosiladefenidol, and a pKB of 7.78 and 7.95 was calculated for the proximal and distal vagina, respectively. Inositol phosphate production was significantly increased in both regions of the vagina following 20-min exposure to 50 μM carbachol with higher levels detected in the proximal vagina compared with the distal (P < 0.05). Preliminary experiments indicated the presence of M2 and M3 receptors in the human vaginal muscularis as well as contraction of human vaginal muscularis to carbachol, indicating that our animal studies are relevant to human tissue. Our results provide strong evidence for the functional significance of M3 receptor expression in the vaginal muscularis. PMID:19741053

Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

PubMed

Alattar, M H; Ravindranath, T M; Choudhry, M A; Muraskas, J K; Namak, S Y; Dallal, O; Sayeed, M M

2001-01-01

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats. Copyright 2001 S. Karger AG, Basel

Directing Spinal Cord Plasticity: The Impact of Stretch Therapy on Functional Recovery after Spinal Cord Injury

DTIC Science & Technology

2013-10-01

of this award, we have found that stretching negatively influences locomotor function in animals with both acute (within days) and chronic (after 3...stretching is stopped, and both acute and chronic animals show a similar time course of recovery. Finally, in very preliminary studies, we have found...glove, data acquisition system and software work very well. The results demonstrate that forces about the ankle of the rat during therapeutic

Microsurgical robotic system for the deep surgical field: development of a prototype and feasibility studies in animal and cadaveric models.

PubMed

Morita, Akio; Sora, Shigeo; Mitsuishi, Mamoru; Warisawa, Shinichi; Suruman, Katopo; Asai, Daisuke; Arata, Junpei; Baba, Shoichi; Takahashi, Hidechika; Mochizuki, Ryo; Kirino, Takaaki

2005-08-01

To enhance the surgeon's dexterity and maneuverability in the deep surgical field, the authors developed a master-slave microsurgical robotic system. This concept and the results of preliminary experiments are reported in this paper. The system has a master control unit, which conveys motion commands in six degrees of freedom (X, Y, and Z directions; rotation; tip flexion; and grasping) to two arms. The slave manipulator has a hanging base with an additional six degrees of freedom; it holds a motorized operating unit with two manipulators (5 mm in diameter, 18 cm in length). The accuracy of the prototype in both shallow and deep surgical fields was compared with routine freehand microsurgery. Closure of a partial arteriotomy and complete end-to-end anastomosis of the carotid artery (CA) in the deep operative field were performed in 20 Wistar rats. Three routine surgical procedures were also performed in cadavers. The accuracy of pointing with the nondominant hand in the deep surgical field was significantly improved through the use of robotics. The authors successfully closed the partial arteriotomy and completely anastomosed the rat CAs in the deep surgical field. The time needed for stitching was significantly shortened over the course of the first 10 rat experiments. The robotic instruments also moved satisfactorily in cadavers, but the manipulators still need to be smaller to fit into the narrow intracranial space. Computer-controlled surgical manipulation will be an important tool for neurosurgery, and preliminary experiments involving this robotic system demonstrate its promising maneuverability.

Optical coherence tomography and optical coherence domain reflectometry for deep brain stimulation probe guidance

NASA Astrophysics Data System (ADS)

Jeon, Sung W.; Shure, Mark A.; Baker, Kenneth B.; Chahlavi, Ali; Hatoum, Nagi; Turbay, Massud; Rollins, Andrew M.; Rezai, Ali R.; Huang, David

2005-04-01

Deep Brain Stimulation (DBS) is FDA-approved for the treatment of Parkinson's disease and essential tremor. Currently, placement of DBS leads is guided through a combination of anatomical targeting and intraoperative microelectrode recordings. The physiological mapping process requires several hours, and each pass of the microelectrode into the brain increases the risk of hemorrhage. Optical Coherence Domain Reflectometry (OCDR) in combination with current methodologies could reduce surgical time and increase accuracy and safety by providing data on structures some distance ahead of the probe. For this preliminary study, we scanned a rat brain in vitro using polarization-insensitive Optical Coherence Tomography (OCT). For accurate measurement of intensity and attenuation, polarization effects arising from tissue birefringence are removed by polarization diversity detection. A fresh rat brain was sectioned along the coronal plane and immersed in a 5 mm cuvette with saline solution. OCT images from a 1294 nm light source showed depth profiles up to 2 mm. Light intensity and attenuation rate distinguished various tissue structures such as hippocampus, cortex, external capsule, internal capsule, and optic tract. Attenuation coefficient is determined by linear fitting of the single scattering regime in averaged A-scans where Beer"s law is applicable. Histology showed very good correlation with OCT images. From the preliminary study using OCT, we conclude that OCDR is a promising approach for guiding DBS probe placement.

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

NASA Astrophysics Data System (ADS)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

NASA Desert RATS 2010: Preliminary Results for Science Operations Conducted in the San Francisco Volcanic Field, Arizona

NASA Technical Reports Server (NTRS)

Gruener, J. E.; Lofgren, G. E.; Bluethmann, W. J.; Bell, E. R.

2011-01-01

The National Aeronautics and Space Administration (NASA) is working with international partners to develop the space architectures and mission plans necessary for human spaceflight beyond earth orbit. These mission plans include the exploration of planetary surfaces with significant gravity fields. The Apollo missions to the Moon demonstrated conclusively that surface mobility is a key asset that improves the efficiency of human explorers on a planetary surface. NASA's Desert Research and Technology Studies (Desert RATS) is a multi-year series tests of hardware and operations carried out annually in the high desert of Arizona. Conducted since 1998, these activities are designed to exercise planetary surface hardware and operations in relatively harsh climatic conditions where long-distance, multi-day roving is achievable

Effect of long-term caloric restriction on brain monoamines in aging male and female Fischer 344 rats.

PubMed

Kolta, M G; Holson, R; Duffy, P; Hart, R W

1989-05-01

The present study examines the changes in central monoamines and their metabolites in aged male and female rats after long-term caloric restriction. Fischer 344 rats of both sexes (n = 5-10/group) were maintained on one of two dietary regimens: ad libitum NIH 31 diet or 60% by weight of the ad lib. intake (restricted), supplemented with vitamins and minerals. Animals received these diets from the age of 14 weeks until killed at 22.25 months of age. Caudate nucleus (CN), hypothalamus (HYPO), olfactory bulb (OB) and nucleus accumbens (NA) were assayed for content of norepinephrine (NE), dopamine (DA) and its metabolites (dihydroxyphenylacetic acid, DOPAC, and homovanillic acid, HVA) and serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) using HPLC/EC. Relative to the ad lib. group, restricted rats of both sex showed significant decreases in NE content in CN, HYPO and OB. DA and 5-HT content were decreased significantly in the CN and HYPO. No significant changes were found in the levels of DA metabolites in all brain regions studied. While the 5-HIAA level was significantly reduced in the HYPO and NA of the female restricted rats, it was increased several-fold in the OB of the male restricted animals. These preliminary results suggest that long-term caloric restriction alters brain monoamine concentrations, an effect which may in turn modify the normal rate of aging.

A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

PubMed

Taki, Faten A; Abdel-Rahman, Abdel A; Zhang, Baohong

2014-01-01

Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2) is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR). The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs) as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder) was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO), ovariectomized rats in the absence (OVX) or presence of E2 (OVXE2). These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

Low Intensity Pulsed Ultrasound (LIPUS) for the treatment of intervertebral disc degeneration

NASA Astrophysics Data System (ADS)

Horne, Devante; Jones, Peter; Salgaonkar, Vasant; Adams, Matt; Ozilgen, B. Arda; Zahos, Peter; Tang, Xinyan; Liebenberg, Ellen; Coughlin, Dezba; Lotz, Jeffrey; Diederich, Chris

2017-02-01

Discogenic back pain presents a major public health issue, with current therapeutic interventions limited to short-term symptom relief without providing regenerative remedies for diseased intervertebral discs (IVD). Many of these interventions are invasive and can diminish the biomechanical integrity of the IVDs. Low intensity pulsed ultrasound (LIPUS) is a potential treatment option that is both non-invasive and regenerative. LIPUS has been shown to be a clinically effective method for the enhancement of wound and fracture healing. Recent in vitro studies have shown that LIPUS stimulation induces an upregulation functional matrix proteins and downregulation of inflammatory factors in cultured IVD cells. However, we do not know the effects of LIPUS on an in vivo model for intervertebral disc degeneration. The objective of this study was to show technical feasibility of building a LIPUS system that can target the rat tail IVD and apply this setup to a model for acute IVD degeneration. A LIPUS exposimetry system was built using a 1.0 MHz planar transducer and custom housing. Ex vivo intensity measurements demonstrated LIPUS delivery to the center of the rat tail IVD. Using an established stab-incision model for disc degeneration, LIPUS was applied for 20 minutes daily for five days. For rats that displayed a significant injury response, LIPUS treatment caused significant upregulation of Collagen II and downregulation of Tumor Necrosis Factor - α gene expression. Our preliminary studies indicate technical feasibility of targeted delivery of ultrasound to a rat tail IVD for studies of LIPUS biological effects.

Overt and Latent Cardiac Effects of Ozone Inhalation in Rats: Evidence for Autonomic Modulation and Increased Myocardial Vulnerability

EPA Science Inventory

Background: Ozone (03) is a well-documented respiratory oxidant, but increasing epidemiologic evidence points to extra-pulmonary effects including positive associations between ambient 03 concentrations and cardiovascular morbidity/mortality. Objectives: With preliminary reports ...

Evidence for the contribution of multiple mechanisms in the feeding pattern of rats exposed to p-chloro-diphenyl diselenide-supplemented diets.

PubMed

Bortolatto, Cristiani F; Heck, Suélen O; Zborowski, Vanessa A; Gai, Bibiana M; Neto, José S S; Nogueira, Cristina W

2015-11-01

Preliminary findings suggest that food intake reduction induced by p-chloro-diphenyl diselenide [(p-ClPhSe)2] in rats is mediated by a satiating action; however, additional experiments are necessary to clarify its actions. The purpose of this study was to investigate the effects of diets supplemented with (p-ClPhSe)2 on feeding behavior of rats as well as the (p-ClPhSe)2 effectiveness in producing aversive reactions or specific flavor. The results demonstrated that behavioral satiety sequence (BSS) was preserved in animals exposed to (p-ClPhSe)2-supplemented diets (0.01 and 0.1%) and associated with a shift of the onset of resting to the left indicating a satiating action at the first contact. In addition, the frequency, the mean duration and the mean size of meals were decreased in rats exposed to a 0.1% (p-ClPhSe)2 diet. Alternatively, a second contact with a 0.01% (p-ClPhSe)2 diet caused disruption of BSS and pronounced changes in the meal pattern, suggesting that it produces aversiveness. In fact, rats developed a significant taste aversion to the saccharin solution after receiving the administration of (p-ClPhSe)2 (1 and 10mg/kg; i.p.). Lastly, a diet containing 0.1% of (p-ClPhSe)2 seems to alter the palatability of food given that rats had a preference for the control diet. The findings of the present study suggest that (p-ClPhSe)2 reduced the food intake of rats by inducing a satiating action at the first contact, but it also produced aversive reactions when rats were re-exposed to it. A specific flavor seems also to contribute to (p-ClPhSe)2 suppressant effects on feeding. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the Thermal Spread of Three Different Electrosurgical Generators on Rat Uterus: A Preliminary Experimental Study.

PubMed

Karacan, Tolga; Usta, Taner; Ozkaynak, Aysel; Onur Cakir, Omer; Kahraman, Aslı; Ozyurek, Eser

2018-05-23

The objective of this study was to compare the depth and width of thermal spread caused on rat uterine tissue after application of 3 different electrosurgical generators. Alsa Excell 350 MCDSe (Unit A), Meditom DT-400P (Unit M), and ERBE Erbotom VIO 300 D (Unit E) electrosurgical units (ESUs) were used. The number of Wistar Hannover rats required to obtain valid results was 10. The primary objective of the study was to compare the 3 ESUs using the same instrument and the same waveform. The secondary objective of the study was to compare the differences between monopolar and bipolar systems of each ESU separately using the same waveform. The thermal spread caused by each ESU using monopolar instruments with continuous and interrupted waveforms was significantly different. Among the 3 devices, Unit A caused the largest thermal uterine tissue spread. On the other hand, Unit E caused the most superficial thermal tissue spread, and the smallest thermal spread among all ESUs. Surgeons should note that different ESUs used with the same power output might create different thermal effects especially in the monopolar configuration within the same waveform, for the same duration, and with the same instrument. © 2018 S. Karger AG, Basel.

Hormone synthesis and secretion by rat parathyroid glands in tissue culture

PubMed Central

Au, William Y. W.; Poland, Alan P.; Stern, Paula H.; Raisz, Lawrence G.

1970-01-01

Rat parathyroid glands maintained in organ culture secrete biologically active parathyroid hormone (PTH) and synthesize and secrete labeled proteins from 3H- or 14C-labeled amino acids added to the medium. The amounts of biological activity and labeled protein in the medium are both inversely proportional to the calcium concentration. Some of the labeled low molecular weight protein was identified as PTH which had been synthesized and secreted in culture by preliminary isolation on Sephadex G-100 columns and further purification using an antibody to bovine PTH which cross-reacted with rat PTH. The cross-reacting antibody inhibited the biological effects of rat PTH and caused hypocalcemia in intact rats. The antibody bound some of the labeled low molecular weight protein of the medium at neutral pH so that it migrated as a large molecular weight complex on Sephadex. Biologically active, labeled PTH was recovered by dissociation of this complex in acid and rechromatography. PMID:5449703

Preliminary Characterization of a Leptin Receptor Knockout Rat Created by CRISPR/Cas9 System.

PubMed

Bao, Dan; Ma, Yuanwu; Zhang, Xu; Guan, Feifei; Chen, Wei; Gao, Kai; Qin, Chuan; Zhang, Lianfeng

2015-11-05

Leptin receptor, which is encoded by the diabetes (db) gene and is highly expressed in the choroid plexus, regulatesenergy homeostasis, the balance between food intake and energy expenditure, fertility and bone mass. Here, using CRISPR/Cas9 technology, we created the leptin receptor knockout rat. Homozygous leptin receptor null rats are characterized by obesity, hyperphagia, hyperglycemia, glucose intolerance, hyperinsulinemia and dyslipidemia. Due to long-term poor glycemic control, the leptin receptor knockout rats also develop some diabetic complications such as pancreatic, hepatic and renal lesions. In addition, the leptin receptor knockout rats show a significant decrease in bone volume and bone mineral density of the femur compared with their wild-type littermates. Our model has rescued some deficiency of the existing rodent models, such as the transient hyperglycemia of db/db mice in the C57BL/6J genetic background and the delayed onset of glucose intolerance in the Zucker rats, and it is proven to be a useful animal model for biomedical and pharmacological research on obesity and diabetes.

Effect of Hydrocortisone on Uptake of Iron-59 in Incubated Rat Red Cells in vitro

DOE Office of Scientific and Technical Information (OSTI.GOV)

CLARK, PEGGY

Hydrocortisone added to blood contalnlng reticulocytes in a suitable substrate did not alter the rate of synthesis of hemoglobin and no evidence was obtained that it influenced the rate of ripening of reticulocytes. This applied to various dosage-levels in vitro and to plasma obtained from rats which were injected with large doses of hydrocortisone. It was shown, however, that preliminary incubation of reticulocytes with hydrocortisone before the addition of iron-59 reduces the amount of iron-59 which enters the reticulocytes. (N.W.R.)

Effects of Repeated Sublethal VX Exposure on Operant Time Estimation in Rats

DTIC Science & Technology

2007-08-01

1 week of food restriction, preliminary behavioral training ( autoshaping ) began. Apparatus Eight commercially available operant chambers for... Autoshaping was used to produce acquisition of lever pressing. Every 50 seconds (range = 10-90 s) on average, the cue light was illuminated and

Imaging and sensing based on dual-pulse nonlinear photoacoustic contrast: a preliminary study on fatty liver

NASA Astrophysics Data System (ADS)

Tian, Chao; Xie, Zhixing; Fabiilli, Mario; Wang, Xueding

2015-03-01

We developed a simple and effective contrast for tissue characterization based on the recently proposed dual-pulse nonlinear photoacoustic technology. The new contrast takes advantage of the temperature dependence of Grüneisen parameter of tissue and involves a dual-pulse laser excitation process. A short pulse first heats the sample and causes a temperature jump, which then leads to the change of Grüneisen parameter and amplitude of the photoacoustic signal of the second pulse. For different tissues, the induced rate or trend of change is expected to be different, which constitutes the basis of the new contrast. Preliminary phantom experiment in blood and lipid mixtures and in vitro experiment in fatty rat liver have demonstrated that the proposed contrast has the capability of fast characterization of lipid-rich and blood-rich tissues.

Preliminary investigation of changes in the sexually dimorphic nucleus of the rat medial preoptic area following prenatal exposure to fenitrothion.

PubMed

Struve, Melanie F; Turner, Katie J; Dorman, David C

2007-01-01

In vitro, the organophosphate insecticide fenitrothion is a potent competitive androgen receptor antagonist, whereas in vivo it affects the development of the male rat reproductive system. The purpose of this pilot study was to determine whether prenatal exposure to fenitrothion affects development of the rat sexually dimorphic nucleus of the medial preoptic area (SDN-POA). Pregnant rats (n = 5-6 litters/group) were orally dosed with corn oil (vehicle) or fenitrothion (20 or 25 mg kg(-1) day(-1)) from gestation day (GD) 12-21. Offspring were euthanized after reaching sexual maturity (females 60-65 days old and males 96-105 days old) and the SDN-POA volumes determined for two rats/sex/litter. Tremors, increased lacrimation and decreased body weight gain were observed in dams from both fenitrothion exposure groups. Reproductive effects in male offspring, including reduced anogenital distance on postnatal day (PND) 1 and increased retention of areolae (PND 13) were observed following fenitrothion exposure at these dose levels. These effects did not persist into adulthood. There was a dose-related increase in the SDN-POA volume in males and a dose-related decrease in SDN-POA volume in females exposed to fenitrothion. These SDN-POA volume changes contrast with those seen with flutamide, another potent anti-androgen, and suggest that fenitrothion may have mixed endocrine effects on the developing brain.

EPO improved neurologic outcome in rat pups late after traumatic brain injury.

PubMed

Schober, Michelle E; Requena, Daniela F; Rodesch, Christopher K

2018-05-01

In adult rats, erythropoietin improved outcomes early and late after traumatic brain injury, associated with increased levels of Brain Derived Neurotrophic Factor. Using our model of pediatric traumatic brain injury, controlled cortical impact in 17-day old rats, we previously showed that erythropoietin increased hippocampal neuronal fraction in the first two days after injury. Erythropoietin also decreased activation of caspase3, an apoptotic enzyme modulated by Brain Derived Neurotrophic Factor, and improved Novel Object Recognition testing 14 days after injury. Data on long-term effects of erythropoietin on Brain Derived Neurotrophic Factor expression, histology and cognitive function after developmental traumatic brain injury are lacking. We hypothesized that erythropoietin would increase Brain Derived Neurotrophic Factor and improve long-term object recognition in rat pups after controlled cortical impact, associated with increased neuronal fraction in the hippocampus. Rats pups received erythropoietin or vehicle at 1, 24, and 48 h and 7 days after injury or sham surgery followed by histology at 35 days, Novel Object Recognition testing at adulthood, and Brain Derived Neurotrophic Factor measurements early and late after injury. Erythropoietin improved Novel Object Recognition performance and preserved hippocampal volume, but not neuronal fraction, late after injury. Improved object recognition in erythropoietin treated rats was associated with preserved hippocampal volume late after traumatic brain injury. Erythropoietin is approved to treat various pediatric conditions. Coupled with exciting experimental and clinical studies suggesting it is beneficial after neonatal hypoxic ischemic brain injury, our preliminary findings support further study of erythropoietin use after developmental traumatic brain injury. Copyright © 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Design, Synthesis, and Preliminary Evaluation of SPECT Probes for Imaging β-Amyloid in Alzheimer's Disease Affected Brain.

PubMed

Okumura, Yuki; Maya, Yoshifumi; Onishi, Takako; Shoyama, Yoshinari; Izawa, Akihiro; Nakamura, Daisaku; Tanifuji, Shigeyuki; Tanaka, Akihiro; Arano, Yasushi; Matsumoto, Hiroki

2018-04-06

In this study, we synthesized of a series of 2-phenyl- and 2-pyridyl-imidazo[1,2- a]pyridine derivatives and examine their suitability as novel probes for single-photon emission computed tomography (SPECT)-based imaging of β-amyloid (Aβ). Among the 11 evaluated compounds, 10 showed moderate affinity to Aβ(1-42) aggregates, exhibiting half-maximal inhibitory concentrations (IC 50 ) of 14.7 ± 6.07-87.6 ± 39.8 nM. In vitro autoradiography indicated that 123 I-labeled triazole-substituted derivatives displayed highly selective binding to Aβ plaques in the hippocampal region of Alzheimer's disease (AD)-affected brain. Moreover, biodistribution studies performed on normal rats demonstrated that all 123 I-labeled probes featured high initial uptake into the brain followed by a rapid washout and were thus well suited for imaging Aβ plaques, with the highest selectivity observed for a 1 H-1,2,3-triazole-substituted 2-pyridyl-imidazopyridine derivative, [ 123 I]ABC577. This compound showed good kinetics in rat brain as well as moderate in vivo stability in rats and is thus a promising SPECT imaging probe for AD in clinical settings.

Preliminary studies of the effects of psychological stress on circulating lymphocytes analyzed by synchrotron radiation based-Fourier transform infrared microspectroscopy

NASA Astrophysics Data System (ADS)

Vargas-Caraveo, Alejandra; Castillo-Michel, Hiram; Mejia-Carmona, Gloria Erika; Pérez-Ishiwara, David Guillermo; Cotte, Marine; Martínez-Martínez, Alejandro

2014-07-01

Psychological stress is a condition that not only generates behavioral disorders but also disrupts homeostasis and immune activity that can exacerbate or lead to inflammatory diseases. The aim of this work was to study biochemical changes in circulating immune cells from rats under psychological stress by using vibrational spectroscopy. A stress model was used, where exposure to a stressor was repeated for 5 days. Subsequently, circulating lymphocytes were examined for their biomolecular vibrational fingerprints with synchrotron radiation based-Fourier transform infrared microspectroscopy. The results showed an increased absorption at the ester lipid region (1720-1755 cm-1) in lymphocytes from stressed rats, suggesting lipid peroxidation. Statistical significant changes in wavenumber peak position and absorbance in the nucleic acid region were also observed (915-950 cm-1 Z-DNA, 1090-1150 cm-1 symmetric stretching of Psbnd Osbnd C, 1200-1260 cm-1 asymmetric PO2 and 1570-1510 cm-1 methylated nucleotides) which suggest a reduction of transcriptional activity in lymphocytes from stressed rat. These results unravel part of the mechanisms by which psychological stress may affect the immune system leading to systemic consequences.

Protective effect of Hibiscus anthocyanins against tert-butyl hydroperoxide-induced hepatic toxicity in rats.

PubMed

Wang, C J; Wang, J M; Lin, W L; Chu, C Y; Chou, F P; Tseng, T H

2000-05-01

Hibiscus anthocyanins (HAs), a group of natural pigments occurring in the dried flowers of Hibiscus sabdariffa L., which is a local soft drink material and medical herb, were studied for antioxidant bioactivity. The preliminary study showed that HAs were able to quench the free radicals of 1,1-diphenyl-2-picrylhydrazyl. This antioxidant bioactivitiy was further evaluated using the model of tert-butyl hydroperoxide (t-BHP)-induced cytotoxicity in rat primary hepatocytes and hepatotoxicity in rats. The results demonstrated that HAs, at the concentrations of 0.10 and 0.20 mg/ml, significantly decreased the leakage of lactate dehydrogenase and the formation of malondialdehyde induced by a 30-min treatment of t-BHP (1.5 mM). The in vivo investigation showed that the oral pretreatment of HAs (100 and 200 mg/kg) for 5 days before a single dose of t-BHP (0.2 mmol/kg, ip) significantly lowered the serum levels of hepatic enzyme markers (alanine and aspartate aminotransferase) and reduced oxidative liver damage. The histopathological evaluation of the liver revealed that Hibiscus pigments reduced the incidence of liver lesions including inflammatory, leucocyte infiltration, and necrosis induced by t-BHP in rats. Based on the results described above, we speculate that Hibiscus pigments may play a role in the prevention of oxidative damage in living systems.

Change in blood glucose level in rats after immobilization

NASA Technical Reports Server (NTRS)

Platonov, R. D.; Baskakova, G. M.; Chepurnov, S. A.

1981-01-01

Experiments were carried out on male white rats divided into four groups. In group one the blood glucose level was determined immediately after immobilization. In the other three groups, two hours following immobilization, the blood glucose level was determined every 20 minutes for 3 hours 40 minutes by the glucose oxidase method. Preliminary immobilization for 2 hours removed the increase in the blood glucose caused by the stress reaction. By the 2nd hour of immobilization in the presence of continuing stress, the blood glucose level stabilized and varied within 42 + or - 5.5 and 47 + or - 8.1 mg %. Within 2 hours after the immobilization, the differences in the blood glucose level of the rats from the control groups were statistically insignificant.

Leptin administration affects growth and skeletal development in a rat intrauterine growth restriction model: preliminary study.

PubMed

Bar-El Dadon, Shimrit; Shahar, Ron; Katalan, Vered; Monsonego-Ornan, Efrat; Reifen, Ram

2011-09-01

Skeletal abnormalities are one of the hallmarks of growth delay during gestation. The aim of this study was to determine changes induced by leptin in skeletal growth and development in a rat model of intrauterine growth retardation (IUGR) and to elucidate the possible underlying mechanisms. Intrauterine growth retardation was induced prepartum and the effects of leptin to mothers prenatally or to offspring postnatally were studied. Radii were harvested and tested mechanically and structurally. Tibias were evaluated for growth-plate morphometry. On day 40 postpartum, total bone length and mineral density and tibial growth-plate width and numbers of cells within its zones of offspring treated with leptin were significantly greater than in the control group. Postnatal leptin administration in an IUGR model improves the structural properties and elongation rate of bone. These findings could pave the way to preventing some phenotypic presentations of IUGR. Copyright © 2011 Elsevier Inc. All rights reserved.

Hippocampal FXR plays a role in the pathogenesis of depression: A preliminary study based on lentiviral gene modulation.

PubMed

Chen, Wei-Guan; Zheng, Jia-Xuan; Xu, Xi; Hu, Yu-Ming; Ma, Yu-Min

2018-06-01

As a well-known bile acid receptor, the role of Farnesoid X receptor (FXR) in the digestive system and cardiovascular system has been widely explored. However, there are very few studies involving FXR in the central nervous system. In this study, we explored the role of FXR in the pathogenesis of depression, a serious and worldwide neuropsychiatric disease. It was found that chronic unpredictable mild stress (CUMS) fully enhanced the protein and mRNA expressions of FXR in hippocampus, but not medial prefrontal cortex (mPFC). Overexpression of hippocampal FXR induced notable depressive-like behaviors and decreased expression of brain-derived neurotrophic factor (BDNF) in naïve rats, while knockdown of hippocampal FXR fully prevented the effects of CUMS on rat behaviors and hippocampal BDNF expression. Taken together, our research extends the knowledge of FXR's role in the central nervous system, and may provide a potential and novel therapeutic target for treating depression. Copyright © 2018 Elsevier B.V. All rights reserved.

Effect of Space Flight on Adrenal Medullary Function

NASA Technical Reports Server (NTRS)

Lelkes, Peter I.

1999-01-01

We hypothesize that microgravity conditions during space flight alter the expression and specific activities of the adrenal medullary CA synthesizing enzymes (CASE). Previously, we examined adrenals from six rats flown for six days aboard STS 54 and reported that microgravity induced a decrease in the expression and specific activity of rat adrenal medullary tyrosine hydroxylase, the rate limiting enzyme of CA synthesis, without affecting the expression of other CASE. In the past, we analyzed some of the > 300 adrenals from two previous Space Shuttle missions (PARE 03 and SLS 2). The preliminary results (a) attest to the good state of tissue preservation, thus proving the feasibility of subsequent large-scale evaluation, and (b) confirm and extend our previous findings. With this grant we will be able to expeditiously analyze all our specimens and to complete our studies in a timely fashion.

Assessment of multislice CT to quantify pulmonary emphysema function and physiology in a rat model

NASA Astrophysics Data System (ADS)

Cao, Minsong; Stantz, Keith M.; Liang, Yun; Krishnamurthi, Ganapathy; Presson, Robert G., Jr.

2005-04-01

Purpose: The purpose of this study is to evaluate multi-slice computed tomography technology to quantify functional and physiologic changes in rats with pulmonary emphysema. Method: Seven rats were scanned using a 16-slice CT (Philips MX8000 IDT) before and after artificial inducement of emphysema. Functional parameters i.e. lung volumes were measured by non-contrast spiral scan during forced breath-hold at inspiration and expiration followed by image segmentation based on attenuation threshold. Dynamic CT imaging was performed immediately following the contrast injection to estimate physiology changes. Pulmonary perfusion, fractional blood volume, and mean transit times (MTTs) were estimated by fitting the time-density curves of contrast material using a compartmental model. Results: The preliminary results indicated that the lung volumes of emphysema rats increased by 3.52+/-1.70mL (p<0.002) at expiration and 4.77+/-3.34mL (p<0.03) at inspiration. The mean lung densities of emphysema rats decreased by 91.76+/-68.11HU (p<0.01) at expiration and low attenuation areas increased by 5.21+/-3.88% (p<0.04) at inspiration compared with normal rats. The perfusion for normal and emphysema rats were 0.25+/-0.04ml/s/ml and 0.32+/-0.09ml/s/ml respectively. The fractional blood volumes for normal and emphysema rats were 0.21+/-0.04 and 0.15+/-0.02. There was a trend toward faster MTTs for emphysema rats (0.42+/-0.08s) than normal rats (0.89+/-0.19s) with p<0.006, suggesting that blood flow crossing the capillaries increases as the capillary volume decreases and which may cause the red blood cells to leave the capillaries incompletely saturated with oxygen if the MTTs become too short. Conclusion: Quantitative measurement using CT of structural and functional changes in pulmonary emphysema appears promising for small animals.

Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats.

PubMed

Uboh, Friday E; Okon, Iniobong E; Ekong, Moses B

2010-02-01

Serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), albumin and total protein levels, as well as the tissue histological assay are known to be useful in assessing the functional integrity of the liver. Also, assessment of red and white blood cells count, hematocrit and hemoglobin concentrations is useful in determining the effect of some chemical substances on hemotopoietic system. In recent times, reports from medicinal plants research indicate that extracts from some plants are both hepatotoxic and hematotoxic, while others on the other hand are reported to be hepatoprotective and hematopoietic in action. This study considers the effects of aqueous extract of Psidium guajava (P. guajava) leaves on the histology and biochemical indices of liver function as well as hematological indices in rats. In this study, phytochemical screening of the aqueous extract of P. guajava leaves was carried out. Also, male and female rats were administered with 200 mg/kg body weight oral daily doses of aqueous extract of P. guajava leaves for a period of 30 days. At the end of the administration period, the rats were anaesthesized with chloroform vapors and dissected for the collection of blood and liver tissues which were used for the hematopoietic and liver functions investigations. Preliminary phytochemical analysis of the plant leaves showed the presence of alkaloids, flavonoids, glycosides, polyphenols, reducing compounds, saponins and tannins. Liver function tests revealed that the serum ALT, AST and ALP, as well as the concentrations of total protein and albumin in male and female rats were not significantly (P > 0.05) affected by the oral administration of the extract. Histopathological study also did not show any adverse alteration in the morphological architecture of the liver tissues in both sexes of the animal model. However, red blood cell counts, hemotocrit and hemoglobin concentrations increased significantly (P < 0.05) on administration of the extract in both male and female rats. It was therefore observed that the effect of the extract on male rats was not significantly different (P > 0.05) from that obtained for the female rats. The results of this present study suggested that aqueous extract of Psidium guajava leaves may be hepatoprotective, and not hepatotoxic, with hematopoietic potentials in both male and female rats. These findings are therefore of clinical importance given the various reported medicinal potentials of the plant.

Modeling the functional repair of nervous tissue in spinal cord injury

NASA Astrophysics Data System (ADS)

Mantila, Sara M.; Camp, Jon J.; Krych, Aaron J.; Robb, Richard A.

2004-05-01

Functional repair of traumatic spinal cord injury (SCI) is one of the most challenging goals in modern medicine. The annual incidence of SCI in the United States is approximately 11,000 new cases. The prevalence of people in the U.S. currently living with SCI is approximately 200,000. Exploring and understanding nerve regeneration in the central nervous system (CNS) is a critical first step in attempting to reverse the devastating consequences of SCI. At Mayo Clinic, a preliminary study of implants in the transected rat spinal cord model demonstrates potential for promoting axon regeneration. In collaborative research between neuroscientists and bioengineers, this procedure holds promise for solving two critical aspects of axon repair-providing a resorbable structural scaffold to direct focused axon repair, and delivery of relevant signaling molecules necessary to facilitate regeneration. In our preliminary study, regeneration in the rat's spinal cord was modeled in three dimensions utilizing an image processing software system developed in the Biomedical Imaging Resource at Mayo Clinic. Advanced methods for image registration, segmentation, and rendering were used. The raw images were collected at three different magnifications. After image processing the individual channels in the scaffold, axon bundles, and macrophages could be identified. Several axon bundles could be visualized and traced through the entire volume, suggesting axonal growth throughout the length of the scaffold. Such information could potentially allow researchers and physicians to better understand and improve the nerve regeneration process for individuals with SCI.

The teratogenic effects of dietary Cassava on the pregnant albino rat: a preliminary report.

PubMed

Singh, J D

1981-12-01

Cassava is a tuberous root of a shrublike plant cultivated in tropical rain forests as a staple food in South Eastern Nigeria. Reports are on record showing correlation between cassava intake and occurrence of various types of neuropathies (Money, '59; Monekosso and Wilson, '66; Osuntokun et al., '68,'69). About 0.1-2 mg of cyanide/100 gm is released from Cassava by action of hydrolase (Paula and Rangel, '46). It has been suspected by several local clinicians as a cause of congenital anomalies if consumed in excess during pregnancy. However, it remains a controversial problem and precise scientific data is lacking. This study was conducted on albino rats by giving them milled cassava powder as 50% and 80% of their diet during the first 5 days of pregnancy. Fetuses collected on day 20 from the group receiving cassava as 80% of the diet showed a low incidence of limb defects, open eye, microcephaly, and growth retardation in the rat. Interpretation of this data for the human should be made with caution.

Anti-arthritic activity of ethanolic extract of Tridax procumbens (Linn.) in Sprague Dawley rats.

PubMed

Petchi, R Ramesh; Vijaya, C; Parasuraman, S

2013-04-01

To determine the anti-arthritic effect of whole plant ethanolic extract of Tridax procumbens (Asteraceae) in female Sprague Dawley (SD) rats using the Freund's Complete Adjuvant (FCA) model. The plant was collected from different regions of Madurai District, Tamil Nadu, and the phytoconstituents were identified through chemical tests. Ethanol (95%) was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for anti-arthritic screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of T. procumbens was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, the liver enzyme levels were determined and a radiological examination was carried out. The preliminary phytochemical analysis of the ethanolic extract of T. procumbens indicated the presence of alkaloids, tannins, flavonoids and saponins. T. procumbens at 250 and 500 mg/kg significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control animals exhibited a significant decrease in body weight compared with control animals without arthritis. T. procumbens animals showed dose dependent reduction in decrees in body weight and arthritis. At the same time, T. procumbens significantly altered the biochemical and haematological changes induced by FCA (P < 0.05). The anti-arthritic effect of T. procumbens was comparable with that of indomethacin. The whole plant extract of T. procumbens showed significant anti-arthritic activity against FCA-induced arthritis in female SD rats.

Preliminary study of efficacy of hyaluronic acid on caustic esophageal burns in an experimental rat model.

PubMed

Cevik, Muazez; Demir, Tuncer; Karadag, Cetin Ali; Ketani, Muzaffer Aydin; Celik, Hakim; Kaplan, Davut Sinan; Boleken, Mehmet Emin

2013-04-01

The aim of this study was to investigate the effectiveness of hyaluronic acid on the prevention of esophageal damage and stricture formation after experimental caustic (alkaline) esophageal injury in rats. Twenty-one Wistar albino rats were randomly divided into three groups. A caustic esophageal burn was created following the Gehanno model: Group l (n=7) underwent operation, but no injury; Group 2 (n=7) was injured and left untreated; and Group 3 (n=7) was injured and treated with hyaluronic acid, first topically and then orally by gavage (2×0.3mL; 12.5mg/mL for 7days). The caustic esophageal burn was created by instilling 25% NaOH into the distal esophagus. All rats were euthanized on day 22 for evaluation. The efficacy of hyaluronic acid treatment was assessed histopathologically and biochemically via blood determination of the total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), and sulfhydryl group (SH) and lipid hydroperoxidase (LOOH) levels. Statistical analyses were performed. Weight gain was significantly lower in Group 2 than in the other two groups (P<0.05). The mean stenosis index, histopathologic damage score, TAS, TOS, OSI, and SH and LOOH levels were higher in Group 2 than in the other two groups. The mean stenosis index, inflammation, TAS, SH and OSI in Group 2 were significantly different than those in the other two groups (P<0.05). Hyaluronic acid treatment is effective in treating damage and preventing strictures after caustic esophageal burn in rats. Copyright © 2013 Elsevier Inc. All rights reserved.

Study on the inhibition of Mfn1 by plant-derived miR5338 mediating the treatment of BPH with rape bee pollen.

PubMed

Chen, Xuan; Wu, Ren-Zhao; Zhu, Yong-Qiang; Ren, Ze-Ming; Tong, Ye-Ling; Yang, Feng; Dai, Guan-Hai

2018-01-30

Recent studies have found that plant derived microRNA can cross-kingdom regulate the expression of genes in humans and other mammals, thereby resisting diseases. Can exogenous miRNAs cross the blood-prostate barrier and entry prostate then participate in prostate disease treatment? Using HiSeq sequencing and RT-qPCR technology, we detected plant miRNAs that enriched in the prostates of rats among the normal group, BPH model group and rape bee pollen group. To forecast the functions of these miRNAs, the psRobot software and TargetFinder software were used to predict their candidate target genes in rat genome. The qRT-PCR technology was used to validate the expression of candidate target genes. Plant miR5338 was enriched in the posterior lobes of prostate gland of rats fed with rape bee pollen, which was accompanied by the improvement of BPH. Among the predicted target genes of miR5338, Mfn1 was significantly lower in posterior lobes of prostates of rats in the rape bee pollen group than control groups. Further experiments suggested that Mfn1 was highly related to BPH. These results suggesting that plant-derived miR5338 may involve in treatment of rat BPH through inhibiting Mfn1 in prostate. These results will provide more evidence for plant miRNAs cross-kingdom regulation of animal gene, and will provide preliminary theoretical and experimental basis for development of rape bee pollen into innovative health care product or medicine for the treatment of BPH.

Preliminary observations on whole-ovary xenotransplantation as an experimental model for fertility preservation.

PubMed

Nichols-Burns, Stephanie M; Lotz, Laura; Schneider, Heike; Adamek, Edyta; Daniel, Christoph; Stief, Andrea; Grigo, Christina; Klump, Dorothee; Hoffmann, Inge; Beckmann, Matthias W; Dittrich, Ralf

2014-11-01

Ovarian tissue preservation and retransplantation is a promising strategy to restore fertility in cancer survivors. Ischaemia accompanying ovarian tissue grafting, however, can lead to significant follicle loss. Transplantation of the whole ovary by vascular anastomosis has been considered as an alternative to prevent widespread ischaemic damage. In this study, the feasibility and function of transplanting whole ovary with intact vasculature were evaluated, with the goal of developing a xenograft model for studies using donated human ovaries. Whole-swine ovaries with vascular pedicles were perfused and transplanted as intact ovaries by anastomosis into irradiated ovariectomized nude rats (n = 10). The observation period was between 1 and 4 weeks. Fresh swine ovaries served as controls (n = 10). Ovarian stroma and follicle populations were assessed through histological examination in both transplanted and control ovaries. Most of the transplanted whole ovaries (n = 6) maintained stromal quality and all preantral follicle classes were represented, although follicle numbers decreased compared with fresh control. Four transplanted ovaries were fibrotic after 1-4 weeks within the nude rat. Our results demonstrate transplantation of whole-pig ovary into nude rats is possible and support development of this xenograft model system for human studies. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

A Proposed Neurologic Pathway for Scalp Acupuncture: Trigeminal Nerve-Meninges-Cerebrospinal Fluid-Contacting Neurons-Brain.

PubMed

Wang, Shuya; Liu, Kun; Wang, Yuan; Wang, Shuyou; He, Xun; Cui, Xiang; Gao, Xinyan; Zhu, Bing

2017-10-01

Objective: Scalp acupuncture is a somatic stimulation therapy that produces prominent clinical effects when used to treat cerebral diseases. However, this acupuncture's therapeutic mechanisms have not yet been well-addressed. Scalp acupoints are innervated by the trigeminal nerve, which is coincident with the intracranial sensory afferents as well as with the meningeal vessels. In recent years, cerebrospinal fluid-contacting neurons have been found and proved to transmit allergic substances between brain the parenchyma and meninges, representing a possible network between scalp acupuncture and the brain. The aim of the current study was to observe the connections between scalp acupoints and the meninges and to establish a possible mechanism for scalp acupuncture. Materials and Methods: Twenty-five adult Sprague-Dawley rats were used for the present study. Evans Blue dye (Sigma Chemical Co, St. Louis, MO) was injected though each rat's caudal vein after trigeminal stimulation for plasma extravasation observation. Cerebral blood flow (CBF) values of the rat's brain surface were measured at different timepoints before and after electroacupuncture (EA) on GB 15 ( Toulinqi ) or ST 36 ( Zusanli ). Results: These preliminary studies indicated that neurogenic plasma extravasation on a rat's skin and dura mater after mechanical or electrical stimulation of the trigeminal nerves is a reliable way to show the pathologic connection between scalp acupoints and the meninges. Moreover, CBF of the rat's brain surface is increased significantly after EA stimulation at GB 15 ( Toulinqi ), which is located in the receptive field of the supraorbital nerve. Conclusions: These findings suggest that the mechanism of scalp acupuncture might lie in the specific neurologic pathway that could be termed as trigeminal nerve-meninges-cerebrospinal fluid-contacting neurons-brain , which is a possible shortcut to brain functional regulation and cerebral disease treatment.

Atrial natriuretic factor receptor heterogeneity in rat tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andresen, J.W.; Kuno, T.; Kamisaki, Y.

1986-03-01

Rat /sup 125/I-atrial natriuretic factor (ANF, 8-33) was used to identify ANF receptors in membrane preparations from rat adrenal gland and lung. When solubilized with Lubrol-PX, the receptors retained a binding profile and properties that correspond to the high affinity and specificity found in crude membranes. Single peaks of binding activity were observed in gel permeation HPLC and density gradient centrifugation analysis of the solubilized preparations. However, when membranes and solubilized preparations were labeled with /sup 125/I-ANF, treated with crosslinking reagent (disuccinimidyl suberate), and analyzed by SDS gel electrophoresis several specifically labeled bands (120,000, 70,000, and 60,000 daltons) were identifiedmore » by autoradiography. The relative distribution of the specifically labeled proteins varied significantly between rat adrenal gland and lung. In adrenal glands the 120K dalton band was the most prominent specifically labeled protein, while the 60K and 70K dalton proteins were labeled to a lesser degree. In lung membranes the lower molecular weight proteins were more prominent. These results suggest the presence of multiple ANF receptor subtypes, the distribution of which varies among tissues. Chromatographic separation and further characterization of these receptors are currently in progress, and preliminary purification studies support this hypothesis.« less

Feasibility of recording high frequency oscillations with tripolar concentric ring electrodes during pentylenetetrazole-induced seizures in rats.

PubMed

Makeyev, Oleksandr; Liu, Xiang; Wang, Liling; Zhu, Zhenghan; Taveras, Aristides; Troiano, Derek; Medvedev, Andrei V; Besio, Walter G

2012-01-01

As epilepsy remains a refractory condition in about 30% of patients with complex partial seizures, electrical stimulation of the brain has recently shown potential for additive seizure control therapy. Previously, we applied noninvasive transcranial focal stimulation via novel tripolar concentric ring electrodes (TCREs) on the scalp of rats after inducing seizures with pentylenetetrazole (PTZ). We developed a close-loop system to detect seizures and automatically trigger the stimulation and evaluated its effect on the electrographic activity recorded by TCREs in rats. In our previous work the detectors of seizure onset were based on seizure-induced changes in signal power in the frequency range up to 100 Hz, while in this preliminary study we assess the feasibility of recording high frequency oscillations (HFOs) in the range up to 300 Hz noninvasively with scalp TCREs during PTZ-induced seizures. Grand average power spectral density estimate and generalized likelihood ratio tests were used to compare power of electrographic activity at different stages of seizure development in a group of rats (n= 8). The results suggest that TCREs have the ability to record HFOs from the scalp as well as that scalp-recorded HFOs can potentially be used as features for seizure onset detection.

Aphrodisiac and spermatogenic potential of alkaloidal fraction of Hygrophila spinosa T. Ander in rats.

PubMed

Vyas, Niraj Y; Raval, Manan A

2016-12-24

Seeds of Hygrophila spinosa T. Ander (Acanthaceae) are traditionally used as aphrodisiac and spermatogenic in Indian System of medicine. Preliminary phytochemical screening of plant revealed the presence of alkaloids in seeds. As, alkaloidal fractions of several plants showed aphrodisiac and spermatogenic potential, set of experiments were designed to assess alkaloid enriched fraction of seeds of the plant for spermatogenic and aphrodisiac activity using in vitro and in vivo methods. Alkaloid enriched fraction was prepared and assessed for spermatogenic activity using isolated rat Leydig cells in vitro. The fraction was further evaluated in vivo for spermatogenic and aphrodisiac potential using rat as an experimental animal. Increase in weight of reproductive organs, biochemical evaluation of selected parameters, histological studies of testes and sexual behavioral studies were selected as evaluation parameters for in vivo studies. Isolated rat Leydig cells treated with the fraction showed increased amount of testosterone present in culture media (14.7µg/ml) as compared to that of control (0.8µg/ml). Results of in vivo studies showed increase in serum testosterone level in treated animals (50mg/kg) by (115%), increase in weight of testes (8.0%) as compared to control. Marked improvement in testis histo-architecture of rats evident preliminarily by observing overcrowding of spermatozoa in enlarged lumen of seminiferous tubules in animals treated with testosterone and test fraction. Sertoli cells in treated animals were enlarged with highly granulated cytoplasm. Leydig cells also showed enlarged nucleus and darkly stained cytoplasm as compared to control. Mounting behavior of test animals improved, while latency period was decreased, as observed in behavioral studies. The set studies confirmed the ability of the fraction to stimulate Leydig cells and increased serum testosterone level. Increased testosterone level might be responsible for higher number of spermatozoa in testicular lumen as seen in testicular histology as well as increased libido as observed in behavioral studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Antifertility effect of betal leaf stalk (Tambul patrabrint): a preliminary experimental study.

PubMed

Tewari, P V; Chaturvedi, C; Dixit, S N

1970-01-01

This study was undertaken to determine possible antifertility properties of the stalk of the betel plant, Piper betle, which is extensively cultivated in warm moist parts of India for its leaves. The thin stalks were dried, powdered, and extracted with alcohol; the residue was used in the study and named betel leaf stalk extract (BLSE). It was macerated with gum acacia, suspended in distilled water, and diluted to 25 mg/ml. The drug was fed by oral intubation. Initially 20 rats were used in 2 groups, one receiving BLSE 50 mg/kg body weight for 10 days and the other vehicle only. Both were caged with males for 15 days. Only 2 of 10 rats receiving BLSE gave birth to litters while 9 of 10 controls delivered. Number of pups was also reduced. In another experiment using 60 female rats to 30 while BLSE at 50 mg/100 gm body weight was fed for 3 days during diestrus to 30 while 30 controls received vehicle only. Successful mating was confirmed by sperm in vaginal smears. 8 of 30 treated rats delivered 3.5 pups each while 29 of 30 controls delivered 7 pups per rat. In a third experiment 10 female rats were given BLSE 50mg/100 gm body weight, 10 vehicle only, and 10 neoclinesterol 150 mcg/100 gm body weight for 4 consecutive days. On Day 5 the animals were sacrificed and weights of uterus and ovaries recorded. Antiestrogenic properties were studied in oophorectomized rats given stilbestrol 150 mcg/100 gm body weight by injection, then fed 150 mcg/100 gm body weight of neoclinesterol or BLSE, 50 mg/100 gm, but the neoclinesterol. Vaginal smears were examined for cornification on Days 2, 3, and 4. Progestational activity was studied in 12 immature female rabbits injected with stilbestrol then treated with BLSE or leutocycline. Tests for estrogenic and antiestrogenic activity of BLSE were negative. A mild progestational activity was found in immature estrogen-primed rabbits but some follicle depressant type action was noted as several graffian follicles were seen in their regressive phase when ovaries were sectioned. Similar findings were obtained in rats treated after spaying. Results show BLSE has a definite antifertility activity. When fed in diestrus phase the estrus cycle was not altered nor was any estrogenic or antiestrogenic effect noted.

AS30D Model of Hepatocellular Carcinoma: Tumorigenicity and Preliminary Characterization by Imaging, Histopathology, and Immunohistochemistry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Scott M.; Callstrom, Matthew R.; Knudsen, Bruce

This study was designed to determine the tumorigenicity of the AS30D HCC cell line following orthotopic injection into rat liver and preliminarily characterize the tumor model by both magnetic resonance imaging (MRI) and ultrasound (US) as well as histopathology and immunohistochemistry.MaterialsAS30D cell line in vitro proliferation was assessed by using MTT assay. Female rats (N = 5) underwent injection of the AS30D cell line into one site in the liver. Rats subsequently underwent MR imaging at days 7 and 14 to assess tumor establishment and volume. One rat underwent US of the liver at day 7. Rats were euthanized atmore » day 7 or 14 and livers were subjected to gross, histopathologic (H and E), and immunohistochemical (CD31) analysis to assess for tumor growth and neovascularization. AS30D cell line demonstrated an in vitro doubling time of 33.2 {+-} 5.3 h. MR imaging demonstrated hyperintense T2-weighted and hypointense T1-weighted lesions with tumor induction in five of five and three of three sites at days 7 and 14, respectively. The mean (SD) tumor volume was 126.1 {+-} 36.2 mm{sup 3} at day 7 (N = 5). US of the liver demonstrated a well-circumscribed, hypoechoic mass and comparison of tumor dimensions agreed well with MRI. Analysis of H and E- and CD31-stained sections demonstrated moderate-high grade epithelial tumors with minimal tumor necrosis and evidence of diffuse intratumoral and peritumoral neovascularization by day 7. AS30D HCC cell line is tumorigenic following orthotopic injection into rat liver and can be used to generate an early vascularizing, slower-growing rat HCC tumor model.« less

THE EFFECTS OF IONIZING RADIATIONS ON THE BIOCHEMISTRY OF MAMMALIAN TISSUES. III. STUDIES ON THE TOXICITY AND MECHANISM OF ACTION OF 2-MERCAPTOETHYLAMINE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hietbrink, B.E.; Yam, K.M.

1964-10-31

A study was conducted to determine the effect of dibenzyline, dihydroergotamine, and adrenal demedullation on the mercaptoethylamine-induced increase in the blood glucose level of adult female rats. The results of these studies showed that the administration of dibenzyline or dihydroergotamine 10 min before 200 mg/kg of MEA inhibited the marked increase in blood glucose levels usually observed following this dose of MEA and substantially reduced the duration of action of this sulfur-containing compound. Adrenal demedullation almost completely prevented the increase in blood glucose levels caused by 200 mg/ kg of MEA. MEA caused a marked hypoglycemia in the demedullated animalsmore » during the latter part of the 5-hr observation period. Results of experiments on the influence of chronic administration of MEA on the blood glucose level of the rat indicated that repeated doses of MEA do not appear to cause drug tolerance. Studies on the influence of MEA on the acetylcholinesterase activity of the brain and serum of rats indicated that the gross toxic symptoms observed following the administration of MEA were not due to cholinesterase inhibition. The results of preliminary studies on the influence of sodium pentobarbital on the acute toxicity of MEA indicated that 25 mg/kg of pentobarbital prevented the lethal effect of doses of MEA as great as 325 mg/kg. (auth)« less

EFFECTS OF GESTATIONAL EXPOSURE TO ETHANE DIMETHANESULFONATE IN CD-1 MICE: MICROTIA AND PRELIMINARY HEARING TESTS

EPA Science Inventory

Microtia is a reduction in pinna size, usually seen in humans in conjunction with other medical conditions. Here we report microtia in CD-1 mice following gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and adult rat Leydig cell toxicant. Methods...

Overt and Latent Cardiac Effects of Ozone Inhalation in Rats: Evidence for Autonomic Modulation and Increased Myocardial Vulnerability*

EPA Science Inventory

Ozone (O3) is a well-documented respiratory oxidant, but increasing epidemiologic evidence points to extra-pulmonary effects including positive associations between ambient O3 concentrations and cardiovascular morbidity/mortality. With preliminary reports linking O3 exposure wit...

Alkaline comet assay in liver and stomach, and micronucleus assay in bone marrow, from rats treated with 2-acetylaminofluorene, azidothymidine, cisplatin, or isobutyraldehyde.

PubMed

Kraynak, A R; Barnum, J E; Cunningham, C L; Ng, A; Ykoruk, B A; Bennet, B; Stoffregen, D; Merschman, M; Freeland, E; Galloway, S M

2015-07-01

As part of the Japanese Center for the Validation of Alternative Methods (JaCVAM) initiative international validation study of the in vivo rat alkaline comet assay (comet assay), we examined the ability of the assay to determine the genotoxicity of 2-acetylaminofluorene (AAF), azidothymidine (AZT), cisplatin (CPN), and isobutyraldehyde (IBA) in liver and glandular stomach of male Sprague-Dawley rats. Rats were given oral doses of test compound or control once daily for three days. High dose levels were approximately maximum tolerated doses and were based on preliminary range-finding studies. Tissues were harvested 3h after the final dose (48h after the initial dose). A bone marrow micronucleus assay (MN) was also conducted on the rats treated with AZT, CPN, and IBA. Acute toxic effects of treatment were determined primarily through histomorphologic analysis of liver and stomach but also by body weight and serum liver enzyme changes. The comet assay was conducted on fresh tissue preparations but frozen samples from two studies were also assayed. Statistically significant dose-related differences in comet % DNA in tail were found in liver and stomach for the genotoxin AZT and in liver for the genotoxin CPN, but not in liver or stomach for the non-genotoxin IBA. Statistically significant differences in % DNA in tail were measured in liver for the low and mid dose of the genotoxin AAF, but not the high dose. The comet assays of frozen liver suspensions from CPN- and AAF-treated rats yielded comparable results to the assays of fresh preparations. There were no indications of significant toxicity induced by any treatment. The micronucleus assay was positive for CPN and AZT and negative for IBA. In conclusion, the in vivo comet assay is capable of detecting genotoxic effects of a variety of chemicals and may fill an important role in the genotoxicity test battery. Copyright © 2015 Elsevier B.V. All rights reserved.

An easy-to-use liquid chromatography assay for the analysis of lamotrigine in rat plasma and brain samples using microextraction by packed sorbent: Application to a pharmacokinetic study.

PubMed

Ventura, Sandra; Rodrigues, Márcio; Pousinho, Sarah; Falcão, Amílcar; Alves, Gilberto

2016-11-01

A simple and rapid high-performance liquid chromatography method with diode-array detection (HPLC-DAD) using microextraction by packed sorbent (MEPS) during the sample preparation step was developed and validated to quantify lamotrigine (LTG) in rat plasma and brain samples. MEPS variables such as pH, number of draw-eject cycles, and washing and desorption conditions were optimized. The chromatographic resolution of LTG and chloramphenicol, used as internal standard (IS), was accomplished in less than 5min on a C18 column, at 35°C, using an isocratic elution with acetonitrile (13%), methanol (13%) and water-triethylamine (99.7:0.3, v/v; pH 6.0) pumped at a flow rate of 1mL/min. Detection was performed at 215nm. Calibration curves were linear over the range of 0.1-20μg/mL (r 2 ≥0.9947) for LTG in both rat plasma and brain homogenate samples. The intra and interday imprecision did not exceed 8.6% and the intra and interday inaccuracy ranged from -8.1 to 13.5%. LTG was extracted from rat plasma and brain homogenate samples with an average absolute recovery ranging from 68.0 to 86.7%, and its stability was demonstrated in the assayed conditions. No interferences were observed at the retention times of the analyte (LTG) and IS. To the best of our knowledge, this is the first bioanalytical assay that uses MEPS procedure for the determination of LTG not only in rat plasma but also in tissue (brain) samples. This novel method was successfully applied to a preliminary pharmacokinetic study in rats and it seems to be a cost-effective tool to support non-clinical pharmacokinetic-based studies involving LTG treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Photodynamic impact induces ischemic tolerance in models in vivo and in vitro

NASA Astrophysics Data System (ADS)

Demyanenko, Svetlana; Sharifulina, Svetlana; Berezhnaya, Elena; Kovaleva, Vera; Neginskaya, Maria; Zhukovskaya, Ludmila

2016-04-01

Ischemic tolerance determines resistance to lethal ischemia gained by a prior sublethal stimulus (i.e., preconditioning). We reproduced this effect in two variants. In vitro the preliminary short (5 s) photodynamic treatment (PDT) (photosensitizer Photosens, 10 nM, 30 min preincubation; laser: 670 nm, 100 mW/cm2) significantly reduced the necrosis of neurons and glial cells in the isolated crayfish stretch receptor, which was caused by following 30-min PDT by 66% and 46%, respectively. In vivo PDT of the rat cerebral cortex with hydrophilic photosensitizer Rose Bengal (i.v. administration, laser irradiation: 532 nm, 60 mW/cm2, 3 mm beam diameter, 30 min) caused occlusion of small brain vessels and local photothrombotic infarct (PTI). It is a model of ischemic stroke. Cerebral tissue edema and global necrosis of neurons and glial cells occurred in the infarction core, which was surrounded by a 1.5 mm transition zone, penumbra. The maximal pericellular edema, hypo- and hyperchromia of neurons were observed in penumbra 24 h after PTI. The repeated laser irradiation of the contralateral cerebral cortex also caused PTI but lesser as compared with single PDT. Preliminary unilateral PTI provided ischemic tolerance: at 14 day after second exposure the PTI volume significantly decreased by 24% than in the case of a single exposure. Sensorimotor deficits in PDT-treated rats was registered using the behavioral tests. The preliminary PTI caused the preconditioning effect.

Neuroprotective antioxidants from marijuana.

PubMed

Hampson, A J; Grimaldi, M; Lolic, M; Wink, D; Rosenthal, R; Axelrod, J

2000-01-01

Cannabidiol and other cannabinoids were examined as neuroprotectants in rat cortical neuron cultures exposed to toxic levels of the neurotransmitter, glutamate. The psychotropic cannabinoid receptor agonist delta 9-tetrahydrocannabinol (THC) and cannabidiol, (a non-psychoactive constituent of marijuana), both reduced NMDA, AMPA and kainate receptor mediated neurotoxicities. Neuroprotection was not affected by cannabinoid receptor antagonist, indicating a (cannabinoid) receptor-independent mechanism of action. Glutamate toxicity can be reduced by antioxidants. Using cyclic voltametry and a fenton reaction based system, it was demonstrated that Cannabidiol, THC and other cannabinoids are potent antioxidants. As evidence that cannabinoids can act as an antioxidants in neuronal cultures, cannabidiol was demonstrated to reduce hydroperoxide toxicity in neurons. In a head to head trial of the abilities of various antioxidants to prevent glutamate toxicity, cannabidiol was superior to both alpha-tocopherol and ascorbate in protective capacity. Recent preliminary studies in a rat model of focal cerebral ischemia suggest that cannabidiol may be at least as effective in vivo as seen in these in vitro studies.

Microscopic distribution patterns of microspheres deposited by inhalation in lungs of rats, guinea pigs, and dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snipes, M.B.; Guilmette, R.A.; Nikula, K.J.

1995-12-01

Acute inhalation exposures of mammalian species to small amounts of poorly soluble particles result in deposition of the particles in the head airways, tracheobronchial region, and pulmonary region of the respiratory tract. Most of the particles that deposit in the head airways and tracheobronchial region are believed to clear rapidly, but some as yet undefined fraction of the particles is retained in the airway epithelium or subepithelial interstitium for extended times. This long-term retention has important implications for the new respiratory tract dosimetry model of the International Commission on Radiological Protection because particles retained within the region can result inmore » long-term exposure of airway epithelial cells. Preliminary results from this study demonstrate that a substantial fraction of the PSL microspheres inhaled by these rats, guinea pigs, and dogs was incorporated into the epithelium and interstitium of the tracheobronchial region.« less

The Effects of Partial Mechanical Loading and Ibandronate on Skeletal Tissues in the Adult Rat Hindquarter Suspension Model for Microgravity

NASA Technical Reports Server (NTRS)

Schultheis, Lester W.

1999-01-01

We report initial data from a suspended rat model that quantitatively relates chronic partial weightbearing to bone loss. Chronic partial weightbearing is our simulation of the effect of limited artificial gravity aboard spacecraft or reduced planetary gravity. Preliminary analysis of bone by PQCT, histomorphometry, mechanical testing and biochemistry suggest that chronic exposure to half of Earth gravity is insufficient to prevent severe bone loss. The effect of episodic full weightbearing activity (Earth Gravity) on rats otherwise at 50% weightbearing was also explored. This has similarity to treatment by an Earth G-rated centrifuge on a spacecraft that normally maintained artificial gravity at half of Earth G. Our preliminary evidence, using the above techniques to analyze bone, indicate that 2 hours daily of full weightbearing was insufficient to prevent the bone loss observed in 50% weightbearing animals. The effectiveness of partial weightbearing and episodic full weightbearing as potential countermeasures to bone loss in spaceflight was compared with treatment by ibandronate. Ibandronate, a long-acting potent bisphosphonate proved more effective in preventing bone loss and associated functionality based upon structure than our first efforts at mechanical countermeasures. The effectiveness of ibandronate was notable by each of the testing methods we used to study bone from gross structure and strength to tissue and biochemistry. These results appear to be independent of generalized systemic stress imposed by the suspension paradigm. Preliminary evidence does not suggest that blood levels of vitamin D were affected by our countermeasures. Despite the modest theraputic benefit of mechanical countermeasures of partial weightbearing and episodic full weightbearing, we know that some appropriate mechanical signal maintains bone mass in Earth gravity. Moreover, the only mechanism that correctly assigns bone mass and strength to oppose regionally specific force applied to bone is mechanical, a process based upon bone strain. Substantial evidence indicates that the specifics of dynamic loading i.e. time-varying forces are critical. Bone strain history is a predictor of the effect that mechanical conditions have on bone structure mass and strength. Using servo-controlled force plates on suspended rats with implanted strain gauges we manipulated impact forces of ambulation in the frequency (Fourier) domain. Our results indicate that high frequency components of impact forces are particularly potent in producing bone strain independent of the magnitude of the peak force or peak energy applied to the leg. Because a servo-system responds to forces produced by the rat's own muscle activity during ambulation, the direction of ground-reaction loads act on bone through the rat's own musculature. This is in distinction to passive vibration of the floor where forces reach bone through the natural filters of soft tissue and joints. Passive vibration may also be effective, but it may or may not increase bone in the appropriate architectural pattern to oppose the forces of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of normal ambulatory activity. Effectiveness of high frequency mechanical stimulation in producing regional (muscle directed) bone response will be limited by 1. the sensitivity of bone to a particular range of frequencies and 2. the inertia of the muscles, limiting their response to external forces by increasing tension along insertions. We have begun mathematical modeling of the rat forelimb as a transfer function between impact force and bone strain to predict optimal dynamic loading conditions for this system. We plan additional studies of mechanical counter-measures that incorporate improved dynamic loading, features relevant to anticipated evaluation of artificial gravity, exercise regimens and exposure to Martian gravity, The combination of mechanical countermeasures with ibandronate will also be investigated for signs of synergy.

Nuclear medicine technology progress report for quarter ending June 30, 1978. ABELLED COMPOUNDS; PATIENTS; POSITRON SOURCES; CARBON 11; ISOMERIC NUCLEI; LABELLED COMPOUNDS; BIOLOGICAL LOCALIZATION; CHEMICAL PREPARATION; ISOMERIC NUCLEI; LABELLED COMPOUNDS; RATS; CHEMICAL PREPARATION; LABELLED COMPOUNDS; RATS; TISSUE DISTRIBUTION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Knapp, Jr., F. F.

Progress is reported for the applications of /sup 11/C, /sup 195m/Pt, /sup 75/Se, and /sup 123m/Te. Additional human clinical trials with /sup 11/C-DL-tryptophan and /sup 11/C-l-aminocyclobutane carboxylic acid have been completed. The modified Buecherer-Strecker amino acid synthesis has been used to prepare /sup 11/C-DL-phenylglycine and /sup 11/C-DL-phenylalanine. These two new /sup 11/C-labeled amino acids will be studied as potential tumor localizing agents. Preliminary studies concerning the comparative organ and subcellular distribution of /sup 195m/Pt-labeled cis- and trans- dichlorodiamineplatinum(II) have been completed. The results of in vivo studies have shown the cis isomer to bind to nuclear DNA to a significantlymore » greater extent than the trans isomer. A series of /sup 123m/Te-labeled long-chain fatty acid analogs have been prepared as isosteres of unsaturated fatty acids. Several of these compounds show pronounced heart uptake in rats and may represent a new class of potential myocardial imaging agents. Studies on the preparation and tissue distribution of /sup 75/Se-..beta..-aminoethyl selenosulfate continue.« less

Four-point bending as a method for quantitatively evaluating spinal arthrodesis in a rat model.

PubMed

Robinson, Samuel T; Svet, Mark T; Kanim, Linda A; Metzger, Melodie F

2015-02-01

The most common method of evaluating the success (or failure) of rat spinal fusion procedures is manual palpation testing. Whereas manual palpation provides only a subjective binary answer (fused or not fused) regarding the success of a fusion surgery, mechanical testing can provide more quantitative data by assessing variations in strength among treatment groups. We here describe a mechanical testing method to quantitatively assess single-level spinal fusion in a rat model, to improve on the binary and subjective nature of manual palpation as an end point for fusion-related studies. We tested explanted lumbar segments from Sprague-Dawley rat spines after single-level posterolateral fusion procedures at L4-L5. Segments were classified as 'not fused,' 'restricted motion,' or 'fused' by using manual palpation testing. After thorough dissection and potting of the spine, 4-point bending in flexion then was applied to the L4-L5 motion segment, and stiffness was measured as the slope of the moment-displacement curve. Results demonstrated statistically significant differences in stiffness among all groups, which were consistent with preliminary grading according to manual palpation. In addition, the 4-point bending results provided quantitative information regarding the quality of the bony union formed and therefore enabled the comparison of fused specimens. Our results demonstrate that 4-point bending is a simple, reliable, and effective way to describe and compare results among rat spines after fusion surgery.

High concentrations of landiolol, a beta(1)-adrenoceptor antagonist, stimulate smooth muscle contraction of the rat trachea through the Rho-kinase pathway.

PubMed

Shibata, Osamu; Nishioka, Kenji; Yamaguchi, Masakazu; Makita, Tetsuji; Sumikawa, Koji

2008-01-01

Gradually progressing contraction of airway smooth muscle is suggested to be due to the Rho-kinase signaling pathway. In our preliminary study in rat tracheas, landiolol, a beta(1)-adrenoceptor antagonist, at high doses caused gradually progressing contraction, and this contraction reached a plateau after 20 min. Therefore, this study was carried out to clarify whether landiolol could stimulate the Rho-kinase pathway or the phosphatidylinositol (PI) response in the rat trachea. Seventy-eight male Wistar rats weighing 250-350 g were used for the experiments. Their tracheas were cut into 3-mm-wide ring segments or 1-mm-wide slices. Measurements of isometric tension and [(3)H] inositol monophosphate (IP(1)) production were conducted, using these tracheal rings or slices. Data values are expressed as means +/- SD, and statistical significance (P < 0.05) was determined using analysis of variance (ANOVA). Landiolol (700 microM)-induced contraction was completely inhibited by fasudil at 30 microM, while the landiolol-induced contraction was not inhibited by 4-diphenylacetoxy-N-methyl-piperidine methobromide (4-DAMP), ketanserin, or nicardipine. Landiolol did not stimulate IP(1) production. These results suggest that high concentrations of landiolol could cause airway smooth muscle contraction through the Rho-kinase pathway, but not through the PI response coupled with muscarinic M(3) receptors, 5-HT receptors or the activation of L-type Ca(2+) channels.

Impact of e-cigarette refill liquid exposure on rat kidney.

PubMed

Golli, Narges El; Jrad-Lamine, Aicha; Neffati, Hajira; Dkhili, Houssem; Rahali, Dalila; Dallagi, Yosra; El May, Michele V; El Fazaa, Saloua

2016-06-01

Electronic-cigarettes (e-cigarette), the alternative to classic cigarettes are becoming extremely popular but their safety is not still established. Recent studies have showed cytotoxic effects of the electronic cigarette and its recharge e-liquid, in vitro. The present study was designed to evaluate e-cigarette liquid nephrotoxicity in rats. For this purpose, 32 rats were treated for 28 days as follows: Control group was injected intraperitoneally with NaCl 9 g/l; e-cigarette 0% treated group received an intraperitoneal injection of e-liquid without nicotine diluted in NaCl 9 g/l, e-cigarette treated group, received an intraperitoneal injection of e-liquid containing 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l and nicotine-treated group received an intraperitoneal injection of 0.5 mg of nicotine/kg of body weight/day diluted in NaCl 9 g/l. In nicotine group, creatinine level was increased, whereas urea and acid uric levels were decreased. In e-liquid-exposed groups, levels of uric acid and mainly urea were lower. Interestingly, after e-liquid exposure, oxidative stress status showed increased total protein and sulfhydril content, whereas superoxide dismutase and catalase activities were decreased. However, the levels of lipid peroxides were not increased after e-liquid exposure. Histological studies identified excess of cells with reduced and dark nuclei exclusively located in the renal collecting ducts. Thus, e-liquid seems to alter anti-oxidant defense and to promote minor changes in renal function parameters. This preliminary study raises some flags about possible nephrotoxicity of e-cigarette liquids in rats. As some features observed in rats may not be observed in human smokers, additional studies are needed to further qualify conclusions that might be applicable to actual users of e-cigarettes. Copyright © 2016 Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

The influence of alkaline earth metals on the distribution and excretion of strostium was studied in rats, sheep, and dairy cattle. The effects of dietary phosphorus and high levels of vitamin D on strontium distribution was observed. The influence of diuretics on potussium and cesium excretion was studied in sheep. Conventional and radiochemical procedures were used in studies of mineral metabolism in farm animals. Tracer studies are reported on copper- magnesium interrelationships in sheep; the calcium balance in sheep, swine, and steers as affected by stilbestrol, magnesium, ether extract, and zinc; and the relation of ccrtain blood plasma constituents tomore » milk in the dairy cow. Studies of the effects of radiation on reproduction were continued in cattle, swine, and rats. Standard psychological tests were applied to pre- and post-natally irradiated rats in an effort to assess the effects of radiation on various behavior characteristics. An effort is being made to develop similar techniques applicable to farm animals. Clinical, hematologic, and opthalmologic examinations were continued on burros exposed to fission weapon neutron-gamma irradiation. One burro was exposed to gamma-neutron radiation from a critical assembly in order to provide blood fur sodium activation analysis. Levels were compared wath human vaiues due to accidental exposure. Preliminary studies were initiated to study the role of water in the radiosensitivity of dormant seeds. The program of seed and plant irradiation was continued with the irradiation of 25 samples. (For preceding period see ORO-174.) (C.H.)« less

The function of androgen/androgen receptor and insulin growth factor‑1/insulin growth factor‑1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise.

PubMed

Wu, Yin; Yang, Hongfang; Wang, Xiaohui

2017-09-01

Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment. The rats of the E and E+TT groups underwent high intensity exercise with a progressively increasing load for 5 weeks, and TT extracts were intragastrically administered in the TT and E+TT rats 30 min prior to training. TT extract composition was analyzed using ultra‑high performance liquid chromatography‑quadrupole‑time of flight mass spectrometry. Testosterone and IGF‑1 plasma levels and AR, IGF‑1R and myosin heavy chain (MHC) protein levels in muscles were determined by ELISA and western blotting, respectively. The saponins tigogenin and diosgenin comprised ~71.35% of the total peak area. Compared with the E group, TT extracts increased the testosterone and IGF‑1 plasma levels, and AR, IGF‑1R and MHC protein levels in the gastrocnemius of rats undergoing high intensity exercise, accompanied with increased body weight and gastrocnemius weight. In conclusion, the effect of TT extracts on the performance of high intensity exercise rats may be attributed to increased levels of circulating testosterone and IGF‑1 and increased AR and IGF‑1R protein expression levels in the gastrocnemius, resulting in increased muscle weight and increased MHC in the gastrocnemius. The present study provided preliminary evidence supporting the use of TT extracts as a dietary supplement for the promotion of skeletal muscle mass increase and the enhancement of athletic performance in humans performing high intensity exercise.

In vivo absorption and disposition of α-cedrene, a sesquiterpene constituent of cedarwood oil, in female and male rats.

PubMed

Kim, Tae Hwan; Yoo, Sun Dong; Lee, Hye Suk; Lee, Kyoung Mee; Seok, Su Hyun; Kim, Min Gi; Jung, Byung Hwa; Kim, Min Gyu; Shin, Beom Soo

2015-04-01

This study aimed to evaluate the potential of α-cedrene as a new anti-obesity drug by characterizing absorption, metabolism and pharmacokinetics in rats. α-Cedrene was administered intravenously (10 and 20 mg/kg) and orally (50 and 100 mg/kg) to female and male Sprague-Dawley rats. Blood, tissues, urine, and feces were collected at predetermined times. α-Cedrene concentrations were determined by a validated gas chromatography-tandem mass spectrometry (GC-MS/MS). A gas chromatography-mass selective detection (GC-MSD) method was used to identify the major metabolite. After i.v. injection, α-cedrene exhibited a rapid clearance (98.4-120.3 ml/min/kg), a large distribution volume (35.9-56.5 l/kg), and a relatively long half-life (4.0-6.4 h). Upon oral administration, it was slowly absorbed (Tmax = 4.4 h) with bioavailability of 48.7-84.8%. No gender differences were found in its pharmacokinetics. Upon oral administration, α-cedrene was highly distributed to tissues, with the tissue-to-plasma partition coefficients (Kp) far greater than unity for all tissues. In particular, its distribution to lipid was notably high (Kp = 132.0) compared to other tissues. A mono-hydroxylated metabolite was identified as a preliminary metabolite in rat plasma. These results suggest that α-cedrene has the favorable pharmacokinetic characteristics to be further tested as an anti-obesity drug in clinical studies. Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.

Effects of the dimeric PSD-95 inhibitor UCCB01-144 on functional recovery after fimbria-fornix transection in rats.

PubMed

Sommer, Jens Bak; Bach, Anders; Malá, Hana; Strømgaard, Kristian; Mogensen, Jesper; Pickering, Darryl S

2017-10-01

Pharmacological inhibition of PSD-95 is a promising therapeutic strategy in the treatment of stroke, and positive effects of monomeric and dimeric PSD-95 inhibitors have been reported in numerous studies. However, whether therapeutic effects will generalize to other types of acute brain injury such as traumatic brain injury (TBI), which has pathophysiological mechanisms in common with stroke, is currently uncertain. We have previously found a lack of neuroprotective effects of dimeric PSD-95 inhibitors in the controlled cortical impact model of TBI in rats. However, as no single animal model is currently able to mimic the complex and heterogeneous pathophysiology of TBI, it is necessary to assess treatment effects across a range of models. In this preliminary study we investigated the neuroprotective abilities of the dimeric PSD-95 inhibitor UCCB01-144 after fimbria-fornix (FF) transection in rats. UCCB01-144 or saline was injected into the lateral tail vein of rats immediately after sham surgery or FF-transection, and effects on spatial delayed alternation in a T-maze were assessed over a 28-day period. Task acquisition was significantly impaired in FF-transected animals, but there were no significant effects of UCCB01-144 on spatial delayed alternation after FF-transection or sham surgery, although decelerated learning curves were seen after treatment with UCCB01-144 in FF-transected animals. The results of the present study are consistent with previous research showing a lack of neuroprotective effects of PSD-95 inhibition in experimental models of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

Mechanical Stress and Antioxidant Protection in the Retina of Hindlimb Suspended Rats

NASA Technical Reports Server (NTRS)

Glass, Aziza; Theriot, Corey A.; Alway, Stephen E.; Zanello, Susana B.

2012-01-01

It has been postulated that hindlimb suspension (HS) causes a cephalad fluid shift in quadrupeds similar to that occurring to humans in microgravity. Therefore, HS may provide a suitable animal model in which to recapitulate the ocular changes observed in the human Visual Impairment and Intracranial Pressure (VIIP) syndrome. This work reports preliminary results from a tissue sharing project using 34 week-old Brown Norway rats. Two different experiments compared normal posture controls and HS rats for 2 weeks and rats exposed to HS for 2 weeks but allowed to recover in normal posture for 2 additional weeks. The effects of two nutritional countermeasures, green tea extract (GT) and plant polyphenol resveratrol (Rv), were also evaluated. Green tea contains the antioxidant epigallocatechin gallate (EGCG). qPCR gene expression analysis of selected targets was performed on RNA from isolated retinas, and histologic analysis was done on one fixed eye per rat. The transcription factor early growth response protein 1 (Egr1) was upregulated almost 2-fold in HS retinas relative to controls (P = 0.059), and its expression returned to control levels after 2 weeks of recovery in normal posture (P = 0.023). HS-induced upregulation of Egr1 was attenuated (but not significantly) in retinas from rats fed an antioxidant rich (GT extract) diet. In rats fed the GT-enriched diet, antioxidant enzymes were induced, evidenced by the upregulation of the gene heme oxygenase 1 (Hmox1) (P = 0.042) and the gene superoxide dismutase 2 (Sod2) (P = 0.0001). Egr1 is a stretch-activated transcription factor, and the Egr1 mechanosensitive response to HS may have been caused by a change in the translaminal pressure and/or mechanical deformation of the eye globe. The observed histologic measurements of the various retinal layers in the HS rats were lower in value than those of the control animal (n = 1), however insufficient data were available for statistical analysis. Aquaporin 4, a water-selective channel involved in interstitial fluid homeostasis, showed an upregulated trend in HS retinas; however, these results are preliminary. Total retinal thickness increased significantly (P = 0.049) in HS rats fed a resveratrol enriched diet compared to HS rats on a normal diet. This change appeared to be reversed during the 2 weeks of recovery post HS, but no differences in retina thickness were observed between HS animals and HS recovered animals when both groups consumed a normal diet. The reversibility of the increase in retinal thickness induced by resveratrol during HS may therefore reflect an interaction between the stress provoked by HS and the cytoprotective mechanisms elicited by resveratrol

Desert Research and Technology Studies 2005 Report

NASA Technical Reports Server (NTRS)

Ross, Amy J.; Kosmo, Joseph J.; Janoiko, Barbara A.; Bernard, Craig; Splawn, Keith; Eppler, Dean B.

2006-01-01

During the first two weeks of September 2005, the National Aeronautics and Space Administration (NASA) Johnson Space Center (JSC) Advanced Extravehicular Activity (AEVA) team led the field test portion of the 2005 Research and Technology Studies (RATS). The Desert RATS field test activity is the culmination of the various individual science and advanced engineering discipline areas year-long technology and operations development efforts into a coordinated field test demonstration under representative (analog) planetary surface terrain conditions. The purpose of the RATS is to drive out preliminary exploration concept of operations EVA system requirements by providing hands-on experience with simulated planetary surface exploration extravehicular activity (EVA) hardware and procedures. The RATS activities also are of significant importance in helping to develop the necessary levels of technical skills and experience for the next generation of engineers, scientists, technicians, and astronauts who will be responsible for realizing the goals of the Constellation Program. The 2005 Desert RATS was the eighth RATS field test and was the most systems-oriented, integrated field test to date with participants from NASA field centers, the United States Geologic Survey (USGS), industry partners, and research institutes. Each week of the test, the 2005 RATS addressed specific sets of objectives. The first week focused on the performance of surface science astro-biological sampling operations, including planetary protection considerations and procedures. The second week supported evaluation of the Science, Crew, Operations, and Utility Testbed (SCOUT) proto-type rover and its sub-systems. Throughout the duration of the field test, the Communications, Avionics, and Infomatics pack (CAI-pack) was tested. This year the CAI-pack served to provide information on surface navigation, science sample collection procedures, and EVA timeline awareness. Additionally, 2005 was the first year since the Apollo program that two pressurized suited test subjects have worked together simultaneously. Another first was the demonstration of recharge of cryogenic life support systems while in-use by the suited test subjects. The recharge capability allowed the simulated EVA test duration to be doubled, facilitating SCOUT proto-type rover testing. This paper summarizes Desert RATS 2005 test hardware, detailed test objectives, test operations and test results.

Anti-arthritic activity of ethanolic extract of Tridax procumbens (Linn.) in Sprague Dawley rats

PubMed Central

Petchi, R Ramesh; Vijaya, C; Parasuraman, S

2013-01-01

Objective: To determine the anti-arthritic effect of whole plant ethanolic extract of Tridax procumbens (Asteraceae) in female Sprague Dawley (SD) rats using the Freund's Complete Adjuvant (FCA) model. Materials and Methods: The plant was collected from different regions of Madurai District, Tamil Nadu, and the phytoconstituents were identified through chemical tests. Ethanol (95%) was used to obtain the whole plant extraction through Soxhlet extractor. Female SD rats were used for anti-arthritic screening. Arthritis was induced using FCA, and the anti-arthritic effect of the ethanolic extract of T. procumbens was studied at doses of 250 and 500 mg/kg. The effects were compared with those of indomethacin (10 mg/kg). At the end of the study, the liver enzyme levels were determined and a radiological examination was carried out. Result: The preliminary phytochemical analysis of the ethanolic extract of T. procumbens indicated the presence of alkaloids, tannins, flavonoids and saponins. T. procumbens at 250 and 500 mg/kg significantly inhibited the FCA-induced arthritis in the rats. This was manifested by as a decrease in the paw volume. The arthritic control animals exhibited a significant decrease in body weight compared with control animals without arthritis. T. procumbens animals showed dose dependent reduction in decrees in body weight and arthritis. At the same time, T. procumbens significantly altered the biochemical and haematological changes induced by FCA (P < 0.05). The anti-arthritic effect of T. procumbens was comparable with that of indomethacin. Conclusion: The whole plant extract of T. procumbens showed significant anti-arthritic activity against FCA-induced arthritis in female SD rats. PMID:23798886

Toxicological evaluation of 5-methoxy-2-aminoindane (MEAI): Binge mitigating agent in development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimshoni, Jakob A., E-mail: jakobshimshoni@gmail.

5-Methoxy-2-aminoindane (MEAI) is a psychoactive compound of the aminoindane class, which in recent years has been recreationally used by many people, who reported of a mild euphoric, alcohol-like tipsy experience and reduced desire to consume alcoholic beverages. In the light of these observations it was decided to progress MEAI through a preliminary drug development route and evaluate the acute and subacute toxicity of MEAI administrated orally to Sprague Dawley rats, as well as to determine potential in-vitro cytotoxic and mutagenic effects using state-of-the-art protocols. Furthermore, the interaction of MEAI at the highest non-toxic concentration (100 mg/L) with ethanol at cytotoxicmore » levels of 6% and 7.5% was explored, in order to identify possible additive or synergistic effects. MEAI showed a good safety profile in rats at 10 and 30 mg/kg body weight, corresponding to the human doses of 1.6 mg/kg and 4.8 mg/kg body weight, respectively. Cytotoxic effect was demonstrated using concentrations of 500 and 1000 mg/L with calculated IC{sub 50} value of 368.2 mg/L for rat brain striatum primary neurons and 403.1 mg/L for human primary healthy hepatocytes. The combination of 6% or 7.5% ethanol with 100 mg/L MEAI revealed no statistically significant increase of cytotoxic effect. Further studies, especially long term chronic and addictive behavior studies, are required in-order to assess MEAI safety profile. - Highlights: • Single oral administration of MEAI (10 mg/kg) to rats was well tolerated. • Five-day oral administration of MEAI (30 mg/kg) to rats was well tolerated. • Low cytotoxicity was observed in the in vitro cytotoxicity assays. • Ethanol-MEAI mixtures induced no synergistic/additive neurotoxicity.« less

Comparison of Three Wind Measuring Systems for Flight Test

NASA Technical Reports Server (NTRS)

Teets, Edward H., Jr.; Harvey, Philip O.

2000-01-01

A preliminary field test of the accuracy of wind velocity measurements obtained using global positioning system-tracked rawinsonde balloons has been performed. Wind comparisons have been conducted using global positioning system (GPS) and radio automatic theodolite sounder (RATS) rawinsondes and a high-precision range instrumentation radar-tracked reflector. Wind velocity differences between the GPS rawinsondes and the radar were significantly less than between the RATS rawinsondes and the radar. These limited test results indicate a root-mean-square wind velocity difference from 4.98 kn (2.56 m/sec) for the radar and RATS to 1.09 kn (0.56 m/sec) for the radar and GPS. Differences are influenced by user reporting requirements, data processing techniques, and the inherent tracking accuracies of the system. This brief field test indicates that the GPS sounding system tracking data are more precise than the RATS system. When high-resolution wind data are needed, use of GPS rawinsonde systems can reduce the burden on range radar operations.

Geolab 2010: Desert Rats Field Demonstration

NASA Technical Reports Server (NTRS)

Evans, Cindy A.; Calaway, M. J.; Bell, M. S.

2009-01-01

In 2010, Desert Research and Technology Studies (Desert RATS), NASA's annual field exercise designed to test spacesuit and rover technologies, will include a first generation lunar habitat facility, the Habitat Demonstration Unit (HDU). The habitat will participate in joint operations in northern Arizona with the Lunar Electric Rover (LER) and will be used as a multi-use laboratory and working space. A Geology Laboratory or GeoLab is included in the HDU design. Historically, science participation in Desert RATS exercises has supported the technology demonstrations with geological traverse activities that are consistent with preliminary concepts for lunar surface science Extravehicular Activities (EVAs). Next year s HDU demonstration is a starting point to guide the development of requirements for the Lunar Surface Systems Program and test initial operational concepts for an early lunar excursion habitat that would follow geological traverses along with the LER. For the GeoLab, these objectives are specifically applied to support future geological surface science activities. The goal of our GeoLab is to enhance geological science returns with the infrastructure that supports preliminary examination, early analytical characterization of key samples, and high-grading lunar samples for return to Earth [1, 2] . Figure 1: Inside view schematic of the GeoLab a 1/8 section of the HDU, including a glovebox for handling and examining geological samples. Other outfitting facilities are not depicted in this figure. GeoLab Description: The centerpiece of the GeoLab is a glovebox, allowing for samples to be brought into the habitat in a protected environment for preliminary examination (see Fig. 1). The glovebox will be attached to the habitat bulkhead and contain three sample pass-through antechambers that would allow direct transfer of samples from outside the HDU to inside the glovebox. We will evaluate the need for redundant chambers, and other uses for the glovebox antechambers, such as a staging area for additional tools or samples. The sides of the glovebox are designed with instrument ports and additional smaller ports for cable pass-through, imagery feeds and environmental monitoring. This first glovebox version will be equipped with basic tools for manipulating, viewing, and early analysis of samples. The GeoLab was also designed for testing additional analytical instruments in a field setting.

Effect of Aqueous Extract of Psidium Guajava Leaves on Liver Enzymes, Histological Integrity and Hematological Indices in Rats

PubMed Central

Uboh, Friday E.; Okon, Iniobong E.; Ekong, Moses B.

2010-01-01

Background Serum alanine aminotransferase (ALT), aspartate aminotransferase(AST), alkaline phosphatase (ALP), albumin and total protein levels, as well as the tissue histological assay are known to be useful in assessing the functional integrity of the liver. Also, assessment of red and white blood cells count, hematocrit and hemoglobin concentrations is useful in determining the effect of some chemical substances on hemotopoietic system. In recent times, reports from medicinal plants research indicate that extracts from some plants are both hepatotoxic and hematotoxic, while others on the other hand are reported to be hepatoprotective and hematopoietic in action. This study considers the effects of aqueous extract of Psidium guajava (P. guajava) leaves on the histology and biochemical indices of liver function as well as hematological indices in rats. Methods In this study, phytochemical screening of the aqueous extract of P. guajava leaves was carried out. Also, male and female rats were administered with 200 mg/kg body weight oral daily doses of aqueous extract of P. guajava leaves for a period of 30 days. At the end of the administration period, the rats were anaesthesized with chloroform vapors and dissected for the collection of blood and liver tissues which were used for the hematopoietic and liver functions investigations. Results Preliminary phytochemical analysis of the plant leaves showed the presence of alkaloids, flavonoids, glycosides, polyphenols, reducing compounds, saponins and tannins. Liver function tests revealed that the serum ALT, AST and ALP, as well as the concentrations of total protein and albumin in male and female rats were not significantly (P > 0.05) affected by the oral administration of the extract. Histopathological study also did not show any adverse alteration in the morphological architecture of the liver tissues in both sexes of the animal model. However, red blood cell counts, hemotocrit and hemoglobin concentrations increased significantly (P < 0.05) on administration of the extract in both male and female rats. It was therefore observed that the effect of the extract on male rats was not significantly different (P > 0.05) from that obtained for the female rats. Conclusions The results of this present study suggested that aqueous extract of Psidium guajava leaves may be hepatoprotective, and not hepatotoxic, with hematopoietic potentials in both male and female rats. These findings are therefore of clinical importance given the various reported medicinal potentials of the plant. PMID:27956982

Bilirubin modulated cytokines, growth factors and angiogenesis to improve cutaneous wound healing process in diabetic rats.

PubMed

Ram, Mahendra; Singh, Vishakha; Kumawat, Sanjay; Kant, Vinay; Tandan, Surendra Kumar; Kumar, Dinesh

2016-01-01

Bilirubin has shown cutaneous wound healing potential in some preliminary studies. Here we hypothesize that bilirubin facilitates wound healing in diabetic rats by modulating important healing factors/candidates and antioxidant parameters in a time-dependent manner. Diabetes was induced in male Wistar rats by streptozotocin. In all diabetic rats wounds were created under pentobarbitone anesthesia. All the rats were divided into two groups, of which one (control) was treated with ointment base and other with bilirubin ointment (0.3%). Wound closer measurement and tissue collection were done on days 3, 7, 14 and 19 post-wounding. The relative expressions of hypoxia inducible factor-1 alpha (HIF-1α), vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 alpha (SDF-1α), transforming growth factor- beta1 (TGF-β1()), tumor necrosis factor-α (TNF-α) and interlukin-10 (IL-10) mRNA and proteins and the mRNA of interlukin-1 beta (IL-1β) and matrix metalloprteinase-9 (MMP-9) were determined in the wound tissues. CD-31 staining and collagen content were evaluated by immunohistochemistry and picrosirius red staining, respectively. Histopathological changes were assessed by H&E staining. The per cent wound closer was significantly higher from day 7 onwards in bilirubin-treated rats. HIF-1α, VEGF, SDF-1α, TGF-β1, IL-10 mRNA and protein levels were significantly higher on days 3, 7 and 14 in bilirubin-treated rats. The mRNA expression and protein level of TNF-α and the mRNA of IL-1β and MMP-9 were progressively and markedly reduced in bilirubin-treated rats. The collagen deposition and formation of blood vessels were greater in bilirubin-treated rats. Bilirubin markedly facilitated cutaneous wound healing in diabetic rats by modulating growth factors, cytokines, neovasculogenesis and collagen contents to the wound site. Topical application of bilirubin ointment might be of great use in cutaneous wound healing in diabetic patients. Copyright © 2015 Elsevier B.V. All rights reserved.

Synthesis and preliminary biological evaluation of potent and selective 2-(3-alkoxy-1-azetidinyl) quinolines as novel PDE10A inhibitors with improved solubility.

PubMed

Rzasa, Robert M; Frohn, Michael J; Andrews, Kristin L; Chmait, Samer; Chen, Ning; Clarine, Jeffrey G; Davis, Carl; Eastwood, Heather A; Horne, Daniel B; Hu, Essa; Jones, Adrie D; Kaller, Matthew R; Kunz, Roxanne K; Miller, Silke; Monenschein, Holger; Nguyen, Thomas; Pickrell, Alexander J; Porter, Amy; Reichelt, Andreas; Zhao, Xiaoning; Treanor, James J S; Allen, Jennifer R

2014-12-01

We report the discovery of a novel series of 2-(3-alkoxy-1-azetidinyl) quinolines as potent and selective PDE10A inhibitors. Structure-activity studies improved the solubility (pH 7.4) and maintained high PDE10A activity compared to initial lead compound 3, with select compounds demonstrating good oral bioavailability. X-ray crystallographic studies revealed two distinct binding modes to the catalytic site of the PDE10A enzyme. An ex vivo receptor occupancy assay in rats demonstrated that this series of compounds covered the target within the striatum.

Effects of the antituberculous drug ethambutol on zinc balance, distribution, and turnover: short-term studies modeling chronic toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

King, A.B.

1987-01-01

Alterations in Zn metabolism have been reported in both tuberculous patients and experimental animals receiving ethambutol (d-2-2'-ethylenediimino-di-1-butanol dihydrochloride) (EMB), and these changes have been associated with ocular side effects of EMB. EMB has chelating properties but is not likely to chelate Zn at physiologic pH. However, its acid metabolite is a stronger chelator. This research addressed whether EMB affects the absorption and disposition of dietary Zn, and whether effects of EMB on Zn are modified by (a) marginal Zn intake of (b) drugs that may induce metabolism of EMB. Weanling male Sprague-Dawley rats fed an AIN-76A diet received daily bymore » gavage either deionized water or EMB doses of 400-1600 mg/kg bw. in a preliminary, 15-day dose-response study and 400-600 mg/kg in three subsequent 15- to 30-day studies. Apparent absorption and biological turnover of Zn were measured by /sup 65/Zn balance and retention in rats fed adequate (49 ppm) or marginal (11 ppm) Zn. Effects of EMB were similar in both dietary groups. EMB treatment produced alopecia and reduced feed intake, feed efficiency, weight gain, and serum Zn, but showed no effect on hepatic, renal, or femoral Zn concentrations. Absorption, turnover, and urinary excretion of Zn were increased in rats fed EMB.« less

Design, synthesis and biological activity of 6-substituted carbamoyl benzimidazoles as new nonpeptidic angiotensin II AT₁ receptor antagonists.

PubMed

Zhang, Jun; Wang, Jin-Liang; Zhou, Zhi-Ming; Li, Zhi-Huai; Xue, Wei-Zhe; Xu, Di; Hao, Li-Ping; Han, Xiao-Feng; Fei, Fan; Liu, Ting; Liang, Ai-Hua

2012-07-15

A series of 6-substituted carbamoyl benzimidazoles were designed and synthesised as new nonpeptidic angiotensin II AT(1) receptor antagonists. The preliminary pharmacological evaluation revealed a nanomolar AT(1) receptor binding affinity for all compounds in the series, and a potent antagonistic activity in an isolated rabbit aortic strip functional assay for compounds 6f, 6g, 6h and 6k was also demonstrated. Furthermore, evaluation in spontaneous hypertensive rats and a preliminary toxicity evaluation showed that compound 6g is an orally active AT(1) receptor antagonist with low toxicity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hepatic transcriptomic alterations for N,N-dimethyl-p-toluidine (DMPT) and p-toluidine after 5-day exposure in rats.

PubMed

Dunnick, June K; Shockley, Keith R; Morgan, Daniel L; Brix, Amy; Travlos, Gregory S; Gerrish, Kevin; Michael Sanders, J; Ton, T V; Pandiri, Arun R

2017-04-01

N,N-dimethyl-p-toluidine (DMPT), an accelerant for methyl methacrylate monomers in medical devices, was a liver carcinogen in male and female F344/N rats and B6C3F1 mice in a 2-year oral exposure study. p-Toluidine, a structurally related chemical, was a liver carcinogen in mice but not in rats in an 18-month feed exposure study. In this current study, liver transcriptomic data were used to characterize mechanisms in DMPT and p-toluidine liver toxicity and for conducting benchmark dose (BMD) analysis. Male F344/N rats were exposed orally to DMPT or p-toluidine (0, 1, 6, 20, 60 or 120 mg/kg/day) for 5 days. The liver was examined for lesions and transcriptomic alterations. Both chemicals caused mild hepatic toxicity at 60 and 120 mg/kg and dose-related transcriptomic alterations in the liver. There were 511 liver transcripts differentially expressed for DMPT and 354 for p-toluidine at 120 mg/kg/day (false discovery rate threshold of 5 %). The liver transcriptomic alterations were characteristic of an anti-oxidative damage response (activation of the Nrf2 pathway) and hepatic toxicity. The top cellular processes in gene ontology (GO) categories altered in livers exposed to DMPT or p-toluidine were used for BMD calculations. The lower confidence bound benchmark doses for these chemicals were 2 mg/kg/day for DMPT and 7 mg/kg/day for p-toluidine. These studies show the promise of using 5-day target organ transcriptomic data to identify chemical-induced molecular changes that can serve as markers for preliminary toxicity risk assessment.

The Effect of Consumption of Citrus Fruit and Olive Leaf Extract on Lipid Metabolism.

PubMed

Merola, Nicola; Castillo, Julián; Benavente-García, Obdulio; Ros, Gaspar; Nieto, Gema

2017-09-26

Citrus fruit and olive leaves are a source of bioactive compounds such as biophenols which have been shown to ameliorate obesity-related conditions through their anti-hyperlipidemic and anti-inflammatory effect, and by regulating lipoproteins and cholesterol body levels. Citrolive™ is a commercial extract which is obtained from the combination of both citrus fruit and olive leaf extracts; hence, it is hypothesised that Citrolive™ may moderate metabolic disorders that are related to obesity and their complications. Initially, an in vitro study of the inhibition of pancreatic lipase activity was made, however, no effect was found. Both preliminary and long-term evaluations of Citrolive™ on lipid metabolism were conducted in an animal model using Wistar rats. In the preliminary in vivo screening, Citrolive™ was tested on postprandial plasma triglyceride level after the administration of an oil emulsion, and a significant reduction in postprandial triacylglycerol (TAG) levels was observed. In the long-term study, Citrolive™ was administered for 60 days on Wistar rats that were fed a high-fat diet. During the study, several associated lipid metabolism indicators were analysed in blood and faeces. At the end of the experiment, the livers were removed and weighed for group comparison. Citrolive™ treatment significantly reduced the liver-to-body-weight ratio, as supported by reduced plasma transaminases compared with control, but insignificantly reduced plasma low density lipoprotein (LDL) and postprandial TAG plasma levels. In addition, faecal analysis showed that the treatment significantly increased total cholesterol excretion. On the other hand, no effect was found on faecal TAG and pancreatic lipase in vitro. In conclusion, treatment ameliorates liver inflammation symptoms that are worsened by the effects of high fat diet.

The Effect of Consumption of Citrus Fruit and Olive Leaf Extract on Lipid Metabolism

PubMed Central

Merola, Nicola; Castillo, Julián; Benavente-García, Obdulio; Ros, Gaspar

2017-01-01

Citrus fruit and olive leaves are a source of bioactive compounds such as biophenols which have been shown to ameliorate obesity-related conditions through their anti-hyperlipidemic and anti-inflammatory effect, and by regulating lipoproteins and cholesterol body levels. Citrolive™ is a commercial extract which is obtained from the combination of both citrus fruit and olive leaf extracts; hence, it is hypothesised that Citrolive™ may moderate metabolic disorders that are related to obesity and their complications. Initially, an in vitro study of the inhibition of pancreatic lipase activity was made, however, no effect was found. Both preliminary and long-term evaluations of Citrolive™ on lipid metabolism were conducted in an animal model using Wistar rats. In the preliminary in vivo screening, Citrolive™ was tested on postprandial plasma triglyceride level after the administration of an oil emulsion, and a significant reduction in postprandial triacylglycerol (TAG) levels was observed. In the long-term study, Citrolive™ was administered for 60 days on Wistar rats that were fed a high-fat diet. During the study, several associated lipid metabolism indicators were analysed in blood and faeces. At the end of the experiment, the livers were removed and weighed for group comparison. Citrolive™ treatment significantly reduced the liver-to-body-weight ratio, as supported by reduced plasma transaminases compared with control, but insignificantly reduced plasma low density lipoprotein (LDL) and postprandial TAG plasma levels. In addition, faecal analysis showed that the treatment significantly increased total cholesterol excretion. On the other hand, no effect was found on faecal TAG and pancreatic lipase in vitro. In conclusion, treatment ameliorates liver inflammation symptoms that are worsened by the effects of high fat diet. PMID:28954421

Preliminary experiences on diode laser welding of skin

NASA Astrophysics Data System (ADS)

Reali, Umberto M.; Borgognoni, L.; Martini, L.; Chiarugi, C.; Gori, F.; Pini, Roberto; Toncelli, F.; Vanni, U.

1994-12-01

Dye enhanced laser welding has been recently proposed for skin closures to exploit the advantages of laser procedure (possible reduction of scar formation, no inflammatory reaction). In this preliminary study we used the diode laser-assisted technique to perform welding of rats' skin. In the pilot phase of the study we investigated the effect of the interaction between diode laser radiation and 20 full thickness skin wounds, performed on the shaved backs of 10 Wistar rats, using laser power in the range of 200 - 150 mW and, as the photoenhancing chromophore, Indocyanine Cardio-green (ICG) dye saturated solution in plasma. Ten wounds were sutured with 4.0 nylon thread, to provide a comparison with the traditional procedure. Wounds' samples were explanted on day 3 and 7 after the treatment, for histological evaluation. Clinical examination on the same days showed a high percentage of wounds dehiscence and presence of scales and crusts. Histologic examination demonstrated evidence of thermal injury and a heightened inflammation, superior to that of suture closures. In the second phase of the study, a lower laser power (150 - 80 mW), ICG-plasma-non saturated solution (ICG-sol) and ICG-plasma-saturated-sodium hyaluronate gel (ICG-gel), were used. Six wounds were filled with ICG-sol and six with ICG-gel, then irradiated at 150, 120 and 80 mW. Postoperative explants were performed on day 3 and 7. Clinical and histological results from this group were satisfactory: we recorded only one case of dehiscence, well healed wounds, no epidermal necrosis and a mild inflammatory reaction, reduced respect to that of traditional closure. We characterized the optimum range of parameters of diode laser-assisted technique to achieve an effective skin welding and the corresponding clinical and histologic pattern was described.

Progranulin inhibits platelet aggregation and prolongs bleeding time in rats.

PubMed

Al-Yahya, A M; Al-Masri, A A; El Eter, E A; Hersi, A; Lateef, R; Mawlana, O

2018-05-01

Several adipokines secreted by adipose tissue have an anti-thrombotic and anti-atherosclerotic function. Recently identified adipokine progranulin was found to play a protective role in atherosclerosis. Bearing in mind the central role of platelets in inflammation and atherosclerosis, we aimed, in this study, to examine the effect of progranulin on platelet function and coagulation profile in rats. Healthy male albino Wistar rats weighing (250-300 g) were divided into 4 groups. Three groups were given increasing doses of progranulin (0.001 µg, 0.01 µg, and 0.1 µg) intraperitoneally, while the control group received phosphate-buffered saline (PBS). Bleeding time, prothrombin time, activated partial thromboplastin time and platelet aggregation responses to adenosine diphosphate and arachidonic acid were assessed. Administration of progranulin resulted in a significant inhibition of platelet aggregation in response to both adenosine diphosphate, and arachidonic acid. Bleeding time, prothrombin time and activated partial thromboplastin time were significantly prolonged in all groups that received progranulin, in particular, the 0.1 µg dose, in comparison to the control group. This preliminary data is first suggesting that the antiplatelet and anticoagulant action of progranulin could have a physiological protective function against thrombotic disorders associated with obesity and atherosclerosis. However, these results merit further exploration.

Tri-ortho-cresyl phosphate induces autophagy of rat spermatogonial stem cells.

PubMed

Liu, Meng-Ling; Wang, Jing-Lei; Wei, Jie; Xu, Lin-Lin; Yu, Mei; Liu, Xiao-Mei; Ruan, Wen-Li; Chen, Jia-Xiang

2015-02-01

Tri-ortho-cresyl phosphate (TOCP) has been widely used as plasticizers, plastic softeners, and flame retardants in industry and reported to have a deleterious effect on the male reproductive system in animals besides delayed neurotoxicity. Our preliminary results found that TOCP could disrupt the seminiferous epithelium in the testis and inhibit spermatogenesis, but the precise mechanism is yet to be elucidated. This study shows that TOCP inhibited viability of rat spermatogonial stem cells in a dose-dependent manner. TOCP could not lead to cell cycle arrest in the cells; the mRNA levels of p21, p27, p53, and cyclin D1 in the cells were also not affected by TOCP. Meanwhile, TOCP did not induce apoptosis of rat spermatogonial stem cells. After treatment with TOCP, however, both LC3-II and the ratio of LC3-II/LC3-I were markedly increased; autophagy proteins ATG5 and beclin 1 were also increased after treatment with TOCP, indicating that TOCP could induce autophagy in the cells. Ultrastructural observation under the transmission electron microscopy indicated that autophagic vesicles in the cytoplasm containing extensively degraded organelles such as mitochondria and endoplasmic reticulum increased significantly after the cells were treated with TOCP. In summary, we have shown that TOCP can inhibit viability of rat spermatogonial stem cells and induce autophagy of the cells, without affecting cell cycle and apoptosis. © 2015 Society for Reproduction and Fertility.

Dopamine dysregulation in the prefrontal cortex relates to cognitive deficits in the sub-chronic PCP-model for schizophrenia: A preliminary investigation.

PubMed

McLean, Samantha L; Harte, Michael K; Neill, Joanna C; Young, Andrew Mj

2017-06-01

Dopamine dysregulation in the prefrontal cortex (PFC) plays an important role in cognitive dysfunction in schizophrenia. Sub-chronic phencyclidine (scPCP) treatment produces cognitive impairments in rodents and is a thoroughly validated animal model for cognitive deficits in schizophrenia. The aim of our study was to investigate the role of PFC dopamine in scPCP-induced deficits in a cognitive task of relevance to the disorder, novel object recognition (NOR). Twelve adult female Lister Hooded rats received scPCP (2 mg/kg) or vehicle via the intraperitoneal route twice daily for 7 days, followed by 7 days washout. In vivo microdialysis was carried out prior to, during and following the NOR task. Vehicle rats successfully discriminated between novel and familiar objects and this was accompanied by a significant increase in dopamine in the PFC during the retention trial ( p < 0.01). scPCP produced a significant deficit in NOR ( p < 0.05 vs. control) and no PFC dopamine increase was observed. These data demonstrate an increase in dopamine during the retention trial in vehicle rats that was not observed in scPCP-treated rats accompanied by cognitive disruption in the scPCP group. This novel finding suggests a mechanism by which cognitive deficits are produced in this animal model and support its use for investigating disorders in which PFC dopamine is central to the pathophysiology.

Diabetes-induced changes in the alternative splicing of the slo gene in corporal tissue.

PubMed

Davies, Kelvin P; Zhao, Weixin; Tar, Moses; Figueroa, Johanna C; Desai, Pratik; Verselis, Vytas K; Kronengold, Jack; Wang, Hong-Zhan; Melman, Arnold; Christ, George J

2007-10-01

Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel alpha-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function. Reverse transcriptase-polymerase chain reaction was used to compare Slo splice variant expression in corporal tissue excised from control and streptozotocin (STZ)-induced diabetic Fischer F-344 rats. Splice variants were sequenced, characterized by patch clamping, and fused to green fluorescent protein to determine cellular localization. The impact of altered Slo expression on erectile function was further evaluated in vivo. A novel Slo splice variant (SVcyt, with a cytoplasmic location) was predominantly expressed in corporal tissue from control rats. STZ-diabetes caused upregulation of a channel-forming transcript SV0. Preliminary results suggest that SV0 was also more prevalent in the corporal tissue of human diabetic compared with nondiabetic patients. The change in isoform expression in STZ-treated rats was partially reversed by insulin treatment. Intracorporal injection of a plasmid expressing the SV0 transcript, but not SVcyt, restored erectile function in STZ-diabetic rats. Alternative splicing of the Slo transcript may represent an important compensatory mechanism to increase the ease with which relaxation of corporal tissue may be triggered as a result of a diabetes-related decline in erectile capacity.

The effect of phosphorylation of the EF-2 isolated from rat liver cells on protein biosynthesis in vitro.

PubMed

Gajko, A; Sredzińska, K; Marcinkiewicz, C; Gałasiński, W

1991-01-01

The activity of EF-2 was distinctly decreased after phosphorylation catalysed by a partly purified calmodulin and Ca2+ dependent protein kinase III. At the same time 32P from [gamma-32P]ATP was incorporated into EF-2 molecule. After dephosphorylation of EF-2 catalysed by alkaline phosphatase the activity of this factor was increased. This suggests that the phosphorylation-dephosphorylation of EF-2 is the regulatory process in the elongation step of the translation. Preliminary purification of the kinase III from rat liver resulted in 8-fold purified enzyme with a recovery of 60%.

Spikes, Local Field Potentials, and Electrocorticogram Characterization during Motor Learning in Rats for Brain Machine Interface Tasks.

PubMed

Marzullo, T C; Dudley, J R; Miller, C R; Trejo, L; Kipke, D R

2005-01-01

Brain machine interface development typically falls into two arenas, invasive extracellular recording and non-invasive electroencephalogram recording methods. The relationship between action potentials and field potentials is not well understood, and investigation of interrelationships may improve design of neuroprosthetic control systems. Rats were trained on a motor learning task whereby they had to insert their noses into an aperture while simultaneously pressing down on levers with their forepaws; spikes, local field potentials (LFPs), and electrocorticograms (ECoGs) over the motor cortex were recorded and characterized. Preliminary results suggest that the LFP activity in lower cortical layers oscillates with the ECoG.

Polidocanol injection for chemical delay and its effect on the survival of rat dorsal skin flaps.

PubMed

Menevşe, Gülsüm Tetik; TeomanTellioglu, Ali; Altuntas, Nurgül; Cömert, Ayhan; Tekdemir, Ibrahim

2014-06-01

Surgical delay is an invasive method requiring a two-stage surgical procedure. Hence, methods that may serve as an alternative to surgical delay have become the focus of interest of research studies. From a conceptual view, any technique that interrupts the blood flow along the edges of a proposed flap will render the flap ischemic and induce a delay phenomenon. Polidocanol (Aethoxysklerol(®)-Kreussler) was initially used as a local anesthetic. Nowadays, it has been used as a sclerosing agent to treat telangiectasias and varicose veins. The aim of this experimental study was to investigate the effects of polidocanol injected around the periphery of a random flap as a sclerosing agent on flap delay and survival in a random flap model. A preliminary histopathologic study was performed on two rats to evaluate the sclerosing effect and distribution of polidocanol injection. After the preliminary study, the main study was carried out with three groups: group 1: dorsal flap (n = 10); group 2: dorsal flap + surgical delay (n = 10), group 3: dorsal flap + chemical delay (n = 10). Tissue samples obtained from the flap and injection area revealed destruction of intradermal vessels. The area affected with sclerosis was limited to 0.1 cm beyond the injection site. Mean viable flap areas were 52.1 ± 4.38% (44.0-58.2) in group 1, 64.8 ± 8.92% (57.2-89.2) in group 2, and 71.8 ± 5.18% (64.0-84.0) in group 3. A statistically highly significant difference was found between the surgical delay and chemical delay groups versus the group without delay (p < 0.001 and p < 0.001, respectively). The difference between the mean viable flap areas was not statistically significant in the surgical and chemical delay groups (p = 0.056). In conclusion, this study has shown that polidocanol injection around the dorsal flap in the rat is a safe and easy method for nonsurgical delay. The results have shown a flap survival benefit that is superior to controls and equivalent to surgical delay. The clinical application of polidocanol, already in clinical practice for occlusal of telangiectasias, for surgical delay appears feasible. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Neuroprotective effect of lurasidone via antagonist activities on histamine in a rat model of cranial nerve involvement.

PubMed

He, Baoming; Yu, Liang; Li, Suping; Xu, Fei; Yang, Lili; Ma, Shuai; Guo, Yi

2018-04-01

Cranial nerve involvement frequently involves neuron damage and often leads to psychiatric disorder caused by multiple inducements. Lurasidone is a novel antipsychotic agent approved for the treatment of cranial nerve involvement and a number of mental health conditions in several countries. In the present study, the neuroprotective effect of lurasidone by antagonist activities on histamine was investigated in a rat model of cranial nerve involvement. The antagonist activities of lurasidone on serotonin 5‑HT7, serotonin 5‑HT2A, serotonin 5‑HT1A and serotonin 5‑HT6 were analyzed, and the preclinical therapeutic effects of lurasidone were examined in a rat model of cranial nerve involvement. The safety, maximum tolerated dose (MTD) and preliminary antitumor activity of lurasidone were also assessed in the cranial nerve involvement model. The therapeutic dose of lurasidone was 0.32 mg once daily, administered continuously in 14‑day cycles. The results of the present study found that the preclinical prescriptions induced positive behavioral responses following treatment with lurasidone. The MTD was identified as a once daily administration of 0.32 mg lurasidone. Long‑term treatment with lurasidone for cranial nerve involvement was shown to improve the therapeutic effects and reduce anxiety in the experimental rats. In addition, treatment with lurasidone did not affect body weight. The expression of the language competence protein, Forkhead‑BOX P2, was increased, and the levels of neuroprotective SxIP motif and microtubule end‑binding protein were increased in the hippocampal cells of rats with cranial nerve involvement treated with lurasidone. Lurasidone therapy reinforced memory capability and decreased anxiety. Taken together, lurasidone treatment appeared to protect against language disturbances associated with negative and cognitive impairment in the rat model of cranial nerve involvement, providing a basis for its use in the clinical treatment of patients with cranial nerve involvement.

Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Yunli, E-mail: chrisyu1255@yahoo.com.cn; Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009; Wang, Xinting, E-mail: wxinting1986@yahoo.com.cn

Accumulating evidences have showed that gatifloxacin causes dysglycemia in both diabetic and non-diabetic patients. Our preliminary study demonstrated that gatifloxacin stimulated glucagon-like peptide 1 (GLP-1) secretion from intestinal cells. The aim of the study was to investigate the association between gatifloxacin-stimulated GLP-1 release and dysglycemia in both normal and streptozotocin-induced diabetic rats and explore the possible mechanisms. Oral administration of gatifloxacin (100 mg/kg/day and 200 mg/kg/day) for 3 and 12 days led to marked elevation of GLP-1 levels, accompanied by significant decrease in insulin levels and increase in plasma glucose. Similar results were found in normal rats treated with 3-daymore » gatifloxacin. Gatifloxacin-stimulated GLP-1 release was further confirmed in NCI-H716 cells, which was abolished by diazoxide, a K{sub ATP} channel opener. QT-PCR analysis showed that gatifloxacin also upregulated expression of proglucagon and prohormone convertase 3 mRNA. To clarify the contradiction on elevated GLP-1 without insulinotropic effect, effects of GLP-1 and gatifloxacin on insulin release were investigated using INS-1 cells. We found that short exposure (2 h) to GLP-1 stimulated insulin secretion and biosynthesis, whereas long exposure (24 h and 48 h) to high level of GLP-1 inhibited insulin secretion and biosynthesis. Moreover, we also confirmed gatifloxacin acutely stimulated insulin secretion while chronically inhibited insulin biosynthesis. All the results gave an inference that gatifloxacin stimulated over-secretion of GLP-1, in turn, high levels of GLP-1 and gatifloxacin synergistically impaired insulin release, worsening hyperglycemia. -- Highlights: ► Gatifloxacin induced hyperglycemia both in diabetic rats and normal rats. ► Gatifloxacin enhanced GLP-1 secretion but inhibited insulin secretion in rats. ► Long-term exposure to high GLP-1 inhibited insulin secretion and biosynthesis. ► GLP-1 over-secretion may be involved in gatifloxacin-induced hyperglycemia.« less

Hyperpolarized xenon magnetic resonance of the lung and the brain

NASA Astrophysics Data System (ADS)

Venkatesh, Arvind Krishnamachari

2001-04-01

Hyperpolarized noble gas Magnetic Resonance Imaging (MRI) is a new diagnostic modality that has been used successfully for lung imaging. Xenon is soluble in blood and inhaled xenon is transported to the brain via circulating blood. Xenon also accumulates in the lipid rich white matter of the brain. Hyperpolarized xenon can hence be used as a tissue- sensitive probe of brain function. The goals of this study were to identify the NMR resonances of xenon in the rat brain and evaluate the role of hyperpolarized xenon for brain MRI. We have developed systems to produce sufficient volumes of hyperpolarized xenon for in vivo brain experiments. The specialized instrumentation developed include an apparatus for optical pump-cell manufacture and high purity gas manifolds for filling cells. A hyperpolarized gas delivery system was designed to ventilate small animals with hyperpolarized xenon for transport to the brain. The T1 of xenon dissolved in blood indicates that the lifetime of xenon in the blood is sufficient for significant magnetization to be transferred to distal tissues. A variety of carrier agents for intravenous delivery of hyperpolarized xenon were tested for transport to distal tissues. Using our new gas delivery system, high SNR 129Xe images of rat lungs were obtained. Spectroscopy with hyperpolarized xenon indicated that xenon was transported from the lungs to the blood and tissues with intact magnetization. After preliminary studies that indicated the feasibility for in vivo rat brain studies, experiments were performed with adult rats and young rats with different stages of white matter development. Both in vivo and in vitro experiments showed the prominence of one peak from xenon in the rat brain, which was assigned to brain lipids. Cerebral brain perfusion was calculated from the wash-out of the hyperpolarized xenon signal in the brain. An increase in brain perfusion during maturation was observed. These experiments showed that hyperpolarized xenon MRI can be used to develop unique approaches to studying white matter and gray matter in the brain. Some of the possible applications of hyperpolarized xenon MRI in the brain are clinical diagnosis of white matter diseases, functional MRI (fMRI) and measurement of cerebral blood perfusion.

Influence of low-power laser radiation on mast cells function and biogenic amines content in stress

NASA Astrophysics Data System (ADS)

Brill, Gregory E.; Dobrovolsky, Gennady A.; Romanova, Tatyana P.; Brill, Alexander G.

1997-06-01

In experiments on white male rats stress was modeled by combined action of immobilization and sound stimulus during 2 h. It was established that stress induced storage of secretory material and accumulation of biogenic amines in mast cells. Preliminary transcutaneous He-Ne laser irradiation prevented stress-induced changes.

Speech and swallowing disorders in Parkinson disease.

PubMed

Sapir, Shimon; Ramig, Lorraine; Fox, Cynthia

2008-06-01

To review recent research and clinical studies pertaining to the nature, diagnosis, and treatment of speech and swallowing disorders in Parkinson disease. Although some studies indicate improvement in voice and speech with dopamine therapy and deep brain stimulation of the subthalamic nucleus, others show minimal or adverse effects. Repetitive transcranial magnetic stimulation of the mouth motor cortex and injection of collagen in the vocal folds have preliminary data supporting improvement in phonation in people with Parkinson disease. Treatments focusing on vocal loudness, specifically LSVT LOUD (Lee Silverman Voice Treatment), have been effective for the treatment of speech disorders in Parkinson disease. Changes in brain activity due to LSVT LOUD provide preliminary evidence for neural plasticity. Computer-based technology makes the Lee Silverman Voice Treatment available to a large number of users. A rat model for studying neuropharmacologic effects on vocalization in Parkinson disease has been developed. New diagnostic methods of speech and swallowing are also available as the result of recent studies. Speech rehabilitation with the LSVT LOUD is highly efficacious and scientifically tested. There is a need for more studies to improve understanding, diagnosis, prevention, and treatment of speech and swallowing disorders in Parkinson disease.

Animals in biomedical space research

NASA Technical Reports Server (NTRS)

Phillips, R. W.

1986-01-01

Rat and squirrel monkeys experiments have been planned in concert with human experiments to help answer fundamental questions concerning the effect of weightlessness on mammalism function. For the most part, these experiments focus on identified changes noted in humans during space flight. Utilizing space laboratory facilities, manipulative experiments can be completed while animals are still in orbit. Other experiments are designed to study changes in gravity receptor structure and function and the effect of weightlessness on early vertibrate development. Following these preliminary animal experiments on Spacelab Shuttle flights, longer term programs of animal investigation will be conducted on Space Station.

Effect of Pulsed Radiofrequency on Rat Sciatic Nerve Chronic Constriction Injury: A Preliminary Study

PubMed Central

Li, Duo-Yi; Meng, Lan; Ji, Nan; Luo, Fang

2015-01-01

Background: Pulsed radiofrequency (PRF) application to the dorsal root ganglia can reduce neuropathic pain (NP) in animal models, but the effect of PRF on damaged peripheral nerves has not been examined. We investigated the effect of PRF to the rat sciatic nerve (SN) on pain-related behavior and SN ultrastructure following chronic constriction injury (CCI). Methods: The analgesic effect was measured by hindpaw mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). Twenty rats with NP induced by ligating the common SN were then randomly divided into a PRF treatment group and a sham group. The contralateral SN served as a control. The MWT and TWL were determined again 2, 4, 6, 8, 10, 12, and 14 days after the PRF or sham treatment. On day 14, ipsilateral and contralateral common SNs were excised and examined by electron microscopy. Results: Ipsilateral MWT was significantly reduced and TWL significantly shorter compared to the contralateral side 14 days after CCI (both P = 0.000). In the PRF group, MWT was significantly higher and TWL significantly longer 14 days after the PRF treatment compared to before PRF treatment (both P = 0.000), while no such difference was observed in the sham group (P > 0.05). Electron microscopy revealed extensive demyelination and collagen fiber formation in the ipsilateral SN of sham-treated rats but sparse demyelination and some nerve fiber regrowth in the PRF treatment group. Conclusions: Hyperalgesia is relieved, and ultrastructural damage ameliorated after direct PRF treatment to the SN in the CCI rat model of NP. PMID:25673460

Determination of metabolic profile of anti-malarial trioxane CDRI 99/411 in rat liver microsomes using HPLC.

PubMed

Mishra, Smriti; Manickavasagam, Lakshmi; Jain, Girish Kumar

2012-01-01

CDRI 99/411 is a potent 1,2,4-trioxane anti-malarial candidate compound of the Central Drug Research Institute, India. This study aimed to conduct comprehensive in vitro metabolic investigations of CDRI 99/411 to corroborate its preclinical investigations. Preliminary in vitro metabolic investigations were performed to assess the metabolic stability [in vitro half-life (t(1/2) ) and in vitro hepatic intrinsic clearance (Cl(int) )] of CDRI 99/411 in male Sprague-Dawley rat and human liver microsomes using validated high-performance liquid chromatography with photodiode array detector. The observed in vitro t(1/2) of the compound in rat and human liver microsomes was 13 min with in vitro Cl(int) 130.7±25.0 μL/min/mg and 19 min with in vitro Cl(int) 89.3 ± 17.40 μL/min/mg. These observations suggested moderate metabolic degradation and in vitro Cl(int) with insignificant difference (p>0.05) in the metabolic stability profile in rat and human. Hence, in vitro metabolic investigations were performed with rat liver microsomes. It was observed that CDRI 99/411 exhibited sigmoidal kinetics. At nonlinear regression (r ≥ 0.99) EC(50) and Hill slope values were 17 µm and 1.50, respectively. The metabolism of CDRI 99/411 was primarily mediated by CYP3A2 and was inferred by CYP reaction phenotyping with known potent inhibitors. Two metabolites of CDRI 99/411 were detected which were undetectable on incubation with 1-aminobenzotriazole and ketoconazole. Copyright © 2011 John Wiley & Sons, Ltd.

A preliminary exploration of the potential of Eugenia uvalha Cambess juice intake to counter oxidative stress.

PubMed

Lopes, J M M; Lage, N N; Guerra, J F C; Silva, M; Bonomo, L F; Paulino, A H S; Regis, A L R S; Pedrosa, M L; Silva, M E

2018-03-01

The ability of foods to aid in the prevention of chronic metabolic diseases, has recently become an area of increased interest. In addition, there is growing interest in exploring the benefits of consuming underutilized fruits as alternatives to commercially available fruits. Eugenia uvalha Cambess (uvaia) is a native fruit of Brazil with great market and phytotherapy potential. The present study was conducted to investigate the effects of uvaia juice (UJ) on the levels of protein carbonyls (PCO) and antioxidant enzymes in the livers of rats fed a high-fat diet. Thirty-two female rats were randomly assigned to four groups. The rats were fed either a standard diet (group C) or a high-fat diet (group HF). In addition, groups CUJ and HFUJ were treated with UJ (2mL/day) administered via gavage for 8weeks. In our study, UJ displayed high antioxidant activity (135.14±9.74 GAE/100g). Administration of UJ caused a significantly reduced concentration of rat liver PCO (47.4%), which was associated with a 29% increase in catalase activity. A significant increase in the concentration of oxidized glutathione (GSSG) (15.04±5.08nmol/ml) and a reduction in the reduced glutathione/oxidized glutathione ratio (GSH/GSSG) (11.30±2.68) were found in the HF group, whilst these changes were not observed in the HFUJ group (a result similar to that of group C). Our results demonstrate that UJ decreases oxidative damage by improving antioxidant efficiency and attenuating oxidative damage to proteins. Copyright © 2017 Elsevier Ltd. All rights reserved.

Possible application of urinary analysis to estimate dissolution of some man-made vitreous fibers.

PubMed Central

Wastiaux, A; Blanchard, O; Honnons, S

1994-01-01

A preliminary study at the institut National de l'Environnement Industriel et des Risques (INERIS) examined the dissolution of three man-made vitreous fiber samples (glasswool, rockwool, glass microfibers: JM 100) after intraperitoneal injections in male Wistar rats. The chemical composition of the original fibers was determined by inductively coupled plasma spectrometry (ICP). The urine of the rats was collected at fixed times between day 1 and day 204, and the ICP was used to look for elements known to be present in the original fibers. At day 204, a piece of omentum was removed at autopsy, ashed and analyzed by energy dispersive X-ray analysis (EDXA) to identify the elements remaining in the fibers. Silicon and aluminium were retained in the fibers from all samples at day 204. Losses in calcium, sodium, magnesium, and sulfur were observed, but these elements were not studied in the urine samples because they are naturally present in relatively high concentrations in rat cells and biological fluids. Although there was a loss of zinc from the glass microfibers, no corresponding difference was observed between the zinc levels excreted by the treated animals and by the controls. Similarly, despite the loss of manganese from the rockwool fibers at day 204, none was detectable in the urine samples. Titanium, present at the 0.3% level in rockwool, was not detectable by EDXA at day 204, but small quantities were detected in the first 2 weeks in the urine samples of rats treated with rockwool.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7882936

The Antinociceptive Effects of Tualang Honey in Male Sprague-Dawley Rats: A Preliminary Study

PubMed Central

Aziz, Che Badariah Abd; Ismail, Che Aishah Nazariah; Hussin, Che Maraina Che; Mohamed, Mahaneem

2014-01-01

Tualang honey (蜂蜜 Fēng Mì) is known to have anti-inflammatory property, but its antinociceptive property has not been extensively investigated. In this study, we examined the preemptive effects on administering different doses of Tualang honey and prednisolone on the nociceptive response in male Sprague-Dawley rats. Thirty-five male Sprague-Dawley rats were randomized into five groups (n = 7) and each group received either distilled water, Tualang honey (0.2, 1.2 or 2.4 g/kg) or prednisolone (10 mg/kg) for 10 days. The response to noxious thermal stimulus was assessed using tail flick test on Day 10. The well-being of the rats was also assessed by monitoring their food intake and body weight. Data were analyzed using one-way Analysis of Variance (ANOVA) with post-hoc Scheffe's test and P value less than 0.05 was considered significant. In tail flick test, the tail flick latency time was significantly higher in the groups that received 1.2 g/kg and 2.4 g/kg of Tualang honey and 10 mg/kg of prednisolone, compared to the control group (P < 0.05). There was significant reduction in the total food pellet intake in the groups receiving prednisolone and Tualang honey (1.2 g/kg and 2.4 g/kg) compared to controls; however, the body weight gain was only significantly reduced in the prednisolone group. All the parameters were not significantly affected in the group receiving 0.2 g/kg of Tualang honey. In conclusion, preemptive administration of Tualang honey (1.2 g/kg and 2.4 g/kg) and prednisolone (10 mg/kg) had reduced the pain responses. The reduced weight gain in the prednisolone group is an unwanted effect due to its metabolic and central actions. Further studies are required to confirm the antinociceptive effects and elucidate the mechanism of antinociceptive action of Tualang honey in the rats. PMID:25379476

Results and Implications of Mineralogical Models for Chemical Sediments at Meridiani Planum

NASA Technical Reports Server (NTRS)

Clark, B. C.; McLennan, S. M.; Morris, R. V.; Gellert, R.; Jolliff, B.; Knoll, A.; Lowenstein, T. K.; Ming, D. W.; Tosca, N. J.; Christensen, P. R.

2005-01-01

The Mars Exploration Rover (MER) "Opportunity" has explored chemically-enriched sedimentary outcrops at Meridiani Planum, Mars. In its first year, three different crater sites - Eagle, Fram and Endurance - have been explored. Nineteen high-interest outcrop rocks were investigated by first grinding a hole to reach the interior (using the Rock Abrasion Tool, RAT), and then conducting APXS (alpha particle x-ray spectrometry) analysis, MB (M ssbauer) analysis, and close up imaging (MI, microscopic imager). Sixteen elements and four Fe-bearing minerals were assayed to good accuracy in each sample, producing 380 compositional data points. The Miniature Thermal Emission Spectrometer (Mini- TES) obtained spectra on outcrop materials which provide direct indication of several mineral classes. Preliminary reports on Eagle crater and three RAT samples have been published. Chemical trends and a derived mineralogical model for all RAT d outcrop samples to date has been developed.

Gadolinium heteropoly complex K 17[Gd(P 2W 17O 61) 2] as a potential MRI contrast agent

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Wu, Huifeng; Pei, Fengkui; Fang, Ke; Lei, Hao

2004-10-01

Gadolinium heteropoly complex K17[Gd(P2W17O61)2] has been evaluated by in vitro and in vivo experiments as a potential contrast agent for magnetic resonance imaging (MRI). The thermal analysis and conductivity study indicate that this complex has good thermal stability and wide pH stability range. The T1 relaxivity is 7.59 mM-1 s-1 in aqueous solution and 7.97 mM-1 s-1 in 0.725 mmol l-1 bovine serum albumin (BSA) solution at 25 °C and 9.39 T, respectively. MR imaging of three male Sprague-Dawley rats showed remarkable enhancement in rat liver after intravenous injection, which persisted longer than with Gd-DTPA. The signal intensity increased by 57.1±16.9% during the whole imaging period at 0.082 mmol kg-1dose. Our preliminary in vitro and in vivo studies indicate that K17[Gd(P2W17O61)2] is a potential liver-specific MRI contrast agent.

Synthesis and evaluation of novel polysaccharide-Gd-DTPA compounds as contrast agent for MRI

NASA Astrophysics Data System (ADS)

Sun, Guoying; Feng, Jianghua; Jing, Fengying; Pei, Fengkui; Liu, Maili

2003-09-01

Macromolecular conjugates of two kinds of natural polysaccharides, that from Panax quinquefolium linn (PQPS) and Ganoderma applanatum pat (GAPS), with gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA) have been synthesized and characterized by means of FTIR, elementary analysis and ICP-AES. Their stability was investigated by competition study with Ca 2+, EDTA (ethylenediaminetetraacetic acid) and DTPA. Polysaccharide-bound complexes exhibit T1 relaxivities of 1.5-1.7 times that of Gd-DTPA in D 2O at 25°C and 9.4 T. MR imaging of Sprague-Dawley (SD) rats showed remarkable enhancement in rat liver and kidney after i.v. injection of these two complexes: liver parenchyma 60.9±5.6%, 57.8±7.4% at 65-85 min; kidney 144.9±14.5%, 199.9±25.4% at 10-30 min for PQPS-Gd-DTPA, GAPS-Gd-DTPA at gadolinium dose of 0.083 and 0.082 mmol/kg, respectively. Our preliminary in vivo and in vitro study indicates that the two kinds of polysaccharide-bound complexes are potential tissue-specific contrast agents for MRI.

Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach.

PubMed

Nara, Hiroshi; Sato, Kenjiro; Naito, Takako; Mototani, Hideyuki; Oki, Hideyuki; Yamamoto, Yoshio; Kuno, Haruhiko; Santou, Takashi; Kanzaki, Naoyuki; Terauchi, Jun; Uchikawa, Osamu; Kori, Masakuni

2014-11-13

Matrix metalloproteinase-13 (MMP-13) has been implicated to play a key role in the pathology of osteoarthritis. On the basis of X-ray crystallography, we designed a series of potent MMP-13 selective inhibitors optimized to occupy the distinct deep S1' pocket including an adjacent branch. Among them, carboxylic acid inhibitor 21k exhibited excellent potency and selectivity for MMP-13 over other MMPs. An effort to convert compound 21k to the mono sodium salt 38 was promising in all animal species studied. Moreover, no overt toxicity was observed in a preliminary repeat dose oral toxicity study of compound 21k in rats. A single oral dose of compound 38 significantly reduced degradation products (CTX-II) released from articular cartilage into the joint cavity in a rat MIA model in vivo. In this article, we report the discovery of highly potent, selective, and orally bioavailable MMP-13 inhibitors as well as their detailed structure-activity data.

Optical coherence tomography based microangiography for quantitative monitoring of structural and vascular changes in a rat model of acute uveitis in vivo: a preliminary study

NASA Astrophysics Data System (ADS)

Choi, Woo June; Pepple, Kathryn L.; Zhi, Zhongwei; Wang, Ruikang K.

2015-01-01

Uveitis models in rodents are important in the investigation of pathogenesis in human uveitis and the development of appropriate therapeutic strategies for treatment. Quantitative monitoring of ocular inflammation in small animal models provides an objective metric to assess uveitis progression and/or therapeutic effects. We present a new application of optical coherence tomography (OCT) and OCT-based microangiography (OMAG) to a rat model of acute anterior uveitis induced by intravitreal injection of a killed mycobacterial extract. OCT/OMAG is used to provide noninvasive three-dimensional imaging of the anterior segment of the eyes prior to injection (baseline) and two days post-injection (peak inflammation) in rats with and without steroid treatments. OCT imaging identifies characteristic structural and vascular changes in the anterior segment of the inflamed animals when compared to baseline images. Characteristics of inflammation identified include anterior chamber cells, corneal edema, pupillary membranes, and iris vasodilation. In contrast, no significant difference from the control is observed for the steroid-treated eye. These findings are compared with the histology assessment of the same eyes. In addition, quantitative measurements of central corneal thickness and iris vessel diameter are determined. This pilot study demonstrates that OCT-based microangiography promises to be a useful tool for the assessment and management of uveitis in vivo.

Effects of syndyphalin-33 on feed intake and circulating measures of growth hormone, cortisol, and immune cell populations in the recently-weaned pig

USDA-ARS?s Scientific Manuscript database

The synthetic met-enkephalin syndyphalin-33 (SD-33) increases feed intake in sheep and transiently increases circulating growth hormone (GH) concentrations in sheep, rats, and pigs. Two experiments were performed to evaluate the effects of SD-33 on recently-weaned pigs. In a preliminary experiment, ...

Use of a simplified method of optical recording to identify foci of maximal neuron activity in the somatosensory cortex of white rats.

PubMed

Inyushin, M Y; Volnova, A B; Lenkov, D N

2001-01-01

Eight mongrel white male rats were studied under urethane anesthesia, and neuron activity evoked by mechanical and/or electrical stimulation of the contralateral whiskers was recorded in the primary somatosensory cortex. Recordings were made using a digital USB chamber attached to the printer port of a Pentium 200MMX computer running standard programs. Optical images were obtained in the barrel-field zone using a differential signal, i.e., the difference signal for cortex images in control and experimental animals. The results obtained here showed that subtraction of averaged sequences of frames yielded images consisting of spots reflecting the probable position of activated groups of neurons. The most effective stimulation consisted of natural low-frequency stimulation of the whiskers. The method can be used for preliminary mapping of cortical zones, as it provides for rapid and reproducible testing of the activity of neuron ensembles over large areas of the cortex.

The predicted secondary structures of class I fructose-bisphosphate aldolases.

PubMed Central

Sawyer, L; Fothergill-Gilmore, L A; Freemont, P S

1988-01-01

The results of several secondary-structure prediction programs were combined to produce an estimate of the regions of alpha-helix, beta-sheet and reverse turns for fructose-bisphosphate aldolases from human and rat muscle and liver, from Trypanosoma brucei and from Drosophila melanogaster. All the aldolase sequences gave essentially the same pattern of secondary-structure predictions despite having sequences up to 50% different. One exception to this pattern was an additional strongly predicted helix in the rat liver and Drosophila enzymes. Regions of relatively high sequence variation generally were predicted as reverse turns, and probably occur as surface loops. Most of the positions corresponding to exon boundaries are located between regions predicted to have secondary-structural elements consistent with a compact structure. The predominantly alternating alpha/beta structure predicted is consistent with the alpha/beta-barrel structure indicated by preliminary high-resolution X-ray diffraction studies on rabbit muscle aldolase [Sygusch, Beaudry & Allaire (1986) Biophys. J. 49, 287a]. Images Fig. 1. (cont.) Fig. 1. PMID:3128269

Toxicokinetic Model Development for the Insensitive Munitions Component 2,4-Dinitroanisole.

PubMed

Sweeney, Lisa M; Goodwin, Michelle R; Hulgan, Angela D; Gut, Chester P; Bannon, Desmond I

2015-01-01

The Armed Forces are developing new explosives that are less susceptible to unintentional detonation (insensitive munitions [IMX]). 2,4-Dinitroanisole (DNAN) is a component of IMX. Toxicokinetic data for DNAN are required to support interpretation of toxicology studies and refinement of dose estimates for human risk assessment. Male Sprague-Dawley rats were dosed by gavage (5, 20, or 80 mg DNAN/kg), and blood and tissue samples were analyzed to determine the levels of DNAN and its metabolite 2,4-dinitrophenol (DNP). These data and data from the literature were used to develop preliminary physiologically based pharmacokinetic (PBPK) models. The model simulations indicated saturable metabolism of DNAN in rats at higher tested doses. The PBPK model was extrapolated to estimate the toxicokinetics of DNAN and DNP in humans, allowing the estimation of human-equivalent no-effect levels of DNAN exposure from no-observed adverse effect levels determined in laboratory animals, which may guide the selection of exposure limits for DNAN. © The Author(s) 2015.

Fibroma induction in rat skin following single or multiple doses of 1.0 GeV/nucleon 56Fe ions from the Brookhaven Alternating Gradient Synchrotron (AGS)

NASA Technical Reports Server (NTRS)

Burns, F. J.; Zhao, P.; Xu, G.; Roy, N.; Loomis, C.

2001-01-01

Rat skin was exposed to the plateau region of the 1.0 GeV/nucleon 56Fe beam at the Brookhaven AGS. Rats were irradiated or not with single of split doses of 56Fe or argon; some 56Fe-exposed rats were fed 250 ppm retinyl acetate continuously in the lab chow beginning 1 week before irradiation. All lesions were noted, photographed and identified for eventual histological diagnosis. The preponderance of the tumors so far are fibromas. The data show that single doses of 56Fe ions are 2 or 3 fold more effective than argon in producing tumors at 4.5 Gy but are about equally effective at 3.0 Gy and 9.0 Gy. The presence of 250 ppm retinyl acetate in the lab chow reduced the incidence of tumors by about 50-60% in comparison to groups exposed only to the radiation. These are preliminary findings based on only about one-fourth the eventual number of tumors expected.

Circadian rhythm of intraocular pressure in the rat.

PubMed

Moore, C G; Johnson, E C; Morrison, J C

1996-02-01

To define the characteristics of the diurnal variation of intraocular pressure (IOP) in eyes of awake rats, ten male brown Norway rats were entrained to a 12-hour light:12-hour dark (12L:12D) lighting schedule and were conditioned to IOP measurement with the TonoPen XL tonometer while awake, using only 0.5% proparacaine HCl anesthesia. The IOP measurements were performed in 4 experiments: Preliminary-IOP was measured at 6-hour intervals in both eyes of each animal, to determine correlation between right and left eyes; Light:Dark-lighting remained the same as in the preliminary experiment, but the measurement schedule was altered so that measurements were obtained at 4-hour intervals in alternating eyes, over two 24-hour light cycles; Dark:Dark-animals were placed in constant dark (0L:24D) and, after 72 h, measurements were obtained at 4-hour intervals in alternating eyes. Animals were then re-entrained to the previous 12L:12D schedule for 7 days, after which they were returned to constant dark and the experiment was repeated; and Dark:Light-animals were entrained to a reversed light:dark cycle (12D:12L) for 28 days, after which measurements were obtained in the same fashion as in the Light:Dark experiment. Close agreement was found between right- and left-eye IOPs. Animals on a 12L:12D schedule exhibited lowest IOP while the lights were on (19.3 +/- 1.9 mm Hg), and highest (31.3 +/- 1.3 mm Hg) while the lights were off. Pressure changes anticipated the change from light to dark and dark to light. This pattern persisted in constant dark, and was reversed when the cycle was changed to 12D:12L. Brown Norway rats possess a regular rhythm of IOP that is entrained by the cycle of light and dark, and persistence of this rhythm in constant dark establishes it as a circadian rhythm. Furthermore, our results indicate that reliable and physiologically meaningful IOP measurements can be obtained in awake rats using the TonoPen XL tonometer.

Vitamin E Phosphate Coating Stimulates Bone Deposition in Implant-related Infections in a Rat Model.

PubMed

Lovati, Arianna B; Bottagisio, Marta; Maraldi, Susanna; Violatto, Martina B; Bortolin, Monica; De Vecchi, Elena; Bigini, Paolo; Drago, Lorenzo; Romanò, Carlo L

2018-06-01

Implant-related infections are associated with impaired bone healing and osseointegration. In vitro antiadhesive and antibacterial properties and in vivo antiinflammatory effects protecting against bone loss of various formulations of vitamin E have been demonstrated in animal models. However, to the best of our knowledge, no in vivo studies have demonstrated the synergistic activity of vitamin E in preventing bacterial adhesion to orthopaedic implants, thus supporting the bone-implant integration. The purpose of this study was to test whether a vitamin E phosphate coating on titanium implants may be able to reduce (1) the bacterial colonization of prosthetic implants and (2) bone resorption and osteomyelitis in a rat model of Staphylococcus aureus-induced implant-related infection. Twelve rats were bilaterally injected in the femurs with S aureus UAMS-1-Xen40 and implanted with uncoated or vitamin E phosphate-coated titanium Kirschner wires without local or systemic antibiotic prophylaxis. Eight rats represented the uninfected control group. A few hours after surgery, two control and three infected animals died as a result of unexpected complications. With the remaining rats, we assessed the presence of bacterial contamination with qualitative bioluminescence imaging and Gram-positive staining and with quantitative bacterial count. Bone changes in terms of resorption and osteomyelitis were quantitatively analyzed through micro-CT (bone mineral density) and semiquantitatively through histologic scoring systems. Six weeks after implantation, we found only a mild decrease in bacterial count in coated versus uncoated implants (Ti versus controls: mean difference [MD], -3.705; 95% confidence interval [CI], -4.416 to -2.994; p < 0.001; TiVE versus controls: MD, -3.063; 95% CI, -3.672 to -2.454; p < 0.001), whereas micro-CT analysis showed a higher bone mineral density at the knee and femoral metaphysis in the vitamin E-treated group compared with uncoated implants (knee joint: MD, -11.88; 95% CI, -16.100 to -7.664; p < 0.001 and femoral metaphysis: MD, -19.87; 95% CI, -28.82 to -10.93; p < 0.001). We found decreased osteonecrosis (difference between medians, 1.5; 95% CI, 1-2; p < 0.002) in the infected group receiving the vitamin E-coated nails compared with the uncoated nails. These preliminary findings indicate that vitamin E phosphate implant coatings can exert a protective effect on bone deposition in a highly contaminated animal model of implant-related infection. The use of vitamin E coatings may open new perspectives for developing coatings that can limit septic loosening of infected implants with bacterial contamination. However, a deeper insight into the mechanism of action and the local release of vitamin E as a coating for orthopaedic implants is required to be used in clinics in the near future. Although this study cannot support the antimicrobial properties of vitamin E, promising results were obtained for bone-implant osseointegration. These preliminary results will require further in vivo investigations to optimize the host response in the presence of antibiotic prophylaxis.

[Preliminary analysis of retinal gene expression profile of diabetic rat].

PubMed

Mei, Yan; Zhou, Hong-ying; Xiang, Tao; Lu, You-guang; Li, Ai-dong; Tang, En-jie; Yang, Hui-jun

2005-10-01

Establishing the retinal gene expression profiles of non-diabetic rat and diabetic rat and comparing the profiles in order to analyze the possible genes related with diabetic retinopathy. The whole retinal transcriptional fragments of non-diabetic rat and 8-week diabetic rat were obtained by restriction fragments differential display-PCR (RFDD-PCR). Bioinformatic analysis of retinal gene expression was performed using soft wares, including Fragment Analysis. After comparison of the expression profiles, the related gene fragments of diabetic retinopathy were initially selected as the target gene of further approach. A total of 3639 significant fragments were obtained. By means of more than 3-fold contrast of fluorescent intensity as the differential expression standard, the authors got 840 differential fragments, accounting for 23.08% of the expressed numbers and including 5 visual related genes, 13 excitatory neruotransmitter genes and 3 inhibitory neurotransmitter genes. At the 8th week, the expression of Rhodopsin kinase, beta-arrestin, Phosducinìrod photoreceptor cGMP-gated channel and Rpe65 as well as iGlu R1-4 were down-regulated. mGluRs and GABA-Rs were all up-regulated, whereas the expression of GlyR was unchanged. These results prompt again that the changes in retinal nervous layer of rat have occurred at an early stage of diabetes. The genes expression pattern of visual related genes and excitatory and inhibitory neurotransmitters in rat diabetic retina have been involved in neuro-dysfunctions of diabetic retina.

Molecular detection of Bartonella coopersplainsensis and B. henselae in rats from New Zealand.

PubMed

Vijayan Genitha Helan, J N; Grinberg, A; Gedye, K; Potter, M A; Harrus, S

2018-06-25

To identify Bartonella spp. in rats from New Zealand using molecular methods. DNA was extracted from the spleens of 143 black rats (Rattus rattus) captured in the Tongariro National Park, New Zealand. PCR was performed using Bartonella genus-specific primers amplifying segments of the 16S-23S rRNA internal transcribed spacer and citrate synthase (gltA) and beta subunit of the RNA polymerase (rpoB) genes. PCR products were sequenced and compared online with sequences stored in the database of the National Center for Biotechnology Information of the United States of America. DNA sequences matching Bartonella coopersplainsensis and B. henselae were detected in samples from 22/143 (15.4%) and 3/143 (2.1%) rats, respectively. Co-occurrence of B. coopersplainsensis and B. henselae sequences was observed in the sample from one rat. Gram-negative fastidious bacteria belonging to the genus Bartonella are associated with a range of human diseases. Rodents play an important role as reservoirs of a broad range of Bartonella species. To our knowledge, this is the first report of a molecular detection of Bartonella spp. DNA in rodents from New Zealand, and the first identification of B. henselae DNA in rats, worldwide. Whereas the public health significance of B. coopersplainsensis remains undefined, B. henselae is the agent of cat scratch disease, and the presence of this bacterium in rats may have public health implications. Our results are preliminary and additional analyses of larger samples, preferably by bacterial culture, would provide more information on the prevalence and diversity of Bartonella spp., in particular B. henselae, in rats.

Diabetes-Induced Changes in the Alternative Splicing of the Slo Gene in Corporal Tissue

PubMed Central

Davies, Kelvin P.; Zhao, Weixin; Tar, Moses; Figueroa, Johanna C.; Desai, Pratik; Verselis, Vytas K.; Kronengold, Jack; Wang, Hong-Zhan; Melman, Arnold; Christ, George J.

2007-01-01

Objectives Erectile dysfunction is a common diabetic complication. Preclinical studies have documented that the Slo gene (encoding the BK or Maxi-K channel α-subunit) plays a critical role in erectile function. Therefore, we determined whether diabetes induces changes in the splicing of the Slo gene relevant to erectile function. Methods Reverse transcriptase-polymerase chain reaction was used to compare Slo splice variant expression in corporal tissue excised from control and streptozotocin (STZ)-induced diabetic Fischer F-344 rats. Splice variants were sequenced, characterized by patch clamping, and fused to green fluorescent protein to determine cellular localization. The impact of altered Slo expression on erectile function was further evaluated in vivo. Results A novel Slo splice variant (SVcyt, with a cytoplasmic location) was predominantly expressed in corporal tissue from control rats. STZ-diabetes caused upregulation of a channel-forming transcript SV0. Preliminary results suggest that SV0 was also more prevalent in the corporal tissue of human diabetic compared with nondiabetic patients. The change in isoform expression in STZ-treated rats was partially reversed by insulin treatment. Intracorporal injection of a plasmid expressing the SV0 transcript, but not SVcyt, restored erectile function in STZ-diabetic rats. Conclusions Alternative splicing of the Slo transcript may represent an important compensatory mechanism to increase the ease with which relaxation of corporal tissue may be triggered as a result of a diabetes-related decline in erectile capacity. PMID:17150299

Endotoxin treatment protects rats against ozone-induced lung edema: with evidence for the role of manganese superoxide dismutase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rahman, I.; Massaro, D.

Ozone is a strong oxidizing agent that can cause lung damage and edema. There is evidence that it does so by causing peroxidation of membrane lipids. However, the elevation in lung activity of copper, zinc superoxide dismutase (Cu, ZnSOD), and manganese superoxide dismutase (MnSOD) during exposure to ozone suggests that increased production of superoxide could contribute to lung edema caused by ozone. This latter observation, and preliminary evidence that treatment of rats with endotoxin elevates lung activity of MnSOD without elevation of the activity of Cu, ZnSOD, catalase (CAT), or glutathione peroxidase (GP), led to the present study. We treatedmore » rats with endotoxin, exposed them to different concentrations of ozone, measured lung wet weight to dry weight ratio, thiobarbituric acid-reactive material (TBAR), and assayed lung tissue for Cu, ZnSOD, MnSOD, CAT, and GP activity. Our major findings are, (1) a strongly edemogenic concentration of ozone-lowered MnSOD activity; (2) endotoxin treatment of air-breathing rats did not decrease lipid peroxidation as indicated by the lung concentration of TBAR; (3) induction of increased MnSOD activity in lung by treatment with endotoxin was associated with virtually complete protection against an otherwise edemogenic concentration of ozone, with less lipid peroxidation, and with less loss of weight; and (4) this protection occurred without elevated Cu, ZnSOD, CAT, or GP activity.« less

Temperature-controlled optical stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Tozburun, Serhat; Hutchens, Thomas C.; McClain, Michael A.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2013-06-01

Optical nerve stimulation (ONS) may be useful as a diagnostic tool for intraoperative identification and preservation of the prostate cavernous nerves (CN), responsible for erectile function, during prostate cancer surgery. Successful ONS requires elevating the nerve temperature to within a narrow range (˜42 to 47°C) for nerve activation without thermal damage to the nerve. This preliminary study explores a prototype temperature-controlled optical nerve stimulation (TC-ONS) system for maintaining a constant (±1°C) nerve temperature during short-term ONS of the rat prostate CNs. A 150-mW, 1455-nm diode laser was operated in continuous-wave mode, with and without temperature control, during stimulation of the rat CNs for 15 to 30 s through a fiber optic probe with a 1-mm-diameter spot. A microcontroller opened and closed an in-line mechanical shutter in response to an infrared sensor, with a predetermined temperature set point. With TC-ONS, higher laser power settings were used to rapidly and safely elevate the CNs to a temperature necessary for a fast intracavernous pressure response, while also preventing excessive temperatures that would otherwise cause thermal damage to the nerve. With further development, TC-ONS may provide a rapid, stable, and safe method for intraoperative identification and preservation of the prostate CNs.

Effects of 3-nitro-l-tyrosine on thyroid function in the rat: an experimental model for the dehalogenase defect

PubMed Central

Green, William L.

1971-01-01

The effects on thyroid function of an inhibitor of tyrosine dehalogenase, 3-nitro-L-tyrosine (MNT) have been investigated in rats. In preliminary studies, marked inhibition of iodotyrosine deiodination was demonstrated in rats drinking 8 mM MNT. A series of experiments was then performed in which rats received Remington low iodine diet and 8 mM MNT as drinking fluid. This regimen had the following effects, compared to the effects of a low iodine diet alone: (a) a decrease in serum protein-bound iodine, elevation of serum thyrotropin level, goiter, and growth inhibition all prevented or reversed by iodine supplements: (b) on initiation of MNT, a 2- to 3-fold increase in the rate of release of radioiodine from the thyroid and concomitant urinary excretion of large amounts of organic iodine: and (c) after 2 wk of MNT, a greatly increased rate of thyroidal uptake and release of 131I, an increase in the ratio of monoiodotyrosine-131I to diiodotyrosine-131I in thyroid proteolysates and the appearance of labeled iodotyrosines in serum. Acute administration of MNT intraperitoneally to rats on either an iodine-deficient or iodine-sufficient diet did not inhibit thyroidal uptake of 131I or alter the distribution of 131I among thyroidal iodoamino acids. It is concluded that MNT is an effective inhibitor of iodotyrosine deiodination in vivo, without other important actions on thyroid function. Thus, MNT treatment affords a model for the human dehalogenase defect. By provoking iodotyrosine secretion and consequent urinary loss of iodine, MNT can exaggerate the effects of a low iodine intake, producing goitrous hypothyroidism despite a rapid rate of iodine turnover in the thyroid. Images PMID:5129302

Effect of co-administration of fluoxetine and amantadine on immunoendocrine parameters in rats subjected to a forced swimming test.

PubMed

Rogóz, Zofia; Kubera, Marta; Rogóz, Katarzyna; Basta-Kaim, Agnieszka; Budziszewska, Bogusława

2009-01-01

Considerable attention has been paid to a possible role of immunological dysregulation in the pathogenesis of depression. It has been reported that combined administration of antidepressant drugs and the non-competitive NMDA receptor antagonist amantadine reduces immobility time in the forced swimming test (FST). Moreover, preliminary clinical data show that such a combination of drugs has a beneficial effect on treatment-resistant depressed patients. Since immune activation and a pro-inflammatory response are clearly evident in treatment-resistant depression, the aim of the present study was to examine the effect of a combination of the antidepressant fluoxetine and amantadine on immunoendocrine parameters in rats subjected to the forced swimming test. The obtained results revealed synergistic antidepressant effects of the combined administration of fluoxetine (10 mg/kg) and amantadine (10 mg/kg) - drugs otherwise ineffective when given separately in the above doses. Antidepressant activity was accompanied with a significant decrease in the capacity of splenocytes to proliferate in response to concanavalin A. Moerover, fluoxetine and the combination of amantadine and fluoxetine reduced relative spleen weight in rats subjected to the FST, compared to rats treated with the vehicle. The combination of amantadine and fluoxetine enhanced the production of the negative immunoregulator interleukin-10 (but not interferon-gamma) in rats subjected to the FST. The exposure to the FST produced an increase in plasma corticosterone levels, which was significantly attenuated by pretreatment with fluoxetine and amantadine. In summary, the antidepressive efficacy of a combination of fluoxetine and amantadine given in suboptimal doses may be related to the negative immunoendocrine effects of these drugs.

Methanol seed extract of Citrus paradisi Macfad lowers blood glucose, lipids and cardiovascular disease risk indices in normal Wistar rats.

PubMed

Adeneye, Adejuwon A

2008-01-01

Alcoholic decoction of Citrus paradisi Macfad (Rutaceae) seed is traditionally used for the management of diabetes mellitus and obesity by the natives of South-West Nigeria. Despite its ancestral use, scientific validations of its therapeutic uses in the management of these conditions are lacking. The present preliminary study was undertaken to evaluate blood glucose and lipid lowering effects as well as cardiovascular disease risk factor-reducing effect of Citrus paradisi Macfad (100% methanol seed extract) in male Wistar rats. Rats, divided into groups I - V, with 6 rats in each group, were gavaged at the dose levels of 10 ml/kg/day of distilled water, 10 ml/kg of body weight/day of dimethyl sulphoxide (DMSO), 100, 300, and 600 mg/kg of body weight/ day of the extract dissolved in 10 ml/kg DMSO, respectively, for 30 days. On day 31, blood samples obtained were assayed for fasting plasma glucose (FPG), total cholesterol (TC), high density lipoprotein (HDL-c), low density lipoprotein (LDL-c), and very low density lipoprotein (VLDL-c) using standard procedures. Cardiovascular disease risk assessing factors such as obesity or body mass index (BMI), atherogenic index (AI), coronary risk index (CRI) were calculated. Results showed significant (p < 0.05, p < 0.001) dose related lowering effects of the extract on FPG, cardiovascular disease risk assessing indices and lipid parameters except HDL-c fraction which was significantly (p < 0.05, p < 0.001) elevated. The extract also induced significant (p < 0.05) dose related weight loss in the treated rats in the latter 15 days of their treatment. These results, therefore, lend support to its therapeutic potentials in the management of suspected type 2 diabetic patients.

Probable neuro sexual mode of action of Casimiroa edulis seed extract versus [correction of verses] sildenafil citrate (Viagra(tm)) on mating behavior in normal male rats.

PubMed

Ali, Syed Tabrez; Rakkah, Nabeeh I

2008-01-01

The present study deals with the aphrodisiac actions of the aqueous extract of the seeds of the hypotensive plant Casimiroa edulis on the sexual behavior of normal male rats. In this investigation 30 healthy male Wister strain white albino rats showing the brisk sexual activity age 15 weeks, weighing 400-450 grams were included. Female rats were artificially brought into estrous by hormonal treatment. Receptivity was checked by exposing them to the male rats and the most receptive females were selected for the stud The mating responses including Mounting Frequency (MF), Intromission Frequency (IF), Mounting Latency (ML), Intromission Latency (IL), Ejaculatory Latency in first and second series (EL1 and EL2) and Post Ejaculatory Interval (PEI) were recorded after treating the animals with 250 mg/kg casimiroa edulis extract (test reference) and 5 mg/kg sildenafil citrate (standard reference) respectively orally per day for 7 days. Both the groups exhibited a significant increase in Mounting Frequency, Intromission Frequency, and first and second ejaculatory latencies, where as Mounting and Intromission latencies and the Post Ejaculatory Interval showed a significant reduction than the controls. Although a similar pattern of mating behavior was observed among the test and the standard groups, however in all the cases as expected, sildenafil produced greater activity than the casimiroa edulis extract. These results suggest the possibility of a similar mode of action of casimiroa edulis and sildenafil citrate on mating behavior in these animals. Our work reported in this research thus provide preliminary evidence that the aqueous seed extract of casimiroa edulis possesses alphrodisiac activity and may be used as an alternative drug therapy to restore sexual functions probably via a neurogenic mode of action.

Potential role of oxidative stress in mediating the effect of altered gravity on the developing rat cerebellum

NASA Astrophysics Data System (ADS)

Sajdel-Sulkowska, Elizabeth M.; Nguon, Kosal; Sulkowski, Zachary L.; Lipinski, Boguslaw

We have previously reported that perinatal exposure to hypergravity affects cerebellar structure and motor coordination in rat neonates. In the present study, we explored the hypothesis that exposure to hypergravity results in oxidative stress that may contribute to the decrease in Purkinje cell number and the impairment of motor coordination in hypergravity-exposed rat neonates. To test this hypothesis we compared cerebellar oxidative stress markers 3-nitrotyrosine (3-NT; an index of oxidative protein modification) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG; an index of oxidative DNA damage) between stationary control (SC) and rat neonates exposed to 1.65 G (HG) on a 24-ft centrifuge from gestational day (G) 8 to postnatal day (P) 21. The levels of 3-NT and 8-OH-dG were determined by specific ELISAs. We also compared the Purkinje cell number (stereorologically) and rotarod performance between the two groups. The levels of 3-NT were increased only in HG females on P6 and on P12 in the cerebellum, and only in HG females on P12 in the extracellabellar tissue. Limited cerebellar data suggests an increase in the levels of 8-OH-dG on P12 only in HG females. In extracerebellar tissue the increase in 8-OH-dG levels was observed in both HG males and HG females except on P6 when it was only observed in HG males. While preliminary, these data suggest that the effect of hypergravity on the developing brain is sex-dependent and may involve oxidative stress. Oxidative stress may, in turn, contribute to the decrease Purkinje cell number and impaired motor behavior observed in hypergravity-exposed rats.

An in vivo MRI Template Set for Morphometry, Tissue Segmentation, and fMRI Localization in Rats

PubMed Central

Valdés-Hernández, Pedro Antonio; Sumiyoshi, Akira; Nonaka, Hiroi; Haga, Risa; Aubert-Vásquez, Eduardo; Ogawa, Takeshi; Iturria-Medina, Yasser; Riera, Jorge J.; Kawashima, Ryuta

2011-01-01

Over the last decade, several papers have focused on the construction of highly detailed mouse high field magnetic resonance image (MRI) templates via non-linear registration to unbiased reference spaces, allowing for a variety of neuroimaging applications such as robust morphometric analyses. However, work in rats has only provided medium field MRI averages based on linear registration to biased spaces with the sole purpose of approximate functional MRI (fMRI) localization. This precludes any morphometric analysis in spite of the need of exploring in detail the neuroanatomical substrates of diseases in a recent advent of rat models. In this paper we present a new in vivo rat T2 MRI template set, comprising average images of both intensity and shape, obtained via non-linear registration. Also, unlike previous rat template sets, we include white and gray matter probabilistic segmentations, expanding its use to those applications demanding prior-based tissue segmentation, e.g., statistical parametric mapping (SPM) voxel-based morphometry. We also provide a preliminary digitalization of latest Paxinos and Watson atlas for anatomical and functional interpretations within the cerebral cortex. We confirmed that, like with previous templates, forepaw and hindpaw fMRI activations can be correctly localized in the expected atlas structure. To exemplify the use of our new MRI template set, were reported the volumes of brain tissues and cortical structures and probed their relationships with ontogenetic development. Other in vivo applications in the near future can be tensor-, deformation-, or voxel-based morphometry, morphological connectivity, and diffusion tensor-based anatomical connectivity. Our template set, freely available through the SPM extension website, could be an important tool for future longitudinal and/or functional extensive preclinical studies. PMID:22275894

Monitoring intracranial pressure based on F-P

NASA Astrophysics Data System (ADS)

Cai, Ting; Tong, Xinglin; Chen, Guangxi

2013-09-01

Intracranial pressure is an important monitoring indicator of neurosurgery. In this paper we adopt all-fiber FP fiber optic sensor, using a minimally invasive operation to realize real-time dynamic monitoring intracranial pressure of the hemorrhage rats, and observe their intracranial pressure regularity of dynamic changes. Preliminary results verify the effectiveness of applications and feasibility, providing some basis for human brain minimally invasive intracranial pressure measurement.

Techniques and instrumental complex for research of influence of microwaves encoded by brain neural signals on biological objects’ psycho physiological state

NASA Astrophysics Data System (ADS)

Gurkovskiy, B. V.; Zhuravlev, B. V.; Onishchenko, E. M.; Simakov, A. B.; Trifonova, N. Yu; Voronov, Yu A.

2016-10-01

New instrumental technique for research of the psycho-physiological reactions of the bio-objects under the microwave electromagnetic radiation, modulated by interval patterns of neural activity in the brain registered under different biological motivations, are suggested. The preliminary results of these new tool tests in real psycho physiological experiments on rats are presented.

Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

PubMed

Foster, Michelle T; Shi, Haifei; Seeley, Randy J; Woods, Stephen C

2011-10-24

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. Published by Elsevier Inc.

Removal of Intra-abdominal Visceral Adipose Tissue Improves Glucose Tolerance in Rats: Role of Hepatic Triglyceride Storage

PubMed Central

Foster, Michelle T.; Shi, Haifei; Seeley, Randy J.; Woods, Stephen C.

2011-01-01

Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. PMID:21683727

Proton density-weighted laryngeal magnetic resonance imaging in systemically dehydrated rats.

PubMed

Oleson, Steven; Lu, Kun-Han; Liu, Zhongming; Durkes, Abigail C; Sivasankar, M Preeti

2018-06-01

Dehydrated vocal folds are inefficient sound generators. Although systemic dehydration of the body is believed to induce vocal fold dehydration, this causative relationship has not been demonstrated in vivo. Here we investigate the feasibility of using in vivo proton density (PD)-weighted magnetic resonance imaging (MRI) to demonstrate hydration changes in vocal fold tissue following systemic dehydration in rats. Animal study. Sprague-Dawley rats (n = 10) were imaged at baseline and following a 10% reduction in body weight secondary to withholding water. In vivo, high-field (7 T), PD-weighted MRI was used to successfully resolve vocal fold and salivary gland tissue structures. Normalized signal intensities within the vocal fold decreased postdehydration by an average of 11.38% ± 3.95% (mean ± standard error of the mean [SEM], P = .0098) as compared to predehydration levels. The salivary glands experienced a similar decrease in normalized signal intensity by an average of 10.74% ± 4.14% (mean ± SEM, P = .0195) following dehydration. The correlation coefficient (percent change from dehydration) between vocal folds and salivary glands was 0.7145 (P = .0202). Ten percent systemic dehydration induced vocal fold dehydration as assessed by PD-weighted MRI. Changes in the hydration state of vocal fold tissue were highly correlated with that of the salivary glands in dehydrated rats in vivo. These preliminary findings demonstrate the feasibility of using PD-weighted MRI to quantify hydration states of the vocal folds and lay the foundation for further studies that explore more routine and realistic magnitudes of systemic dehydration and rehydration. NA. Laryngoscope, 128:E222-E227, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Intravenous mesenchymal stem cell therapy after recurrent laryngeal nerve injury: a preliminary study.

PubMed

Lerner, Michael Z; Matsushita, Takashi; Lankford, Karen L; Radtke, Christine; Kocsis, Jeffery D; Young, Nwanmegha O

2014-11-01

Intravenous administration of mesenchymal stem cells (MSCs) has been recently shown to enhance functional recovery after stroke and spinal cord injury. The therapeutic properties of MSCs are attributed to their secretion of a variety of potent antiinflammatory and neurotrophic factors. We hypothesize that intravenous administration of MSCs after recurrent laryngeal nerve (RLN) injury in the rat may enhance functional recovery. Animal Research. Twelve 250-gram Sprague-Dawley rats underwent a controlled crush injury to the left RLN. After confirming postoperative vocal fold immobility, each rat was intravenously infused with either green fluorescent protein-expressing MSCs or control media in a randomized and blinded fashion. Videolaryngoscopy was performed weekly. The laryngoscopy video recordings were reviewed and rated by a fellowship-trained laryngologist who remained blinded to the intervention using a 0 to 3 scale. At 1 week postinjury, the MSC-infused group showed a trend for higher average functional recovery scores compared to the control group (2.2 vs 1.3), but it did not reach statistical significance (P value of 0.06). By 2 weeks, however, both groups exhibited complete return of function. These pilot data indicate that with complete nerve transection by crush injury of the RLN in rat, there is complete recovery of vocal fold mobility at 2 weeks. At 1 week postinjury, animals receiving intravenous infusion of MSCs showed a trend for greater functional recovery, suggesting a potential beneficial effect of MSCs; however, this did not reach statistical significance. Therefore, no definite conclusions can be drawn from these data and further study is required. N/A. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Can an aversive, extinction-resistant memory trigger impairments in walking adaptability? An experimental study using adult rats.

PubMed

Medeiros, Filipe Mello; de Carvalho Myskiw, Jociane; Baptista, Pedro Porto Alegre; Neves, Laura Tartari; Martins, Lucas Athaydes; Furini, Cristiane Regina Guerino; Izquierdo, Iván; Xavier, Léder Leal; Hollands, Kristen; Mestriner, Régis Gemerasca

2018-02-05

Cognitive demands can influence the adaptation of walking, a crucial skill to maintain body stability and prevent falls. Whilst previous research has shown emotional load tunes goal-directed movements, little attention has been given to this finding. This study sought to assess the effects of suffering an extinction-resistant memory on skilled walking performance in adult rats, as an indicator of walking adaptability. Thus, 36 Wistar rats were divided in a two-part experiment. In the first part (n=16), the aversive, extinction-resistance memory paradigm was established using a fear-conditioning chamber. In the second, rats (n=20) were assessed in a neutral room using the ladder rung walking test before and tree days after inducing an extinction-resistance memory. In addition, the elevated plus-maze test was used to control the influence of the anxiety-like status on gait adaptability. Our results revealed the shock group exhibited worse walking adaptability (lower skilled walking score), when compared to the sham group. Moreover, the immobility time in the ladder rung walking test was similar to the controls, suggesting that gait adaptability performance was not a consequence of the fear generalization. No anxiety-like behavior was observed in the plus maze test. Finally, correlation coefficients also showed the skilled walking performance score was positively correlated with the number of gait cycles and trial time in the ladder rung walking test and the total crossings in the plus maze. Overall, these preliminary findings provide evidence to hypothesize an aversive, extinction-resistant experience might change the emotional load, affecting the ability to adapt walking. Copyright © 2017. Published by Elsevier B.V.

Methodology and evaluation of intracranial pressure response in rats exposed to complex shock waves.

PubMed

Dal Cengio Leonardi, Alessandra; Keane, Nickolas J; Hay, Kathryn; Ryan, Anne G; Bir, Cynthia A; VandeVord, Pamela J

2013-12-01

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.

Radiolabeling of new generation magnetic poly(HEMA-MAPA) nanoparticles with (131) I and preliminary investigation of its radiopharmaceutical potential using albino Wistar rats.

PubMed

Avcıbaşı, Uğur; Demiroğlu, Hasan; Ediz, Melis; Akalın, Hilmi Arkut; Özçalışkan, Emir; Şenay, Hilal; Türkcan, Ceren; Özcan, Yeşim; Akgöl, Sinan; Avcıbaşı, Nesibe

2013-12-01

In this study, N-methacryloyl-l-phenylalanine (MAPA) containing poly(2-hydroxyethylmethacrylate) (HEMA)-based magnetic poly(HEMA-MAPA) nanobeads [mag-poly(HEMA-MAPA)] were radiolabeled with (131) I [(131) I-mag-poly(HEMA-MAPA)], and the radiopharmaceutical potential of (131) I-mag-poly(HEMA-MAPA) was investigated. Quality control studies were carried out by radiochromatographic method to be sure that (131) I binded to mag-poly(HEMA-MAPA) efficiently. In this sense, binding yield of (131) I-mag-poly(HEMA-MAPA) was found to be about 95-100%. In addition to this, optimum radiodination conditions for (131) I-mag-poly(HEMA-MAPA) were determined by thin-layer radiochromatography studies. In addition to thin-layer radiochromatography studies, lipophilicity (partition coefficient) and stability studies for (131) I-mag-poly(HEMA-MAPA) were realized. It was determined that lipophilicities of mag-poly(HEMA-MAPA) and (131) I-mag-poly(HEMA-MAPA) were 0.12 ± 0.01 and 1.79 ± 0.76 according to ACD/logP algorithm program, respectively. Stability of the radiolabeled compound was investigated in time intervals given as 0, 30, 60, 180, and 1440 min. It was found that (131) I-mag-poly(HEMA-MAPA) existed as a stable complex in rat serum within 60 min. After that, biodistribution and scintigraphy studies were carried out by using albino Wistar rats. It was determined that the most important (131) I activity uptake was observed in the breast, the ovary, and the pancreas. Scintigraphy studies well supported biodistribution results. Copyright © 2013 John Wiley & Sons, Ltd.

Intoxication by star fruit (Averrhoa carambola) in six dialysis patients? (Preliminary report)

PubMed

Neto, M M; Robl, F; Netto, J C

1998-03-01

We observed six cases of patients in a dialysis programme who were apparently intoxicated by ingestion of star fruit. After ingestion of 2-3 fruits or 150-200 ml of the fruit juice, the six patients, who had previously been stable in a regular dialysis programme, developed a variety of symptoms ranging from insomnia and hiccups to agitation, mental confusion and (in one case) death. In preliminary investigations to characterize the hypothetical neurotoxin in the fruit, an extract, when injected intraperitoneally or intracerebroventricularly in rats, provoked persistent convulsions of the tonic-clonic type. It appears that star fruit (Averrhoa carambola) contains an excitatory neurotoxin. Patients with renal failure on conservative or dialysis treatment should be dissuaded from ingestion of the fruit.

Chronic implantation of cuff electrodes on the pelvic nerve in rats is well tolerated and does not compromise afferent or efferent fibre functionality

NASA Astrophysics Data System (ADS)

Crook, J. J.; Brouillard, C. B. J.; Irazoqui, P. P.; Lovick, T. A.

2018-04-01

Objective. Neuromodulation of autonomic nerve activity to regulate physiological processes is an emerging field. Vagal stimulation has received most attention whereas the potential of modulate visceral function by targeting autonomic nerves within the abdominal cavity remains under-exploited. Surgery to locate intra-abdominal targets is inherently more stressful than for peripheral nerves. Electrode leads risk becoming entrapped by intestines and loss of functionality in the nerve-target organ connection could result from electrode migration or twisting. Since nociceptor afferents are intermingled with similar-sized visceral autonomic fibres, stimulation may induce pain. In anaesthetised rats high frequency stimulation of the pelvic nerve can suppress urinary voiding but it is not known how conscious animals would react to this procedure. Our objective therefore was to determine how rats tolerated chronic implantation of cuff electrodes on the pelvic nerve, whether nerve stimulation would be aversive and whether nerve-bladder functionality would be compromised. Approach. We carried out a preliminary de-risking study to investigate how conscious rats tolerated chronic implantation of electrodes on the pelvic nerve, their responsiveness to intermittent high frequency stimulation and whether functionality of the nerve-bladder connection became compromised. Main results. Implantation of cuff electrodes was well-tolerated. The normal diurnal pattern of urinary voiding was not disrupted. Pelvic nerve stimulation (up to 4 mA, 3 kHz) for 30 min periods evoked mild alerting at stimulus onset but no signs of pain. Stimulation evoked a modest (<0.5 °C) increase in nerve temperature but the functional integrity of the nerve-bladder connection, reflected by contraction of the detrusor muscle in response to 10 Hz nerve stimulation, was not compromised. Significance. Chronic implantation of cuff electrodes on the pelvic nerve was found to be a well-tolerated procedure in rats and high frequency stimulation did not lead to loss of nerve functionality. Pelvic nerve stimulation has development potential for normalizing voiding dysfunction in conscious rats.

Preliminary investigation for effects of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin system on regulation of high-altitude acclimatization.

PubMed

Liu, Yong-Nian; Ma, Qi-Sheng; Wu, Qiong

2017-05-01

This study aims to investigate the mechanism of hypothalamic Leptin/Ghrelin and arcuate nucleus pro-opiomelanocortin (POMC) system in the regulation of high-altitude acclimatization. SD rats (male) were divided into two groups and separately fed at the 2260m and 4700m altitude. Tow groups contained 5 small groups separately, including 1 d, 3 d, 7 d, 15 d and 30 d, and 8 rats in each group. Blood, cerebrospinal fluid and tissues were taken at setting time. Leptin and Ghrelin were detected by using radioactivity immuno-assay. RNA expression of NPY and POMC were detected by using RT-PCR assay. The number of NPY positive neurons was detected by using immunofluorescence (IF) and cell counting. Other rats were sent to the 4300m and fed in animal room with regular diet and drinking. The results indicated that after being sent to high altitude region, Leptin levels at the 3rd and 7th day were significantly higher than the 1st day, while decreased at 15th, and the level at 30th day was closed to the 1st day. Ghrelin levels decreased at the 3rd, 7th and 15th day, and were lower at the 30th day. Comparing to the 1st day, NPY transcription levels increased at the 7th day, while decreased at the 30th. POMC transcription level decreased at the 7th day, while increased at the 30th gradually. The feeding of the rats fed at the 4300m decreased at the 3rd and the 5th, while increased at the 7th, 15th and 30th day. The weight of the rats changed as the feeding changing. In conclusion, after being sent to the high region, the rats were adaptive to the hypoxia environment gradually, and the steady of neuro-endocrine regulation recovered or established. Copyright © 2017. Published by Elsevier Masson SAS.

Evolutionary Design and Simulation of a Tube Crawling Inspection Robot

NASA Technical Reports Server (NTRS)

Craft, Michael; Howsman, Tom; ONeil, Daniel; Howell, Joe T. (Technical Monitor)

2002-01-01

The Space Robotics Assembly Team Simulation (SpaceRATS) is an expansive concept that will hopefully lead to a space flight demonstration of a robotic team cooperatively assembling a system from its constitutive parts. A primary objective of the SpaceRATS project is to develop a generalized evolutionary design approach for multiple classes of robots. The portion of the overall SpaceRats program associated with the evolutionary design and simulation of an inspection robot's morphology is the subject of this paper. The vast majority of this effort has concentrated on the use and modification of Darwin2K, a robotic design and simulation software package, to analyze the design of a tube crawling robot. This robot is designed for carrying out inspection duties in relatively inaccessible locations within a liquid rocket engine similar to the SSME. A preliminary design of the tube crawler robot was completed, and the mechanical dynamics of the system were simulated. An evolutionary approach to optimizing a few parameters of the system was utilized, resulting in a more optimum design.

Vascularized anal autotransplantation model in rats: preliminary report.

PubMed

Araki, J; Mihara, M; Narushima, M; Iida, T; Sato, T; Koshima, I

2011-11-01

Ostomy has served as an effective surgery for various anorectal disfunctions. However, it must also be noted that those patients suffered greatly from stresses caused by their stoma. Many alternative therapies have been developed, but none have solved this critical issue. Meanwhile, due to the improvements in operative methods and immunosuppressive therapy, allotranplantation has gained great popularity in recent years. Therefore, we began development of an anal transplantation model. The operation was performed in six adult Wistar rats that were divided into two groups. Group 1 underwent vascular anastomoses, while group 2 did not Group 1 grafts survived, fully recovering anal function. However, many of the group 2 grafts did not survive; those that did survive showed major defects in their anus, never recovering anal function. We succeeded in establishing the rat anal transplantation model utilizing super-microsurgery. While research in anal transplantation was behind compared to that in other fields, we hope that this model will bring significant possibilities for the future. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinically Relevant Levels of 4-Aminopyridine Strengthen Physiological Responses in Intact Motor Circuits in Rats, Especially After Pyramidal Tract Injury.

PubMed

Sindhurakar, Anil; Mishra, Asht M; Gupta, Disha; Iaci, Jennifer F; Parry, Tom J; Carmel, Jason B

2017-04-01

4-Aminopyridine (4-AP) is a Food and Drug Administration-approved drug to improve motor function in people with multiple sclerosis. Preliminary results suggest the drug may act on intact neural circuits and not just on demyelinated ones. To determine if 4-AP at clinically relevant levels alters the excitability of intact motor circuits. In anesthetized rats, electrodes were placed over motor cortex and the dorsal cervical spinal cord for electrical stimulation, and electromyogram electrodes were inserted into biceps muscle to measure responses. The motor responses to brain and spinal cord stimulation were measured before and for 5 hours after 4-AP administration both in uninjured rats and rats with a cut lesion of the pyramidal tract. Blood was collected at the same time as electrophysiology to determine drug plasma concentration with a goal of 20 to 100 ng/mL. We first determined that a bolus infusion of 0.32 mg/kg 4-AP was optimal: it produced on average 61.5 ± 1.8 ng/mL over the 5 hours after infusion. This dose of 4-AP increased responses to spinal cord stimulation by 1.3-fold in uninjured rats and 3-fold in rats with pyramidal tract lesion. Responses to cortical stimulation also increased by 2-fold in uninjured rats and up to 4-fold in the injured. Clinically relevant levels of 4-AP strongly augment physiological responses in intact circuits, an effect that was more robust after partial injury, demonstrating its broad potential in treating central nervous system injuries.

Predicting lung dosimetry of inhaled particleborne benzo[a]pyrene using physiologically based pharmacokinetic modeling

PubMed Central

Campbell, Jerry; Franzen, Allison; Van Landingham, Cynthia; Lumpkin, Michael; Crowell, Susan; Meredith, Clive; Loccisano, Anne; Gentry, Robinan; Clewell, Harvey

2016-01-01

Abstract Benzo[a]pyrene (BaP) is a by-product of incomplete combustion of fossil fuels and plant/wood products, including tobacco. A physiologically based pharmacokinetic (PBPK) model for BaP for the rat was extended to simulate inhalation exposures to BaP in rats and humans including particle deposition and dissolution of absorbed BaP and renal elimination of 3-hydroxy benzo[a]pyrene (3-OH BaP) in humans. The clearance of particle-associated BaP from lung based on existing data in rats and dogs suggest that the process is bi-phasic. An initial rapid clearance was represented by BaP released from particles followed by a slower first-order clearance that follows particle kinetics. Parameter values for BaP-particle dissociation were estimated using inhalation data from isolated/ventilated/perfused rat lungs and optimized in the extended inhalation model using available rat data. Simulations of acute inhalation exposures in rats identified specific data needs including systemic elimination of BaP metabolites, diffusion-limited transfer rates of BaP from lung tissue to blood and the quantitative role of macrophage-mediated and ciliated clearance mechanisms. The updated BaP model provides very good prediction of the urinary 3-OH BaP concentrations and the relative difference between measured 3-OH BaP in nonsmokers versus smokers. This PBPK model for inhaled BaP is a preliminary tool for quantifying lung BaP dosimetry in rat and humans and was used to prioritize data needs that would provide significant model refinement and robust internal dosimetry capabilities. PMID:27569524

Identifying 2 prenylflavanones as potential hepatotoxic compounds in the ethanol extract of Sophora flavescens.

PubMed

Yu, Qianqian; Cheng, Nengneng; Ni, Xiaojun

2013-11-01

Zhixue capsule is a prescription for hemorrhoid commonly used in traditional Chinese medicine. This drug was recalled by the State Food and Drug Administration in 2008 because of severe adverse hepatic reactions. Zhixue capsule is composed of ethanol extracts of Cortex Dictamni (ECD) and Sophora flavescens (ESF). In our preliminary study, we observed the hepatotoxic effects of ESF on rat primary hepatocytes. However, ECD did not exhibit hepatotoxicity at the same concentration range. In this study, ESF was evaluated for its potential hepatotoxic effects on rats. Bioassay-guided isolation was used to identify the material basis for hepatotoxicity. Treatment with 1.25 g/kg and 2.5 g/kg ESF significantly elevated the alanine aminotransferase and aspartate aminotransferase levels in the serum. The changes in the levels of transaminases were supported by the remarkable fatty degeneration of liver histopathology. Further investigations using bioassay-guided isolation and analysis indicated that prenylated flavanones accounted for the positive hepatotoxic results. Two isolated compounds were identified, kurarinone and sophoraflavanone G, using nuclear magnetic resonance and mass spectrometry techniques. These compounds have potent toxic effects on primary rat hepatocytes (with IC50 values of 29.9 μM and 16.5 μM) and human HL-7702 liver cells (with IC50 values of 48.2 μM and 40.3 μM), respectively. Consequently, the hepatotoxic constituents of S. flavescens were determined to be prenylated flavanones, kurarinone, and sophoraflavanone G. © 2013 Institute of Food Technologists®

Dot enzyme-linked immunosorbent assay (ELISA) for the detection of Toxocara infection using a rat model.

PubMed

Paller, Vachel Gay V; Besana, Cyrelle M; Valdez, Isabel Kristine M

2017-12-01

Toxocariasis is a zoonotic disease usually caused by dog and cat roundworms, Toxocara canis and T. cati. Detection and diagnosis is difficult in paratenic and accidental hosts, including humans, as they cannot be detected through conventional methods such as fecal examination. Diagnosis therefore relies on immunological methods and molecular methods such as enzyme-linked immunosorbent assay (ELISA) and Western Blot, which are both time-consuming and requires sophisticated equipment. In the Philippines, only a few studies are available on Toxocara seroprevalence. Therefore, there is a need to adapt methods for serodiagnosis of Toxocara infection in humans for the Philippine setting. A dot enzyme linked immunosorbent assay (dot-ELISA) was standardized using T. canis excretory-secretory antigens. Test sera were collected from laboratory rats (Sprague-Dawley strain) experimentally infected with embryonated eggs of T. canis and Ascaris suum as well as rice field rats naturally infected with Taenia taeniaeformis and Nippostrongylus sp. Optimum conditions used were 20 µg/ml antigen concentration and 1:10 serum dilution. The sensitivity, specificity, positive, and negative predictive values were 90% (95% CI 55.5-99.7%), 100% (95% CI 69.2-100.0%), 100% (95% CI 66.4-100%), and 90.9% (95% CI 58.7-99.8%), respectively. Dot-ELISA has the potential to be developed as a cheaper, simpler, and more practical method for detection of anti- Toxocara antibodies on accidental hosts. This is a preliminary study conducted on experimental animals before optimization and standardization for human serum samples.

[Abdominal wall reconstruction with collagen membrane in an animal model of abdominal hernia. A preliminary report].

PubMed

Łukasiewicz, Aleksander; Drewa, Tomasz; Skopińska-Wiśniewska, Joanna; Molski, Stanisław

2008-01-01

Abdominal hernia repair is one of the most common surgical procedures. Current data indicate that the best treatment results are achieved with use of synthetic material to reinforce weakened abdominal wall. Prosthetic materials utilized for hernia repair induce adhesions with underlying viscera. They should be therefore separated from them by a layer of peritoneum otherwise adhesions may cause to serious complications such as bowel-skin fistulas. The aim of our work was to determine if implantation of our collagen membrane into abdominal wall defect induce adhesions in rat model of ventral hernia. The collagen film was obtained by acetic acid extraction of rat tail tendons and than casting the soluble fraction onto polyethylene shits. Abdominal wall defect was created in 10 Wistar male rats. Collagen membranes were implanted into the defect using interrupted polypropylene stitches. After 3 months of observation all animals were sacrificed. No adhesions between path structure and bowel developed. In one often rats (10%) adhesion between fixating stitch and omentum was observed. Complete mesothelium lining and vascular ingrowth were microscopically observed within implanted structure. Promising result requires further confirmation in a larger series of animals.

Simple equation for calculation of plasma clearance for evaluation of renal function without urine collection in rats.

PubMed

Liu, Xiang; Peng, Dejun; Tian, Hao; Lu, Chengyu

2017-01-01

To develop an equation for the evaluation of renal function in rats using three dilutions of plasma samples and to validate this method by comparison with a reference method. The investigation was conducted in Sprague-Dawley (SD) rats after delivery of three doses of iohexol, with blood samples collected before and after dosage using a quantitative blood collection method. Plasma iohexol concentrations were detected by high performance liquid chromatography (HPLC). The extraction recovery of iohexol from plasma was >97.30% and the calibration curve was linear (r 2  = 0.9997) over iohexol concentrations ranging from 10 to 1000 µg/mL. The method had an RE of <9.310 and intra- and inter-day RSD of <5.137% and <3.693%, respectively. The plasma clearance values obtained from the equation correlated closely (r = 0.763) with those obtained using the reference method. The relatively correlation in the results obtained using the method under investigation and the reference method indicate that this new equation can be used for preliminary assessment of renal function in rats. © 2016 Asian Pacific Society of Nephrology.

Regulation of Heat Stress by HSF1 and GR

DTIC Science & Technology

2016-09-01

Geiger PC. (2009). Heat treatment improves glucose tolerance and prevents skeletal muscle insulin resistance in rats fed a high -fat diet . Diabetes...appear to have different effects on the mitochondrial morphology and fission protein in skeletal muscle cells. The signaling pathways involving HSF1...preliminary results show that mitochondrial uncoupling proteins 2 and 3 (UCP2, UCP3) were down-regulated in in the gastrocnemius muscles of INT mice

Retrograde Amnesia in Rats, Produced by Electron Beam Exposure.

DTIC Science & Technology

1983-02-01

radiation. Am J Physiol 215:803-806, 1968. 6. Cronholm, B., and L. Molander. Memory disturbances after electroconvulsive therapy : conditions one month after...stimuli have been demonstrated to be effective in producing RA: e.g., electroconvulsive shock (ECS) (14,19); hypoxia (9); and drugs (3,7). Preliminary...effect argues against ionization as a mechanism of CNS activation. Current induction via electroconvulsive shock (ECS) is known to produce RA (14,19

Synaptic Plasticity In Mammalian Gravity Sensors: Preliminary Results From SLS-2

NASA Technical Reports Server (NTRS)

Ross, M. D.; Hargens, Alan R. (Technical Monitor)

1996-01-01

Sensory conflict is the prevalent theoretical explanation for space adaptation syndrome. This ultrastructural study tests the hypothesis that peripheral gravity sensors (maculae) play a role. Results were obtained from the medial part of utricular maculae of adult rats exposed to microgravity for 14 days, and from controls. Means and statistical significance of synapse counts were calculated using SUPERANOVA(Trademark) and Scheffe's procedure for post-hoc comparisons. Preliminary findings are from 2 sets of 100 serial sections for each dataset. Synapses were doubled numerically in type II hair cells of utricular maculae collected on day 13 inflight compared to controls (11.4 +/- 7.1 vs. 5.3 +/- 3.8; p < 0.0001). Flight mean synaptic number declined rapidly postflight and became comparable to means of controls. Synapses also increased numerically in type I cells inflight (2.4 +/- 1.6 vs. 1.7 +/- 1.0; p < 0.0341). Postflight there were no significant differences in counts. Results concerning shifts in ribbon type and distribution are also largely replicating previous findings from flight studies. Results indicate that mammalian maculae are adaptive endorgans that retain the property of synaptic plasticity into the adult stage. Macular plasticity has clinical implications for balance disorders of peripheral origin.

Preliminary toxicity study of dichloromethane extract of Kielmeyera coriacea stems in mice and rats.

PubMed

Obici, Simoni; Otobone, Fernanda Jacques; da Silva Sela, Vânia Ramos; Ishida, Kelly; da Silva, José Carlos; Nakamura, Celso Vataru; Garcia Cortez, Diógenes Aparício; Audi, Elisabeth Aparecida

2008-01-04

Kielmeyera coriacea Mart. (Clusiaceae), known as "Pau Santo" or "Saco de Boi" in the central Brazilian plateau region, is used to treat several tropical diseases. The present study evaluated the toxic effects of dichloromethane (DcM) extract of Kielmeyera coriacea stems, administered to rodents. In the acute toxicity tests, mice receiving doses of this extract by the oral and intraperitoneal routes, showed reversible effects, with LD50 values of 1503.0 and 538.8 mg/kg, respectively. In the repeated-dose oral (90 days) toxicity tests, male and female Wistar rats were treated by gavage with different doses of DcM extract (5, 25 or 125 mg/kg). In biochemical and haematological evaluations, the results varied widely in respect to dose and sex, with no linear profile, and did not show clinical correlations. In the histopathological examinations, the groups exhibited some changes, but there were no significant differences between the groups compared to the controls. In conclusion, these investigations appeared to indicate the safety of acute and repeated oral administration of the DcM extract of Kielmeyera coriacea stems, which can therefore be continuously used with safety.

St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu Zeping; Yang Xiaoxia; Chan Suiyung

Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1{beta}, IL-2, IL-6), interferon (IFN-{gamma}) and tumor necrosis factor-{alpha} (TNF-{alpha}) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oralmore » SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1{beta}, IL-2, IL-6, IFN-{gamma} and TNF-{alpha} and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1{beta}, IFN-{gamma} and TNF-{alpha} was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-{alpha} mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities.« less

Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats.

PubMed

Ahmed, Danish; Kumar, Vikas; Verma, Amita; Gupta, Pushpraj S; Kumar, Hemant; Dhingra, Vishal; Mishra, Vatsala; Sharma, Manju

2014-07-16

Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats. The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats. Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p < 0.05) decreased the level of TC, TG, and LDL-c, VLDL-c. While it increases the level of HDL-c to a significant (p < 0.05) level. The treatment also resulted in a marked increase in reduced glutathione, glutathione Peroxidase, catalase and superoxide dismutase and diminished level of lipid peroxidation in liver and kidney of STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage. Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Medin, Paul M., E-mail: Paul.medin@utsouthwestern.ed; Boike, Thomas P.

Clinical implementation of spinal radiosurgery has increased rapidly in recent years, but little is known regarding human spinal cord tolerance to single-fraction irradiation. In contrast, preclinical studies in single-fraction spinal cord tolerance have been ongoing since the 1970s. The influences of field length, dose rate, inhomogeneous dose distributions, and reirradiation have all been investigated. This review summarizes literature regarding single-fraction spinal cord tolerance in preclinical models with an emphasis on practical clinical significance. The outcomes of studies that incorporate uniform irradiation are surprisingly consistent among multiple small- and large-animal models. Extensive investigation of inhomogeneous dose distributions in the rat hasmore » demonstrated a significant dose-volume effect while preliminary results from one pig study are contradictory. Preclinical spinal cord dose-volume studies indicate that dose distribution is more critical than the volume irradiated suggesting that neither dose-volume histogram analysis nor absolute volume constraints are effective in predicting complications. Reirradiation data are sparse, but results from guinea pig, rat, and pig studies are consistent with the hypothesis that the spinal cord possesses a large capacity for repair. The mechanisms behind the phenomena observed in spinal cord studies are not readily explained and the ability of dose response models to predict outcomes is variable underscoring the need for further investigation. Animal studies provide insight into the phenomena and mechanisms of radiosensitivity but the true significance of animal studies can only be discovered through clinical trials.« less

Preliminary comparative study on the effect of different chinese drugs for strengthening Pi in antagonizing diet induced obesity.

PubMed

Li, Xiao; Jiang, Ping; Fu, Chang-geng

2010-04-01

To observe the difference in fatty degree, glucose-lipid disorder and adipose-hormones between diet induced obesity (DIO) rats and diet induced obesity resistance (DIO-R) rats, and to explore the effect and acting mechanism of Chinese drugs for strengthening Pi (CD-SP) and those for both strengthening Pi and dissolving phlegm (CD-SPDP) in inhibiting obesity. Excepting eight rats allocated in the blank control group, the other 54 rats were fed with high-lipid forage for 12 weeks to establish models of obesity. Finally, 30 DIO rats and 8 DIO-R rats (shown by their body weight) were obtained. The DIO rats were divided into three groups, which were given gastric perfusion, respectively, with normal saline (Group A), CD-SP (Group B), and CD-SPDP (Group C). Fourteen weeks later, the animals' body weight (BW), length (BL), blood levels of fasting insulin (FIn), fasting glucose (FBG), triglyceride (TG), cholesterol (TC), leptin (LP), neuropeptide Y (NPY), C-reactive protein (CRP), tumor necrosis factor-alpha(TNF-alpha), adiponectin (AN), and resistin (RS) were measured; insulin resistance index (IRI) was calculated, and the degree of obesity and lipid content in abdominal cavity of rats were estimated. Moreover, the levels of LP, CRP, TNF-alpha, AN and RS in homogenate of rats' adipose tissues (ATH) were determined. After 12 weeks of high-lipid diet, the BW of DIO rats was higher than that of normal or DIO-R rats. After a 14-week continuous high-lipid diet feeding, in DIO rats, BW, lipid coefficient (LC), and IRI were significantly increased (P<0.01); serum levels of TNF-alpha, LP and AN were lower, NPY was higher, while the ATH levels of LP and AN were lower and TNF-alpha was higher in DIO rats than in DIO-R rats (P<0.05 or P<0.01); blood levels of FBG and lipids in DIO rats showed an increasing trend but was statistically insignificant (P>0.05); no significant difference was found in serum levels of CRP and RS due to the overly high data dispersion. Comparisons of the 3 DIO groups showed that BW, body weight index (BWI), LC and IRI were significantly lowered after treatment (P<0.01) in Group C, while these indexes were not significantly different between Group A and B; the serum levels of TNF-alpha, LP, and AN increased, NPY decreased in Group B and C, ATH levels of LP and AN increased, and TNF-alpha decreased in the two groups; but NPY, LP, and AN in blood and ATH were higher in Group C than those in Group B (P<0.05 or P<0.01). CD-SPDP could inhibit DIO and IR, showing that the effect is better than that of CD-SP, and its mechanism is related to promotion of LP and AN secretion and elevation of serum NPY.

[The role of non-NMDA glutamate receptors in the EEG effects of chronic administration of noopept GVS-111 in awake rats].

PubMed

Kovalev, G I; Vorob'ev, V V

2002-01-01

Participation of the non-NMDA glutamate receptor subtype in the formation of the EEG frequency spectrum was studied in wakeful rats upon a long-term (10 x 0.2 mg/kg, s.c.) administration of the nootropic dipeptide GVS-111 (noopept or N-phenylacetyl-L-prolyglycine ethylate). The EEGs were measured with electrodes implanted into somatosensor cortex regions, hippocampus, and a cannula in the lateral ventricle. The acute reactions (characteristic of nootropes) in the alpha and beta ranges of EEG exhibited inversion after the 6th injection of noopept and almost completely vanished after the 9th injection. Preliminary introduction of the non-NMDA antagonist GDEE (glutamic acid diethyl ester) in a dose of 1 mumole into the lateral ventricle restored the EEG pattern observed upon the 6th dose of GVS-111. The role of glutamate receptors in the course of a prolonged administration of nootropes, as well as the possible mechanisms accounting for a difference in the action of GVS-111 and piracetam are discussed.

Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats.

PubMed

Andino-Pavlovsky, Victoria; Souza, Annie C; Scheffer-Teixeira, Robson; Tort, Adriano B L; Etchenique, Roberto; Ribeiro, Sidarta

2017-01-01

Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC.

Different patterns of collagen-proteoglycan interaction: a scanning electron microscopy and atomic force microscopy study.

PubMed

Raspanti, M; Congiu, T; Alessandrini, A; Gobbi, P; Ruggeri, A

2000-01-01

The extracellular matrix of unfixed, unstained rat corneal stroma, visualized with high-resolution scanning electron microscopy and atomic force microscopy after minimal preliminary treatment, appears composed of straight, parallel, uniform collagen fibrils regularly spaced by a three-dimensional, irregular network of thin, delicate proteoglycan filaments. Rat tail tendon, observed under identical conditions, appears instead made of heterogeneous, closely packed fibrils interwoven with orthogonal proteoglycan filaments. Pre-treatment with cupromeronic blue just thickens the filaments without affecting their spatial layout. Digestion with chondroitinase ABC rids the tendon matrix of all its interconnecting filaments while the corneal stroma architecture remains virtually unaffected, its fibrils always being separated by an evident interfibrillar spacing which is never observed in tendon. Our observations indicate that matrix proteoglycans are responsible for both the highly regular interfibrillar spacing which is distinctive of corneal stroma, and the strong interfibrillar binding observed in tendon. These opposite interaction patterns appear to be distinctive of different proteoglycan species. The molecular details of proteoglycan interactions are still incompletely understood and are the subject of ongoing research.

Dopamine Modulates Delta-Gamma Phase-Amplitude Coupling in the Prefrontal Cortex of Behaving Rats

PubMed Central

Andino-Pavlovsky, Victoria; Souza, Annie C.; Scheffer-Teixeira, Robson; Tort, Adriano B. L.; Etchenique, Roberto; Ribeiro, Sidarta

2017-01-01

Dopamine release and phase-amplitude cross-frequency coupling (CFC) have independently been implicated in prefrontal cortex (PFC) functioning. To causally investigate whether dopamine release affects phase-amplitude comodulation between different frequencies in local field potentials (LFP) recorded from the medial PFC (mPFC) of behaving rats, we used RuBiDopa, a light-sensitive caged compound that releases the neurotransmitter dopamine when irradiated with visible light. LFP power did not change in any frequency band after the application of light-uncaged dopamine, but significantly strengthened phase-amplitude comodulation between delta and gamma oscillations. Saline did not exert significant changes, while injections of dopamine and RuBiDopa produced a slow increase in comodulation for several minutes after the injection. The results show that dopamine release in the medial PFC shifts phase-amplitude comodulation from theta-gamma to delta-gamma. Although being preliminary results due to the limitation of the low number of animals present in this study, our findings suggest that dopamine-mediated modification of the frequencies involved in comodulation could be a mechanism by which this neurotransmitter regulates functioning in mPFC. PMID:28536507

Phosphodiesterase-3 inhibitor cilostazol reverses endothelial dysfunction with ageing in rat mesenteric resistance arteries.

PubMed

Moreira, Hicla S; Lima-Leal, Geórgia A; Santos-Rocha, Juliana; Gomes-Pereira, Leonardo; Duarte, Gloria P; Xavier, Fabiano E

2018-03-05

Ageing impairs endothelial function, which is considered a hallmark of the development of cardiovascular diseases in elderly. Cilostazol, a phosphodiesterase-3 inhibitor, has antiplatelet, antithrombotic and protective effects on endothelial cells. Here, we hypothesized that cilostazol could improve endothelial function in mesenteric resistance arteries (MRA) from old rats. Using eight-week cilostazol-treated (100mg/kg/day) or untreated 72-week-old Wistar rats, we evaluate the relaxation to acetylcholine, sodium nitroprusside (SNP), forskolin and isoproterenol and the noradrenaline-induced contraction in MRA. Superoxide anion and nitric oxide (NO) was measured by dihydroethidium- and diaminofluorescein-2-emitted fluorescence, respectively. Normotensive old rats had impaired acetylcholine-induced NO- and EDHF-mediated relaxation and increased noradrenaline vasoconstriction than young rats. This age-associated endothelial dysfunction was restored by cilostazol treatment. Relaxation to SNP, forskolin or isoproterenol remained unmodified by cilostazol. Diaminofluorescein-2-emitted fluorescence was increased while dihydroethidium-emitted was decreased by cilostazol, indicating increased NO and reduced superoxide generation, respectively. Cilostazol improves endothelial function in old MRA without affecting blood pressure. This protective effect of cilostazol could be attributed to reduced oxidative stress, increased NO bioavailability and EDHF-type relaxation. Although these results are preliminary, we believe that should stimulate further interest in cilostazol as an alternative for the treatment of age-related vascular disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Preliminary evidence that abscisic acid improves spatial memory in rats.

PubMed

Qi, Cong-Cong; Ge, Jin-Fang; Zhou, Jiang-Ning

2015-02-01

Abscisic acid (ABA) is a crucial phytohormone that exists in a wide range of animals, including humans, and has multiple bioactivities. As direct derivatives of carotenoids, ABA and retinoic acid (RA) share similar molecular structures, and RA has been reported to improve spatial memory in rodents. To explore the potential effects of ABA on spatial learning and memory in rodents, 20mg/kg ABA was administered to young rats for 6weeks, and its effects on behaviour performance were evaluated through a series of behavioural tests. ABA pharmacokinetic analysis revealed that the exogenous ABA was distributed widely in the rat brain, characterised by rapid absorption and slow elimination. The behavioural tests showed that ABA increased both the duration spent in the target quadrant and the frequency it was entered in the probe test of the Morris water maze (MWM) and decreased the latency to locate the target quadrant. Moreover, ABA decreased the latency to enter the novel arm in the Y-maze test, accompanied by increases in the total entries and distance travelled in the three arms. However, there were no significant differences between the ABA-treated and control rats in the open field test and elevated plus-maze test. These results preliminarily indicate that ABA improves spatial memory in MWM and exploratory activity in Y-maze in young rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Fluoroquinolones impair tendon healing in a rat rotator cuff repair model: a preliminary study.

PubMed

Fox, Alice J S; Schär, Michael O; Wanivenhaus, Florian; Chen, Tony; Attia, Erik; Binder, Nikolaus B; Otero, Miguel; Gilbert, Susannah L; Nguyen, Joseph T; Chaudhury, Salma; Warren, Russell F; Rodeo, Scott A

2014-12-01

Recent studies suggest that fluoroquinolone antibiotics predispose tendons to tendinopathy and/or rupture. However, no investigations on the reparative capacity of tendons exposed to fluoroquinolones have been conducted. Fluoroquinolone-treated animals will have inferior biochemical, histological, and biomechanical properties at the healing tendon-bone enthesis compared with controls. Controlled laboratory study. Ninety-two rats underwent rotator cuff repair and were randomly assigned to 1 of 4 groups: (1) preoperative (Preop), whereby animals received fleroxacin for 1 week preoperatively; (2) pre- and postoperative (Pre/Postop), whereby animals received fleroxacin for 1 week preoperatively and for 2 weeks postoperatively; (3) postoperative (Postop), whereby animals received fleroxacin for 2 weeks postoperatively; and (4) control, whereby animals received vehicle for 1 week preoperatively and for 2 weeks postoperatively. Rats were euthanized at 2 weeks postoperatively for biochemical, histological, and biomechanical analysis. All data were expressed as mean ± standard error of the mean (SEM). Statistical comparisons were performed using either 1-way or 2-way ANOVA, with P < .05 considered significant. Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analysis revealed a 30-fold increase in expression of matrix metalloproteinase (MMP)-3, a 7-fold increase in MMP-13, and a 4-fold increase in tissue inhibitor of metalloproteinases (TIMP)-1 in the Pre/Postop group compared with the other groups. The appearance of the healing enthesis in all treated animals was qualitatively different than that in controls. The tendons were friable and atrophic. All 3 treated groups showed significantly less fibrocartilage and poorly organized collagen at the healing enthesis compared with control animals. There was a significant difference in the mode of failure, with treated animals demonstrating an intrasubstance failure of the supraspinatus tendon during testing. In contrast, only 1 of 10 control samples failed within the tendon substance. The healing enthesis of the Pre/Postop group displayed significantly reduced ultimate load to failure compared with the Preop, Postop, and control groups. There was no significant difference in load to failure in the Preop group compared with the Postop group. Pre/Postop animals demonstrated significantly reduced cross-sectional area compared with the Postop and control groups. There was also a significant reduction in area between the Preop and control groups. In this preliminary study, fluoroquinolone treatment negatively influenced tendon healing. These findings indicate that there was an active but inadequate repair response that has potential clinical implications for patients who are exposed to fluoroquinolones before tendon repair surgery. © 2014 The Author(s).

Changes in calcium and iron levels in the brains of rats during kainate induced epilepsy

NASA Astrophysics Data System (ADS)

Ren, Min-Qin; Ong, Wei-Yi; Makjanic, Jagoda; Watt, Frank

1999-10-01

Epilepsy is a recurrent disorder of cerebral function characterised by sudden brief attacks of altered consciousness, motor activity or sensory phenomena, and affects approximately 1% of the population. Kainic acid injection induces neuronal degeneration in rats, is associated with glial hypertrophy and proliferation in the CA3-CA4 fields of hippocampal complex, and is a model for temporal lobe epilepsy. In this study we have applied Nuclear Microscopy to the investigation of the elemental changes within the hippocampus and the cortex areas of the rat brain following kainate injection. Analyses of unstained freeze dried tissue sections taken at 1 day and 1, 2, 3 and 4 weeks following injection were carried out using the Nuclear Microscopy facility at the Research Centre for Nuclear Microscopy, National University of Singapore. Quantitative analysis and elemental mapping indicates that there are significant changes in the calcium levels and distributions in the hippocampus as early as 1 day following injection. Preliminary results indicate a rapid increase in cellular calcium. High levels of calcium can activate calcium dependent proteins and phospholipases. Activation of phospholipase A 2 can be harmful to surrounding neurons through free radical damage. In addition to observed increases in calcium, there was evidence of increases in iron levels. This is consistent with measurements in other degenerative brain disorders, and may signal a late surge in free radical production.

Developmental Exposure to Mild Variable Stress: Adult ...

EPA Pesticide Factsheets

In utero exposure to mild variable stress has been reported to influence learning and memory formation in offspring. Our research aims to examine whether nonchemical environmental stressors will exacerbate effects to chemical exposure. This study utilized a varying stress paradigm to simulate human psychosocial stress incurred during and after pregnancy to identify phenotypic learning changes in adult offspring that are potential stress markers. We additionally wanted to compare these behavioral outcomes to rat performance induced by perinatal exposure to manganese (Mn), a neurotoxic environmental element, at 2 or 5 g/l in drinking water throughout gestation and lactation. Pregnant Long Evans rats were exposed to an unpredictable series of mild stressful events which had previously been shown to increase maternal corticosterone levels. Nonchemical stressors were presented from GD 13 through GD 21 and included varying noise, light, housing, and confinement during both sleep and wake cycles. A subgroup of offspring was also exposed to periods of maternal separation. Starting at PND 97 offspring were trained with a trace fear conditioning protocol whereby rats were exposed to a compound cue (light and tone) followed by 30 seconds (trace period) and a mild foot shock (1mA, 0.5 seconds). Five paired training sessions occurred on the first day. The following day, context and cue learning were assessed by measuring motor activity. Preliminary data suggests adu

Toxicological investigations on the methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

PubMed

Lohiya, Nirmal K; Manivannan, Boomi; Garg, Shipra

2006-10-01

Pre-clinical acute and sub-chronic toxicity studies of the methanol sub-fraction (MSF) of the seeds of Carica papaya, a putative male contraceptive, have been investigated in rats to evaluate safety of the test substance. A single oral dose of MSF at 2000 mg/kg body weight was studied over 14 days for acute toxicity, and daily oral doses of 50, 100, 250 and 500 mg/kg body weight were studied for 28- and 90-day periods for sub-chronic toxicity. Body weight, food and water intake and phenotypical toxicological symptoms were recorded daily. Sperm analysis, hematology, serum clinical biochemistry, libido and pathological examination of vital organs were recorded at the termination of the experimental periods. We observed no overt general toxicity in exposed animals. Food and water intake showed daily fluctuations within control limits. Sperm density showed a significant decrease in all 28- and 90-day repeated dose treated animals whereas total sperm motility inhibition was observed at 250 and 500 mg/kg dose levels at the 28-day time interval but in all dose groups at the 90-day interval. The preliminary results suggest the test substance may be a safe approach to male anti-fertility.

Safety Parameter Considerations of Anodal Transcranial Direct Current Stimulation in Rats

DTIC Science & Technology

2017-10-01

under standard laboratory conditions, including a 12 hour light/ dark cycle with food and water available ad libitum. Following a ten day quarantine...values greater than 7.04619 A/m2 are presented in dark red. The maximum threshold was determined by preliminary analysis corresponding the first...increased. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.). 11

Evaluation of performance impairment by spacecraft contaminants

NASA Technical Reports Server (NTRS)

Geller, I.; Hartman, R. J., Jr.; Mendez, V. M.

1977-01-01

The environmental contaminants (isolated as off-gases in Skylab and Apollo missions) were evaluated. Specifically, six contaminants were evaluated for their effects on the behavior of juvenile baboons. The concentrations of contaminants were determined through preliminary range-finding studies with laboratory rats. The contaminants evaluated were acetone, methyl ethyl ketone (MEK), methyl isobutyl ketone (MIBK), trichloroethylene (TCE), heptane and Freon 21. When the studies of the individual gases were completed, the baboons were also exposed to a mixture of MEK and TCE. The data obtained revealed alterations in the behavior of baboons exposed to relatively low levels of the contaminants. These findings were presented at the First International Symposium on Voluntary Inhalation of Industrial Solvents in Mexico City, June 21-24, 1976. A preprint of the proceedings is included.

Speckle-correlation monitoring of the microhemodynamics of internal organs

NASA Astrophysics Data System (ADS)

Zimnyakov, D. A.; Khmara, M. B.; Vilensky, M. A.; Kozlov, V. V.; Sadovoĭ, A. V.; Gorfinkel, I. V.; Zdrajevsky, R. A.; Isaeva, A. A.

2009-12-01

The results of preliminary experimental studies of the possibility of monitoring blood microcirculation in surface layers of internal organs of laboratory animals in the course of laparotomy using full-field speckle correlometry are presented. The transmission of laser radiation to the probed part of the organ and the delivery of scattered speckle-modulated radiation to the detector (a CMOS camera) are performed using a fiberoptic endoscopic system. In the course of experiments, the microhemodynamics of the intestine, liver, spleen, kidneys, and pancreas in rat in a normal state and under induced ischemia and peritonitis, as well as under the action of drugs with clearly pronounced vasodilative effects (lidocaine, papaverine), is studied. The problems and prospects of speckle-correlation monitoring of the microhemodynamics of internal organs under laboratory and clinical conditions are discussed.

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Pan, Y. T.; Xie, T. Q.; Du, C. W.; Bastacky, S.; Meyers, S.; Zeidel, M. L.

2003-12-01

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

Anti-Cataract Potential of Heliotropium indicum Linn on Galactose-Induced Cataract in Sprague-Dawley Rats.

PubMed

Kyei, Samuel; Koffuor, George A; Ramkissoon, Paul; Abu, Emmanuel K; Sarpong, Josephine F

2017-03-01

To evaluate the anti-cataract potential of an aqueous whole plant extract of Heliotropium indicum (HIE) on galactose-induced cataract in Sprague-Dawley rats. Cataract scores were recorded in 3-week-old Sprague-Dawley rats in which cataract was being induced by an oral administration of 1500 mgkg -1 galactose twice daily for 4 weeks, and concurrently being treated with 30, 100, or 300 mgkg -1 HIE daily over the induction period. Fasting blood glucose was monitored at weekly intervals. Changes in body weight as well as total lens protein, lens glutathione, and superoxide dismutase (SOD) were determined initially, and at the end of the experimental period. Crystalline lens weight-to-body-weight ratio was also determined for the various treatment groups at the end of the experimental period. Preliminary phytochemical screening, total antioxidant capacity, and reducing power assays were conducted on HIE. The 30 and 100 mgkg -1 HIE-treated rats recorded significantly lower (p ≤ 0.05-0.001) cataract scores (indicating very significant delays in cataractogenesis by the 3 rd and 4 th weeks of treatment) and blood glucose levels. Rats with delayed cataractogenesis also exhibited significant (p ≤ 0.05-0.001) weight gain, and reduction in lens weight. Total lens proteins glutathione and SOD levels in the crystalline lens were also significantly preserved (p ≤ 0.01-0.001). HIE showed substantial antioxidant capacity and reducing power. The aqueous whole plant extract of Heliotropium indicum delays cataractogenesis at an optimum dose of 30 mgkg -1 in Sprague-Dawley rats.

In vivo neurometabolic profiling to characterize the effects of social isolation and ketamine-induced NMDA antagonism: a rodent study at 7.0 T.

PubMed

Napolitano, Antonio; Shah, Khalid; Schubert, Mirjam I; Porkess, Veronica; Fone, Kevin C F; Auer, Dorothee P

2014-05-01

Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy ((1)H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-D-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent (1)H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthesia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development.

Development of a liquid chromatography assay for the determination of opicapone and BIA 9-1079 in rat matrices.

PubMed

Gonçalves, Daniela; Alves, Gilberto; Fortuna, Ana; Soares-da-Silva, Patrício; Falcão, Amílcar

2016-03-01

Opicapone is a novel potent, reversible and purely peripheral third generation catechol-O-methyltransferase inhibitor, currently under clinical trials as an adjunct to levodopa therapy for Parkinson's disease. To support additional nonclinical pharmacokinetic studies, a novel high-performance liquid chromatographic method coupled to a diode array detector (HPLC-DAD) to quantify opicapone and its active metabolite (BIA 9-1079) in rat plasma and tissues (liver and kidney) is herein reported. The analytes were extracted from rat samples through a deproteinization followed by liquid-liquid extraction. Chromatographic separation was achieved in less than 10 min on a reversed-phase C18 column, applying a gradient elution program with 0.05 M monosodium phosphate solution (pH 2.45 ± 0.05) and acetonitrile. Calibration curves were linear (r(2)  ≥ 0.994) within the ranges of 0.04-6.0 µg/mL for both analytes in plasma, 0.04-4.0 µg/mL for opicapone in liver and kidney homogenates, and 0.07-4.0 µg/mL and 0.06-4.0 µg/mL for BIA 9-1079 in liver and kidney homogenates, respectively. The overall intra- and inter-day accuracy ranged from -12.68% to 7.70% and the imprecision values did not exceed 11.95%. This new HPLC-DAD assay was also successfully applied to quantify opicapone and BIA 9-1079 in a preliminary pharmacokinetic study. Copyright © 2015 John Wiley & Sons, Ltd.

Quantitative assessment of lung ventilation and microstructure in an animal model of idiopathic pulmonary fibrosis using hyperpolarized gas MRI.

PubMed

Stephen, Michael J; Emami, Kiarash; Woodburn, John M; Chia, Elaine; Kadlecek, Stephen; Zhu, Jianliang; Pickup, Stephen; Ishii, Masaru; Rizi, Rahim R; Rossman, Milton

2010-11-01

The use of hyperpolarized (3)He magnetic resonance imaging as a quantitative lung imaging tool has progressed rapidly in the past decade, mostly in the assessment of the airway diseases chronic obstructive pulmonary disease and asthma. This technique has shown potential to assess both structural and functional information in healthy and diseased lungs. In this study, the regional measurements of structure and function were applied to a bleomycin rat model of interstitial lung disease. Male Sprague-Dawley rats (weight, 300-350 g) were administered intratracheal bleomycin. After 3 weeks, apparent diffusion coefficient and fractional ventilation were measured by (3)He magnetic resonance imaging and pulmonary function testing using a rodent-specific plethysmography chamber. Sensitized and healthy animals were then compared using threshold analysis to assess the potential sensitivity of these techniques to pulmonary abnormalities. No significant changes were observed in total lung volume and compliance between the two groups. Airway resistance elevated and forced expiratory volume significantly declined in the 3-week bleomycin rats, and fractional ventilation was significantly decreased compared to control animals (P < .0004). The apparent diffusion coefficient of (3)He showed a smaller change but still a significant decrease in 3-week bleomycin animals (P < .05). Preliminary results suggest that quantitative (3)He magnetic resonance imaging can be a sensitive and noninvasive tool to assess changes in an animal interstitial lung disease model. This technique may be useful for longitudinal animal studies and also in the investigation of human interstitial lung diseases. Copyright © 2010 AUR. Published by Elsevier Inc. All rights reserved.

In Vivo Neurometabolic Profiling to Characterize the Effects of Social Isolation and Ketamine-Induced NMDA Antagonism: A Rodent Study at 7.0 T

PubMed Central

Napolitano, Antonio

2014-01-01

Continued efforts are undertaken to develop animal models of schizophrenia with translational value in the quest for much needed novel drugs. Existing models mimic specific neurobiological aspects of schizophrenia, but not its full complexity. Here, we used proton magnetic resonance spectroscopy (1H-MRS) to assess the metabolic profile in the prefrontal cortex (PFC) of two established models, rearing in social isolation and acute N-methyl-d-aspartate receptor (NMDA-R) antagonism and their combination. Rats reared in social isolation or group housed underwent ​1H-MRS at baseline and dynamically after ketamine challenge (25mg/kg, intraperitoneal) under isoflurane anesthe sia. A 7 T animal scanner was used to perform spectra acquisition from the anterior cingulate/medial PFC. LCModel was used for metabolite quantification and effects of rearing and ketamine injection were analyzed. Social isolation did not lead to significant differences in the metabolic profile of the PFC at baseline. Ketamine induced a significant increase in glutamine in both groups with significance specifically reached by the group-housed animals alone. Only rats reared in social isolation showed a significant 11% γ-aminobutyric acid (GABA) decrease. This study provides preliminary evidence that social interactions in early life predict the glutamatergic and GABAergic response to acute NMDA-R blockade. The similarity between the prefrontal GABA reduction in patients with schizophrenia and in rats reared as social isolates after challenge with ketamine suggests good potential translational value of this combined animal model for drug development. PMID:23671195

Conservation of body calcium by increased dietary intake of potassium: A potential measure to reduce the osteoporosis process during prolonged exposure to microgravity

NASA Technical Reports Server (NTRS)

Nechay, Bohdan R.

1989-01-01

During the 1988 NASA Summer Faculty Fellowship Program, it was proposed that the loss of skeletal calcium upon prolonged exposure to microgravity could be explained, in part, by a renal maladjustment characterized by an increased urinary excretion of calcium. It was theorized that because the conservation of body fluids and electrolytes depends upon the energy of adenosine triphosphate and enzymes that control the use of its energy for renal ion transport, an induction of renal sodium and potassium-dependent adenosine triphosphatase (Na + K ATPase) by oral loading with potassium would increase the reabsorption of sodium directly and that of calcium indirectly, leading to improved hydration and to reduced calcium loss. Preliminary studies showed the following. Rats drinking water containing 0.2 M potassium chloride for six to 13 days excreted in urine 22 muEq of calcium and 135 muEq of sodium per 100 grams of body weight per day. The corresponding values for control rats drinking tap water were 43 muEq and 269 muEq respectively. Renal Na + K ATPase activity in potassium loaded rats was higher than in controls. Thus, oral potassium loading resulted in increased Na + K ATPase activity and diminished urinary excretion of calcium and of sodium as predicted by the hypothesis. An extension of these studies to humans has the potential of resulting in development of harmless, non-invasive, drug-free, convenient measures to reduce bone loss and other electrolyte and fluid problems in space travelers exposed to prolonged periods of microgravity.

Antihypertensive effect of the methanolic extract from Eruca sativa Mill., (Brassicaceae) in rats: muscarinic receptor-linked vasorelaxant and cardiotonic effects.

PubMed

Salma, Umme; Khan, Taous; Shah, Abdul Jabbar

2018-06-15

Eruca sativa Mill., (Brassicaceae) is a popular remedy for the treatment of hypertension in Pakistan. However, direct effect of the extract and its fractions on blood pressure and vascular tone are unknown. This investigation was aimed to explore the pharmacological base for the traditional use of E. sativa in hypertension. In-vivo blood pressure study was carried out using normotensive and high salt-induced hypertensive rats under anaesthesia. The cardiovascular mechanisms were explored using rat aorta and atria in-vitro. Preliminary phytochemical analysis, spectrophotometric detection of total phenols, flavonoids and HPLC analysis of crude extract were performed using quercetin and erucin as marker compounds. Intravenous injection of crude extract induced a fall in mean arterial pressure (MAP) in both normotensive (max fall: 41.79±1.55% mmHg) and hypertensive (max fall: 58.25±0.91% mmHg) rats. Atropine (1mg/kg) pretreatment attenuated this effect significantly (p < 0.001), suggesting the involvement of muscarinic receptor in its antihypertensive effect. Fractions also induced atropine-sensitive antihypertensive effect. Similarly, oral administration of crude and aqueous extracts resulted a fall in MAP in the hypertensive rats. In isolated rat aortic rings from normotensive rats, crude extract and fractions induced an endothelium-dependent relaxation. This relaxation was partially inhibited with L- NAME and atropine pretreatment and with denudation of aortic rings, indicating involvement of muscarinic receptor-linked nitric oxide (NO). In aorta from the hypertensive rats, crude extract and fractions induced endothelium-independent relaxation. This relaxation was not affected by pretreatment with L- NAME or atropine. Crude extract and fractions also suppressed phenylephrine contractions in Ca +2 free/EGTA medium. In isolated rat atrial preparations, crude extract and fractions induced negative inotropic and chronotropic effects with a positive inotropic effect by the n-hexane fraction, which were not affected with atropine pretreatment. Phytochemical screening and spectrophotometric analysis indicated the presence of phenols and flavonoids, whereas HPLC analysis of crude extract revealed the presence of quercetin (flavonoid) and erucin (isothiocyanate). The results suggest that E. sativa is an antihypertensive remedy which is mainly due to its vasodilatory and partly cardiac effects. Muscarinic receptors-linked NO release and dual inhibitory effect on Ca +2 influx and release underlie the vasodilation. This finding provides pharmacological base to the traditional use of E. sativa in hypertension. The presence of quercetin and erucin further support this finding. Copyright © 2018. Published by Elsevier B.V.

Salubrious effect of Kalpaamruthaa, a modified indigenous preparation in adjuvant-induced arthritis in rats--a biochemical approach.

PubMed

Mythilypriya, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanadam

2008-05-28

Interactions between the phytochemicals and drugs and their combinations are capable of providing longer remissions and perhaps a complete cure for many diseases including rheumatoid arthritis (RA). In addition to articular manifestations in RA, extra-articular signs involving reticuloendothelial and hepatic systems are an indication of more severe disease and thus, have prognostic value. The present study was designed to illustrate the beneficial outcome of the drug Kalpaamruthaa (constituting Semecarpus anacardium nut milk extract, fresh dried powder of Emblica officinalis fruit and honey) in adjuvant-induced arthritic rat model with respect to the changes in extra-articular manifestation involving hematological and cellular constituents. Levels of hematological parameters, cellular constituents, activities of marker enzymes and the level of DNA damage were assessed in control, arthritis-induced, SA, KA and drug control treated rats. Significant decrease (p<0.005) in the levels of Hb, RBC, PCV, total protein, albumin, A/G ratio, plasma uric acid, urinary urea, uric acid, creatinine, FFA, HDL and significant increase (p<0.05) in the levels of WBC, platelet count, ESR, globulin, plasma creatinine, blood glucose, urea, AST, ALT, ALP, TC, FC, TG, PL, LDL and VLDL were observed in arthritic rats. No other significant change was observed in tissue DNA and RNA levels of control and experimental animals. On the contrary an increase in DNA damage was observed in arthritic rats when compared to control animals. The above said derangements were brought back to near normal levels upon SA and KA treatments and KA revealed a profound beneficial effect than SA. The enhanced effect of KA might be attributed to the combined effects of phytoconstituents such as flavonoids, tannins and other compounds such as vitamin C present in KA. Thus KA via this preliminary protective effect might contribute to the amelioration of the disease process.

Laser acupuncture and analgesia: preliminary evidence for a transient and opioid-mediated effect

NASA Astrophysics Data System (ADS)

Whittaker, Peter

2006-02-01

Acupuncture is frequently used to treat pain. Although human pain quantification is difficult and often subjective, in rodent models the tail-flick test provides a well-established and objective assessment of analgesia. This test measures the time taken before a rat withdraws its tail from a heat source. Needle and electroacupuncture at the acupuncture point Spleen-6, located at the tibia's posterior margin above the medial malleolus, has been found to increase tail-flick time in rats. The aim of the current study was to determine if laser acupuncture had a similar effect. A 550 μm diameter optic fiber was used to irradiate Spleen-6 for 2 minutes (690 nm, 130 mW) in female Sprague-Dawley rats. In addition, control experiments were performed in which rats were subjected to sham treatment (restraint but no irradiation) or irradiation of an non-acupuncture point (the tail's dorsal surface, 1cm from the base) using the same laser parameters. The baseline tail-flick time was measured and 15 minutes later the laser acupuncture or the control protocols were performed and tail-flick time re-measured 10 minutes after treatment. Additional experiments were done in which the opioid-blocker naloxone (20 mg/kg, intraperitoneal injection) was administered one hour before laser acupuncture. Tailflick time increased after laser acupuncture (P = 0.0002), but returned to baseline values one hour later. In contrast, no increase was found after either sham treatment or tail irradiation. Pretreatment with naloxone attenuated the increase in tail-flick time. In summary, laser acupuncture exerts a transient analgesic effect which may act via an opioid-mediated mechanism.

Matrix Metalloproteinase-Mediated Blood-Brain Barrier Dysfunction in Epilepsy.

PubMed

Rempe, Ralf G; Hartz, Anika M S; Soldner, Emma L B; Sokola, Brent S; Alluri, Satya R; Abner, Erin L; Kryscio, Richard J; Pekcec, Anton; Schlichtiger, Juli; Bauer, Björn

2018-05-02

The blood-brain barrier is dysfunctional in epilepsy, thereby contributing to seizure genesis and resistance to antiseizure drugs. Previously, several groups reported that seizures increase brain glutamate levels, which leads to barrier dysfunction. One critical component of barrier dysfunction is brain capillary leakage. Based on our preliminary data, we hypothesized that glutamate released during seizures mediates an increase in matrix-metalloproteinase (MMP) expression and activity levels, thereby contributing to barrier leakage. To test this hypothesis, we exposed isolated brain capillaries from male Sprague Dawley rats to glutamate ex vivo and used an in vivo / ex vivo approach of isolated brain capillaries from female Wistar rats that experienced status epilepticus as an acute seizure model. We found that exposing isolated rat brain capillaries to glutamate increased MMP-2 and MMP-9 protein and activity levels, and decreased tight junction protein levels, which resulted in barrier leakage. We confirmed these findings in vivo in rats after status epilepticus and in brain capillaries from male mice lacking cytosolic phospholipase A 2 Together, our data support the hypothesis that glutamate released during seizures signals an increase in MMP-2 and MMP-9 protein expression and activity levels, resulting in blood-brain barrier leakage. SIGNIFICANCE STATEMENT The mechanism leading to seizure-mediated blood-brain barrier dysfunction in epilepsy is poorly understood. In the present study, we focused on defining this mechanism in the brain capillary endothelium. We demonstrate that seizures trigger a pathway that involves glutamate signaling through cytosolic phospholipase A 2 , which increases MMP levels and decreases tight junction protein expression levels, resulting in barrier leakage. These findings may provide potential therapeutic avenues within the blood-brain barrier to limit barrier dysfunction in epilepsy and decrease seizure burden. Copyright © 2018 the authors 0270-6474/18/384301-15$15.00/0.

Honey prevents neurobehavioural deficit and oxidative stress induced by lead acetate exposure in male Wistar rats- a preliminary study.

PubMed

Abdulmajeed, Wahab Imam; Sulieman, Habeeb Bolakale; Zubayr, Maymunah Oloruntosin; Imam, Aminu; Amin, Abdulbasit; Biliaminu, Sikiru Abayomi; Oyewole, Lukuman Aboyeji; Owoyele, Bamidele Victor

2016-02-01

This research sought to investigate the possible neuroprotective effects of honey against lead (Pb)-induced neurotoxicity. Twenty four male Wistar rats were divided into four groups: Control group that received 1 ml/kg distilled orally for 28 days; while groups II-IV received 0.2% lead in drinking water and 1 ml/kg of distilled water, 1 ml/kg of honey, 1.5 ml/kg of honey respectively for 28 days. Anxiety and exploratory activities were determined in the open field test. Memory function was determined using Morris water maze after which the animals were sacrificed. The brains were then excised, homogenized and Lipid peroxidation (MDA), Superoxide dismutase (SOD), Catalase, Glutathione (GSH) and Glutathione -S- Transferase (GST) activities were determined in the brains. Results showed that lead exposure causes decrease in locomotor and exploratory activities; increase anxiety, memory impairment, lipid peroxidation and decrease antioxidant activities. However, co-administration of honey with lead inhibited neurotoxicity as indicated by the improvement in memory function as evidenced by decreased latency period and increased in time spent in target quadrant in honey-fed rats compared to the lead-exposed animals. Furthermore, honey increased locomotion, exploration and decreased anxiety in lead-exposed rats as indicated by the frequency of rearing, freezing duration and the number of line crossed by animals. Also administration of honey improves antioxidant activities as shown by increased brain SOD, GST and GSH activities compared to the lead-treated groups but no significant effect on MDA level. It can be concluded that honey has neuroprotective effects against lead-induced cognitive deficit probably by enhancing antioxidant activities.

A new class of sulfoxide surfactants derived from Tris. Synthesis and preliminary assessments of their properties.

PubMed

Barthélémy, P; Maurizis, J C; Lacombe, J M; Pucci, B

1998-06-16

A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulfide group in sulfoxide moiety in order to provide water solubility to the molecule. The detergent efficiency of these new surfactants were assayed on rat liver cells.

Identification of miRNA Signatures Associated with Epithelial Ovarian Cancer Chemoresistance with Further Biological and Functional Validation of Identified Key miRNAS

DTIC Science & Technology

2016-04-01

hindered by the unreliable analytical results owing largely to biocompatibility problems induced by sensorimplantation (e.g., inflammatory/foreign body...sensors with outer polymeric coatings that slowlygenerate low levels of nitric oxide (NO). Release of NO has been shown to enhance the biocompatibility ...Preliminary biocompatibility experimentssuggested that RSNO levels within the SQ fluid of rats may be sufficient to generate enough local NO to

Rapamycin has paradoxical effects on S6 phosphorylation in rats with and without seizures.

PubMed

Chen, Linglin; Hu, Lin; Dong, Jing-Yin; Ye, Qing; Hua, Nan; Wong, Michael; Zeng, Ling-Hui

2012-11-01

  Accumulating data have demonstrated that seizures induced by kainate (KA) or pilocarpine activate the mammalian target of rapamycin (mTOR) pathway and that mTOR inhibitor rapamycin can inhibit mTOR activation, which subsequently has potential antiepileptic effects. However, a preliminary study showed a paradoxical exacerbation of increased mTOR pathway activity reflected by S6 phosphorylation when rapamycin was administrated within a short period before KA injection. In the present study, we examined this paradoxical effect of rapamycin in more detail, both in normal rats and KA-injected animals.   Normal rats or KA-treated rats pretreated with rapamycin at different time intervals were sacrificed at various time points (1, 3, 6, 10, 15, and 24 h) after rapamycin administration or seizure onset for western blotting analysis. Phosphorylation of mTOR signaling target of Akt, mTOR, Rictor, Raptor, S6K, and S6 were analyzed. Seizure activity was monitored behaviorally and graded according to a modified Racine scale (n = 6 for each time point). Neuronal cell death was detected by Fluoro-Jade B staining.   In normal rats, we found that rapamycin showed the expected dose-dependent inhibition of S6 phosphorylation 3-24 h after injection, whereas a paradoxical elevation of S6 phosphorylation was observed 1 h after rapamycin. Similarly, pretreatment with rapamycin over 10 h before KA inhibited the KA seizure-induced mTOR activation. In contrast, rapamycin administered 1-6 h before KA caused a paradoxical increase in the KA seizure-induced mTOR activation. Rats pretreated with rapamycin 1 h prior to KA exhibited an increase in severity and duration of seizures and more neuronal cell death as compared to vehicle-treated groups. In contrast, rapamycin pretreated 10 h prior to KA had no effect on the seizures and decreased neuronal cell death. The paradoxical effect of rapamycin on S6 phosphorylation was correlated with upstream mTOR signaling and was reversed by pretreatment of perifosine, an Akt inhibitor.   These data indicate the complexity of S6 regulation and its effect on epilepsy. Paradoxical effects of rapamycin need to be considered in clinical applications, such as for potential treatment for epilepsy and other neurologic disorders. Wiley Periodicals, Inc. © 2012 International League Against Epilepsy.

Rapamycin has Paradoxical Effects on S6 Phosphorylation in Rats With and Without Seizures

PubMed Central

Chen, Linglin; Hu, Lin; Dong, Jing-Yin; Ye, Qing; Hua, Nan; Wong, Michael; Zeng, Ling-Hui

2012-01-01

Summary Purpose Accumulating data have demonstrated that seizures induced by kainate (KA) or pilocarpine activate the mammalian target of rapamycin (mTOR) pathway and mTOR inhibitor rapamycin can inhibit mTOR activation which subsequently has potential anti-epileptic effects. However, a preliminary study showed a paradoxical exacerbation of increased mTOR pathway activity reflected by S6 phosphorylation when rapamycin was administrated within a short period before KA injection. In the present study, we examined this paradoxical effect of rapamycin in more detail, both in normal rats and KA-injected animals. Methods Normal Rats or KA-treated rats pretreated with rapamycin at different time interval were sacrificed at various time points (1h, 3h, 6h, 10h, 15h and 24h) after rapamycin administration or seizure onset for Western blotting analysis. Phosphorylation of mTOR signaling target of Akt, mTOR, Rictor, Raptor, S6K and S6 were analyzed. Seizure activity was monitored behaviorally and graded according to a modified Racine scale (n=6 for each time point). Neuronal cell death was detected by Fluoro-Jade B staining. Key findings In normal rats, we found that rapamycin showed the expected dose-dependent inhibition of S6 phosphorylation 3–24 h after injection, while a paradoxical elevation of S6 phosphorylation was observed 1 hour after rapamycin. Similarly, pretreatment with rapamycin over 10 h prior to KA inhibited the KA seizure induced mTOR activation. In contrast, rapamycin administered 1 to 6 hours before KA caused a paradoxical increase in the KA seizure-induced mTOR activation. Rats pretreated with rapamycin 1 h prior to KA exhibited an increase in severity and duration of seizures and more neuronal cell death as compared to vehicle treated groups. In contrast, rapamycin pretreated 10 h prior to KA had no effect on the seizures and decreased neuronal cell death. The paradoxical effect of rapamycin on S6 phosphorylation was correlated with upstream mTOR signaling and was reversed by pre-treatment of perifosine, an Akt inhibitor. Significance These data indicate the complexity of S6 regulation and its effect on epilepsy. Paradoxical effects of rapamycin need to be considered in clinical applications, such as for potential treatment for epilepsy and other neurological disorders. PMID:23145776

[The role of opiate receptors and ATP-dependent potassium channels of mitochondria in the formation of myocardial adaptive resistance to the arrhythmogenic effect of ischemia and reperfusion].

PubMed

Lishmanov, Iu B; Naryzhnaia, N V; Krylatov, A V; Maslov, L N; Bogomaz, S A; Ugdyzhekova, D S; Gross, G J; Stefano, J B

2003-01-01

Preliminary stimulation of opiate receptors (ORs) by intravenous administration of mu agonist DALDA (0.5 mg/kg), delta 1 agonist DPDPE (0.5 mg/kg), and kappa agonist (-)-U-50.488 (1 mg/kg) increases rat myocardial resistance to arrhythmogenic effect of coronary occlusion (10 min) and reperfusion (10 min). Activation of delta 2 ORs (DSLET, 0.5 mg/kg) has no effect on the incidence rate of ischemic and reperfusion arrhythmias. Preliminary administration of glibenclamide (0.3 mg/kg), an inhibitor of KATP channels, blocks the antiarrhythmic effect of DALDA and DPDPE. Repeated short-term exposures of rats to immobilization within two weeks increases the heart tolerance to the arrhythmogenic effect of coronary occlusion and reperfusion. This effect disappears after administration of CTAP (0.5 mg/kg), a mu antagonist, or injection of 5-hydroxydecanoate (5 mg/kg), an inhibitor of mitochondrial KATP channels. The selective antagonists of delta and kappa ORs have no effect on cardiac adaptation-induced resistance to the arrhythmogenic effect of ischemia and reperfusion. We believe that stimulation of mu, delta, and kappa ORs increases myocardial tolerance to the arrhythmogenic effect of ischemia and reperfusion through activation of KATP channels. The antiarrhythmic effect of the adaptation is mediated by stimulation of mu ORs and mitochondrial KATP channels.

Evaluation of efficacy and safety of a herbal medicine used for the treatment of malaria.

PubMed

Ankrah, Nii-Ayi; Nyarko, Alexander K; Addo, Phyllis G A; Ofosuhene, Mark; Dzokoto, Comfort; Marley, Ethel; Addae, Michael M; Ekuban, Frederick A

2003-06-01

Resistance of Plasmodium falciparum to chloroquine has been reported in several countries. Other anti-malarial drugs in use are expensive and not readily accessible to most people in malaria endemic countries. This has led to renewed interest in the development of herbal medicines that have the potential to treat malaria with little or no side effects. This study obtained a preliminary information on the safety and effectiveness of a plant decoction (AM-1), used in treating malaria. The AM-1 is formulated from Jatropha curcas, Gossypium hirsutum, Physalis angulata and Delonix regia. Patients with suspected malaria attending a herbal clinic were enrolled in the study on voluntary basis. They were hospitalized for treatment, clinical observation, biochemical and haematological monitoring, and parasite clearance while on AM-1. In addition male and female Sprague Dawley rats were used to evaluate the acute and subchronic toxicity effects of AM-1. The AM-1 eliminated malaria parasites (Plasmodium falciparum and Plasmodium malarie) from the peripheral blood of patients with malaria. In addition the AM-1 did not show any undesired effects in the patients as well as in laboratory rats. The AM-1, however, showed differential effect on the activities of selected cytochrome P450 isozymes (7-pentoxyresorufin-O-depentylation, 7-ethoxyresorufin-O-deethylation and p-nitrophenol hydroxylase) in relation to sex of the laboratory rats. These results indicate that AM-1 could be used to treat malaria. However, it could precipitate interactions with other drugs via their biotransformation and elimination. The obtained data warrant further studies in a large number of malaria subjects with monitoring for possible drug interactions. Copyright 2003 John Wiley & Sons, Ltd.

Alleviation of ischaemia-reperfusion injury by endogenous estrogen involves maintaining Bcl-2 expression via the ERα signalling pathway.

PubMed

Zhang, Zeng-Li; Qin, Pei; Liu, Yuhong; Zhang, Li-Xia; Guo, Hang; Deng, You-Liang; Yizhao-Liu; Hou, Yu-Shu; Wang, Li-Yang; Miao, Yi; Ma, Yu-Long; Hou, Wu-Gang

2017-04-15

The neuroprotective effects of estrogen against cerebral ischaemia have been confirmed by multiple basic and clinical studies. However, most of these studies used exogenous estrogen administered via different injection methods, and the neuroprotective effects of endogenous estrogen produced by ovaries during different phases of estrous cycle and the underlying mechanisms involved have rarely been explored. In this study, we first identified the stage of estrous cycle via vaginal smears and then measured serum estradiol levels at each phase via radioimmunoassay. We found that the estradiol level was highest in the proestrous and lowest in the diestrous. However, ovariectomy or treatment with the aromatase inhibitor letrozole significantly decreased estradiol levels compared to that of rats in diestrous. Western blotting showed that ovariectomy or letrozole treatment significantly decreased ERα and Bcl-2 protein expression and dramatically increased Bax protein expression compared with the rats in diestrous or proestrous. Rats also underwent 2h of ischaemia via middle cerebral artery occlusion followed by a 24-h reperfusion. Ovariectomy or letrozole treatment significantly decreased the neurological scores and the number of intact neurons detected via Nissl staining and dramatically increased the infarct volume detected via TTC staining and the extent of apoptosis detected via TUNEL staining and Western blotting for cleaved-caspase 3 protein expression. These results demonstrate that endogenous estrogen alleviates ischaemia-reperfusion injury by maintaining Bcl-2 expression via ERα signalling pathway and highlight the neuroprotective effects of endogenous estrogen during different stages of the estrous cycle, providing preliminary information on the underlying mechanism of this process. Copyright © 2017 Elsevier B.V. All rights reserved.

The protective role of the immunomodulator AS101 against chemotherapy-induced alopecia studies on human and animal models.

PubMed

Sredni, B; Xu, R H; Albeck, M; Gafter, U; Gal, R; Shani, A; Tichler, T; Shapira, J; Bruderman, I; Catane, R; Kaufman, B; Whisnant, J K; Mettinger, K L; Kalechman, Y

1996-01-03

The immunomodulator AS101 has been demonstrated to exhibit radioprotective and chemoprotective effects in mice. Following phase-I studies, preliminary results from phase-II clinical trials on non-small-cell-lung-cancer patients showed a reduction in the severity of alopecia in patients treated with AS101 in combination with chemotherapy. To further substantiate these findings, the present study was extended to include 58 patients treated either with the optimal dose of 3 mg/m2 AS101 combined with carboplatin and VP-16, or with chemotherapy alone. As compared with patients treated with chemotherapy alone, there was a significant decrease in the level of alopecia in patients receiving the combined therapy. The newly developed rat model was used to elucidate the protective mechanism involved in this effect. We show that significant prevention of chemotherapy-induced alopecia is obtained in rats treated with Ara-C combined with AS101, administered i.p. or s.c. or applied topically to the dorsal skin. We show that this protection by AS101 is mediated by macrophage-derived factors induced by AS101. Protection by AS101 can be ascribed, at least in part, to IL-1, since treatment of rats with IL-1 RA largely abrogated the protective effect of AS101. Moreover, we demonstrate that in humans there is an inverse correlation between the grade of alopecia and the increase in IL-1 alpha. In addition, protection by AS101 could be related to PGE2 secretion, since injection of indomethacin before treatment with AS101 and Ara-C partly abrogated the protective effect of AS101. To assess the ability of AS101 to protect against chemotherapy-induced alopecia, phase-II clinical trials have been initiated with cancer patients suffering from various malignancies.

Calcium phosphate cement chamber as an immunoisolative device for bioartificial pancreas: in vitro and preliminary in vivo study.

PubMed

Yang, Kai-Chiang; Wu, Chang-Chin; Sumi, Shoichiro; Tseng, Ching-Li; Wu, Yueh-Hsiu Steven; Kuo, Tzong-Fu; Lin, Feng-Huei

2010-05-01

This study examined a calcium phosphate cement (CPC) chamber as an immunoisolative device to facilitate the use of xenogeneic cell sources without immunosuppression for the bioartificial pancreas (BAP). Mouse insulinoma cells were encapsulated in agarose gel and then enclosed in a CPC chamber to create a BAP. Bioartificial pancreas were evaluated by cell viability, live-dead cell ratio, and cytokine-mediated cytotoxicity assay and implanted into the peritoneal cavity of diabetic rats. Nonfasting blood glucose and serum insulin levels were analyzed perioperatively; BAPs were also retrieved for histological examination. Insulinoma cells enclosed in the CPC chamber had normal viability, cell survival, and insulin secretion that was even cultured in media with cytokines. The nonfasting blood glucose level of rats was decreased from 460 +/- 50 to 132 +/- 43 mg/dL and maintained euglycemia for 22 days; serum insulin level was increased from 0.34 +/- 0.11 to 1.43 +/- 0.30 microg/dL after operation. Histological examination revealed the fibrous tissue envelopment, and immune-related cells that competed for oxygen resulting in hypoxia could be attributed to the dysfunction of BAPs. This study proved the feasibility for using a CPC chamber as an immunoisolative device for the BAP. An alternative implanted site should be considered to extend the functional longevity of BAPs in further study.

Increased expression of cyclooxygenase-2 protein during rat hepatocarcinogenesis caused by a choline-deficient, L-amino acid-defined diet and chemopreventive efficacy of a specific inhibitor, nimesulide.

PubMed

Denda, Ayumi; Kitayama, Wakashi; Murata, Akiko; Kishida, Hideki; Sasaki, Yasutaka; Kusuoka, Osamu; Tsujiuchi, Toshifumi; Tsutsumi, Masahiro; Nakae, Dai; Takagi, Hidetoshi; Konishi, Yoichi

2002-02-01

Expression of cyclooxygenase (COX)-2 protein during rat hepatocarcinogenesis associated with fatty change, fibrosis, cirrhosis and oxidative DNA damage, caused by a choline-deficient, L-amino acid-defined (CDAA) diet were investigated in F344 male rats, along with the chemopreventive efficacy of the specific COX-2 inhibitor, nimesulide (NIM). Nimesulide, which was administered in the diet at concentrations of 200, 400, 600 and 800 p.p.m. for 12 weeks, decreased the number and size of preneoplastic enzyme-altered liver foci, levels of oxidative DNA damage, and the grade and incidence of fibrosis in a dose-dependent manner. A preliminary long-term study of 65 weeks also revealed that 800 p.p.m. NIM decreased the multiplicity of neoplastic nodules and hepatocellular carcinomas and prevented the development of cirrhosis. Western blot analysis revealed that COX-2 protein was barely expressed in control livers and increased approximately 2.9-fold in the livers of rats fed on a CDAA diet for 12 weeks and approximately 4.5-5.4-fold in tumors, with a diameter larger than 5 mm, at 80 weeks. Immunohistochemically, COX-2 protein was positive in sinusoidal and stromal cells in fibrotic septa, which were identified by immunoelectron microscopy as Kupffer cells, macrophages, either activated Ito cells or fibroblasts, after exposure to the CDAA diet for 12 weeks, whereas it was only occasionally weakly positive in sinusoidal, probably Kupffer, cells in control livers. In neoplastic nodules in rats fed on a CDAA diet for 30 and 80 weeks, sinusoidal cells and cells with relatively large round nuclei and scanty cytoplasm were strongly positive for COX-2 protein, with the neoplastic hepatocytes in the minority of the nodules, but not the cancer cells, being moderately positive. These results clearly indicate that rat hepatocarcinogenesis, along with fatty change, fibrosis and cirrhosis, is associated with increased expression of COX-2 protein, and point to the chemopreventive efficacy of a selective COX-2 inhibitor against, at least, the early stages of hepatocarcinogenesis.

Effects of repeated administration of the monoamine oxidase inhibitor phenelzine on the discriminability of d-lysergic acid diethylamide (LSD) and 1-(m-trifluoromethylphenyl) piperazine (TFMPP).

PubMed

Cunningham, K A; Carroll, B A; Appel, J B

1986-01-01

Rats trained to discriminate d-lysergic acid diethylamide (LSD; 0.08 mg/kg) or 1-(m-trifluoromethylphenyl) piperazine (TFMPP; 0.8 mg/kg) were treated with the monoamine oxidase inhibitor (MAOI) phenelzine (10 mg/kg/day) for 7 days. After a 24 h "washout" period, they were challenged with the training drug (and dose) or saline, during extinction test sessions. Following 0.08 mg/kg LSD, LSD-trained rats responded primarily on the saline lever (29% drug-appropriate responding) while, after TFMPP (0.8 mg/kg), TFMPP-trained animals responded on the drug lever (75% drug-appropriate responding). These preliminary data suggest that, if serotonin receptors are involved in the behavioral effects of TFMPP, these receptors differ from those involved in the effects of LSD.

Proteomic Analysis of Rat Hippocampus under Simulated Microgravity

NASA Astrophysics Data System (ADS)

Wang, Yun; Li, Yujuan; Zhang, Yongqian; Liu, Yahui; Deng, Yulin

It has been found that microgravity may lead to impairments in cognitive functions performed by CNS. However, the exact mechanism of effects of microgravity on the learning and memory function in animal nervous system is not elucidated yet. Brain function is mainly mediated by membrane proteins and their dysfunction causes degeneration of the learning and memory. To induce simulated microgravity, the rat tail suspension model was established. Comparative O (18) labeling quantitative proteomic strategy was applied to detect the differentially expressed proteins in rat brain hippocampus. The proteins in membrane fraction from rat hippocampus were digested by trypsin and then the peptides were separated by off-gel for the first dimension with 24 wells device encompassing the pH range of 3 - 10. An off-gel fraction was subjected into LC-ESI-QTOF in triplicate. Preliminary results showed that nearly 77% of the peptides identified were specific to one fraction. 676 proteins were identified among which 108 proteins were found differentially expressed under simulated microgravity. Using the KOBAS server, many enriched pathways, such as metabolic pathway, synaptic vesicle cycle, endocytosis, calcium signaling pathway, and SNAREs pathway were identified. Furthermore, it has been found that neurotransmitter released by Ca (2+) -triggered synaptic vesicles fusion may play key role in neural function. Rab 3A might inhibit the membrane fusion and neurotransmitter release. The protein alteration of the synaptic vesicle cycle may further explain the effects of microgravity on learning and memory function in rats. Key words: Microgravity; proteomics; synaptic vesicle; O (18) ({}) -labeling

Effectiveness of lycopene on experimental testicular torsion.

PubMed

Güzel, Mahmut; Sönmez, Mehmet Fatih; Baştuğ, Osman; Aras, Necip Fazıl; Öztürk, Ayşe Betül; Küçükaydın, Mustafa; Turan, Cüneyt

2016-07-01

We aimed to demonstrate the long term effectiveness of lycopene, a precursor of vitamin A, on the testes for ischemia-reperfusion injury. Seventy male Wistar albino rats were used for this experiment. The rats were divided into seven groups. Group 1 served as the control group; group 2 was sham-operated; group 3 received 20mg/kg/day lycopene (intraperitoneally); in group 4, the right testes of rats were kept torted for 2hours and then were detorted and the animals lived for three days; in group 5, the right testes of rats were kept torted for 2hours and then were detorted and the animals lived for ten days; in group 6, the right testes of the rats were kept torted for 2hours and then detorted and the animals received 20mg/kg/day lycopene (intraperitoneally) for three days; in group 7, the right testes of the rats were kept torted for 2hours and then were detorted and the animals received 20mg/kg/day lycopene (intraperitoneally) for ten days. Lycopene was used intraperitoneally. Some of the testes tissues were used for biochemical analyses and the other tissues were used for histological procedures. The Johnsen's score was used for seminiferous tubule deterioration. The TUNEL method was utilized to show apoptosis of testicular tissue. Testosterone levels were measured from blood samples and SOD, MDA, TNF-α, IL-1β and IL-6 measurements were recorded from tissue samples. The results were analyzed statistically. In groups 1, 2 and 3 there was normal testicular structure. Rats in groups 4 and 5 had damaged testicular tissues. In groups 6 and 7, in which we used lycopene, the testes were not better than those in groups 4 and 5. The MSTD and JTBS values were better in group 6, but not in group 7 among the torsion groups. As a result, MDA, SOD, TNF-α and IL-1β were increased and serum testosterone and IL-6 levels were decreased in groups 4 and 5 compared to group 1. There was no improvement in the groups treated with lycopene for therapeutic purposes. It was shown that lycopene, as an antioxidant agent, is not effective for testicular torsion in the long term. This study can be considered as a preliminary study showing the need for further researches using different antioxidant agents to determine their long term effects in ischemia-reperfusion injuries in an appropriate experimental design. Copyright © 2016 Elsevier Inc. All rights reserved.

Renal redox stress and remodeling in metabolic syndrome, type 2 diabetes mellitus, and diabetic nephropathy: paying homage to the podocyte.

PubMed

Hayden, Melvin R; Whaley-Connell, Adam; Sowers, James R

2005-01-01

Type 2 diabetes mellitus has reached epidemic proportions and diabetic nephropathy is the leading cause of end-stage renal disease. The metabolic syndrome constitutes a milieu conducive to tissue redox stress. This loss of redox homeostasis contributes to renal remodeling and parallels the concurrent increased vascular redox stress associated with the cardiometabolic syndrome. The multiple metabolic toxicities, redox stress and endothelial dysfunction combine to weave the complicated mosaic fabric of diabetic glomerulosclerosis and diabetic nephropathy. A better understanding may provide both the clinician and researcher tools to unravel this complicated disease process. Cellular remodeling of podocyte foot processes in the Ren-2 transgenic rat model of tissue angiotensin II overexpression (TG(mREN-2)27) and the Zucker diabetic fatty model of type 2 diabetes mellitus have been observed in preliminary studies. Importantly, angiotensin II receptor blockers have been shown to abrogate these ultrastructural changes in the foot processes of the podocyte in preliminary studies. An integrated, global risk reduction, approach in therapy addressing the multiple metabolic abnormalities combined with attempts to reach therapeutic goals at an earlier stage could have a profound effect on the development and progressive nature to end-stage renal disease and ultimately renal replacement therapy.

Maternal consumption of high-fat diet and grape juice modulates global histone H4 acetylation levels in offspring hippocampus: A preliminary study.

PubMed

Gonçalves, Luciana Kneib; da Silva, Ivy Reichert Vital; Cechinel, Laura Reck; Frusciante, Marina Rocha; de Mello, Alexandre Silva; Elsner, Viviane Rostirola; Funchal, Claudia; Dani, Caroline

2017-11-20

This study aimed to investigate the impact of maternal consumption of a hyperlipid diet and grape juice on global histone H4 acetylation levels in the offsprinǵs hippocampus at different stages of development. During pregnancy and lactation of offspring, dams were divided into 4 groups: control diet (CD), high-fat diet (HFD), control diet and purple grape juice (PGJCD) and purple grape juice and high-fat diet (PGJHFD). Male Wistar rats were euthanized at 21days of age (PN21, adolescents) and at 50days of age (PN50, adults). The maternal consumption of grape juice increased global histone H4 acetylation levels in hippocampus of adolescents pups (PN21), an indicative of enhanced transcriptional activity and increased gene expression. On the other hand, the maternal high-fat diet diminished significantly this epigenetic marker in the adult phase (PN50), suggesting gene silencing. These preliminary findings demonstrated that the maternal choices are able to induce changes on histone H4 acetylation status in hippocampus of the offspring, which may modulate the expression of specific genes. Interestingly, this response occurs in an age and stimuli-dependent manner and strongly reinforce the importance of maternal choices during gestation. Copyright © 2017 Elsevier B.V. All rights reserved.

Effects of hyperbaric, normobaric and hypobaric oxygen supplementation on retinal vessels in newborn rats: a preliminary study.

PubMed

Ricci, B

1987-03-01

An experimental study was conducted on eight litters of newborn rats to evaluate the effects of supplemental oxygen administration on the retinal vasculature. The animals and their mothers were kept inside a pressure chamber and treated for the first 5 days of life. On the sixth day, they were removed and kept for five more days under room air and normobaric conditions. Three litters received continuous flow oxygen at 80% at a compression pressure of +81 kPa, one litter oxygen at 80% at a pressure of -39.5 kPa atms and three other litters received oxygen at 80% under normobaric conditions. The eighth litter was treated with room air oxygen at a compression pressure of +81 kPa. A severe retinopathy with marked retinal neovascularization was seen only in the newborn animals of the litters that received oxygen supplementation under normobaric or hypobaric conditions. Retinal vessels showed no pathological changes in the litters treated with hyperbaric normoxia or hyperoxia. It is possible to hypothesize that the prolonged period of oxygen supplementation failed to produce harmful effects on the retinal vasculature because the moderate hyperbarism caused mild retinal and choroidal vasoconstriction thus preventing excessive oxygen transport to the inner retina from the choroid during hyperoxia without inducing structural damage to the retinal tissue.

A compact, inexpensive infrared laser system for continuous-wave optical stimulation of the rat prostate cavernous nerves

NASA Astrophysics Data System (ADS)

Perkins, William C.; Lagoda, Gwen A.; Burnett, Arthur L.; Fried, Nathaniel M.

2014-03-01

Optical nerve stimulation (ONS) has been commonly performed in the laboratory using high-power, pulsed, infrared (IR) lasers including Holmium:YAG, diode, and Thulium fiber lasers. However, the relatively high cost of these lasers in comparison with conventional electrical nerve stimulation (ENS) equipment may represent a significant barrier to widespread adoption of ONS. Optical stimulation of the prostate cavernous nerves (CN's) has recently been reported using lower cost, continuous-wave (CW), all-fiber-based diode lasers. This preliminary study describes further miniaturization and cost reduction of the ONS system in the form of a compact, lightweight, cordless, and inexpensive IR laser. A 140-mW, 1560-nm diode laser was integrated with a green aiming beam and delivery optics into a compact ONS system. Surface and subsurface ONS was performed in a total of 5 rats, in vivo, with measurement of an intracavernous pressure (ICP) response during CW laser irradiation for 30 s with a spot diameter of 0.7 mm. Short-term, CW ONS of the prostate CN's is feasible using a compact, inexpensive, batterypowered IR laser diode system. This ONS system may represent an alternative to ENS for laboratory studies, and with further development, a handheld option for ONS in the clinic to identify and preserve the CN's during prostate cancer surgery.

Animals in biomedical space research

NASA Astrophysics Data System (ADS)

Phillips, Robert W.

The use of experimental animals has been a major component of biomedical research progress. Using animals in space presents special problems, but also provides special opportunities. Rat and squirrel monkeys experiments have been planned in concert with human experiments to help answer fundamental questions concerning the effect of weightlessness on mammalian function. For the most part, these experiments focus on identified changes noted in humans during space flight. Utilizing space laboratory facilities, manipulative experiments can be completed while animals are still in orbit. Other experiments are designed to study changes in gravity receptor structure and function and the effect of weightlessness on early vertebrate development. Following these preliminary animals experiments on Spacelab Shuttle flights, longer term programs of animal investigation will be conducted on Space Station.

Antidiabetic, renal/hepatic/pancreas/cardiac protective and antioxidant potential of methanol/dichloromethane extract of Albizzia Lebbeck Benth. stem bark (ALEx) on streptozotocin induced diabetic rats

PubMed Central

2014-01-01

Background Hypoglycemic and/or anti-hyperglycemic activities have been recorded with numerous plants, many of which are used as traditional herbal treatments of diabetes. Albizzia Lebbeck Benth. stem bark have been used in traditional medicine along with some preliminary reports on its hypoglycemic action. The aim of present investigation was to evaluate the antidiabetic and antioxidant activities of methanolic extract of stem bark of Albizzia Lebbeck Benth. in streptozotocin induced diabetic rats. Methods The powdered stem bark of Albizzia Lebbeck Benth.. was extracted with methanol (MeOH) using soxhlation method and subjected to phytochemical analysis. The methanol/dichloromethane extract of Albizzia Lebbeck Benth. (ALEx) was concentrated to dryness using Rotary Evaporator. Diabetes was experimentally induced in the rats by single intraperitoneal administration of Streptozotocin (60 mg/kg). They glycemic control was measured by the blood glucose, glycated heamoglobin and plasma insulin. The oxidative stress was evaluated in the liver and kidney by level of antioxidant markers and various biochemical parameters were assessed in diabetic control and extract treated rats. Results Streptozotocin induced diabetic rats depicted the increased blood glucose levels, total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-c), diminished level of high density lipoprotein cholesterol (HDL-c) level and perturb level of antioxidant markers. Oral administration of MeAL at a concentration of 100, 200, 300 and 400 mg/kg b.w daily for 30 days results a momentous decrease in fasting blood glucose, glycated heamoglobin and enhancement of plasma insulin level as compared with STZ induced diabetic rats. Furthermore, it significantly (p < 0.05) decreased the level of TC, TG, and LDL-c, VLDL-c. While it increases the level of HDL-c to a significant (p < 0.05) level. The treatment also resulted in a marked increase in reduced glutathione, glutathione Peroxidase, catalase and superoxide dismutase and diminished level of lipid peroxidation in liver and kidney of STZ induced diabetic rats. Histopathological studies suggest the diminution in the pancreatic, liver and cardiac muscle damage. Conclusion Our research exertion clearly indicates the considerable antihyperglycemic, antihyperlipidemic, antioxidant & pancreas/renal/hepatic/cardiac protective action of ALEx. PMID:25026962

Low-level laser therapy (LLLT) at 830 nm positively modulates healing of tracheal incisions in rats: a preliminary histological investigation.

PubMed

Grendel, Tomáš; Sokolský, Ján; Vaščáková, Andrea; Hrehová, Blanka; Poláková, Martina; Bobrov, Nikita; Sabol, František; Gál, Peter

2011-09-01

The aim of the present study was to evaluate whether LLLT at 830 nm is able to positively modulate trachea incisional wound healing in Sprague-Dawley rats. Tracheotomy may be associated with numerous complications. Development of excess granulation tissue represents a late complication that may lead to airway occlusion. Low-level laser therapy (LLLT) has been shown to have stimulatory effects on wound healing of different tissues. Therefore, it may be suggested that LLLT could be able to positively modulate trachea wound healing as well. Using general anesthesia, a median incision was performed from the second to the fifth tracheal cartilage ring in 24 rats. Animals were then randomly divided into sham-irradiated control and laser-treated groups. LLLT (power density: 450 mW/cm(2); total daily dose: 60 J/cm(2); irradiated area ∼1 cm(2)) treatment was performed daily during the first week after surgery. Samples for histological evaluation were removed 7 and 28 days after surgical procedure. Histological sections were stained with hematoxylin-eosin and van Gieson. Results from our investigation showed that LLLT was able to reduce granulation tissue formation and simultaneously increase new cartilage development at both evaluated time intervals. From this point of view, LLLT at 830 nm may be a valuable tool in trachea wound healing modulation. Nevertheless, further detailed research is needed to find optimal therapeutic parameters and to test these findings on other animal models.

Effects of Chronic Fluoxetine Treatment on Neurogenesis and Tryptophan Hydroxylase Expression in Adolescent and Adult Rats

PubMed Central

Meerhoff, Gideon F.

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population. PMID:24827731

Development of a bio-magnetic measurement system and sensor configuration analysis for rats

NASA Astrophysics Data System (ADS)

Kim, Ji-Eun; Kim, In-Seon; Kim, Kiwoong; Lim, Sanghyun; Kwon, Hyukchan; Kang, Chan Seok; Ahn, San; Yu, Kwon Kyu; Lee, Yong-Ho

2017-04-01

Magnetoencephalography (MEG) based on superconducting quantum interference devices enables the measurement of very weak magnetic fields (10-1000 fT) generated from the human or animal brain. In this article, we introduce a small MEG system that we developed specifically for use with rats. Our system has the following characteristics: (1) variable distance between the pick-up coil and outer Dewar bottom (˜5 mm), (2) small pick-up coil (4 mm) for high spatial resolution, (3) good field sensitivity (45 ˜ 80 fT /cm/√{Hz} ) , (4) the sensor interval satisfies the Nyquist spatial sampling theorem, and (5) small source localization error for the region to be investigated. To reduce source localization error, it is necessary to establish an optimal sensor layout. To this end, we simulated confidence volumes at each point on a grid on the surface of a virtual rat head. In this simulation, we used locally fitted spheres as model rat heads. This enabled us to consider more realistic volume currents. We constrained the model such that the dipoles could have only four possible orientations: the x- and y-axes from the original coordinates, and two tangentially layered dipoles (local x- and y-axes) in the locally fitted spheres. We considered the confidence volumes according to the sensor layout and dipole orientation and positions. We then conducted a preliminary test with a 4-channel MEG system prior to manufacturing the multi-channel system. Using the 4-channel MEG system, we measured rat magnetocardiograms. We obtained well defined P-, QRS-, and T-waves in rats with a maximum value of 15 pT/cm. Finally, we measured auditory evoked fields and steady state auditory evoked fields with maximum values 400 fT/cm and 250 fT/cm, respectively.

Effects of chronic fluoxetine treatment on neurogenesis and tryptophan hydroxylase expression in adolescent and adult rats.

PubMed

Klomp, Anne; Václavů, Lena; Meerhoff, Gideon F; Reneman, Liesbeth; Lucassen, Paul J

2014-01-01

The antidepressant drug fluoxetine (Prozac) has been increasingly prescribed to children and adolescents with depressive disorders despite a lack of thorough understanding of its therapeutic effects in the paediatric population and of its putative neurodevelopmental effects. Within the framework of PRIOMEDCHILD ERA-NET, we investigated; a) effects of chronic fluoxetine treatment on adult hippocampal neurogenesis, a structural readout relevant for antidepressant action and hippocampal development; b) effects on tryptophan hydroxylase (TPH) expression, a measure of serotonin synthesis; c) whether treatment effects during adolescence differed from treatment at an adult age, and d) whether they were subregion-specific. Stereological quantification of the number of proliferating (Ki-67+) cells and of the number of young migratory neurons (doublecortin+), revealed a significant age-by-treatment interaction effect, indicating that fluoxetine affects both proliferation and neurogenesis in adolescent-treated rats differently than it does in adult-treated rats. In terms of subregional differences, fluoxetine enhanced proliferation mainly in the dorsal parts of the hippocampus, and neurogenesis in both the suprapyramidal and infrapyramidal blades of the dentate gyrus in adolescent-treated rats, while no such differences were seen in adult-treated rats. Fluoxetine exerted similar age-by-treatment interaction effects on TPH cells mainly in the ventral portion of the dorsal raphe nucleus. We conclude that fluoxetine exerts divergent effects on structural plasticity and serotonin synthesis in adolescent versus adult-treated rats. These preliminary data indicate a differential sensitivity of the adolescent brain to this drug and thus warrant further research into their behavioural and translational aspects. Together with recent related findings, they further call for caution in prescribing these drugs to the adolescent population.

Amodiaquine analogues containing NO-donor substructures: synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria.

PubMed

Bertinaria, Massimo; Guglielmo, Stefano; Rolando, Barbara; Giorgis, Marta; Aragno, Cristina; Fruttero, Roberta; Gasco, Alberto; Parapini, Silvia; Taramelli, Donatella; Martins, Yuri C; Carvalho, Leonardo J M

2011-05-01

The synthesis and physico-chemical properties of novel compounds obtained by conjugation of amodiaquine with moieties containing either furoxan or nitrooxy NO-donor substructures are described. The synthesised compounds were tested in vitro against both the chloroquine sensitive, D10 and the chloroquine resistant, W-2 strains of Plasmodium falciparum (P. falciparum). Most of the compounds showed an antiplasmodial activity comparable to that of the parent drug. By comparing the activities of simple related structures devoid of the ability to release NO, it appears that the contribution of NO to the antiplasmodial action in vitro is marginal. All the compounds were able to relax rat aorta strips with a NO-dependent mechanism, thus showing their capacity to release NO in the vessels. A preliminary in vivo study using Plasmodium berghei ANKA-infected mice showed a trend for prolonged survival of mice with cerebral malaria treated with compound 40, which is potent and fast amodiaquine-derived NO-donor, when compared with amodiaquine alone or with compound 31, a milder NO-donor. The two compounds showed in vivo antiplasmodial activity similar to that of amodiaquine. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

[The immunology of cholera and the molecular biology of cholera toxin. Recent progress and future perspectives].

PubMed

Carrada-Bravo, T

1994-01-01

Vibrio cholerae has recently called the attention of researchers due to its strong immunogenicity and also because it serves as coadjunct immunomodulator of the immune response of the intestinal mucosae for the mixed added antigens as well as for those covalently linked to the toxin. The immunopathogeny of cholera is a complex phenomenon. This article presents the preliminary results of experiments conducted with laboratory rats in order to find the IgA intestinal response of rodents and humans.

[Evaluation on a fast weight reduction model in vitro].

PubMed

Li, Songtao; Li, Ying; Wen, Ying; Sun, Changhao

2010-03-01

To establish a fast and effective model in vitro for screening weight-reducing drugs and taking preliminary evaluation of the model. Mature adipocytes of SD rat induced by oleic acid were used to establish a obesity model in vitro. Isoprel, genistein, caffeine were selected as positive agents and curcumine as negative agent to evaluate the obesity model. Lipolysis of adipocytes was stimulated significantly by isoprel, genistein and caffeine rather than curcumine. This model could be used efficiently for screening weight-losing drugs.

Ultrasonic Estimation of Mechanical Properties of Pulmonary Arterial Wall Under Normoxic and Hypoxic Conditions

NASA Astrophysics Data System (ADS)

Waters, Kendall R.; Mukdadi, Osama M.

2005-04-01

Secondary pediatric pulmonary hypertension is a disease that could benefit from improved ultrasonic diagnostic techniques. We perform high-frequency in vitro ultrasound measurements (25 MHz to 100 MHz) on fresh and fixed pulmonary arterial walls excised from normoxic and hypoxic Long-Evans rat models. Estimates of the elastic stiffness coefficients are determined from measurements of the speed of sound. Preliminary results indicate that hypoxia leads to up to increase of 20 % in stiffening of the pulmonary arterial wall.

Signals for a promoting action of radiation in cancer incidence data.

PubMed

Heidenreich, W F

2002-09-01

The two-stage clonal expansion model allows us in principle to separate the initiating and promoting action of radiation. Features of the relative risk functions which indicate the action of promotion most clearly are identified for acute and for protracted exposures. They are compared with data: for acute exposure, some results of a preliminary analysis of the atomic-bomb survivor data are given; for protracted exposure, patterns in the fatal lung tumours of radon-exposed rats are discussed.

Influence of He-Ne laser radiation on biogenic amines content and cytochemical parameters of polymorphonuclear leukocytes in short-term stress

NASA Astrophysics Data System (ADS)

Brill, Gregory E.; Dobrovolsky, Gennady A.; Romanova, Tatyana P.; Porozova, Svetlana G.; Brill, Alexander G.

1997-06-01

In experiments on white male rats short-term immobilization- sound stress was modelled. Decrease of glycogen content and myeloperoxidase activity, increase of lysosomal cationic proteins level and NBT-test parameters as well as fall of adrenaline, dopamine and 5-hydroxytryptamine amount in polymorphonuclear leukocytes were observed. Preliminary transcutaneous He-Ne laser irradiation modified metabolic reaction of leukocytes to stress and prevented stress- induced decrease of biogenic amines content in cells.

Five heads are better than one: preliminary results of team-based learning in a communication disorders graduate course.

PubMed

Epstein, Baila

2016-01-01

Clinical problem-solving is fundamental to the role of the speech-language pathologist in both the diagnostic and treatment processes. The problem-solving often involves collaboration with clients and their families, supervisors, and other professionals. Considering the importance of cooperative problem-solving in the profession, graduate education in speech-language pathology should provide experiences to foster the development of these skills. One evidence-based pedagogical approach that directly targets these abilities is team-based learning (TBL). TBL is a small-group instructional method that focuses on students' in-class application of conceptual knowledge in solving complex problems that they will likely encounter in their future clinical careers. The purpose of this pilot study was to investigate the educational outcomes and students' perceptions of TBL in a communication disorders graduate course on speech and language-based learning disabilities. Nineteen graduate students (mean age = 26 years, SD = 4.93), divided into three groups of five students and one group of four students, who were enrolled in a required graduate course, participated by fulfilling the key components of TBL: individual student preparation; individual and team readiness assurance tests (iRATs and tRATs) that assessed preparedness to apply course content; and application activities that challenged teams to solve complex and authentic clinical problems using course material. Performance on the tRATs was significantly higher than the individual students' scores on the iRATs (p < .001, Cohen's d = 4.08). Students generally reported favourable perceptions of TBL on an end-of-semester questionnaire. Qualitative analysis of responses to open-ended questions organized thematically indicated students' high satisfaction with application activities, discontent with the RATs, and recommendations for increased lecture in the TBL process. The outcomes of this pilot study suggest the effectiveness of TBL as an instructional method that provides student teams with opportunities to apply course content in problem-solving activities followed by immediate feedback. This research also addresses the dearth of empirical information on how graduate programmes in speech-language pathology bridge students' didactic learning and clinical practice. Future studies should examine the utility of this approach in other courses within the field and with more heterogeneous student populations. © 2015 Royal College of Speech and Language Therapists.

Amelioration of apoptotic events in the skeletal muscle of intra-nigrally rotenone-infused Parkinsonian rats by Morinda citrifolia--up-regulation of Bcl-2 and blockage of cytochrome c release.

PubMed

Narasimhan, Kishore Kumar S; Paul, Liya; Sathyamoorthy, Yogesh Kanna; Srinivasan, Ashokkumar; Chakrapani, Lakshmi Narasimhan; Singh, Abhilasha; Ravi, Divya Bhavani; Krishnan, Thulasi Raman; Velusamy, Prema; Kaliappan, Kathiravan; Radhakrishnan, Rameshkumar; Periandavan, Kalaiselvi

2016-02-01

Parkinson's disease is a progressive neurodegenerative movement disorder with the cardinal symptoms of bradykinesia, resting tremor, rigidity, and postural instability, which lead to abnormal movements and lack of activity, which in turn cause muscular damage. Even though studies have been carried out to elucidate the causative factors that lead to muscular damage in Parkinson's disease, apoptotic events that occur in the skeletal muscle and a therapeutical approach to culminate the muscular damage have not been extensively studied. Thus, this study evaluates the impact of rotenone-induced SNPc lesions on skeletal muscle apoptosis and the efficacy of an ethyl acetate extract of Morinda citrifolia in safeguarding the myocytes. Biochemical assays along with apoptotic markers studied by immunoblot and reverse transcription-polymerase chain reaction in the current study revealed that the supplementation of Morinda citrifolia significantly reverted alterations in both biochemical and histological parameters in rotenone-infused PD rats. Treatment with Morinda citrifolia also reduced the expression of pro-apoptotic proteins Bax, caspase-3 and caspase-9 and blocked the release of cytochrome c from mitochondria induced by rotenone. In addition, it augmented the expression of Bcl2 both transcriptionally and translationally. Thus, this preliminary study paves a way to show that the antioxidant and anti-apoptotic activities of Morinda citrifolia can be exploited to alleviate skeletal muscle damage induced by Parkinsonism.

Pyropheophorbide 2-deoxyglucosamide: a new photosensitizer targeting glucose transporters.

PubMed

Zhang, Min; Zhang, Zhihong; Blessington, Dana; Li, Hui; Busch, Theresa M; Madrak, Vanessa; Miles, Jeremy; Chance, Britton; Glickson, Jerry D; Zheng, Gang

2003-01-01

To prepare near-infrared fluorescence imaging and photodynamic therapy agents targeted at glucose transporters, pyropheophorbide 2-deoxyglucosamide (Pyro-2DG) was synthesized and evaluated in a 9L glioma rat model. Fluorescence imaging studies demonstrate that Pyro-2DG is selectively accumulated in the tumor. Upon its photoactivation, we demonstrate that this agent efficiently causes selective mitochondrial damage to the region of a tumor that was photoirradiated after administration of this agent, but does not affect tissues photoirradiated in the absence of the agent or tissues treated with the agent that are not photoirradiated. Preliminary confocal microscopy studies suggest that Pyro-2DG is delivered and trapped in tumor cells via the GLUT/hexokinase pathway and therefore is useful both as a tumor-targeted NIR fluorescence imaging probe and as a PDT agent for the destruction of cancer.

Ovarian folliculogenesis: detrimental effect of prenatal exposure to cyclophosphamide: a preliminary study.

PubMed

Ray, B; Potu, B K

2010-01-01

To investigate whether cyclophosphamide interferes with ovarian folliculogenesis. In this experiment, pregnant rats (n=12) were randomly assigned into two groups, control group (n=6) and cyclophosphamide treatment group (n=6). In the cyclophosphamide treatment group cyclophosphamide was injected intraperitoneally from day 10 of gestation till 20th day, at 2 mg/kg of body weight. The pregnant rats were sacrificed on gestation day 20 and the fetus was collected. The collected fetuses were processed for sectioning and stained with haematoxyline and eosin for microscopic observation of the ovaries. A meshwork-like appearance of mesenchyme with decreased number of somatic cells and absence of the majority of the germ cells in the ovarian follicles were found in treated fetus. Non-availability of primordial germ cells stopped the interaction between primordial germ cells and somatic supporting cells leading to nonproliferation and degeneration of somatic cells and fluid-filled vacant spaces in the meshwork -like arrangement of mesenchymal cells. We conclude that cyclophosphamide exposure prevents folliculogenesis by causing anovulation and results in infertility. The same detrimental effect might be seen in human fertility with environmental pollutants which are also metabolites of the drug (Fig. 2, Ref. 25).

Elevated Peritoneal Fluid TNF-α Incites Ovarian Early Growth Response Factor 1 Expression and Downstream Protease Mediators

PubMed Central

Birt, Julie A.; Nabli, Henda; Stilley, Julie A.; Windham, Emma A.; Frazier, Shellaine R.

2013-01-01

Endometriosis-associated infertility manifests itself via multiple, poorly understood mechanisms. Our goal was to characterize signaling pathways, between peritoneal endometriotic lesions and the ovary, leading to failed ovulation. Genome-wide microarray analysis comparing ovarian tissue from an in vivo endometriosis model in the rat (Endo) with controls (Sham) identified 22 differentially expressed genes, including transiently expressed early growth response factor 1 (Egr1). The Egr1 regulates gene requisites for ovulation. The Egr1 promoter is responsive to tumor necrosis factor-alpha (TNF-α) signaling. We hypothesized that altered expression of ovarian EGR1 is induced by elevated peritoneal fluid TNF-α which is upregulated by the presence of peritoneal endometriosis. Endo rats, compared to controls, had more peritoneal fluid TNF-α and quantitative, spatial differences in Egr1 mRNA and EGR1 protein localization in follicular compartments. Interactions between elevated peritoneal fluid TNF-α and overexpression of follicular Egr1/EGR1 expression may affect downstream protease pathways impeding ovulation in endometriosis. Preliminary studies identified similar patterns of EGR1 protein localization in human ovaries from women with endometriosis and compared to those without endometriosis. PMID:23427178

Hematopoietic studies in vitamin A deficiency.

PubMed

Hodges, R E; Sauberlich, H E; Canham, J E; Wallace, D L; Rucker, R B; Mejia, L A; Mohanram, M

1978-05-01

Recent studies of experimental vitamin A deficiency in man led the authors to conclude that anemia may result from lack of vitamin A. A review of numerous nutrition surveys in underdeveloped countries enhanced the suspicion that deficiency of vitamin A does contribute to the prevalence of anemia. Preliminary studies of vitamin A-deficient rats confirmed previous observations that anemia may result from lack of this vitamin. The livers of these animals had very low concentrations of vitamin A but normal or increased concentrations of iron. The finding of anemia is in contrast with other reports that vitamin A deficiency may cause elevated values for hemoglobin and hematocrit. The authors suggest that loss of taste and smell as a result of deficiency may account for refusal of experimental animals to eat and drink enough to prevent inanitation and dehydration. The resulting hemoconcentration may mask the true hematological picture, which is one of anemia.

Preliminary results of scientific research on biosatellite Kosmos-1129

NASA Technical Reports Server (NTRS)

1980-01-01

The first physiological study aimed at deeper examination mechanisms of weightlessness and adaptation/readaptation is described. It dealt with metabolism, support motor changes and nonspecific changes connected with stress reaction. Wistar rats were used in a triple setup: flight/vivarium/biosatellite mockup. Animal condition was assessed on motor activity and body temperature. Extensive tables show weight, blood and enzyme analysis, etc. Animals groups were labeled: stress, behavior, body composition, biorhythm, ontogenesis. The second or biological study dealt with tumorous carrot tissues but humidity control was defective: some indices are reported such as cell membrane permeability, tissue respiration, etc. It also was concerned with a fowl embryogenetic experiment (Japanese quail) but mechanical effects on landing reduced its success. The third study, on radiation dosimetry, presents a little tabulated data but chiefly gives lists of satellite detector units of different kinds and from different countries.

3D silicon neural probe with integrated optical fibers for optogenetic modulation.

PubMed

Kim, Eric G R; Tu, Hongen; Luo, Hao; Liu, Bin; Bao, Shaowen; Zhang, Jinsheng; Xu, Yong

2015-07-21

Optogenetics is a powerful modality for neural modulation that can be useful for a wide array of biomedical studies. Penetrating microelectrode arrays provide a means of recording neural signals with high spatial resolution. It is highly desirable to integrate optics with neural probes to allow for functional study of neural tissue by optogenetics. In this paper, we report the development of a novel 3D neural probe coupled simply and robustly to optical fibers using a hollow parylene tube structure. The device shanks are hollow tubes with rigid silicon tips, allowing the insertion and encasement of optical fibers within the shanks. The position of the fiber tip can be precisely controlled relative to the electrodes on the shank by inherent design features. Preliminary in vivo rat studies indicate that these devices are capable of optogenetic modulation simultaneously with 3D neural signal recording.

Preliminary results of scientific research on biosatellite KOSMOS-1129

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1980-08-01

The first physiological study aimed at deeper examination mechanisms of weightlessness and adaptation/readaptation is described. It dealt with metabolism, support motor changes and nonspecific changes connected with stress reaction. Wistar rats were used in a triple setup: flight/vivarium/biosatellite mockup. Animal condition was assessed on motor activity and body temperature. Extensive tables show weight, blood and enzyme analysis, etc. Animals groups were labeled: stress, behavior, body composition, biorhythm, ontogenesis. The second or biological study dealt with tumorous carrot tissues but humidity control was defective: some indices are reported such as cell membrane permeability, tissue respiration, etc. It also was concerned withmore » a fowl embryogenetic experiment (Japanese quail) but mechanical effects on landing reduced its success. The third study, on radiation dosimetry, presents a little tabulated data but chiefly gives lists of satellite detector units of different kinds and from different countries.« less

High Dietary Iron and Radiation Exposure Increase Biomarkers of Oxidative Stress in Blood and Liver of Rats

NASA Technical Reports Server (NTRS)

Morgan, Jennifer L. L.; Theriot, Corey A.; Wu, Honglu; Smith, Scott M.; Zwart, Sara R.

2012-01-01

Radiation exposure and increased iron (Fe) status independently cause oxidative damage that can result in protein, lipid, and DNA oxidation. During space flight astronauts are exposed to both increased radiation and increased Fe stores. Increased body Fe results from a decrease in red blood cell mass and the typically high Fe content of the food system. In this study we investigated the combined effects of radiation exposure (0.375 Gy of Cs-137 every other day for 16 days for a total of 3 Gy) and high dietary Fe (650 mg Fe/kg diet compared to 45 mg Fe/kg for controls) in Sprague-Dawley rats (n=8/group). Liver and serum Fe were significantly increased in the high dietary Fe groups. Likewise, radiation treatment increased serum ferritin and Fe concentrations. These data indicate that total body Fe stores increase with both radiation exposure and excess dietary Fe. Hematocrit decreased in the group exposed to radiation, providing a possible mechanism for the shift in Fe indices after radiation exposure. Markers of oxidative stress were also affected by both radiation and high dietary Fe, evidenced by increased liver glutathione peroxidase (GPX) and serum catalase as well as decreased serum GPX. We thus found preliminary indications of synergistic effects of radiation exposure and increased dietary Fe, warranting further study. This study was funded by the NASA Human Research Project.

Development and characterization of niosomal formulations of doxorubicin aimed at brain targeting.

PubMed

Bragagni, Marco; Mennini, Natascia; Ghelardini, Carla; Mura, Paola

2012-01-01

The aim of the present work was the development and characterization of a niosomal formulation functionalized with the glucose-derivative N-palmitoylglucosamine (NPG) to obtain a potential brain targeted delivery system for the anticancer agent doxorubicin. Five different methods have been examined for vesicle preparation. Light scattering and transmission electron microscopy were used for vesicle characterization, in terms of mean size, homogeneity and Zeta potential, and selection of the best composition and preparation conditions for developing NPG-functionalized niosomes. Drug entrapment efficiency was determined after separation of loaded from unloaded drug by size exclusion chromatography or dialysis. Preliminary in vivo studies were performed on rats, injected i.v. with 12 mg/kg of doxorubicin as commercial solution (Ebewe, 2 mg/mL) or NPG-niosomal formulation. Drug amounts in the blood and in the major organs of the animals, sacrificed 60 min post injection, were determined by HPLC. The selected formulation consisted in Span:cholesterol:Solulan:NPG (50:40:10:10 mol ratio) vesicles obtained by thin-layer evaporation, leading to homogeneous vesicles of less than 200 nm diameter. This formulation was used for preparation of NPG-niosomes loaded with doxorubicin (mean size 161±4 nm, encapsulation efficacy 57.8±1.8%). No significant changes (P>0.05) in vesicle dimensions, Zeta potential or entrapment efficiency were observed after six months storage at room temperature, indicative of good stability. I.v. administration to rats of the NPG-niosomal formulation allowed for reducing drug accumulation in the heart and keeping it longer in the blood circulation with respect to the commercial formulation. Moreover, a doxorubicin brain concentration of 2.9±0.4 μg/g was achieved after 60 min, while the commercial solution yielded undetectable drug brain concentrations (<0.1 μg/g). The developed NPG-niosomal formulation gave rise to stable, nano-sized vesicles, able to improve doxorubicin brain delivery. Positive results of preliminary in vivo studies require future pharmacokinetic studies to gain more insight into the mechanism of drug transport of functionalized niosomes.

Photodynamic therapy for endometrial ablation: a study of treatment parameters and effects

NASA Astrophysics Data System (ADS)

Jerath, Maya R.; Hoopes, P. Jack; Manganiello, Paul D.

1995-05-01

The use of PDT for endometrial ablation has been the focus of much recent research. However, the mechanism of action, optimal treatment parameters, and long-term clinical effect are still poorly understood. This study was undertaken to further the understanding of the endometrial response to this drug/light- induced damage. Postpartum rat (Charles River) uterine horns were used as the animal model for fluorescence and treatment studies. Aminolevulinic acid was administered topically (intrauterine), and following a 0.5- to 3-hour drug incubation time, the endometrium was either removed and processed for fluorescence microscopy to assess drug localization or exposed to 150-200 J/cm2 of 630-nm laser light via a 1-cm cylindrical diffusing tip. The light=treated uterine horns were removed and histologically examine 7 to 10 days following treatment. The extent and character of uterine and endometrial damage (gross and histological analysis) were recorded for the varying light doses and incubation times. With topical (intrauterine) application of photosensitizer, incubation time and penetration ability of drug were found to be crucial factors. The use of a drug penetration enhancing vehicle produced greater tissue effects (endometrial ablation). These preliminary studies also showed that tissue effect is drug and light dose related and that the most profound effects may be vascular mediated. The study provided preliminary information for the use of PDT in gynecological applications such as endometrial ablation and female sterilization through Fallopian tube occlusion.

Determination of Relevant Neuron–Neuron Connections for Neural Prosthetics Using Time-Delayed Mutual Information: Tutorial and Preliminary Results

PubMed Central

Taghva, Alexander; Song, Dong; Hampson, Robert E.; Deadwyler, Sam A.; Berger, Theodore W.

2013-01-01

BACKGROUND Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. METHODS Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. RESULTS Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. CONCLUSIONS Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural prosthetics. PMID:22120279

Determination of relevant neuron-neuron connections for neural prosthetics using time-delayed mutual information: tutorial and preliminary results.

PubMed

Taghva, Alexander; Song, Dong; Hampson, Robert E; Deadwyler, Sam A; Berger, Theodore W

2012-12-01

Identification of functional dependence among neurons is a necessary component in both the rational design of neural prostheses as well as in the characterization of network physiology. The objective of this article is to provide a tutorial for neurosurgeons regarding information theory, specifically time-delayed mutual information, and to compare time-delayed mutual information, an information theoretic quantity based on statistical dependence, with cross-correlation, a commonly used metric for this task in a preliminary analysis of rat hippocampal neurons. Spike trains were recorded from rats performing delayed nonmatch-to-sample task using an array of electrodes surgically implanted into the hippocampus of each hemisphere of the brain. In addition, spike train simulations of positively correlated neurons, negatively correlated neurons, and neurons correlated by nonlinear functions were generated. These were evaluated by time-delayed mutual information (MI) and cross-correlation. Application of time-delayed MI to experimental data indicated the optimal bin size for information capture in the CA3-CA1 system was 40 ms, which may provide some insight into the spatiotemporal nature of encoding in the rat hippocampus. On simulated data, time-delayed MI showed peak values at appropriate time lags in positively correlated, negatively correlated, and complexly correlated data. Cross-correlation showed peak and troughs with positively correlated and negatively correlated data, but failed to capture some higher order correlations. Comparison of time-delayed MI to cross-correlation in identification of functionally dependent neurons indicates that the methods are not equivalent. Time-delayed MI appeared to capture some interactions between CA3-CA1 neurons at physiologically plausible time delays missed by cross-correlation. It should be considered as a method for identification of functional dependence between neurons and may be useful in the development of neural prosthetics. Copyright © 2012 Elsevier Inc. All rights reserved.

Implementation of near-infrared spectroscopy in a rat model of cardiac arrest and resuscitation

NASA Astrophysics Data System (ADS)

Rodriguez, Juan G.; Xiao, Feng; Ferrara, Davon; Ewing, Jennifer; Zhang, Shu; Alexander, Steven; Battarbee, Harold

2002-07-01

Transient global cerebral ischemia accompanying cardiac arrest (CA) often leads to permanent brain damage with poor neurological outcome. The precise chain of events underlying the cerebral damage after CA is still not fully understood. Progress in this area may profit from the development of new non-invasive tools that provide real-time information on the vascular and cellular processes preceding the damage. One way to assess these processes is through near-IR spectroscopy, which has demonstrated the ability to quantify changes in blood volume, hemoglobin oxygenation, cytochrome oxidase redox state, and tissue water content. Here we report on the successful implementation of this form of spectroscopy in a rat model of asphyxial CA and resuscitation, under hypothermic and normothermic conditions. Preliminary results are shown that provide a new temporal insight into the cerebral circulation during CA and post-resuscitation.

Retinal changes in rats flown on Cosmos 936 - A cosmic ray experiment

NASA Technical Reports Server (NTRS)

Philpott, D. E.; Corbett, R.; Turnbill, C.; Black, S.; Dayhoff, D.; Mcgourty, J.; Lee, R.; Harrison, G.; Savik, L.

1980-01-01

Ten rats, five centrifuged during flight to simulate gravity and five stationary in flight and experiencing hypogravity, orbited the Earth. No differences were noted between flight-stationary and flight-centrifuged animals, but changes were seen between these two groups and ground controls. Morphological alterations were observed comparable to those in the experiment flown on Cosmos 782 and to the retinal cells exposed to high-energy particles at Berkeley. Affected cells in the outer nuclear layer showed swelling, clearing of cytoplasm, and disruption of the membranes. Tissue channels were again found, similar to those seen on 782. After space flight, preliminary data indicated an increase in cell size in montages of the nuclear layer of both groups of flight animals. This experiment shows that weightlessness and environmental conditions other than cosmic radiation do not contribute to the observed damage of retinal cells.

β-Sitosterol enhances cellular glutathione redox cycling by reactive oxygen species generated from mitochondrial respiration: protection against oxidant injury in H9c2 cells and rat hearts.

PubMed

Wong, Hoi Shan; Chen, Na; Leong, Pou Kuan; Ko, Kam Ming

2014-07-01

Herba Cistanches (Cistanche deserticola Y. C. Ma) is a 'Yang-invigorating' tonic herb in Chinese medicine. Preliminary chemical analysis indicated that β-sitosterol (BS) is one of the chemical constituents in an active fraction of Herba Cistanches. To investigate whether BS is an active ingredient of Herba Cistanches, the effects of BS on H9c2 cells and rat hearts were examined. The results indicated that BS stimulated the mitochondrial ATP generation capacity in H9c2 cells, which was associated with the increased production of mitochondrial reactive oxygen species. BS also stimulated mitochondrial state 3 and state 4 respiration, with the resultant decrease in coupling efficiency. BS produced an up-regulation of cellular glutathione redox cycling and protected against hypoxia/reoxygenation-induced apoptosis in H9c2 cells. However, the protective effect of BS against myocardial ischemia/reperfusion injury was seen in female but not male rats ex vivo. The cardioprotection afforded by BS was likely mediated by an up-regulation of mitochondrial glutathione redox cycling in female rat hearts. In conclusion, the ensemble of results suggests that BS is an active ingredient of Herba Cistanches. The gender-dependent effect of BS on myocardial protection will further be investigated. Copyright © 2013 John Wiley & Sons, Ltd.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock.

PubMed

Braga, D; Barcella, M; D'Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, M H; DeLano, F A; Baselli, G; Schmid-Schönbein, G W; Kistler, E B; Aletti, F; Barlassina, C

2017-08-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger's shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients.

Vanadium exposure-induced striatal learning and memory alterations in rats.

PubMed

Sun, Liping; Wang, Keyue; Li, Yan; Fan, Qiyuan; Zheng, Wei; Li, Hong

2017-09-01

Occupational and environmental exposure to vanadium has been associated with toxicities in reproductive, respiratory, and cardiovascular systems. The knowledge on whether and how vanadium exposure caused neurobehavioral changes remains incomplete. This study was designed to investigate the changes in learning and memory following drinking water exposure to vanadium, and to conduct the preliminary study on underlying mechanisms. Male Sprague-Dawley rats were exposed to vanadium dissolved in drinking water at the concentration of 0.0, 0.5, 1.0 and 2.0g/L, as the control, low-, medium-, and high- dose groups, respectively, for 12 weeks. The results by the Morris water maze test showed that the time for the testing animal to find the platform in the high exposed group was increased by 82.9% and 49.7%, as compared to animals in control and low-dose groups (p<0.05). There were significantly fewer rats in the medium- and high- dose groups than in the control group who were capable of crossing the platform (p<0.05). Quantitation of vanadium by atomic absorption spectrophotometry revealed a significant dose-dependent accumulation of vanadium in striatum (r=0.931, p<0.01). Histopathological examination further demonstrated a degenerative damage in vanadium-exposed striatum. Interestingly, with the increase of the dose of vanadium, the contents of neurotransmitter ACh, 5-HT and GABA in the striatum increased; however, the levels of Syn1 was significantly reduced in the exposed groups compared with controls (p<0.05). These data suggest that vanadium exposure apparently reduces the animals' learning ability. This could be due partly to vanadium's accumulation in striatum and the ensuing toxicity to striatal structure and synaptic plasticity. Further research is warranted for mechanistic understanding of vanadium-induced neurotoxicity. Copyright © 2017 Elsevier B.V. All rights reserved.

Vanadium exposure-induced striatal learning and memory alterations in rats

PubMed Central

Sun, Liping; Wang, Keyue; Li, Yan; Fan, Qiyuan; Zheng, Wei; Li, Hong

2017-01-01

Occupational and environmental exposure to vanadium has been associated with toxicities in reproductive, respiratory, and cardiovascular systems. The knowledge on whether and how vanadium exposure caused neurobehavioral changes remains incomplete. This study was designed to investigate the changes in learning and memory following drinking water exposure to vanadium, and to conduct the preliminary study on underlying mechanisms. Male Sprague-Dawley rats were exposed to vanadium dissolved in drinking water at the concentration of 0.0, 0.5, 1.0 and 2.0 g/L, as the control, low-, medium-, and high- dose groups, respectively, for 12 weeks. The results by the Morris water maze test showed that the time for the testing animal to find the platform in the high exposed group was increased by 82.9% and 49.7%, as compared to animals in control and low-dose groups (p <0.05). There were significantly fewer rats in the medium- and high- dose groups than in the control group who were capable of crossing the platform (p <0.05). Quantitation of vanadium by atomic absorption spectrophotometry revealed a significant dose-dependent accumulation of vanadium in striatum (r = 0.931, p <0.01). Histopathological examination further demonstrated a degenerative damage in vanadium-exposed striatum. Interestingly, with the increase of the dose of vanadium, the contents of neurotransmitter ACh, 5-HT and GABA in the striatum increased; however, the levels of Syn1 was significantly reduced in the exposed groups compared with controls (p <0.05). These data suggest that vanadium exposure apparently reduces the animals’ learning ability. This could be due partly to vanadium’s accumulation in striatum and the ensuing toxicity to striatal structure and synaptic plasticity. Further research is warranted for mechanistic understanding of vanadium-induced neurotoxicity. PMID:28625925

Preliminary Screening of a Classical Ayurvedic Formulation for Anticonvulsant Activity.

PubMed

Dhar, Arnab; Maurya, Santosh Kumar; Mishra, Ashish; Singh, Gireesh Kumar; Singh, Manoj Kumar; Seth, Ankit

2016-01-01

Epilepsy is a serious and complex central nervous system disorder associated with recurrent episodes of convulsive seizures due to the imbalance between excitatory (glutamatergic) and inhibitory (GABAergic) neurotransmitters level in the brain. The available treatments are neither competent to control the seizures nor prevent progress of disease. Since ages, Herbal medicines have remained important sources of medicines in many parts of world which is evidenced through their uses in traditional systems of medicine i.e. Ayurveda, Siddha, Unani, Homeopathy and Chinese etc. A polyherbal formulation (containing Terminalia chebula Retz., Asparagus racemosus Willd., Embelia ribes Burm. F, Acorus calamus L., Tinospora cordifolia (Willd.) Miers, Convolvulus pluricaulis Choisy, Saussurea lappa C.B.Clarke, Achyranthes aspera L.) is mentioned in Ayurvedic classics Bhaiṣajya Ratnāvali . The aim of the study was to evaluate the anticonvulsant activity of the formulation in Maximum electroshock and Pentylenetetrazole induced convulsions in rats. In the present study, a polyherbal formulation was developed as directed by classical text and evaluated for the anticonvulsant activity using Maximal Electroshock Shock (MES) and Pentylenetetrazole (PTZ) induced convulsions in rats. Statistical comparison was done by one way ANOVA followed by the Tukey's multiple comparison test. The obtained results showed that the PHF had a protective role on epilepsy. Treatment with PHF significantly improves antioxidant enzymes activities of superoxide dismutase (SOD) and glutathione (GSH) levels significantly as compared to controls. PHF also significantly decreased malonaldialdehyde (MDA) levels in the brain. Moreover, it also attenuated the PTZ-induced increase in the activity of GABA-T in the rat brain. These findings suggest that PHF might have possible efficacy in the treatment of epilepsy.

Effects of topical nonsteroidal antiinflammatory drugs on the expression of matrix metalloproteinases in the cornea.

PubMed

Reviglio, Victor E; Rana, Tayyib S; Li, Qian J; Ashraf, M Farooq; Daly, Mary K; O'Brien, Terrence P

2003-05-01

To assess the effects of nonsteroidal antiinflammatory drug (NSAID) eyedrops on the expression of matrix metalloproteinases in corneal tissue. Ocular Microbiology and Immunology Laboratory, Refractive Surgery Research Laboratory, The Wilmer Eye Institute, Johns Hopkins University, Baltimore, Maryland, USA. Seventy rats were divided into 2 groups: intact and debrided epithelium. Uniform central corneal epithelial defects were created in the right eye of the debrided corneal group. Each group was divided into 4 subgroups, each receiving 1 of the following eyedrops or artificial tears: The 3 NSAIDs were diclofenac sodium 0.1% (Falcon or Voltaren) and preservative-free ketorolac 0.5% (Acular PF). The artificial tears were carboxymethylcellulose sodium 0.5% (Refresh Plus PF). The eyedrops were administered 4 times a day for 1 week. The rats were killed on days 2 and 7. The corneas were excised and processed for immunohistochemical staining, Western blot assay, and zymography studies to determine the localization of the production of the following matrix metalloproteinases (MMPs): MMP-1, MMP-2, MMP-8, and MMP-9. Matrix metalloproteinase-1, MMP-8, and MMP-2 were detected in rat corneas at 48 hours in the debrided and intact epithelium groups treated with NSAID eyedrops. The MMP-1 and MMP-8 expression levels were higher in intact corneas in the diclofenac sodium groups than in the ketorolac and artificial tears groups. The expression was localized mostly in the epithelial cells and occasionally in keratocytes. This study provides preliminary evidence that topical application of some NSAIDs can induce the early expression of MMP-1, MMP-2, and MMP-8 in the cornea, suggesting that MMPs play a role in the corneal cytotoxicity of certain NSAIDs.

In vivo observation of the hypo-echoic "black hole" phenomenon in rat arterial bloodstream: a preliminary Study.

PubMed

Nam, Kweon-Ho; Paeng, Dong-Guk

2014-07-01

The "black hole," a hypo-echoic hole at the center of the bloodstream surrounded by a hyper-echoic zone in cross-sectional views, has been observed in ultrasound backscattering measurements of blood with red blood cell aggregation in in vitro studies. We investigated whether the phenomenon occurs in the in vivo arterial bloodstream of rats using a high-frequency ultrasound imaging system. Longitudinal and cross-sectional ultrasound images of the rat common carotid artery (CCA) and abdominal aorta were obtained using a 40-MHz ultrasound system. A high-frame-rate retrospective imaging mode was employed to precisely examine the dynamic changes in blood echogenicity in the arteries. When the imaging was performed with non-invasive scanning, blood echogenicity was very low in the CCA as compared with the surrounding tissues, exhibiting no hypo-echoic zone at the center of the vessel. Invasive imaging of the CCA by incising the skin and subcutaneous tissues at the imaging area provided clearer and brighter blood echo images, showing the "black hole" phenomenon near the center of the vessel in longitudinal view. The "black hole" was also observed in the abdominal aorta under direct imaging after laparotomy. The aortic "black hole" was clearly observed in both longitudinal and cross-sectional views. Although the "black hole" was always observed near the center of the arteries during the diastolic phase, it dissipated or was off-center along with the asymmetric arterial wall dilation at systole. In conclusion, we report the first in vivo observation of the hypo-echoic "black hole" caused by the radial variation of red blood cell aggregation in arterial bloodstream. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Chronic Lunar Dust Exposure on Rat Cornea: Evaluation by Gene Expression Profiling

NASA Technical Reports Server (NTRS)

Theriot, C. A.; Glass, A.; Lam, C-W.; James, J.; Zanello, S. B.

2014-01-01

Lunar dust is capable of entering habitats and vehicle compartments by sticking to spacesuits or other objects that are transferred into the spacecraft from the lunar surface and has been reported to cause irritation upon exposure. During the Apollo missions, crewmembers reported irritation specifically to the skin and eyes after contamination of the lunar and service modules. It has since been hypothesized that ocular irritation and abrasion might occur as a result of such exposure, impairing crew vision. Recent work has shown that both ultrafine and unground lunar dust exhibited minimal irritancy of the ocular surface (i.e., cornea); however, the assessment of the severity of ocular damage resulting from contact of lunar dust particles to the cornea has focused only on macroscopic signs of mechanical irritancy and cytotoxicity. Given the chemical reactive properties of lunar dust, exposure of the cornea may contribute to detrimental effects at the molecular level including but not limited to oxidative damage. Additionally, low level chronic exposures may confound any results obtained in previous acute studies. We report here preliminary results from a tissue sharing effort using 10-week-old Fischer 344 male rats chronically exposed to filtered air or jet milled lunar dust collected during Apollo 14 using a Jaeger-NYU nose-only chamber for a total of 120 hours (6 hours daily, 5 days a week) over a 4-week period. RNA was isolated from corneas collected from rats at 1 day and 7 days after being exposed to concentrations of 0, 20, and 60 mg/m3 of lunar dust. Microarray analysis was performed using the Affymetrix GeneChip Rat Genome 230 2.0 Array with Affymetrix Expression Console and Transcriptome Analysis Console used for normalization and secondary analysis. An Ingenuity iReport"TM" was then generated for canonical pathway identification. The number of differentially expressed genes identified increases with dose compared to controls suggesting a more severe response to the lunar dust insult at higher levels. Pathways of interests that have been identified in all exposed samples include oxidative stress response, mitochondrial dysfunction, fibrosis, epithelial healing, TGF-Beta? signaling, and extracellular matrix remodeling. Several biological processes related to cell migration, cellular proliferation, and eye development were also identified to be altered by exposure to lunar dust. Our preliminary results suggest that even a chronic insult of lunar dust as low as 20 mg/m(exp 3) elicits a molecular response in cornea tissue. Lunar dust on the surface of the moon would have the added properties of ionization and activation potentially leading to further damage to the cornea and greater sensitivity to any other environmental insult such as exposure to radiation. Additional studies are required to fully assess the risk of vision impairment and the mechanistic responses initiated in cornea exposed to lunar dust as well as the potential for long-term effects to astronaut health

Gabapentin Effects on PKC-ERK1/2 Signaling in the Spinal Cord of Rats with Formalin-Induced Visceral Inflammatory Pain

PubMed Central

Li, Mei-yi; Fong, Peter; Zhang, Ji-guo; Zhang, Can-wen; Gong, Ke-rui; Yang, Ming-feng; Niu, Jing-zhong; Ji, Xun-ming; Lv, Guo-wei

2015-01-01

Currently, the clinical management of visceral pain remains unsatisfactory for many patients suffering from this disease. While preliminary animal studies have suggested the effectiveness of gabapentin in successfully treating visceral pain, the mechanism underlying its analgesic effect remains unclear. Evidence from other studies has demonstrated the involvement of protein kinase C (PKC) and extracellular signal-regulated kinase1/2 (ERK1/2) in the pathogenesis of visceral inflammatory pain. In this study, we tested the hypothesis that gabapentin produces analgesia for visceral inflammatory pain through its inhibitory effect on the PKC-ERK1/2 signaling pathway. Intracolonic injections of formalin were performed in rats to produce colitis pain. Our results showed that visceral pain behaviors in these rats decreased after intraperitoneal injection of gabapentin. These behaviors were also reduced by intrathecal injections of the PKC inhibitor, H-7, and the ERK1/2 inhibitor, PD98059. Neuronal firing of wide dynamic range neurons in L6–S1 of the rat spinal cord dorsal horn were significantly increased after intracolonic injection of formalin. This increased firing rate was inhibited by intraperitoneal injection of gabapentin and both the individual and combined intrathecal application of H-7 and PD98059. Western blot analysis also revealed that PKC membrane translocation and ERK1/2 phosphorylation increased significantly following formalin injection, confirming the recruitment of PKC and ERK1/2 during visceral inflammatory pain. These effects were also significantly reduced by intraperitoneal injection of gabapentin. Therefore, we concluded that the analgesic effect of gabapentin on visceral inflammatory pain is mediated through suppression of PKC and ERK1/2 signaling pathways. Furthermore, we found that the PKC inhibitor, H-7, significantly diminished ERK1/2 phosphorylation levels, implicating the involvement of PKC and ERK1/2 in the same signaling pathway. Thus, our results suggest a novel mechanism of gabapentin-mediated analgesia for visceral inflammatory pain through a PKC-ERK1/2 signaling pathway that may be a future therapeutic target for the treatment of visceral inflammatory pain. PMID:26512901

Identification, characterization and potent antitumor activity of ECO-4601, a novel peripheral benzodiazepine receptor ligand.

PubMed

Gourdeau, Henriette; McAlpine, James B; Ranger, Maxime; Simard, Bryan; Berger, Francois; Beaudry, Francis; Farnet, Chris M; Falardeau, Pierre

2008-05-01

ECO-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER technology, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity in the low micromolar range when tested in the NCI 60 cell line panel. In the work presented here, ECO-4601 was further evaluated against brain tumor cell lines. Preliminary mechanistic studies as well as in vivo antitumor evaluation were performed. Since ECO-4601 has a benzodiazepinone moiety, we first investigated if it binds the central and/or peripheral benzodiazepine receptors. ECO-4601 was tested in radioligand binding assays on benzodiazepine receptors obtained from rat hearts. The ability of ECO-4601 to inhibit the growth of CNS cancers was evaluated on a panel of mouse, rat and human glioma cell lines using a standard MTT assay. Antitumor efficacy studies were performed on gliomas (rat and human), human breast and human prostate mouse tumor xenografts. Antitumor activity and pharmacokinetic analysis of ECO-4601 was evaluated following intravenous (i.v.), subcutaneous (s.c.), and intraperitoneal (i.p.) bolus administrations. ECO-4601 was shown to bind the peripheral but not the central benzodiazepine receptor and inhibited the growth of CNS tumor cell lines. Bolus s.c. and i.p. administration gave rise to low but sustained drug exposure, and resulted in moderate to significant antitumor activity at doses that were well tolerated. In a rat glioma (C6) xenograft model, ECO-4601 produced up to 70% tumor growth inhibition (TGI) while in a human glioma (U-87MG) xenograft, TGI was 34%. Antitumor activity was highly significant in both human hormone-independent breast (MDA-MB-231) and prostate (PC-3) xenografts, resulting in TGI of 72 and 100%, respectively. On the other hand, i.v. dosing was followed by rapid elimination of the drug and was ineffective. Antitumor efficacy of ECO-4601 appears to be associated with the exposure parameter AUC and/or sustained drug levels rather than C (max). These in vivo data constitute a rationale for clinical studies testing prolonged continuous administration of ECO-4601.

Clearance of free silica in rat lungs by spraying with chinese herbal kombucha.

PubMed

Fu, Nai-Fang; Luo, Chang-Hui; Wu, Jun-Cai; Zheng, Yan-Yan; Gan, Yong-Jin; Ling, Jian-An; Liang, Heng-Qiu; Liang, Dan-Yu; Xie, Jing; Chen, Xiao-Qin; Li, Xian-Jun; Pan, Rui-Hui; Chen, Zuo-Xing; Jiang, Sheng-Jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases.

Clearance of Free Silica in Rat Lungs by Spraying with Chinese Herbal Kombucha

PubMed Central

Fu, Nai-fang; Luo, Chang-hui; Wu, Jun-cai; Zheng, Yan-yan; Gan, Yong-jin; Ling, Jian-an; Liang, Heng-qiu; Liang, Dan-yu; Xie, Jing; Chen, Xiao-qin; Li, Xian-jun; Pan, Rui-hui; Chen, Zuo-Xing; Jiang, Sheng-jun

2013-01-01

The effects of spraying with kombucha and Chinese herbal kombucha were compared with treatments with tetrandrine in a rat silicosis model. Silica dust (50 mg) was injected into the lungs of rats, which were then treated with one of the experimental treatments for a month. The rats were then killed and the effects of the treatments were evaluated by examining the extent and severity of the histopathological lesions in the animals' lungs, measuring their organ coefficients and lung collagen contents, determining the dry and wet weights of their lungs, and measuring the free silica content of the dried lungs. In addition, lavage was performed on whole lungs taken from selected rats, and the numbers and types of cells in the lavage fluid were counted. The most effective treatment in terms of the ability to reduce lung collagen content and minimize the formation of pulmonary histopathological lesions was tetrandrine treatment, followed by Chinese herbal kombucha and non-Chinese herbal kombucha. However, the lavage fluid cell counts indicated that tetrandrine treatment had severe adverse effects on macrophage viability. This effect was much less pronounced for the kombucha and Chinese herbal kombucha treatments. Moreover, the free silica levels in the lungs of animals treated with Chinese herbal kombucha were significantly lower than those for any other silica-exposed group. These preliminary results indicate that spraying with Chinese herbal kombucha preparations can effectively promote the discharge of silica dust from lung tissues. Chinese herbal kombucha inhalation may thus be a useful new treatment for silicosis and other pneumoconiosis diseases. PMID:24023583

Neurotherapeutic activity of the recombinant heat shock protein Hsp70 in a model of focal cerebral ischemia in rats.

PubMed

Shevtsov, Maxim A; Nikolaev, Boris P; Yakovleva, Ludmila Y; Dobrodumov, Anatolii V; Dayneko, Anastasiy S; Shmonin, Alexey A; Vlasov, Timur D; Melnikova, Elena V; Vilisov, Alexander D; Guzhova, Irina V; Ischenko, Alexander M; Mikhrina, Anastasiya L; Galibin, Oleg V; Yakovenko, Igor V; Margulis, Boris A

2014-01-01

Recombinant 70 kDa heat shock protein (Hsp70) is an antiapoptotic protein that has a cell protective activity in stress stimuli and thus could be a useful therapeutic agent in the management of patients with acute ischemic stroke. The neuroprotective and neurotherapeutic activity of recombinant Hsp70 was explored in a model of experimental stroke in rats. Ischemia was produced by the occlusion of the middle cerebral artery for 45 minutes. To assess its neuroprotective capacity, Hsp70, at various concentrations, was intravenously injected 20 minutes prior to ischemia. Forty-eight hours after ischemia, rats were sacrificed and brain tissue sections were stained with 2% triphenyl tetrazolium chloride. Preliminary treatment with Hsp70 significantly reduced the ischemic zone (optimal response at 2.5 mg/kg). To assess Hsp70's neurotherapeutic activity, we intravenously administered Hsp70 via the tail vein 2 hours after reperfusion (2 hours and 45 minutes after ischemia). Rats were then kept alive for 72 hours. The ischemic region was analyzed using a high-field 11 T MRI scanner. Administration of the Hsp70 decreased the infarction zone in a dose-dependent manner with an optimal (threefold) therapeutic response at 5 mg/kg. Long-term treatment of the ischemic rats with Hsp70 formulated in alginate granules with retarded release of protein further reduced the infarct volume in the brain as well as apoptotic area (annexin V staining). Due to its high neurotherapeutic potential, prolonged delivery of Hsp70 could be useful in the management of acute ischemic stroke.

Microemulsions for oral delivery of insulin: design, development and evaluation in streptozotocin induced diabetic rats.

PubMed

Sharma, G; Wilson, K; van der Walle, C F; Sattar, N; Petrie, J R; Ravi Kumar, M N V

2010-10-01

Insulin loaded microemulsions were developed adopting a low shear reverse micellar approach using didoceyldimethylammonium bromide (DMAB) as the surfactant, propylene glycol (PG) as the co-surfactant, triacetin (TA) as the oil phase and insulin solution as the aqueous phase. A ternary phase diagram was constructed based on multiple cloud point titration to highlight the reverse micellar region. The droplet sizes of the microemulsions were 161.7±24.7nm with PDI of 0.447±0.076 and insulin entrapment of ∼85%. Transmission electron microscopy (TEM) revealed the spherical nature and size homogeneity of the microemulsion droplets. The conformational stability of the entrapped insulin within microemulsions was confirmed by fluorescence spectroscopy and circular dichroism. The microemulsions displayed a 10-fold enhancement in bioavailability compared with plain insulin solution administered per oral in healthy rats. The short-term in vivo efficacy in STZ induced diabetic rats provided the proof of concept by a modest glucose reduction at a dose of 20IU/kg. Together this preliminary data indicate the promise of microemulsions for oral delivery of insulin. Copyright © 2010 Elsevier B.V. All rights reserved.

A Study of an Optical Lunar Surface Communications Network with High Bandwidth Direct to Earth Link

NASA Technical Reports Server (NTRS)

Wilson, K.; Biswas, A.; Schoolcraft, J.

2011-01-01

Analyzed optical DTE (direct to earth) and lunar relay satellite link analyses, greater than 200 Mbps downlink to 1-m Earth receiver and greater than 1 Mbps uplink achieved with mobile 5-cm lunar transceiver, greater than 1Gbps downlink and greater than 10 Mpbs uplink achieved with 10-cm stationary lunar transceiver, MITLL (MIT Lincoln Laboratory) 2013 LLCD (Lunar Laser Communications Demonstration) plans to demonstrate 622 Mbps downlink with 20 Mbps uplink between lunar orbiter and ground station; Identified top five technology challenges to deploying lunar optical network, Performed preliminary experiments on two of challenges: (i) lunar dust removal and (ii)DTN over optical carrier, Exploring opportunities to evaluate DTN (delay-tolerant networking) over optical link in a multi-node network e.g. Desert RATS.

Preliminary evaluation of several disinfection/sterilization techniques for use with microdialysis probes.

PubMed

Huff, Jacquelyn K; Bresnahan, James F; Davies, Malonne I

2003-06-06

This study evaluated the suitability of some disinfection and sterilization methods for use with microdialysis probes. Disinfection or sterilization should minimize the tissue inflammatory reaction and improve the long-term health of rats on study and ensure the quality of data obtained by microdialysis sampling. Furthermore, the treatment should not negatively impact probe integrity or sampling performance. The techniques chosen for evaluation included two disinfection methods (70% ethanol and a commercial contact lens solution) and two sterilization methods (hydrogen peroxide plasma, and e-beam radiation). Linear microdialysis probes treated by these processes were compared to untreated probes removed from the manufacturer's packaging as if sterile (the control group). The probes were aseptically implanted in the livers of rats and monitored for 72 hours. The parameters chosen to evaluate probe performance were relative sample mass recovery and the relative in vivo extraction efficiency of the probe for caffeine. Post mortem bacterial counts and histopathology examination of liver tissue were also conducted. The probes remained intact and functional for the entire study period. The methods tested did not acutely alter the probes although hydrogen peroxide plasma and contact lens solution groups showed reduced extraction efficiencies. Minimal tissue damage was observed surrounding the probes and acute inflammatory reaction was mild to moderate. Low numbers of bacterial colonies from the implantation sites indicates that the health of animals in this study was not impaired. This was also true for the control group (untreated probe).

Discovery of Potent, Orally Bioavailable Inhibitors of Human Cytomegalovirus

PubMed Central

2016-01-01

A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 μM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure–activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat. PMID:27190604

Chloroquine, quinine, procaine, quinidine and clomipramine are prostaglandin agonists and antagonists.

PubMed

Manku, M S; Horrobin, D F

1976-11-01

Chloroquine, quinine, procaine, quinidine and clomipramine behave as prostaglandin (PG) antagonists in a rat mesenteric vascular bed preparation. The ID50 concentrations were within the range of therapeutically effective human plasma levels in each case. Antagonism to PGE2 was studied in detail and seemed to be at least in part competitive. The drugs also antagonized the effects of PGs A1, A2, F2alpha and E1. Each drug also had weak prostaglandin agonist activity but only over a very narrow range of concentrations. It is possible that some of the clinical actions of these drugs may depend on blockade or imitation of natural PG effects. The findings suggest new approaches to the search for PG antagonists, a new screening technique for anti-inflammatory drugs and possible new uses for these established drugs. A preliminary study suggests that chloroquine may be successful in closing a patent ductus arteriosus in infants.

Application of 2-um wavelength holmium lasers for treatment of skin diseases

NASA Astrophysics Data System (ADS)

Shcherbakov, Ivan A.; Klimov, Igor V.; Tsvetkov, Vladimir B.; Nerobeev, Alexander I.; Sadovnikova, Lija B.; Eliseenko, Vladimir I.

1994-09-01

Theoretical and experimental analysis of the efficiency of application of 2 micrometers pulsed holmium laser for cosmetic and plastic surgery and dermatology is carried out. Preliminary experiments were carried out on rats. Solid state 2 micrometers pulsed laser was allowed to operate in free running mode with pulse energy up to 1.5 J and pulse repetition rate up to 5 Hz. To deliver emission to the object a flexible quartz fiber without further focusing of 2.5 m in length and 400 micrometers of the core diameter was used. The effect of the different power density emission on the skin was studied. The second stage was the study of the influence of 2 micrometers emission on human skin. The results of the removal of hemangioma, papilloma, telangiectasia, nevus, nevus acantholytic, xanthelasma palpebral, verruca, chloasma, pigmental spots, tattoos, etc. are presented. Precision, simplicity, efficiency, and the high cosmetic effect of these operations is noted.

Imaging DC MEG Fields Associated with Epileptic Onset

NASA Astrophysics Data System (ADS)

Weiland, B. J.; Bowyer, S. M.; Moran, J. E.; Jenrow, K.; Tepley, N.

2004-10-01

Magnetoencephalography (MEG) is a non-invasive brain imaging modality, with high spatial and temporal resolution, used to evaluate and quantify the magnetic fields associated with neuronal activity. Complex partial epileptic seizures are characterized by hypersynchronous neuronal activity believed to arise from a zone of epileptogenesis. This study investigated the characteristics of direct current (DC) MEG shifts arising at epileptic onset. MEG data were acquired with rats using a six-channel first order gradiometer system. Limbic status epilepticus was induced by IA (femoral) administration of kainic acid. DC-MEG shifts were observed at the onset of epileptic spike train activity and status epilepticus. Epilepsy is also being studied in patients undergoing presurgical mapping from the Comprehensive Epilepsy Center at Henry Ford Hospital using a whole head Neuromagnetometer. Preliminary data analysis shows that DC-MEG waveforms, qualitatively similar to those seen in the animal model, are evident prior to seizure activity in human subjects.

Design and Fabrication of Helmholtz Coils to Study the Effects of Pulsed Electromagnetic Fields on the Healing Process in Periodontitis: Preliminary Animal Results

PubMed Central

Haghnegahdar, A; Khosrovpanah, H; Andisheh-Tadbir, A; Mortazavi, Gh; Saeedi Moghadam, M; Mortazavi, SMJ; Zamani, A; Haghani, M; Shojaei Fard, M; Parsaei, H; Koohi, O

2014-01-01

Background: Effects of electromagnetic fields on healing have been investigated for centuries. Substantial data indicate that exposure to electromagnetic field can lead to enhanced healing in both soft and hard tissues. Helmholtz coils are devices that generate pulsed electromagnetic fields (PEMF). Objective: In this work, a pair of Helmholtz coils for enhancing the healing process in periodontitis was designed and fabricated. Method: An identical pair of square Helmholtz coils generated the 50 Hz magnetic field.  This device was made up of two parallel coaxial circular coils (100 turns in each loop, wound in series) which were separated from each other by a distance equal to the radius of one coil (12.5 cm). The windings of our Helmholtz coil was made of standard 0.95mm wire to provide the maximum possible current. The coil was powered by a function generator.  Results: The Helmholtz Coils generated a uniform magnetic field between its coils. The magnetic field strength at the center of the space between two coils was 97.6 μT. Preliminary biological studies performed on rats show that exposure of laboratory animals to pulsed electromagnetic fields enhanced the healing of periodontitis. Conclusion: Exposure to PEMFs can lead to stimulatory physiological effects on cells and tissues such as enhanced healing of periodontitis. PMID:25505775

Long-term in vivo carcinogenicity tests of potassium bromate, sodium hypochlorite, and sodium chlorite conducted in Japan.

PubMed Central

Kurokawa, Y; Takayama, S; Konishi, Y; Hiasa, Y; Asahina, S; Takahashi, M; Maekawa, A; Hayashi, Y

1986-01-01

Long-term in vivo carcinogenicity tests of potassium bromate (KBrO3), sodium hypochlorite (NaClO), and sodium chlorite (NaClO2) have been conducted in Japan from 1977 to 1985. In these investigations, groups of approximately 50 male and 50 female F344 rats or B6C3F1 mice were given solutions of the compounds as their drinking water ad libitum at two dose levels determined on the basis of preliminary 13-week tests. Control animals were given distilled water. The carcinogenic potential of KBrO3 was tested by administering doses of 500 or 250 ppm to rats for 110 weeks. Significantly elevated incidences of renal cell tumors in males and females and mesotheliomas of the peritoneum in males as compared to controls were observed. When female mice were given KBrO3 at doses of 1000 or 500 ppm for 78 weeks, no significant differences in tumor incidences between experimental and control groups were apparent. NaClO was administered to male and female rats, respectively, at doses of 1000 or 500 ppm and 2000 or 1000 ppm for 104 weeks. In mice, NaClO was given at doses of 1000 or 500 ppm to either sex for 103 weeks. The incidences of tumors in NaClO-treated and control animals of both sexes were not significantly different in both rat and mouse studies. NaClO2 was given to rats of both sexes at a dose of 600 or 300 ppm for 85 weeks. No statistically significant differences were observed in the incidences of tumor formation between NaClO2-treated and control groups of both sexes. NaClO2 was administered to mice at a concentration of 500 or 250 ppm for 85 weeks. In males, the combined incidences of hyperplastic nodules and hepatocellular carcinomas of the liver in a low-dose group, and adenomas and adenocarcinomas of the lung in a high-dose group, were marginally increased compared to controls (p less than 0.05). However, these incidences in treated males were within the range of values of historical control data in our program. We concluded that KBrO3 was carcinogenic in rats of both sexes. NaClO was not carcinogenic in either rats and or mice under the conditions of the present studies. Although NaClO2 was shown to be noncarcinogenic in rats, the results for mice were evaluated as inconclusive. Also the results of two-stage mouse skin carcinogenesis using KBrO3, NaClO, and NaClO2 are presented. The necessity for further testing of oxidant chemicals to determine potential carcinogenic and/or promoting effects is suggested in view of the recently proposed role of active oxygen species in carcinogenesis. Images FIGURE 3. FIGURE 4. PMID:3816726

Intraduodenal infusion of cyanidin-3-glucoside transiently promotes triglyceride excretion into bile in rats.

PubMed

Hashimoto, Naoto; Han, Kyu-Ho; Fukushima, Michihiro

2017-02-01

Flavonoids purportedly have a role in improving lipid metabolism. In our preliminary study, highly concentrated flavonoid metabolites appeared in bile juice in rats, which also contains various lipids. Biliary flavonoid metabolites generally have amphiphilic properties, may influence lipid solubility, and possibly contribute to the improvement of dyslipidemia. However, the influence of biliary flavonoid metabolites on the biliary lipid profile is not well known. Therefore, we hypothesized that the amphiphilic property of biliary flavonoid metabolites alters biliary lipid profiles. To estimate the influence of flavonoids on the biliary lipid profile, we laparotomized rats under anesthesia, intraduodenally injected them with cyanidin-3-glucoside chloride (C3G) or quercetin, and analyzed their biliary metabolite concentrations for 2 hours. Concentrations of C3G and quercetin metabolites peaked at 30 minutes after the injection; those of quercetin were 6 to 10 times higher than those of C3G throughout the sampling period up to 2 hours. Biliary triglyceride (TG) concentrations were higher in the C3G group at 30 and 45 minutes; biliary cholesterol and phospholipid concentrations were lower in the quercetin group at 30 minutes than those in the control group. Hepatic TG content after the 2-hour sampling was lower in the C3G group than in the control group. These results suggest that C3G, but not quercetin, may transiently promote TG excretion into bile, with a reduction in hepatic TG content. This C3G effect may be involved in improvement of TG metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

In vitro inhibition of OATP-mediated uptake of phalloidin using bile acid derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Herraez, Elisa; Macias, Rocio I.R.; Vazquez-Tato, Jose

2009-08-15

Hepatocyte uptake of phalloidin is carried out mainly by OATP1B1. We have used this compound as a prototypic substrate and assayed the ability to inhibit OATP-mediated phalloidin transport of four bile acid derivatives (BALU-1, BALU-2, BALU-3 and BALU-4) that showed positive results in preliminary screening. Using Xenopus laevis oocytes for heterologous expression of transporters, BALUs were found to inhibit taurocholic acid (TCA) transport by OATP1B1 (but not OATP1B3) as well as by rat Oatp1a1, Oatp1a4 and Oatp1b2. The study of their ability to inhibit sodium-dependent bile acid transporters revealed that the four BALUs induced an inhibition of rat Asbt-mediated TCAmore » transport, which was similar to TCA-induced self-inhibition. Regarding human NTCP and rat Ntcp, BALU-1 differs from the other three BALUS in its lack of effect on TCA transport by these proteins. Using HPLC-MS/MS and CHO cells stably expressing OATP1B1 the ability of BALU-1 to inhibit the uptake of phalloidin itself by this transporter was confirmed. Kinetic analysis using X. laevis oocytes revealed that BALU-1-induced inhibition of OATP1B1 was mainly due to a competitive mechanism (Ki = 8 {mu}M). In conclusion, BALU-1 may be useful as a pharmacological tool to inhibit the uptake of compounds mainly taken up by OATP1B1 presumably without impairing bile acid uptake by the major carrier accounting for this process, i.e., NTCP.« less

Reflection on design and testing of pancreatic alpha-amylase inhibitors: an in silico comparison between rat and rabbit enzyme models

PubMed Central

2012-01-01

Background Inhibitors of pancreatic alpha-amylase are potential drugs to treat diabetes and obesity. In order to find compounds that would be effective amylase inhibitors, in vitro and in vivo models are usually used. The accuracy of models is limited, but these tools are nonetheless valuable. In vitro models could be used in large screenings involving thousands of chemicals that are tested to find potential lead compounds. In vivo models are still used as preliminary mean of testing compounds behavior in the whole organism. In the case of alpha-amylase inhibitors, both rats and rabbits could be chosen as in vivo models. The question was which animal could present more accuracy with regard to its pancreatic alpha-amylase. Results As there is no crystal structure of these enzymes, a molecular modeling study was done in order to compare the rabbit and rat enzymes with the human one. The overall result is that rabbit enzyme could probably be a better choice in this regard, but in the case of large ligands, which could make putative interactions with the −4 subsite of pancreatic alpha-amylase, interpretation of results should be made cautiously. Conclusion Molecular modeling tools could be used to choose the most suitable model enzyme that would help to identify new enzyme inhibitors. In the case of alpha-amylase, three-dimensional structures of animal enzymes show differences with the human one which should be taken into account when testing potential new drugs. PMID:23352052

OPC-28326, a selective femoral vasodilator, is an alpha2C-adrenoceptor-selective antagonist.

PubMed

Sun, B; Lockyer, S; Li, J; Chen, R; Yoshitake, M; Kambayashi, J I

2001-11-01

OPC-28326 has been reported to selectively increase femoral blood flow in open-chest dogs and autoperfused canine femoral artery preparations. Preliminary data indicated that OPC-28326 has a high affinity at the alpha2-adrenoceptor. In the present study, we tested OPC-28326 in isoflurane anesthetized rats at a dose of 3 mg/kg of body weight, given intraduodenally. OPC-28326 significantly increased femoral blood flow, by 44.7 +/- 13.8%, 45 min after drug administration, whereas carotid blood flow increased by only 3.6 +/- 5.5% (n = 6). Chinese hamster ovary cell lines overexpressing rat alpha2D-, alpha2B-, or alpha2C-adrenoceptor were established. These cells also coexpress luciferase, driven by cAMP elevation. In radioligand binding assays using cell membrane preparations, OPC-28326 dose dependently competed with [3H]RX821002 binding, with calculated K(i) values of 3840 +/- 887, 633 +/- 46, and 13.7 +/- 1.9 nM on alpha2D-, alpha2B-, and alpha2C-adrenoceptor, respectively. A similar affinity and rank order of potency were also found for OPC-28326 on the alpha2-subtypes using epinephrine as agonist in luciferase assays. No agonistic effect of OPC-28326 was detected on any of the alpha2-adrenoceptors. Finally, in situ hybridization performed on skeletal muscle tissue sections collected from rat hind limb (musculus gastrocnemius) demonstrated a high level expression of alpha2C in the vascular tissues. Thus, the abundance of alpha2C in the skeletal muscle may account for the selective effect of OPC-28326 in increasing femoral blood flow.

Microspheres for the oral delivery of insulin: preparation, evaluation and hypoglycaemic effect in streptozotocin-induced diabetic rats.

PubMed

Zhang, Huan; Wang, Weimei; Li, Haoran; Peng, Yi; Zhang, Zhiqing

2018-01-01

Insulin-loaded microspheres were prepared by alternating deposition film layers that were composed of insulin and poly(vinyl sulfate) potassium on the surface of poly(lactic acid) (PLA) microspheres. The preparation of the insulin-loaded microspheres was optimized by an orthogonal test design, and the relationship between drug loading (DL) and film layers was studied. The particle size, DL and encapsulation efficiency of the obtained insulin-loaded microspheres with 10 films were 5.25 ± 0.15 µm, 111.33 ± 1.15 mg/g and 33.7 ± 0.19%, respectively. Following this, the physical characteristics of the insulin-loaded microspheres were investigated. The results from scanning electron microscopy and a laser particle size analyzer (LPSA) indicated the spherical morphology, rough surface and increasing particle sizes of the insulin-loaded microspheres, which were compared to those of PLA microspheres. An in vitro release study showed that the insulin-loaded microspheres were stable in HCl solution (pH 1.0) and released insulin slowly in phosphate-buffered solution (pH 6.8). Finally, the drug efficacy of the prepared insulin-loaded microspheres via oral administration was evaluated in rats with diabetes induced by streptozotocin, and an obvious dose-dependent hypoglycemic effect was observed. This preliminary data could illustrate the prospect of using microspheres for the oral delivery of insulin.

Tumor necrosis factor-α-dependent infiltration of macrophages into the dorsal root ganglion in a rat disc herniation model.

PubMed

You, Changcheng; Zhu, Kai; Liu, Xiaoqi; Xi, Chunyang; Zhang, Zhipeng; Xu, Gongping; Yan, Jinglong

2013-11-01

A prospective molecular mechanism of macrophages infiltration in experimental disc herniation. To investigate the mechanisms of macrophages infiltration into the dorsal root ganglion (DRG) in a rat model of disc herniation. Macrophages infiltrate the DRG after application of nucleus pulposus (NP) on the DRG, and may play an important role in radiculopathy. However, the mechanisms of macrophages infiltration after NP application remain poorly understood. After experimental disc herniation in this study, we investigated changes in the expression of ED1 (a marker of macrophages) and vascular cell adhesion molecule-1 (VCAM-1) in DRG using immunofluorescence. We also investigated the expression of ED1 and VCAM-1 in DRG by treatment with tumor necrosis factor-α (TNF-α) inhibitor at the time of surgery. We found a massive ED1-positive macrophages infiltrated the DRG, and VCAM-1-like immunoreactivity vessels became evident after NP application. Furthermore, both macrophage infiltration and VCAM-1 expression were prevented by treatment with TNF-α inhibitor at the time of surgery. These findings indicated that macrophages infiltration into the DRG was TNF-α-dependent, and might be partly mediated by VCAM-1 in the early stage of experimental lumbar disc herination. Taken together, this study provides important preliminary data suggesting that TNF-α plays an important role in the macrophage infiltration. N/A.

Platelet-rich plasma, low-level laser therapy, or their combination promotes periodontal regeneration in fenestration defects: a preliminary in vivo study.

PubMed

Nagata, Maria J H; de Campos, Natália; Messora, Michel R; Pola, Natália M; Santinoni, Carolina S; Bomfim, Suely R M; Fucini, Stephen E; Ervolino, Edilson; de Almeida, Juliano M; Theodoro, Letícia H; Garcia, Valdir G

2014-06-01

This study histomorphometrically analyzes the influence of platelet-rich plasma (PRP), low-level laser therapy (LLLT), or their combination on the healing of periodontal fenestration defects (PFDs) in rats. PFDs were surgically created in the mandibles of 80 rats. The animals were randomly divided into four groups: 1) C (control) and 2) PRP, defects were filled with blood clot or PRP, respectively; 3) LLLT and 4) PRP/LLLT, defects received laser irradiation, were filled with blood clot or PRP, respectively, and then irradiated again. Animals were euthanized at either 10 or 30 days post-surgery. Percentage of new bone (NB), density of newly formed bone (DNB), new cementum (NC), and extension of remaining defect (ERD) were histomorphometrically evaluated. Data were statistically analyzed (analysis of variance; Tukey test, P <0.05). At 10 days, group PRP presented ERD significantly lower than group C. At 30 days, group PRP presented NB and DNB significantly greater than group C. Groups LLLT, PRP, and PRP/LLLT showed significant NC formation at 30 days, with collagen fibers inserted obliquely or perpendicularly to the root surface. NC formation was not observed in any group C specimen. LLLT, PRP, or their combination all promoted NC formation with a functional periodontal ligament. The combination PRP/LLLT did not show additional positive effects compared to the use of either therapy alone.

Biochemical correlates in an animal model of depression

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, J.O.

1986-01-01

A valid animal model of depression was used to explore specific adrenergic receptor differences between rats exhibiting aberrant behavior and control groups. Preliminary experiments revealed a distinct upregulation of hippocampal beta-receptors (as compared to other brain regions) in those animals acquiring a response deficit as a result of exposure to inescapable footshock. Concurrent studies using standard receptor binding techniques showed no large changes in the density of alpha-adrenergic, serotonergic, or dopaminergic receptor densities. This led to the hypothesis that the hippocampal beta-receptor in responses deficient animals could be correlated with the behavioral changes seen after exposure to the aversive stimulus.more » Normalization of the behavior through the administration of antidepressants could be expected to reverse the biochemical changes if these are related to the mechanism of action of antidepressant drugs. This study makes three important points: (1) there is a relevant biochemical change in the hippocampus of response deficient rats which occurs in parallel to a well-defined behavior, (2) the biochemical and behavioral changes are normalized by antidepressant treatments exhibiting both serotonergic and adrenergic mechanisms of action, and (3) the mode of action of antidepressants in this model is probably a combination of serotonergic and adrenergic influences modulating the hippocampal beta-receptor. These results are discussed in relation to anatomical and biochemical aspects of antidepressant action.« less

ALA-induced PpIX fluorescence in epileptogenic tissue

NASA Astrophysics Data System (ADS)

Kleen, Jonathan K.; Valdes, Pablo A.; Harris, Brent T.; Holmes, Gregory L.; Paulsen, Keith D.; Roberts, David W.

2011-03-01

Astrogliotic tissue displays markedly increased levels of ALA-induced PpIX fluorescence, making it useful for fluorescence-guided resection in glioma surgery. In patients with temporal lobe epilepsy (TLE) and corresponding animal models, there are areas of astrogliosis that often co-localize with the epileptic focus, which can be resected to eliminate seizures in the majority of treated patients. If this epileptogenic tissue can exhibit PpIX fluorescence that is sufficiently localized, it could potentially help identify margins in epilepsy surgery. We tested the hypothesis that ALA-induced PpIX fluorescence could visually accentuate epileptogenic tissue, using an established animal model of chronic TLE. An acute dose of pilocarpine was used to induce chronic seizure activity in a rat. This rat and a normal control were given ALA, euthanized, and brains examined post-mortem for PpIX fluorescence and neuropathology. Preliminary evidence indicates increased PpIX fluorescence in areas associated with chronic epileptic changes and seizure generation in TLE, including the hippocampus and parahippocampal areas. In addition, strong PpIX fluorescence was clearly observed in layer II of the piriform cortex, a region known for epileptic reorganization and involvement in the generation of seizures in animal studies. We are further investigating whether ALA-induced PpIX fluorescence can consistently identify epileptogenic zones, which could warrant the extension of this technique to clinical studies for use as an adjuvant guidance technology in the resection of epileptic tissue.

Identification and hit-to-lead optimization of a novel class of CB1 antagonists.

PubMed

Letourneau, Jeffrey J; Jokiel, Patrick; Olson, John; Riviello, Christopher M; Ho, Koc-Kan; McAleer, Lihong; Yang, Jingchun; Swanson, Robert N; Baker, James; Cowley, Phillip; Edwards, Darren; Ward, Nick; Ohlmeyer, Michael H J; Webb, Maria L

2010-09-15

The discovery, synthesis and preliminary structure-activity relationships (SARs) of a novel class of CB1 antagonists is described. Initial optimization of benzimidazole-based screening hit 4 led to the identification of 'inverted' indole-based lead compound 18c with improved properties versus compound 4 including reduced AlogP, improved microsomal stability and improved aqueous solubility. Compound 18c demonstrates in vivo CB1 antagonist efficacy (CB1 agonist induced hypothermia model) and is orally bioavailable in rat. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Radiolabelled D2 agonists as prolactinoma imaging agents

DOE Office of Scientific and Technical Information (OSTI.GOV)

Otto, C.A.

1989-08-01

During the past year, further studies on mAChR were conducted. These studies included verification of the difference in pituitary distribution based on ligand charge. The pituitary localization of TRB. A neutral mAChR ligand, was verified. The lack of QNB blockade of TRB uptake was tested by blockage with scopolamine, another mAChR antagonist and by testing the effect in a different strain of rat. Neither scopolamine or change of rat strain had any effect. We concluded that TRB uptake in pituitary is not a receptor-mediated process. Further studies were conducted with an additional quaternized mAChR ligand: MQNB. Pituitary localization of MQNB,more » like MTRB, could be blocked by pretreatment with QNB. We have tentatively concluded that permanent charge on a mAChR antagonist changes the mechanism of uptake in the pituitary. Time course studies and the effects of DES on myocardial uptake are reported. A brief report on preliminary results of evaluation of quaternized mAChR ligands in the heart is included. In a limited series of such ligands, we have observed a single binding site and a difference in B{sub max} values: QNB competition studies yield larger B{sub max} values than studies with {sup 3}H-NMS. Progress in the synthesis of D{sub 2} agonists includes solving a synthetic problem and preparation of the cold'' analogue of N-0437 using procedures applicable to eventual synthesis with {sup 11}C-CH{sub 3}I. 2 refs., 5 figs., 1 tab.« less

Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats--Is there a potential for Alzheimer's disease treatment?

PubMed

Misik, Jan; Korabecny, Jan; Nepovimova, Eugenie; Kracmarova, Alzbeta; Kassa, Jiri

2016-01-26

Inhibitors of cholinesterase are important drugs for therapy of Alzheimer's disease and the search for new modifications is extensive, including dual inhibitors or multi-target hybrid compounds. The aim of the present study was a preliminary evaluation of pro-cognitive effects of newly-developed 7-MEOTA-donepezil like hybrids (compounds no. 1 and 2) and N-alkylated tacrine derivatives (compounds no. 3 and 4) using an animal model of pharmacologically-induced cognitive deficit. Male Wistar rats were subjected to tests of learning and memory in a water maze and step-through passive avoidance task. Cognitive impairment was induced by 3-quinuclidinyl benzilate (QNB, 2mgkg(-1)), administered intraperitoneally 1h before training sessions. Cholinesterase inhibitors were administered as a single therapeutic dose following the QNB at 30min at the following dose rates; 1 (25.6mgkg(-1)), 2 (12.3mgkg(-1)), 3 (5.7mgkg(-1)), 4 (5.2mgkg(-1)). The decrease in total path within the 10-swim session (water maze), the preference for target quadrant (water maze) and the entrance latency (passive avoidance) were taken as indicators of learning ability in rats. The effects of novel compounds were compared to that of standards tacrine (5.2mgkg(-1)) and donepezil (2.65mgkg(-1)). QNB significantly impaired spatial navigation as well as fear learning. Generally, the performance of rats was improved when treated with novel inhibitors and this effect reached efficiency of standard donepezil at selected doses. There was a significant improvement in the groups treated with compounds 2 and 3 in all behavioral tasks. The rest of the novel compounds succeed in the passive avoidance test. In summary, the potential of novel inhibitors (especially compounds 2 and 3) was proved and further detailed evaluation of these compounds as potential drugs for Alzheimer's disease treatment is proposed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Bilirubin provides perforator flap protection from ischaemia-reperfusion injury in a rat model: a preliminary result.

PubMed

Kim, Sung Young; Rah, Dong Kyun; Chong, Yosep; Lee, Song Hyun; Park, Tae Hwan

2016-10-01

The use of bilirubin, a well-known and powerful antioxidant, has gained popularity in recent years because of its role in the prevention of ischaemic heart disease in patients with Gilbert's syndrome. We investigate the effects of bilirubin on ischaemia-reperfusion (I/R) injury using a rat perforator flap model. Forty-eight rats were randomly divided into two groups: experimental (bilirubin) group (n = 24) and control group (n = 24). In each group, elevated bilateral deep inferior epigastric perforator (DIEP) flaps were created. The right (no ischaemia side) and left (ischaemia side) DIEP flaps were separated according to the presence of ischaemia induction. Ischaemia was induced in anaesthetised rats by perforator clamping for 15 or 30 minutes. After surgery, the flap survival was assessed daily on postoperative days 0 to 5, and overall histological changes of DIEP flaps above the perforator were analysed at postoperative day 5. The flap survival rate in the bilirubin group was significantly higher than that in the control group at the ischaemia side following perforator clamping for 15 or 30 minutes (93·42 ± 4·48% versus 89·63 ± 3·98%, P = 0·002; and 83·96 ± 4·23% versus 36·46 ± 6·38%, P < 0·001, respectively). The difference in flap survival between the two groups was the most prominent on the ischaemic side following 30 minutes of perforator clamping. From a morphologic perspective, pre-treatment with bilirubin was found to alleviate perforator flap necrosis caused by I/R injury in this experimental rat model. © 2015 Medicalhelplines.com Inc and John Wiley & Sons Ltd.

Molecular cloning and characterization of rat sperm surface antigen 2B1, a glycoprotein implicated in sperm-zona binding.

PubMed

Hou, S T; Ma, A; Jones, R; Hall, L

1996-10-01

The rat sperm surface antigen, 2B1, that has been proposed to play a key role in sperm adhesion to the zona pellucida, has been cloned and its entire cDNA sequenced. Northern blot analysis indicates that 2B1 is encoded by a 2.2-kb RNA transcript that is abundantly expressed in the testis. The deduced protein sequence contains 512 amino-acid residues with a strong candidate signal sequence and C-terminal transmembrane domain. Data base searches reveal a high degree of sequence similarity to guinea pig, rabbit, monkey, and human PH20 sperm surface antigens, and a lower degree of similarity to honey bee and whiteface hornet venom hyaluronidases. Rat 2B1 antigen also possesses hyaluronidase activity, suggesting that it is a bifunctional protein with putative roles in the dispersion of cumulus oophorus cells as well as zona adhesion. However, while it would appear that 2B1 is the rat homologue of the guinea pig PH20 antigen, they differ in a number of important biochemical respects (including their mode of attachment to the sperm membrane and distribution between soluble and membrane-bound fractions), as well as in their localization on the sperm membrane. Expression of regions of the 2B1 protein in recombinant bacterial cells has allowed a preliminary mapping of the 2B1 epitope, and has provided more definitive information on the endoproteolytic processing of 2B1 during epididymal transit.

Gene transfer with a vector expressing Maxi-K from a smooth muscle-specific promoter restores erectile function in the aging rat.

PubMed

Melman, A; Biggs, G; Davies, K; Zhao, W; Tar, M T; Christ, G J

2008-03-01

Previous reports have demonstrated that gene transfer with the alpha, or pore-forming, subunit of the human Maxi-K channel (hSlo) restores the decline in erectile capacity observed in established rat models of diabetes and aging. Preliminary data from a human clinical trial also showed safety and potential efficacy in 11 men treated with the same plasmid construct expressing the Maxi-K channel. In all instances, the original plasmid was driven by the heterologous cytomegalovirus promoter which is broadly active in a wide variety of cell and tissue types. To more precisely determine the contribution of the corporal myocyte to the observed physiological effects in vivo, we report here our initial work using a distinct vector (pSMAA-hSlo) in which hSlo gene expression was driven off the mouse smooth muscle alpha-actin (SMAA) promoter. Specifically, older rats, with diminished erectile capacity, were given a single intracorporal injection with either 100 mug pVAX-hSlo or 10, 100 or 1000 mug pSMAA-hSlo, or vector or vehicle alone. Significantly increased intracavernous pressure (ICP) responses to cavernous nerve stimulation were observed for all doses of both plasmids encoding hSlo, relative to control injections. These data confirm and extend previous observations to document that smooth muscle cell-specific expression of hSlo in corporal tissue is both necessary and sufficient to restore erectile function in aging rats.

Rapid and reliable healing of critical size bone defects with genetically modified sheep muscle.

PubMed

Liu, F; Ferreira, E; Porter, R M; Glatt, V; Schinhan, M; Shen, Z; Randolph, M A; Kirker-Head, C A; Wehling, C; Vrahas, M S; Evans, C H; Wells, J W

2015-09-21

Large segmental defects in bone fail to heal and remain a clinical problem. Muscle is highly osteogenic, and preliminary data suggest that autologous muscle tissue expressing bone morphogenetic protein-2 (BMP-2) efficiently heals critical size defects in rats. Translation into possible human clinical trials requires, inter alia, demonstration of efficacy in a large animal, such as the sheep. Scale-up is fraught with numerous biological, anatomical, mechanical and structural variables, which cannot be addressed systematically because of cost and other practical issues. For this reason, we developed a translational model enabling us to isolate the biological question of whether sheep muscle, transduced with adenovirus expressing BMP-2, could heal critical size defects in vivo. Initial experiments in athymic rats noted strong healing in only about one-third of animals because of unexpected immune responses to sheep antigens. For this reason, subsequent experiments were performed with Fischer rats under transient immunosuppression. Such experiments confirmed remarkably rapid and reliable healing of the defects in all rats, with bridging by 2 weeks and remodelling as early as 3-4 weeks, despite BMP-2 production only in nanogram quantities and persisting for only 1-3 weeks. By 8 weeks the healed defects contained well-organised new bone with advanced neo-cortication and abundant marrow. Bone mineral content and mechanical strength were close to normal values. These data demonstrate the utility of this model when adapting this technology for bone healing in sheep, as a prelude to human clinical trials.

Vitamin K3 increased BMD at 1 and 2 months post-surgery and the maximum stress of the middle femur in the rat.

PubMed

Hong, You-jia; Liu, Sheng; Jiang, Ning-yi; Jiang, Sen; Liang, Jiu-gen

2015-02-01

The therapeutic effects of vitamin K3 (VK3) on osteoporosis are still unknown. In this study, we hypothesized that VK3 possesses therapeutic effects on osteoporosis; to verify this hypothesis, the ovariectomized rat was used as an osteoporosis model. Fifty-six Sprague-Dawley female rats aged 8 to 9 months were randomly assigned to 4 groups: sham surgery, ovariectomy with saline, ovariectomy with low-dose VK3, and ovariectomy with high-dose VK3. Intramuscular injection of VK3 was performed every other day beginning 1 month postoperatively. The therapeutic effects of VK3 on osteoporosis were evaluated by measurement of bone mineral density (BMD), bone biochemical markers, biomechanical properties, and bone morphometric parameters. The overall average BMD in VK3-treated groups increased to a level between those of the ovariectomy group and the sham surgery group. The procollagen I N-terminal peptide level peaked at 2 months after surgery in all groups except in the group that had undergone ovariectomy with low-dose VK3. The tartrate-resistant acid phosphatase 5b level increased more slowly at 4 months after surgery than at 2 months after surgery in the VK3-treated groups. The ovariectomy with high-dose VK3 group had the highest maximum stress of the middle femur of all groups. With VK3 treatment, the trabecular bone area percentage increased. All morphometric indicators for the middle tibia in the VK3-treated groups reached the levels found in the sham surgery group. In summary, VK3 therapy increased BMD at 1 and 2 months postsurgery and the maximum stress of the middle femur. In addition, VK3 therapy slowed the increase in bone turnover in ovariectomized rats. Furthermore, VK3 can improve morphometric indicators for the middle tibia. Our preliminary study indicates that VK3 has a potential therapeutic effect on osteoporosis and is worthy of further investigation. Copyright © 2015 Elsevier Inc. All rights reserved.

Part 1. Biologic responses in rats and mice to subchronic inhalation of diesel exhaust from U.S. 2007-compliant engines: report on 1-, 3-, and 12-month exposures in the ACES bioassay.

PubMed

Mcdonald, Jacob D; Doyle-Eisele, Melanie; Gigliotti, Andrew; Miller, Rodney A; Seilkop, Steve; Mauderly, Joe L; Seagrave, JeanClare; Chow, Judith; Zielinska, Barbara

2012-09-01

The Health Effects Institute and its partners conceived and funded a program to characterize the emissions from heavy-duty diesel engines compliant with the 2007 and 2010 on-road emissions standards in the United States and to evaluate indicators of lung toxicity in rats and mice exposed repeatedly to diesel exhaust (DE*) from 2007-compliant engines. The preliminary hypothesis of this Advanced Collaborative Emissions Study (ACES) was that 2007-compliant on-road diesel emissions ". . . will not cause an increase in tumor formation or substantial toxic effects in rats and mice at the highest concentration of exhaust that can be used . . . although some biological effects may occur." This hypothesis is being tested at the Lovelace Respiratory Research Institute (LRRI) by exposing rats by chronic inhalation as a carcinogenicity bioassay, measuring indicators of pulmonary toxicity in rats after 1, 3, 12, and 24-30 months of exposure (final time point depends on the survival of animals), and measuring similar indicators of pulmonary toxicity in mice after 1 and 3 months of exposure. This report provides results of exposures through 3 months in rats and mice. Emissions from a 2007-compliant, 500-horsepower-class engine and aftertreatment system operated on a variable-duty cycle were used to generate the animal inhalation test atmospheres. Four treatment groups were exposed to one of three concentrations (dilutions) of exhaust combined with crankcase emissions, or to clean air as a negative control. Dilutions of exhaust were set to yield average integrated concentrations of 4.2, 0.8, and 0.1 ppm nitrogen dioxide (NO2). Exposure atmospheres were analyzed by daily measurements of key components and periodic detailed physical-chemical characterizations. Exposures were conducted 16 hr/dy (overnight), 5 dy/wk. Rats were evaluated for hematology, serum chemistry, bronchoalveolar lavage (BAL), lung cell proliferation, and histopathology after 1 month of exposure, and the same indicators plus pulmonary function after 3 months. Mice were evaluated for BAL, lung cell proliferation, and respiratory tract histopathology after 1 month of exposure, and the same indicators plus hematology and serum chemistry after 3 months. Samples from both species were collected for ancillary studies performed by investigators who were not at LRRI and were funded separately. Exposures were accomplished as planned, with average integrated exposure concentrations within 20% of the target dilutions. The major components were the gaseous inorganic compounds, nitrogen monoxide (NO), NO2, and carbon monoxide (CO). Minor components included low concentrations of diesel particulate matter (DPM) and volatile and semivolatile organic compounds (VOCs and SVOCs). There were no exposure-related differences in mortality or clinically evident morbidity. Among the more than 100 biologic response variables evaluated, the majority showed no significant difference from control as a result of exposure to DE. There was evidence of early lung changes in the rats, accompanied by a number of statistically significant increases in inflammatory and oxidative stress indicators, and some evidence of subtle changes in pulmonary function. In general, statistically significant effects were observed only at the highest exposure level. The mice did not have the same responses as the rats, but did have small but statistically significant increases in lavage neutrophils and the cytokine IL-6 at 1 month (but not at 3 months). These findings suggest that the rats were more sensitive than mice to the subchronic exposures.

A PET Tracer for Brain α2C Adrenoceptors, (11)C-ORM-13070: Radiosynthesis and Preclinical Evaluation in Rats and Knockout Mice.

PubMed

Arponen, Eveliina; Helin, Semi; Marjamäki, Päivi; Grönroos, Tove; Holm, Patrik; Löyttyniemi, Eliisa; Någren, Kjell; Scheinin, Mika; Haaparanta-Solin, Merja; Sallinen, Jukka; Solin, Olof

2014-07-01

We report the development of a PET tracer for α2C adrenoceptor imaging and its preliminary preclinical evaluation. α2C adrenoceptors in the human brain may be involved in various neuropsychiatric disorders, such as depression, schizophrenia, and neurodegenerative diseases. PET tracers are needed for imaging of this receptor system in vivo. High-specific-activity (11)C-ORM-13070 (1-[(S)-1-(2,3-dihydrobenzo[1,4]dioxin-2-yl)methyl]-4-(3-(11)C-methoxymethylpyridin-2-yl)-piperazine) was synthesized by (11)C-methylation of O-desmethyl-ORM-13070 with (11)C-methyl triflate, which was prepared from cyclotron-produced (11)C-methane via (11)C-methyl iodide. Rats and mice were investigated in vivo with PET and ex vivo with autoradiography. The specificity of (11)C-ORM-13070 binding to α2 adrenoceptors was demonstrated in rats pretreated with atipamezole, an α2 adrenoceptor antagonist. The α2C adrenoceptor selectivity of the tracer was determined by comparing tracer binding in wild-type and α2A- and α2AC adrenoceptor knockout (KO) mice. (11)C-ORM-13070 and its radioactive metabolites in rat plasma and brain tissue were analyzed with radio-high-performance liquid chromatography and mass spectroscopy. Human radiation dose estimates were extrapolated from rat biodistribution data. The radiochemical yield, calculated from initial cyclotron-produced (11)C-methane, was 9.6% ± 2.7% (decay-corrected to end of bombardment). The specific activity of the product was 640 ± 390 GBq/μmol (decay-corrected to end of synthesis). The radiochemical purity exceeded 99% in all syntheses. The highest levels of tracer binding were observed in the striatum and olfactory tubercle of rats and control and α2A KO mice-that is, in the brain regions known to contain the highest densities of α2C adrenoceptors. In rats pretreated with atipamezole and in α2AC KO mice, (11)C tracer binding in the striatum and olfactory tubercle was low, similar to that of the frontal cortex and thalamus, regions with low densities of α2C adrenoceptors. Two radioactive metabolites were found in rat plasma, but only one of them was found in the brain; their identity was not revealed. The estimated effective radiation dose was comparable with the average exposure level in PET studies with (11)C tracers. An efficient method for the radiosynthesis of (11)C-ORM-13070 was developed. (11)C-ORM-13070 emerged as a potential novel radiotracer for in vivo imaging of brain α2C adrenoceptors. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Complex impairment of IA muscle proprioceptors following traumatic or neurotoxic injury.

PubMed

Vincent, Jacob A; Nardelli, Paul; Gabriel, Hanna M; Deardorff, Adam S; Cope, Timothy C

2015-08-01

The health of primary sensory afferents supplying muscle has to be a first consideration in assessing deficits in proprioception and related motor functions. Here we discuss the role of a particular proprioceptor, the IA muscle spindle proprioceptor in causing movement disorders in response to either regeneration of a sectioned peripheral nerve or damage from neurotoxic chemotherapy. For each condition, there is a single preferred and widely repeated explanation for disability of movements associated with proprioceptive function. We present a mix of published and preliminary findings from our laboratory, largely from in vivo electrophysiological study of treated rats to demonstrate newly discovered IA afferent defects that seem likely to make important contributions to movement disorders. First, we argue that reconnection of regenerated IA afferents with inappropriate targets, although often repeated as the reason for lost stretch-reflex contraction, is not a complete explanation. We present evidence that despite successful recovery of stretch-evoked sensory signaling, peripherally regenerated IA afferents retract synapses made with motoneurons in the spinal cord. Second, we point to evidence that movement disability suffered by human subjects months after discontinuation of oxaliplatin (OX) chemotherapy for some is not accompanied by peripheral neuropathy, which is the acknowledged primary cause of disability. Our studies of OX-treated rats suggest a novel additional explanation in showing the loss of sustained repetitive firing of IA afferents during static muscle stretch. Newly extended investigation reproduces this effect in normal rats with drugs that block Na(+) channels apparently involved in encoding static IA afferent firing. Overall, these findings highlight multiplicity in IA afferent deficits that must be taken into account in understanding proprioceptive disability, and that present new avenues and possible advantages for developing effective treatment. Extending the study of IA afferent deficits yielded the additional benefit of elucidating normal processes in IA afferent mechanosensory function. © 2015 Anatomical Society.

Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: Results from a preliminary study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Benson, D.W.; Hasselgren, P.O.; Hiyama, D.T.

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calciummore » uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle.« less

Preliminary studies of a simultaneous PET/MRI scanner based on the RatCAP small animal tomograph

NASA Astrophysics Data System (ADS)

Woody, C.; Schlyer, D.; Vaska, P.; Tomasi, D.; Solis-Najera, S.; Rooney, W.; Pratte, J.-F.; Junnarkar, S.; Stoll, S.; Master, Z.; Purschke, M.; Park, S.-J.; Southekal, S.; Kriplani, A.; Krishnamoorthy, S.; Maramraju, S.; O'Connor, P.; Radeka, V.

2007-02-01

We are developing a scanner that will allow simultaneous acquisition of high resolution anatomical data using magnetic resonance imaging (MRI) and quantitative physiological data using positron emission tomography (PET). The approach is based on the technology used for the RatCAP conscious small animal PET tomograph which utilizes block detectors consisting of pixelated arrays of LSO crystals read out with matching arrays of avalanche photodiodes and a custom-designed ASIC. The version of this detector used for simultaneous PET/MRI imaging will be constructed out of all nonmagnetic materials and will be situated inside the MRI field. We have demonstrated that the PET detector and its electronics can be operated inside the MRI, and have obtained MRI images with various detector components located inside the MRI field. The MRI images show minimal distortion in this configuration even where some components still contain traces of certain magnetic materials. We plan to improve on the image quality in the future using completely non-magnetic components and by tuning the MRI pulse sequences. The combined result will be a highly compact, low mass PET scanner that can operate inside an MRI magnet without distorting the MRI image, and can be retrofitted into existing MRI instruments.

Discovery of N-{3-[(ethanimidoylamino)methyl]benzyl}-l-prolinamide dihydrochloride: A new potent and selective inhibitor of the inducible nitric oxide synthase as a promising agent for the therapy of malignant glioma.

PubMed

Maccallini, Cristina; Di Matteo, Mauro; Gallorini, Marialucia; Montagnani, Monica; Graziani, Valentina; Ammazzalorso, Alessandra; Amoia, Pasquale; De Filippis, Barbara; Di Silvestre, Sara; Fantacuzzi, Marialuigia; Giampietro, Letizia; Potenza, Maria A; Re, Nazzareno; Pandolfi, Assunta; Cataldi, Amelia; Amoroso, Rosa

2018-05-25

In mammalian cells, aberrant iNOS induction may have detrimental consequences, and seems to be involved in the proliferation and progression of different tumors, such as malignant gliomas. Therefore, selective inhibition of iNOS could represent a feasible therapeutic strategy to treat these conditions. In this context, we have previously disclosed new acetamidines able to inhibit iNOS with a very high selectivity profile over eNOS or nNOS. Here we report the synthesis of a new series of compounds structurally related to the leading scaffold of N-[(3-aminomethyl)benzyl] acetamidine (1400 W), together with their in vitro activity and selectivity. Compound 39 emerged as the most promising molecule of this series, and it was ex vivo evaluated on isolated and perfused resistance arteries, confirming a high selectivity toward iNOS inhibition. Moreover, C6 rat glioma cell lines biological response to 39 was investigated, and preliminary MTT assay showed a significant decrease in cell metabolic activity of C6 rat glioma cells. Finally, results of a docking study shed light on the binding mode of 39 into NOS catalytic site. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Intrathecal Huperzine A Increases Thermal Escape Latency and Decreases Flinching Behavior in the Formalin Test in Rats

PubMed Central

Park, Paula; Schachter, Steven; Yaksh, Tony

2010-01-01

Huperzine A (HupA) is an alkaloid isolated from the Chinese club moss Huperzia serrata and has been used for improving memory, cognitive and behavioral function in patients with Alzheimer's disease in China. It has NMDA antagonist and anticholinesterase activity and has shown anticonvulsant and antinociceptive effects in preliminary studies when administered intraperitoneally to mice. To better characterize the antinociceptive effects of HupA at the spinal level, Holtzman rats were implanted with intrathecal catheters to measure thermal escape latency using Hargreaves thermal escape testing system and flinching behavior using the formalin test. Intrathecal (IT) administration of HupA showed a dose-dependent increase in thermal escape latency with an ED50 of 0.57 μg. Atropine reversed the increase in thermal escape latency produced by 10 μg HupA, indicating an antinociceptive mechanism through muscarinic cholinergic receptors. The formalin test showed that HupA decreased flinching behavior in a dose-dependent manner. Atropine also reversed the decrease in flinching behavior caused by 10 μg HupA. A dose-dependent increase of side effects including scratching, biting, and chewing tails was observed, although antinociceptive effects were observed in doses that did not produce any adverse effects. PMID:20026382

Intrathecal huperzine A increases thermal escape latency and decreases flinching behavior in the formalin test in rats.

PubMed

Park, Paula; Schachter, Steven; Yaksh, Tony

2010-02-05

Huperzine A (HupA) is an alkaloid isolated from the Chinese club moss Huperzia serrata and has been used for improving memory, cognitive and behavioral function in patients with Alzheimer's disease in China. It has NMDA antagonist and anticholinesterase activity and has shown anticonvulsant and antinociceptive effects in preliminary studies when administered intraperitoneally to mice. To better characterize the antinociceptive effects of HupA at the spinal level, Holtzman rats were implanted with intrathecal catheters to measure thermal escape latency using Hargreaves thermal escape testing system and flinching behavior using the formalin test. Intrathecal (IT) administration of HupA showed a dose-dependent increase in thermal escape latency with an ED50 of 0.57 microg. Atropine reversed the increase in thermal escape latency produced by 10 microg HupA, indicating an antinociceptive mechanism through muscarinic cholinergic receptors. The formalin test showed that HupA decreased flinching behavior in a dose-dependent manner. Atropine also reversed the decrease in flinching behavior caused by 10 microg HupA. A dose-dependent increase of side effects including scratching, biting, and chewing tails was observed, although antinociceptive effects were observed in doses that did not produce any adverse effects. (c) 2009 Elsevier Ireland Ltd. All rights reserved.

The effects of lauromacrogol injection into rat endometrial cysts: a preliminary experimental study.

PubMed

Liu, Wei; Wang, LongXia; Guo, Cui-Xia

2016-09-01

To determine the effectiveness of different concentrations of lauromacrogol injections for the treatment of endometriosis in an experimental animal model and to provide an experimental basis for a pre-clinical application of the drug. After autologous transplantation of endometrial tissue, 40 endometrial cysts were successfully established and randomly divided into three groups: a 1 % lauromacrogol injection group, a 0.5 % lauromacrogol injection group, and cysts without intervention (control group). We measured the changes in the volumes of the cysts in each group. We then compared the volumes of the endometrial implants before and after treatment and between the different groups and examined the histological findings. A significant difference in the spherical volume was found between the 1 % lauromacrogol injection group (P < 0.05). No significant difference was observed between the volume of the endometrial implants in the 0.5 % lauromacrogol injection group (P > 0.05). Regarding the histopathological observations, in the 1 % lauromacrogol injection group, the epithelia of the cystic implants had atrophied, and the glands had atrophied and were reduced in number. The surrounding stromal tissue had become loose and edematous. A 1 % lauromacrogol injection produced significant regression of the endometrial foci compared with a 0.5 % lauromacrogol injection or no treatment in a rat model of endometriosis.

Preliminary study of coconut water for graft tissues preservation in transplantation.

PubMed

César, Jorge Miguel Schettino; Petroianu, Andy; Vasconcelos, Leonardo de Souza; Cardoso, Valbert Nascimento; Mota, Luciene das Graças; Barbosa, Alfredo José Afonso; Soares, Cristina Duarte Vianna; de Oliveira, Amanda Lima

2015-01-01

to verify the effectiveness of coconut water in preserving tissues for transplant. Fifty male Wistar rats were randomly distributed in five groups, according to the following preservation solutions for tissue grafts: Group 1: Lactated Ringer; Group 2: Belzer solution; Group 3: mature coconut water; Group 4: green coconut water; Group 5: modified coconut water. In Group 5, the green coconut water has been modified like the Belzer solution. From each animal we harvested the spleen, ovaries and skin of the back segment. These tissues were preserved for six hours in one of the solutions. Then, the grafts were reimplanted. The recovery of the function of the implanted tissues was assessed 90 days after surgery, by splenic scintigraphy and blood exam. The implanted tissues were collected for histopathological examination. The serum levels did not differ among groups, except for the animals in Group 5, which showed higher levels of IgG than Group 1, and differences in relation to FSH between groups 1 and 2 (p <0.001), 4 and 2 (p = 0.03) and 5 and 2 (p = 0.01). The splenic scintigraphy was not different between groups. The ovarian tissue was better preserved in mature coconut water (p <0.007). the coconut water-based solutions preserves spleen, ovary, and rat skin for six hours, maintaining their normal function.

Protective Effects of Medium-Chain Triglycerides on the Liver and Gut in Rats Administered Endotoxin

PubMed Central

Kono, Hiroshi; Fujii, Hideki; Asakawa, Masami; Yamamoto, Masayuki; Matsuda, Masanori; Maki, Akira; Matsumoto, Yoshiro

2003-01-01

Objective To determine if medium-chain triglycerides (MCTs) prevent organ injuries and mortality in rats administered endotoxin and to investigate effects of MCT on the gut. Summary Background Data Since dietary MCTs prevent alcohol-induced liver injury by inhibiting activation of Kupffer cells in the enteral feeding model, the authors hypothesized that MCT could prevent deleterious conditions in endotoxemia. Methods After a preliminary experiment determined the optimal dose of MCT, rats were given MCT (5 g/kg per day) or the same dose of corn oil by gavage daily for 1 week. Then, lipopolysaccharide (LPS) was administered intravenously and survival was assessed for the next 24 hours. For analysis of mechanisms, rats were killed 9 hours after LPS injection and serum and liver sections were collected. To investigate effects of MCT on the gut, pathologic change, permeability, and microflora were assessed. Kupffer cells isolated by collagenase digestion and differential centrifugation were used for endotoxin receptor CD14 immunoblotting, phagocytic index, and TNF-α production assay. Results All rats given corn oil died after LPS administration; however, this mortality was prevented by MCT in a dose-dependent manner. Rats given corn oil showed liver injury after LPS administration. In contrast, MCT prevented this pathologic change nearly completely. MCT blunted CD14 expression on the Kupffer cells and TNF-α production by isolated Kupffer cells; however, there were no differences in phagocytic index between the two groups. The length of the intestinal epithelium was increased in the MCT group compared to the corn oil group. Further, after LPS administration, increases in gut permeability and injury were prevented by MCT. Importantly, MCT also prevented hepatic energy charge and gut injuries in this condition. Conclusions Enteral feeding using MCT could be a practical way of protecting the liver and intestine during endotoxemia. PMID:12560783

Assessment of social behavior directed toward sick partners and its relation to central cytokine expression in rats.

PubMed

Hamasato, Eduardo Kenji; Lovelock, Dennis; Palermo-Neto, João; Deak, Terrence

2017-12-01

Acute illness not only reduces the expression of social behavior by sick rodents, but can also lead to avoidance responses when detected by healthy, would-be social partners. When healthy animals interact with a sick partner, an intriguing question arises: does exposure to a sick conspecific elicit an anticipatory immune response that would facilitate defense against future infection? To address this question, healthy adult male Sprague-Dawley rats (N=64) were given a brief social interaction (30min) with a partner that was either sick (250μg/kg injection with lipopolysaccharide [LPS] 3h prior to test) or healthy (sterile saline injection). During this exposure, social behavior directed toward the healthy or sick conspecific was measured. Additionally, the impact of housing condition was assessed, with rats group- or isolate-housed. Immediately after social interaction, brains were harvested for cytokine assessments within socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and PVN). As expected, behavioral results demonstrated that (i) there was a robust suppression of social interaction directed against sick conspecifics; and (ii) isolate-housing generally increased social behavior. Furthermore, examination of central cytokine expression in healthy experimental subjects revealed a modest increase in TNF-α in rats that interacted with a sick social partner, but only in the olfactory bulb. Among the LPS-injected partners, expected increases in IL-1β, IL-6, and TNF-α expression were observed across all brain sites. Moreover, IL-1β and IL-6 expression was exacerbated in LPS-injected partners that interacted with isolate-housed experimental subjects. Together, these data replicate and extend our prior work showing that healthy rats avoid sick conspecifics, and provide preliminary evidence for an anticipatory cytokine response when rats are exposed to a sick partner. These data also provide new evidence to suggest that recent housing history potently modulates cytokine responses evoked by LPS. Copyright © 2017 Elsevier Inc. All rights reserved.

GeoLab's First Field Trials, 2010 Desert RATS: Evaluating Tools for Early Sample Characterization

NASA Technical Reports Server (NTRS)

Evans, Cindy A.; Bell, M. S.; Calaway, M. J.; Graff, Trevor; Young, Kelsey

2011-01-01

As part of an accelerated prototyping project to support science operations tests for future exploration missions, we designed and built a geological laboratory, GeoLab, that was integrated into NASA's first generation Habitat Demonstration Unit-1/Pressurized Excursion Module (HDU1-PEM). GeoLab includes a pressurized glovebox for transferring and handling samples collected on geological traverses, and a suite of instruments for collecting preliminary data to help characterize those samples. The GeoLab and the HDU1-PEM were tested for the first time as part of the 2010 Desert Research and Technology Studies (DRATS), NASA's analog field exercise for testing mission technologies. The HDU1- PEM and GeoLab participated in two weeks of joint operations in northern Arizona with two crewed rovers and the DRATS science team.

Laser assisted soldering: microdroplet accumulation with a microjet device.

PubMed

Chan, E K; Lu, Q; Bell, B; Motamedi, M; Frederickson, C; Brown, D T; Kovach, I S; Welch, A J

1998-01-01

We investigated the feasibility of a microjet to dispense protein solder for laser assisted soldering. Successive micro solder droplets were deposited on rat dermis and bovine intima specimens. Fixed laser exposure was synchronized with the jetting of each droplet. After photocoagulation, each specimen was cut into two halves at the center of solder coagulum. One half was fixed immediately, while the other half was soaked in phosphate-buffered saline for a designated hydration period before fixation (1 hour, 1, 2, and 7 days). After each hydration period, all tissue specimens were prepared for scanning electron microscopy (SEM). Stable solder coagulum was created by successive photocoagulation of microdroplets even after the soldered tissue exposed to 1 week of hydration. This preliminary study suggested that tissue soldering with successive microdroplets is feasible even with fixed laser parameters without active feedback control.

Proteomic demonstration of the recurrent presence of inter-alpha-inhibitor H4 heavy-chain during aspergillosis induced in an animal model.

PubMed

Desoubeaux, Guillaume; Jourdan, Marie-Lise; Valera, Lionel; Jardin, Bénédicte; Hem, Sonia; Caille, Agnès; Cormier, Bénédicte; Marchand-Adam, Sylvain; Bailly, Éric; Diot, Patrice; Chandenier, Jacques

2014-05-01

Invasive pulmonary aspergillosis remains a matter of great concern in oncology/haematology, intensive care units and organ transplantation departments. Despite the availability of various diagnostic tools with attractive features, new markers of infection are required for better medical care. We therefore looked for potential pulmonary biomarkers of aspergillosis, by carrying out two-dimensional (2D) gel electrophoresis comparing the proteomes of bronchial-alveolar lavage fluids (BALF) from infected rats and from control rats presenting non-specific inflammation, both immunocompromised. A bioinformatic analysis of the 2D-maps revealed significant differences in the abundance of 20 protein spots (ANOVA P-value<0.01; q-value<0.03; power>0.8). One of these proteins, identified by mass spectrometry, was considered of potential interest: inter-alpha-inhibitor H4 heavy-chain (ITIH4), characterised for the first time in this infectious context. Western blotting confirmed its overabundance in all infected BALF, particularly at early stages of murine aspergillosis. Further investigations were carried on rat serum, and confirmed that ITIH4 levels increased during experimental aspergillosis. Preliminary results in human samples strengthened this trend. To our knowledge, this is the first description of the involvement of ITIH4 in aspergillosis. Copyright © 2013 Elsevier GmbH. All rights reserved.

Scanning electron microscopic appearance of rat otocyst of the twelfth postcoital day: elaboration of a method.

PubMed

Marovitz, W F; Khan, K M

1977-01-01

A method for removal, fixation, microdissection, and drying of early rat otocyst for examination by the scanning electron microscope is elaborated. Tissues were dissected, fixed as for conventional transmission electron microscopy and dried by critical point evaporation using amylacetate as the transitional fluid and carbon dioxide as the pressure head. Otocysts were either dissected at the time of initial fixation, or subsequent to drying. The otocyst of the 12th postcoital day was used as a model system in this preliminary report. Critical point drying retained the overall configuration and the fine ultrastructural detail of the otocyst. The interior otocystic surface was visualized and cilia bearing cells of the luminal surface were identified. Most if not all of these cells had a comspicuous, but short kinocillum which terminated in an ovoid bulb. The scanning electron microscopic appearance was correlated to the transmission electron microscopic image seen in the second paper in this Supplement.

Connexin32 expression in central and peripheral nervous systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deschenes, S.M.; Scherer, S.S.; Fischbeck, K.H.

1994-09-01

Mutations have been identified in the gap junction gene, connexin32 (Cx32), in patients affected with the X-linked form of the demyelinating neuropathy, Charcot-Marie-Tooth disease (CMTX). Gap junctions composed of Cx32 are present and developmentally regulated in a wide variety of tissues. In peripheral nerve, our immunohistochemical analysis localized Cx32 to the noncompacted myelin of the paranodal regions and the Schmidt-Lantermann incisures, where previous studies describe gap junctions. In contrast to the location of Cx32 in peripheral nerve and the usual restriction of clinical manifestations to the peripheral nervous system (PNS) (abstract by Paulson describes an exception), preliminary studies show thatmore » Cx32 is present in the compacted myelin of the central nervous system (CNS), as demonstrated by radial staining through the myelin sheath of oligodendrocytes in rat spinal cord. Analysis of Cx32 expression in various regions of rat CNS during development shows that the amount of Cx32 mRNA and protein increases as myelination increases, a pattern observed for other myelin genes. Studies in the PNS provide additional evidence that Cx32 and myelin genes are coordinately regulated at the transcriptional level; Cx32 and peripheral myelin gene PMP-22 mRNAs are expressed in parallel following transient or permanent nerve injury. Differences in post-translational regulation of Cx32 in the CNS and PNS may be indicated by the presence of a faster migrating form of Cs32 in cerebrum versus peripheral nerve. Studies are currently underway to determine the unique role of Cx32 in peripheral nerve.« less

Bone Blood Flow During Simulated Microgravity: Physiological and Molecular Mechanisms

NASA Technical Reports Server (NTRS)

Bloomfield, Susan A.

1999-01-01

Blood flow to bone has been shown to affect bone mass and presumably bone strength. Preliminary data indicate that blood flow to the rat femur decreases after 14 days of simulated microgravity, using hindlimb suspension (HLS). If adult rats subjected to HLS are given dobutamine, a synthetic catecholamine which can cause peripheral vasodilation and increased blood flow, the loss of cortical bone area usually observed is prevented. Further, mechanisms exist at the molecular level to link changes in bone blood flow to changes in bone cell activity, particularly for vasoactive agents like nitric oxide (NO). The decreases in fluid shear stress created by fluid flow associated with the shifts of plasma volume during microgravity may result in alterations in expression of vasoactive agents such as NO, producing important functional effects on bone cells. The primary aim of this project is to characterize changes in 1) bone blood flow, 2) indices of bone mass, geometry, and strength, and 3) changes in gene expression for modulators of nitric oxide activity (e.g., nitric oxide synthase) and other candidate genes involved in signal transduction of mechanical loading after 3, 7, 14, 21, and 28 days of HLS in the adult rat. Using a rat of at least 5 months of age avoids inadvertently studying effects of simulated microgravity on growing, rather than adult, bone. Utilizing the results of these studies, we will then define how altered blood flow contributes to changes in bone with simulated microgravity by administering a vasodilatory agent (which increases blood flow to tissues) during hindlimb suspension. In all studies, responses in the unloaded hindlimb bones (tibial shaft, femoral neck) will be compared with those in the weightbearing humeral shaft and the non-weightbearing calvarium (skull) from the same animal. Bone volumetric mineral density and geometry will be quantified by peripheral quantitative CT; structural and material properties of the long bones will be determined by 3-point bending (tibia, humerus) or compression (femoral neck) testing to failure. A unique aspect of these studies will be defining the time course of changes in gene expression in bone cell populations with unloading, accomplished with Northern blots, in situ hybridization, and immunohistochemistry. These studies have high relevance for concurrent protocols being proposed by investigators on NSBRI Cardiovascular and Muscle teams, with blood flow data available on a number of tissues other than bone. Further, dobutamine and other Beta-agonists have been tested as countermeasures for altered muscle and cardiovascular function. Results of the intervention tested in our studies have potential relevance for a number of systemic changes seen with prolonged spaceflight.

Streptozotocin-induced hippocampal astrogliosis and insulin signaling malfunction as experimental scales for subclinical sporadic Alzheimer model.

PubMed

Rostami, Farzaneh; Javan, Mohammad; Moghimi, Ali; Haddad-Mashadrizeh, Aliakbar; Fereidoni, Masoud

2017-11-01

Insulin signaling malfunction has recently been suggested as a preliminary event involved in the etiology of Sporadic Alzheimer's disease (SAD). In order to develop insulin resistance-related SAD model, rats were treated with streptozotocin, intracerebroventricularly (icv-STZ). Nevertheless, given the lack of knowledge regarding sub-clinical stages of SAD, the current challenging issue is establishing a practical pre-clinical SAD model. Despite some proposed mechanisms, such as insulin malfunction, neuroinflammation, and gliosis, icv-STZ mechanism of action is not fully understood yet and Streptozotocin-induced rat model of Alzheimer has still major shortcomings. Using three STZ doses (0.5, 1, and 3mg/kg) and three testing time (short-term, medium-term and long-term), we sought the best dose of STZ in order to mimic the characteristic feature of sAD in rats. So, we conducted a series of fifteen-week follow-up cognitive and non-cognitive studies. Besides, IR, tau and ChAT mRNA levels were measured, along with histological analysis of astrocyte, dark neuron numbers, and pyramidal layer thickness, in order to compare the effects of different doses of icv-STZ. STZ 3mg/kg caused cognitive and insulin signaling disturbance from the very first testing-time. STZ1-injected animals, however, showed an augmented hippocampal astrocyte numbers in a short time; they, also, were diagnosed with disturbed insulin signaling in medium-term post icv-STZ-injection. Moreover, behavioral, molecular and histological impairments induced by 0.5mg/kg icv-STZ were slowly progressing in comparison to high doses of STZ. STZ1 and 0.5mg/kg-treated animals are, respectively, suggested as a suitable experimental model of MCI, and sub-clinical stage. Copyright © 2017 Elsevier Inc. All rights reserved.

Pharmacokinetic differences of mifepristone between sexes in animals.

PubMed

Chen, Wenge; Cheng, Yunlong; Chen, Jianzhong; Chen, Jiahang; Jiang, Kai; Zhou, Yuyang; Jia, Lee

2018-05-30

Mifepristone (RU486) is developed originally as a contraceptive used by hundreds of millions of women world-wide, and also reported as a safe and long-term psychotic depressant, or as a cancer chemotherapeutic agent used by both sexes. In our preliminary study aimed at developing mifepristone as a cancer metastatic chemopreventive, we coincidentally observed that blood mifepristone concentrations in female rats seem to be higher than those in male ones post administration. To substantiate if the pharmacokinetic differences between sexes exist, we established a fast UPLC-MS/MS method to determine mifepristone concentrations in plasma, and analyzed blood concentrations of mifepristone over time in rats and dogs of both sexes. Mifepristone in plasma or incubation liquid was recovered by liquid-liquid extraction using 1 mL of ethyl acetate. Chromatographic separation was performed on a C 18 column at 35 °C, with a gradient elution consisting of methanol and water containing 0.1% (v/v) formic acid at a flow rate of 0.3 mL/min. And pharmacokinetic parameters such as elimination half-life, and mean residence time were calculated by using the non-compartmental pharmacokinetics data analysis software. In this work, administrations of mifepristone to rats and beagle dogs revealed that the plasma concentrations of mifepristone (AUC, C max ) were significantly higher (P < 0.05) in females than that in males. In vitro liver microsomal incubation experiments showed that the metabolic rate of mifepristone in males was higher than that in females, which was consistent with the results of in vivo experiments. In general, we first found the sex-related differences about pharmacokinetic properties of mifepristone and revealed the metabolism difference of hepatic microsomal enzyme is the main reason. Copyright © 2018 Elsevier B.V. All rights reserved.

POLARIZATION OF NEUTRONS BY THE STRIPPING REACTION C$sup 12$(d,n)N$sup 1$$sup 3$ (in French)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Budzanowski, A.; Grotowski, K.; Niewodniczanski, H.

1960-05-01

The polarization of neutrcns emitted from the stripping reaction C/sup 12/(d,n)N/sup 13/ hns been investigated at the reaction angle was / sub lab/ = 15 tained and deuteron energy E/sub d/ = 12.9 Mev. The polarization of neutrons connected with the 3.56 Mev energy level in N/sup 13/ nucleus was found to be --(0.39 combination rat 0.11). Also some general remarks concerning the preliminary results of the polarization of neutrons at the reaction angles 30 tained , 45 tained , and 60 tained are given. (auth)

Effect of the components extracted from the needles of Taxus baccata on protein biosynthesis in a cell-free rat liver system.

PubMed

Sredzińska, K; Gajko, A; Gałasiński, W; Gindzieński, A

1999-01-01

Various species of Taxus contain taxanes that promote polymerization and stabilization of microtubules. They have been reported as antineoplastic compounds with highly effective chemiotherapeutic application. A decrease in incorporation of the radiolabelled precursors into DNA, RNA and proteins in vivo has been reported too. The preliminary results have shown that also the other compounds present in the aqueous extract from Taxus baccata needles, participate in the inhibition of the protein biosynthesis. The binding site of eEF-2 on the ribosome seems to be the target of this inhibition process.

Nerve growth factor injected into the gastric ulcer base incorporates into endothelial, neuronal, glial and epithelial cells: implications for angiogenesis, mucosal regeneration and ulcer healing.

PubMed

Tanigawa, T; Ahluwalia, A; Watanabe, T; Arakawa, T; Tarnawski, A S

2015-08-01

A previous study has demonstrated that locally administered growth factors such as epidermal growth factor, basic fibroblast growth factor and hepatocyte growth factor can accelerate healing of experimental gastric ulcers in rats. That study indicates that locally administered growth factors can exert potent biological effects resulting in enhanced gastric ulcers healing. However, the fate of injected growth factors, their retention and localization to specific cellular compartments have not been examined. In our preliminary study, we demonstrated that local injection of nerve growth factor to the base of experimental gastric ulcers dramatically accelerates ulcer healing, increases angiogenesis - new blood vessel formation, and improves the quality of vascular and epithelial regeneration. Before embarking on larger, definitive and time sequence studies, we wished to determine whether locally injected nerve growth factor is retained in gastric ulcer's tissues and taken up by specific cells during gastric ulcer healing. Gastric ulcers were induced in anesthetized rats by local application of acetic acid using standard methods; and, 60 min later fluorescein isothiocyanate-labeled nerve growth factor was injected locally to the ulcer base. Rats were euthanized 2, 5 and 10 days later. Gastric specimens were obtained and processed for histology. Unstained paraffin sections were examined under a fluorescence microscope, and the incorporation of fluorescein isothiocyanate-labeled nerve growth factor into various gastric tissue cells was determined and quantified. In addition, we performed immunostaining for S100β protein that is expressed in neural components. Five and ten days after ulcer induction labeled nerve growth factor (injected to the gastric ulcer base) was incorporated into endothelial cells of blood vessels, neuronal, glial and epithelial cells, myofibroblasts and muscle cells. This study demonstrates for the first time that during gastric ulcer healing locally administered exogenous nerve growth factor is retained in gastric tissue and is taken up by endothelial, neural, muscle and epithelial cells. This is likely the basis for the therapeutic action of locally administered nerve growth factor and its stimulation of angiogenesis, tissue regeneration and gastric ulcer healing.

Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

NASA Astrophysics Data System (ADS)

Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

2009-02-01

This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

A preliminary study on postmortem interval estimation of suffocated rats by GC-MS/MS-based plasma metabolic profiling.

PubMed

Sato, Takako; Zaitsu, Kei; Tsuboi, Kento; Nomura, Masakatsu; Kusano, Maiko; Shima, Noriaki; Abe, Shuntaro; Ishii, Akira; Tsuchihashi, Hitoshi; Suzuki, Koichi

2015-05-01

Estimation of postmortem interval (PMI) is an important goal in judicial autopsy. Although many approaches can estimate PMI through physical findings and biochemical tests, accurate PMI calculation by these conventional methods remains difficult because PMI is readily affected by surrounding conditions, such as ambient temperature and humidity. In this study, Sprague-Dawley (SD) rats (10 weeks) were sacrificed by suffocation, and blood was collected by dissection at various time intervals (0, 3, 6, 12, 24, and 48 h; n = 6) after death. A total of 70 endogenous metabolites were detected in plasma by gas chromatography-tandem mass spectrometry (GC-MS/MS). Each time group was separated from each other on the principal component analysis (PCA) score plot, suggesting that the various endogenous metabolites changed with time after death. To prepare a prediction model of a PMI, a partial least squares (or projection to latent structure, PLS) regression model was constructed using the levels of significantly different metabolites determined by variable importance in the projection (VIP) score and the Kruskal-Wallis test (P < 0.05). Because the constructed PLS regression model could successfully predict each PMI, this model was validated with another validation set (n = 3). In conclusion, plasma metabolic profiling demonstrated its ability to successfully estimate PMI under a certain condition. This result can be considered to be the first step for using the metabolomics method in future forensic casework.

In vivo monitoring of glial scar proliferation on chronically implanted neural electrodes by fiber optical coherence tomography

PubMed Central

Xie, Yijing; Martini, Nadja; Hassler, Christina; Kirch, Robert D.; Stieglitz, Thomas; Seifert, Andreas; Hofmann, Ulrich G.

2014-01-01

In neural prosthetics and stereotactic neurosurgery, intracortical electrodes are often utilized for delivering therapeutic electrical pulses, and recording neural electrophysiological signals. Unfortunately, neuroinflammation impairs the neuron-electrode-interface by developing a compact glial encapsulation around the implants in long term. At present, analyzing this immune reaction is only feasible with post-mortem histology; currently no means for specific in vivo monitoring exist and most applicable imaging modalities can not provide information in deep brain regions. Optical coherence tomography (OCT) is a well established imaging modality for in vivo studies, providing cellular resolution and up to 1.2 mm imaging depth in brain tissue. A fiber based spectral domain OCT was shown to be capable of minimally invasive brain imaging. In the present study, we propose to use a fiber based spectral domain OCT to monitor the progression of the tissue's immune response through scar encapsulation progress in a rat animal model. A fine fiber catheter was implanted in rat brain together with a flexible polyimide microelectrode in sight both of which acts as a foreign body and induces the brain tissue immune reaction. OCT signals were collected from animals up to 12 weeks after implantation and thus gliotic scarring in vivo monitored for that time. Preliminary data showed a significant enhancement of the OCT backscattering signal during the first 3 weeks after implantation, and increased attenuation factor of the sampled tissue due to the glial scar formation. PMID:25191264

Macrophages as drug delivery vehicles for photochemical internalization (Conference Presentation)

NASA Astrophysics Data System (ADS)

Madsen, Steen J.; Gonzalez, Jonathan; Molina, Stephanie; Kumar Nair, Rohit; Hirschberg, Henry

2017-02-01

Targeted delivery of chemotherapeutic drugs to tumor sites is a major challenge in cancer chemotherapy. Cell-based vectorization of therapeutic agents has great potential for cancer therapy in that it can target and maintain an elevated concentration of therapeutic agents at the tumor site and prevent their spread into healthy tissue. The use of circulating cells such as monocytes/macrophages (Ma) offers several advantages compared to nanoparticles as targeted drug delivery vehicles. Ma can be easily obtained from the patient, loaded in vitro with drugs and reinjected into the blood stream. Ma can selectively cross the partially compromised blood-brain barrier surrounding brain tumors and are known to actively migrate to tumors, drawn by chemotactic factors, including hypoxic regions where conventional chemo and radiation therapy are least effective. The utility of Ma as targeted drug delivery vehicles for photochemical internalization (PCI) of tumors was investigated in this study. In vitro studies were conducted using a mixture of F98 rat glioma cells and rat macrophages loaded with a variety of chemotherapeutic agents including bleomycin and 5-fluorouracil. Preliminary data show that macrophages are resistant to both chemotherapeutics while significant toxicity is observed for F98 cells exposed to both drugs. Co-incubation of F98 cells with loaded Ma results in significant F98 toxicity suggesting that Ma are releasing the drugs and, hence providing the rationale for their use as delivery vectors for cancer therapies such as PCI.

Reflective THz and MR imaging of burn wounds: a potential clinical validation of THz contrast mechanisms

NASA Astrophysics Data System (ADS)

Bajwa, Neha; Nowroozi, Bryan; Sung, Shijun; Garritano, James; Maccabi, Ashkan; Tewari, Priyamvada; Culjat, Martin; Singh, Rahul; Alger, Jeffry; Grundfest, Warren; Taylor, Zachary

2012-10-01

Terahertz (THz) imaging is an expanding area of research in the field of medical imaging due to its high sensitivity to changes in tissue water content. Previously reported in vivo rat studies demonstrate that spatially resolved hydration mapping with THz illumination can be used to rapidly and accurately detect fluid shifts following induction of burns and provide highly resolved spatial and temporal characterization of edematous tissue. THz imagery of partial and full thickness burn wounds acquired by our group correlate well with burn severity and suggest that hydration gradients are responsible for the observed contrast. This research aims to confirm the dominant contrast mechanism of THz burn imaging using a clinically accepted diagnostic method that relies on tissue water content for contrast generation to support the translation of this technology to clinical application. The hydration contrast sensing capabilities of magnetic resonance imaging (MRI), specifically T2 relaxation times and proton density values N(H), are well established and provide measures of mobile water content, lending MRI as a suitable method to validate hydration states of skin burns. This paper presents correlational studies performed with MR imaging of ex vivo porcine skin that confirm tissue hydration as the principal sensing mechanism in THz burn imaging. Insights from this preliminary research will be used to lay the groundwork for future, parallel MRI and THz imaging of in vivo rat models to further substantiate the clinical efficacy of reflective THz imaging in burn wound care.

N-terminal valine adduct from the anti-HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde in vivo

PubMed Central

Charneira, C; Grilo, NM; Pereira, SA; Godinho, ALA; Monteiro, EC; Marques, MM; Antunes, AMM

2012-01-01

BACKGROUND AND PURPOSE The aim of this study was to obtain evidence for the activation of the nucleoside reverse transcriptase inhibitor abacavir to reactive aldehyde metabolites in vivo. Protein haptenation by these reactive metabolites may be a factor in abacavir-induced toxic events. EXPERIMENTAL APPROACH The formation of N-terminal valine adducts from the abacavir-derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120 mg·kg−1) of abacavir. The analyses were conducted by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry upon comparison with synthetic standards. KEY RESULTS An N-terminal valine haemoglobin adduct derived from an α,β-unsaturated aldehyde metabolite of abacavir was identified in vivo for the first time. CONCLUSIONS AND IMPLICATIONS This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an α,β-unsaturated aldehyde metabolite in vivo and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the N-terminal valine of haemoglobin could be used to investigate abacavir-induced toxicity for accurate risk/benefit estimations. PMID:22725138

N-terminal valine adduct from the anti-HIV drug abacavir in rat haemoglobin as evidence for abacavir metabolism to a reactive aldehyde in vivo.

PubMed

Charneira, C; Grilo, N M; Pereira, S A; Godinho, A L A; Monteiro, E C; Marques, M M; Antunes, A M M

2012-11-01

The aim of this study was to obtain evidence for the activation of the nucleoside reverse transcriptase inhibitor abacavir to reactive aldehyde metabolites in vivo. Protein haptenation by these reactive metabolites may be a factor in abacavir-induced toxic events. The formation of N-terminal valine adducts from the abacavir-derived aldehydes was investigated in the haemoglobin of Wistar rats treated with eight daily doses (120 mg·kg(-1)) of abacavir. The analyses were conducted by high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry upon comparison with synthetic standards. An N-terminal valine haemoglobin adduct derived from an α,β-unsaturated aldehyde metabolite of abacavir was identified in vivo for the first time. This preliminary work on abacavir metabolism provides the first unequivocal evidence for the formation of an α,β-unsaturated aldehyde metabolite in vivo and of its ability to form haptens with proteins. The methodology described herein can be used to assess the formation of this metabolite in human samples and has the potential to become a valuable pharmacological tool for mechanistic studies of abacavir toxicity. In fact, the simplicity of the method suggests that the abacavir adduct with the N-terminal valine of haemoglobin could be used to investigate abacavir-induced toxicity for accurate risk/benefit estimations. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

Topical Therapy with Mesenchymal Stem Cells Following an Acute Experimental Head Injury Has Benefits in Motor-Behavioral Tests for Rodents.

PubMed

Lam, P K; Wang, Kevin K W; Ip, Anthony W I; Ching, Don W C; Tong, Cindy S W; Lau, Henry C H; Kong, Themis H C S; Lai, Paul B S; Wong, George K C; Poon, W S

2016-01-01

The neuroprotective effects of mesenchymal stem cells (MSCs) have been reported in rodent and in preliminary clinical studies. MSCs are usually transplanted to patients by systemic infusion. However, only a few of the infused MSCs are delivered to the brain because of pulmonary trapping and the blood-brain barrier. In this study, MSCs were topically applied to the site of traumatic brain injury (TBI) and the neuroprotective effects were assessed. TBI was induced in Sprague-Dawley (SD) rats with an electromagnetically controlled cortical impact device after craniotomy was performed between the bregma and lambda, 1 mm lateral to the midline. We applied 1.5 million MSCs, derived from the adipose tissue of transgenic green fluorescent protein (GFP)-SD rats, to the exposed cerebral cortex at the injured site. The MSCs were held in position by a thin layer of fibrin. Neurological function in the test (n = 10) and control (n = 10) animals was evaluated using the rotarod test, the water maze test, and gait analysis at different time points. Within 5 days following topical application, GFP-positive cells were found in the brain parenchyma. These cells co-expressed with markers of Glial fibrillary acidic protein (GFAP), nestin, and NeuN. There was less neuronal death in CA1 and CA3 of the hippocampus in the test animals. Neurological functional recovery was significantly improved. Topically applied MSCs can migrate to the injured brain parenchyma and offer neuroprotective effects.

New oil-in-water magnetic emulsion as contrast agent for in vivo magnetic resonance imaging (MRI).

PubMed

Ahmed, Naveed; Jaafar-Maalej, Chiraz; Eissa, Mohamed Mahmoud; Fessi, Hatem; Elaissari, Abdelhamid

2013-09-01

Nowadays, bio-imaging techniques are widely applied for the diagnosis of various diseased/tumoral tissues in the body using different contrast agents. Accordingly, the advancement in bionanotechnology research is enhanced in this regard. Among contrast agents used, superparamagnetic iron oxide nanoparticles were developed by many researchers and applied for in vive magnetic resonance imaging (MRI). In this study, a new oil-in-water magnetic emulsion was used as contrast agent in MRI, after being characterized in terms of particle size, iron oxide content, magnetic properties and colloidal stability using dynamic light scattering (DLS), thermal gravimetric analysis (TGA), vibrating sample magnetometer (VSM) and zeta potential measurement techniques, respectively. The hydrodynamic size and magnetic content of the magnetic colloidal particles were found to be 250 nm and 75 wt%, respectively. In addition, the used magnetic emulsion possesses superparamagentic properties and high colloidal stability in aqueous medium. Then, the magnetic emulsion was highly diluted and administered intravenously to the Sprague dawley rats to be tested as contrast agent for in vivo MRI. In this preliminary study, MRI images showed significant enhancement in contrast, especially for T2 (relaxation time) contrast enhancement, indicating the distribution of magnetic colloidal nanoparticles within organs, like liver, spleen and kidneys of the Sprague dawley rats. In addition, it was found that 500 microL of the highly diluted magnetic emulsion (0.05 wt%) was found adequate for MRI analysis. This seems to be useful for further investigations especially in theranostic applications of magnetic emulsion.

Standardizing therapeutic parameters of acupuncture for pain suppression in rats: preliminary study.

PubMed

Yeo, Sujung; Lim, Hyungtaeck; Choe, Ilwhan; Kim, Sung-Hoon; Lim, Sabina

2014-01-15

Despite acupuncture's wide and successful use, it is still considered as lacking scientifically rigorous evidence, especially with respect to its effectiveness. To address this problem, it is necessary to re-examine the practice of acupuncture using scientific methodology. The standardization of acupuncture practices may offer a solution. As a preliminary step towards the standardization of acupuncture stimulation in animal experiments, this study attempted to clarify the various therapeutic parameters that contribute to acupuncture's efficacy. This study identified specific acupoints, temporal point of needling, rotation of the needle, duration of acupuncture, and diameter of the needle as the parameters, through formalin test. In this test, acupuncture was performed on either the ST36 or LR2 point immediately after pain induction and 5 minutes after pain induction. The formalin test yielded no significant suppression of pain in the case of ST36 and LR2 acupuncture stimulation immediately following pain induction. When acupuncture was applied 5 minutes after pain induction, however, the ST36 stimulation resulted in a significant decrease in pain, while the LR2 stimulation produced no change. The duration of acupuncture, but not the diameter of the needle, was also significant. As for the rotation of the needle, there was no significant difference in the pain reduction achieved in the rotation and non-rotation groups. We determined that specific acupoint, temporal point of needling, and duration of treatment are important factors in the inhibition of pain. These finding strongly suggest that in animal experiments, the application of a set of appropriate therapeutic parameters can significantly influence the outcome.

The effects of programmed administration of human parathyroid hormone fragment (1-34) on bone histomorphometry and serum chemistry in rats

NASA Technical Reports Server (NTRS)

Dobnig, H.; Turner, R. T.

1997-01-01

PTH treatment can result in dramatic increases in cancellous bone volume in normal and osteopenic rats. However, this potentially beneficial response is only observed after pulsatile treatment; continuous infusion of PTH leads to hypercalcemia and bone abnormalities. The purpose of these studies was to determine the optimal duration of the PTH pulses. A preliminary study revealed that human PTH-(1-34) (hPTH) is cleared from circulation within 6 h after sc administration of an anabolic dose of the hormone (80 microg/kg). To establish the effects of gradually extending the duration of exposure to hPTH without increasing the daily dose, we programmed implanted Alzet osmotic pumps to deliver the 80 microg/kg x day dose of the hormone during pulses of 1, 2, and 6 h/day, or 40 microg/kg x day continuously. Discontinuous infusion was accomplished by alternate spacing of external tubing with hPTH solution and sesame oil. After 6 days of treatment, we evaluated serum chemistry and bone histomorphometry. As negative and positive controls, groups of rats received pumps that delivered vehicle only and 80 microg/kg x day hPTH by daily sc injection, respectively. Dynamic and static bone histomorphometry revealed that the daily sc injection and 1 h/day infusion dramatically increased osteoblast number and bone formation in the proximal tibial metaphysis, whereas longer infusion resulted in systemic side-effects, including up to a 10% loss in body weight, hypercalcemia, and histological changes in the proximal tibia resembling abnormalities observed in patients with chronic primary hyperparathyroidism, including peritrabecular marrow fibrosis and focal bone resorption. Infusion for as little as 2 h/day resulted in minor weight loss and changes in bone histology that were intermediate between sc and continuous administration. The results demonstrate that the therapeutic interval for hPTH exposure is brief, but that programmed administration of implanted hormone is a feasible alternative to daily injection as a route for administration of the hormone.

AFPep: an anti-breast cancer peptide that is orally active.

PubMed

Bennett, James A; DeFreest, Lori; Anaka, Ikenna; Saadati, Hamid; Balulad, Sujata; Jacobson, Herbert I; Andersen, Thomas T

2006-07-01

We have synthesized a cyclic nonapeptide (AFPep) that is effective, after being administered by parenteral routes, for the treatment or the prevention of breast cancer. To test the hypothesis that AFPep remains safe and efficacious after oral administration, three different whole-animal bioassays were utilized, and the mechanism by which AFPep functions was investigated. Using a human breast cancer xenograft model in mice for therapeutic activity, a carcinogen-induced breast cancer model in rats for prevention efficacy, and a mouse uterus growth inhibition model of anti-estrogenic activity, AFPep was administered by oral gavage (p.o.) and its effects compared to those following intraperitoneal (i.p.) and subcutaneous (s.c.) administration. Toxicity studies evaluated body weights and organ weights in mice and rats receiving AFPep. Preliminary mechanistic studies were carried out in T47D human breast cancer cells growing in culture and evaluated the effect of AFPep on estrogen-stimulated cell growth, phosphorylation of the estrogen receptor (ER), and on level of ER-related kinases. Orally administered AFPep stopped the growth of human tumor xenografts in mice, decreased the incidence and multiplicity of breast cancers in carcinogen-exposed rats, and inhibited the estrogen-stimulated growth of mouse uteri. In each of these systems, orally administered AFPep produced an effect similar to that obtained for AFPep administered by either i.p or s.c. routes. In rodents, no evidence of toxicity was seen for the peptide, even at very high doses. In culture, AFPep inhibited the estrogen-stimulated growth, but not the basal growth, of T47D cells, and it inhibited the estrogen-stimulated phosphorylation of Serine 118 in the ER of these cells, which was not explainable by early changes in ER-related kinases. Chronic oral administration of AFPep appears to be safe and effective for the treatment or prevention of breast cancer in animal models.

Preliminary profiling of blood transcriptome in a rat model of hemorrhagic shock

PubMed Central

Braga, D; Barcella, M; D’Avila, F; Lupoli, S; Tagliaferri, F; Santamaria, MH; DeLano, FA; Baselli, G; Schmid-Schönbein, GW; Kistler, EB; Aletti, F

2017-01-01

Hemorrhagic shock is a leading cause of morbidity and mortality worldwide. Significant blood loss may lead to decreased blood pressure and inadequate tissue perfusion with resultant organ failure and death, even after replacement of lost blood volume. One reason for this high acuity is that the fundamental mechanisms of shock are poorly understood. Proteomic and metabolomic approaches have been used to investigate the molecular events occurring in hemorrhagic shock but, to our knowledge, a systematic analysis of the transcriptomic profile is missing. Therefore, a pilot analysis using paired-end RNA sequencing was used to identify changes that occur in the blood transcriptome of rats subjected to hemorrhagic shock after blood reinfusion. Hemorrhagic shock was induced using a Wigger’s shock model. The transcriptome of whole blood from shocked animals shows modulation of genes related to inflammation and immune response (Tlr13, Il1b, Ccl6, Lgals3), antioxidant functions (Mt2A, Mt1), tissue injury and repair pathways (Gpnmb, Trim72) and lipid mediators (Alox5ap, Ltb4r, Ptger2) compared with control animals. These findings are congruent with results obtained in hemorrhagic shock analysis by other authors using metabolomics and proteomics. The analysis of blood transcriptome may be a valuable tool to understand the biological changes occurring in hemorrhagic shock and a promising approach for the identification of novel biomarkers and therapeutic targets. Impact statement This study provides the first pilot analysis of the changes occurring in transcriptome expression of whole blood in hemorrhagic shock (HS) rats. We showed that the analysis of blood transcriptome is a useful approach to investigate pathways and functional alterations in this disease condition. This pilot study encourages the possible application of transcriptome analysis in the clinical setting, for the molecular profiling of whole blood in HS patients. PMID:28661205

In vitro antioxidant and in vivo hepatoprotective activity of leave extract of Raphanus sativus in rats using CCL4 model.

PubMed

Syed, Shariq Naeem; Rizvi, Waseem; Kumar, Anil; Khan, Aijaz Ahmad; Moin, Shagufta; Ahsan, Akif

2014-01-01

Raphanus sativus is reported to have a variety of biological activities. This work screened the hepato-protective and antioxidant activity of ethanol (ERS), and aqueous (ARS), extracts of leaves of Raphanus sativus in Carbon tetrachloride (CCl4), model in rats. The extracts were subjected to antioxidant tests (Total reducing power and Total phenolic content), and preliminary phytochemical screening. A pilot study was done on 100 and 300 mg/kg extracts, form which 300 mg was chosen for further experiments. The albino rats (200-250 grams), were divided into 5 groups of 6 animals each (n=6). There were three control groups comprising of normal control (normal saline -1ml/kg), negative control group (CCl4 1ml/kg in olive oil in a ratio of 1:1 v/v), and positive control group (Silymarin 50mg/kg). The Test drugs were given in a dose of 300 mg/kg for both ERS and ARS extract for 7 days. Biochemical parameters (AST, ALT, Alkaline phosphatase, Total Bilirubin), histo-pathological examination of liver and in vivo antioxidant tests [CAT, GSH and MDA] were done. The phytochemical study showed the presence of flavanoids, terpenoids, alkaloids, saponins and sterols. A dose dependent increase in the oxidative potential was observed in both the extracts with total phenolic content 70.1 and 44.4 GAE/g extract for ERS and ARS respectively. ERS 300mg/kg showed a significant (p<0.001) increase in levels of AST, ALT and alkaline phosphatase as compared to negative control (percentage hepatoprotection =45.3%) while ARS 300 mg/kg (p<.01) group showed 30% hepatoprotection. The GSH (p<0.001) and CAT (p<0.05) in ERS and ARS were significantly increased while MDA levels were decreased (P< 0.01), as compared negative control. The findings were confirmed histo-pathological examination. The ethanol and aqueous extract of Raphanus sativus have partial hepatoprotection against CCl4 toxicity.

Ototoxic potential of JP-8 and a Fischer-Tropsch synthetic jet fuel following subacute inhalation exposure in rats.

PubMed

Fechter, Laurence D; Gearhart, Caroline A; Fulton, Sherry

2010-07-01

This study was undertaken to identify the ototoxic potential of two jet fuels presented alone and in combination with noise. Rats were exposed via a subacute inhalation paradigm to JP-8 jet fuel, a kerosene-based fuel refined from petroleum, and a synthetic fuel produced by the Fischer-Tropsch (FT) process. Although JP-8 contains small ( approximately 5%) concentrations of aromatic hydrocarbons some of which known to be ototoxic, the synthetic fuel does not. The objectives of this study were to identify a lowest observed adverse effect level and a no observed adverse effect level for each jet fuel and to provide some preliminary, but admittedly, indirect evidence concerning the possible role of the aromatic hydrocarbon component of petroleum-based jet fuel on hearing. Rats (n = 5-19) received inhalation exposure to JP-8 or to FT fuel for 4 h/day on five consecutive days at doses of 500, 1000, and 2000 mg/m(3). Additional groups were exposed to various fuel concentrations followed by 1 h of an octave band of noise, noise alone, or no exposure to fuel or noise. Significant dose-related impairment in the distortion product otoacoustic emissions (DPOAE) was seen in subjects exposed to combined JP-8 plus noise exposure when JP-8 levels of at least 1000 mg/m(3) were presented. No noticeable impairment was observed at JP-8 levels of 500 mg/m(3) + noise. In contrast to the effects of JP-8 on noise-induced hearing loss, FT exposure had no effect by itself or in combination with noise exposure even at the highest exposure level tested. Despite an observed loss in DPOAE amplitude seen only when JP-8 and noise were combined, there was no loss in auditory threshold or increase in hair cell loss in any exposure group.

Biomolecular imaging of 13C-butyrate with dissolution-DNP: Polarization enhancement and formulation for in vivo studies

NASA Astrophysics Data System (ADS)

Flori, Alessandra; Giovannetti, Giulio; Santarelli, Maria Filomena; Aquaro, Giovanni Donato; De Marchi, Daniele; Burchielli, Silvia; Frijia, Francesca; Positano, Vincenzo; Landini, Luigi; Menichetti, Luca

2018-06-01

Magnetic Resonance Spectroscopy of hyperpolarized isotopically enriched molecules facilitates the non-invasive real-time investigation of in vivo tissue metabolism in the time-frame of a few minutes; this opens up a new avenue in the development of biomolecular probes. Dissolution Dynamic Nuclear Polarization is a hyperpolarization technique yielding a more than four orders of magnitude increase in the 13C polarization for in vivo Magnetic Resonance Spectroscopy studies. As reported in several studies, the dissolution Dynamic Nuclear Polarization polarization performance relies on the chemico-physical properties of the sample. In this study, we describe and quantify the effects of the different sample components on the dissolution Dynamic Nuclear Polarization performance of [1-13C]butyrate. In particular, we focus on the polarization enhancement provided by the incremental addition of the glassy agent dimethyl sulfoxide and gadolinium chelate to the formulation. Finally, preliminary results obtained after injection in healthy rats are also reported, showing the feasibility of an in vivo Magnetic Resonance Spectroscopy study with hyperpolarized [1-13C]butyrate using a 3T clinical set-up.

A preliminary safety evaluation of polyhexamethylene guanidine hydrochloride.

PubMed

Asiedu-Gyekye, Isaac Julius; Mahmood, Seidu Abdulai; Awortwe, Charles; Nyarko, Alexander Kwadwo

2014-01-01

Polyhexamethylene guanidine hydrochloride (PHMGH) is used worldwide as an antimicrobial agent with broad spectra of activity and also for treating pool water. This non-GLP preliminary study aims at investigating in a subchronic toxicity study possible effects at supra-optimal doses of this biocide. Both acute and subchronic toxicity studies were conducted. LD(50) for PHMGH was estimated to be 600 mg/kg (ie LC(50) 2 ml of 7.5% solution) when administered as a single dose by gavage via a stomach tube in accordance with the expected route of administration. The acute studies showed that the median lethal dose (LD(50)) of 600 mg/kg was accompanied by signs of neurotoxicity. Haematological and biochemical parameters of subchronic toxicity studies were non-significant. Subchronic doses of 0.006 mg/kg, 0.012 mg/kg and 0.036 mg/kg were administered. 20% of the animals at a dose of 0.006 mg/kg and 0.036 mg/kg showed mild degrees of hydropic changes in proximal tubules while 10% of animals at all the doses had their liver tissues showing local areas of mild pericentral hepatocytes degeneration. PHMGH did not produce any major organ defect with regard to the kidney, heart, and liver. The LD(50) was much higher than the recommended dosage by a factor of about 50,000. The recommended residual concentration is far less than the median lethal dose using rats as test subjects. These results could serve as a basis for investigating the full toxicological profile if it is to be used for the treatment of raw water to make it potable. © The Author(s) 2014.

[Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats].

PubMed

Alviz, Antistio Aníbal; Salas, Rubén Darío; Franco, Luis Alberto

2013-01-01

Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

High-resolution polarization sensitive OCT for ocular imaging in rodents

NASA Astrophysics Data System (ADS)

Fialová, Stanislava; Rauscher, Sabine; Gröger, Marion; Pircher, Michael; Hitzenberger, Christoph K.; Baumann, Bernhard

2015-03-01

A new high-resolution polarization sensitive optical coherence tomography system was developed for imaging rodent retina. Various light-tissue interactions such as birefringence and depolarization can change the polarization state of light. In the eye, there are several tissues that have these properties, for example retinal pigment epithelium (depolarization) and sclera (birefringence). These layers play key roles in diseases like age-related macular degeneration or glaucoma. Animal models are an important component for understanding disease pathogenesis. The gold standard for the evaluation of preclinical experiments is histology, which is an invasive and terminal procedure. Since OCT is non-invasive, it has the potential to be an alternative to histology with the benefit of long-term study of the disease progression in the same animal. In this study, a superluminescent diode with spectrum width 100 nm and mean wavelength 840 nm is used as a light source in order to enable high axial resolution. Spectrometers are custom built to enable high imaging speed that allows acquiring 3D data sets with 1024x200x1536 voxels in 3.44 s. From the acquired data, images displaying phase retardation induced by birefringence and orientation of birefringent axis were calculated. In first measurements, we were able to identify the RPE-choroid complex (depolarization effect) and the sclera (strong birefringence) in the retina of Long-Evans and Sprague-Dawley rats. Our preliminary results demonstrate the feasibility of the system for high speed/resolution imaging of the rodent retina. This is useful for longitudinal studies of disease models of retinal disease in rats and mice

Real-time control of focused ultrasound heating based on rapid MR thermometry.

PubMed

Vimeux, F C; De Zwart, J A; Palussiére, J; Fawaz, R; Delalande, C; Canioni, P; Grenier, N; Moonen, C T

1999-03-01

Real-time control of the heating procedure is essential for hyperthermia applications of focused ultrasound (FUS). The objective of this study is to demonstrate the feasibility of MRI-controlled FUS. An automatic control system was developed using a dedicated interface between the MR system control computer and the FUS wave generator. Two algorithms were used to regulate FUS power to maintain the focal point temperature at a desired level. Automatic control of FUS power level was demonstrated ex vivo at three target temperature levels (increase of 5 degrees C, 10 degrees C, and 30 degrees C above room temperature) during 30-minute hyperthermic periods. Preliminary in vivo results on rat leg muscle confirm that necrosis estimate, calculated on-line during FUS sonication, allows prediction of tissue damage. CONCLUSIONS. The feasibility of fully automatic FUS control based on MRI thermometry has been demonstrated.

Extracellular matrix integrity: a possible mechanism for differential clinical effects among selective estrogen receptor modulators and estrogens?

PubMed

Cox, David A; Helvering, Leah M

2006-03-09

Recent gene microarray studies have illustrated heterogeneity in gene expression changes not only between estrogens and selective estrogen receptor modulators (SERMs), but also across different SERM molecules. In ovariectomized rats, this phenomenon was observed with respect to a number of genes involved in collagen turnover and extracellular matrix (ECM) integrity in the uterus and vaginal tissues. Preliminary mechanistic data suggest that these effects on ECM integrity may have relevance in the context of the effect of estrogens and some SERMs to increase the risk of pelvic organ prolapse and the incidence of urinary incontinence in postmenopausal women. Given the pivotal role of ECM integrity and collagen turnover in other tissues and disease states, these processes may provide a fruitful target for future research into the mechanisms for the heterogeneous pharmacology of estrogens and SERMs across different cell types and target tissues.

Preliminary Geological Findings on the BP-1 Simulant

NASA Technical Reports Server (NTRS)

Rickman, D. L.

2010-01-01

The following is a summation of information and discussion between Doug Stoeser of the USGS and Doug Rickman of NASA in February and March, 2010 pertaining to the BP-1 simulant. The analytical results and the bulk of the text are from communications from Dr. Stoeser. The BP-1 simulant is made from Black Point Basalt Flow, San Francisco Volcanic Field, northern Arizona. There is an aggregate (road metal) quarry on the northern margin of the flow towards the west end that was used as a Desert Research and Technology Studies (Desert RATS) analog test site. Silty material from this site was also used in laboratory tests and found to have geotechnical properties similar to the LHT-2M and Chenobi regolith simulants and is being proposed as a possible simulant for geotechnical use. It currently has the designation of BP-1 (Black Point 1). Figure

Semi-quantitative ultrastructural analysis of the localization and neuropeptide content of gonadotropin releasing hormone nerve terminals in the median eminence throughout the estrous cycle of the rat.

PubMed

Prevot, V; Dutoit, S; Croix, D; Tramu, G; Beauvillain, J C

1998-05-01

The ultrastructural appearance of gonadotropin releasing hormone-immunoreactive elements was studied in the external zone of the median eminence of adult female Wistar rats. On the one hand, the purpose of the study was to determine the distribution of gonadotropin releasing hormone terminals towards the parenchymatous basal lamina at the level of hypothalamo-hypophyseal portal vessels, throughout the estrous cycle. On the other hand, we have semi-quantified the gonadotropin releasing hormone content in nerve terminals or preterminals during this physiological condition. A morphometric study was coupled to a colloidal 15 mn gold postembedding immunocytochemistry procedure. Animals were killed at 09.00 on diestrus II, 0.900, 10.00, 13.00, 17.00 and 18.00 on proestrus and 09.00 on estrus (n = 4-8 rats/group). A preliminary light microscopic study was carried out to identify an antero-posterior part of median eminence strongly immunostained by anti-gonadotropin releasing hormone antibodies but which was, in addition, easily spotted. This last condition was necessary to make a good comparison between each animal. Contacts between gonadotropin releasing hormone nerve terminals and the basal lamina were observed only the day of proestrus. Such contacts, however, were rare and in the great majority of cases, gonadotropin releasing hormone terminals are separated from basal lamina by tanycytic end feet. The morphometric analysis showed no significant variation in average distance between gonadotropin releasing hormone terminals and capillaries throughout the estrous cycle. Consequently, it did not appear that a large neuroglial plasticity exists during the estrous cycle. However, the observation of contacts only on proestrus together with some ultrastructural images evoke the possibility of a slight plasticity. The semi-quantitative results show that the content of gonadotropin releasing hormone in the nerve endings presented two peaks on proestrus: one at 09.00 (23 +/- 5 particles/micrograms2, P < 0.03) before the onset of luteinizing hormone surge, and the second at 18.00 (16 +/- 2 particles/micrograms2, P < 0.01) concomitantly with the luteinizing hormone surge, when compared to baseline values on proestrus 10.00 (8 +/- particles/micrograms2).

Development and evaluation of a new composite Laserskin graft.

PubMed

Lam, P K; Chan, E S; To, E W; Lau, C H; Yen, S C; King, W W

1999-11-01

Tremendous effort has been made to improve the graft take rate of cultured epidermal autograph. The purpose of this study is to develop and evaluate a new composite Laserskin graft (CLSG) as a human skin substitute for wound resurfacing. The seeding efficacy of cultured keratinocytes on plain Laserskin was compared with the 3T3 cell-seeded Laserskin and allogenic fibroblast-populated Laserskin. Three different types of CLSG, 2 cm in diameter each, were prepared and tested in rats. Type A CLSG consisted of proliferative allogenic rat fibroblasts on both sides of the Laserskin with autologous keratinocytes also on the upper side. Fibroblasts and keratinocytes were seeded only on the upper side of the Laserskin in type B CLSG. Keratinocytes alone were seeded on plain Laserskin in type C CLSG. Type B CLSG consisting of autologous keratinocytes and autologous dermal fibroblasts was tested on five selected wounds (5x5 cm each) of a patient with full-thickness burn. In another burn patient, type B CLSG consisting of autologous keratinocytes and allogenic dermal fibroblasts was grafted onto three wounds (5x5 cm each). The seeding efficacy of human keratinocytes on plain Laserskin increased from 75% to 95% when proliferative allogenic fibroblasts were grown as a feeder layer on the Laserskin. The seeding efficacy of rat keratinocytes increased from 36% to 88% in the presence of a proliferative allogenic fibroblast feeder layer, whereas human/rat keratinocytes had respective seeding efficacy of 98%/91% on Laserskin preseeded with mitomycin C-treated 3T3 cells. Skin biopsies of grafted type A CLSG on day 14 after grafting showed complete epithelialization without severe inflammation in 16 of 20 (80%) grafted surgical wounds in rats. There were eight (40%) and seven (35%) "takes" of the CLSG in types B and C, respectively. The infection rate in type B CLSG was two (10%). There was one (5%) infection in types A and C. The respective take rates on the two patients grafted with type B CLSG were 60% and 100%. The animal experiment and the preliminary clinical data showed that the CSLGs consisting of autologous keratinocytes and of autologous/allogenic fibroblasts are good human skin substitutes in terms of durability, biocompatibility, high seeding efficacy for keratinocytes, high graft take rate, and low infection rate.

Modulatory potentials of the aqueous stem bark extract of Mangifera indica on carbon tetrachloride-induced hepatotoxicity in rats

PubMed Central

Adeneye, Adejuwon Adewale; Awodele, Olufunsho; Aiyeola, Sheriff Aboyade; Benebo, Adokiye Senibo

2015-01-01

Among Yoruba herbalists (Southwest Nigeria), hot water infusion of Mangifera indica L. (芒果 Máng Guǒ) stem bark is reputedly used for the treatment of fever, jaundice and liver disorders. The present study, therefore, investigates the protective effects and mechanism(s) of chemopreventive and curative effects of 125–500 mg/kg/day of Mangifera indica aqueous stem bark extract (MIASE) in acute CCl4-induced liver damage in rats. Rats were treated intragastrically with 125, 250 and 500 mg/kg/day of MIASE for 7 days before and after the administration of CCl4 (3 ml/kg of 20% CCl4, i.p.). The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (ALB), triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-c), low density lipoprotein cholesterol (LDL-c), total bilirubin (TB), conjugated bilirubin (CB) and fasting blood glucose (FBG) levels were estimated. In addition, hepatic tissue reduced glutathione (GSH) and the malondialdehyde (MDA) concentrations, catalase (CAT), superoxide (SOD) activities in the hepatic homogenate, and histopathological changes in the rat liver sections were determined. Preliminary qualitative phytochemical screening for bioactive compounds in MIASE was also conducted. Results showed that oral treatment with 125–500 mg/kg/day of MIASE significantly attenuated the increase in serum ALT, AST, ALP, FBG, TB, CB and LDL-c levels in acute liver injury induced by CCl4 treatment. Findings also revealed significant elevations in the serum TC, TG, HDL-c, TP and ALB levels. There was marked architectural remodeling in the hepatic lesions of hepatocyte vacuolation and centrilobular necrosis induced by CCl4 treatment, coupled with significant weight loss. MIASE also markedly enhanced SOD and CAT activities while reducing MAD formation; and increased GSH concentration in the hepatic homogenate compared with untreated CCl4-intoxicated group, with more protection offered in the curative than the chemopreventive models of CCl4 hepatotoxicity. Thus, these results indicate that MIASE has a profound protective effect against acute CCl4-induced hepatotoxicity in rats, which may be due to its free radicals scavenging effect, inhibition of lipid peroxidation, and its ability to increase antioxidant activity. PMID:26151020

Drug functionalized microbial polysaccharide based nanofibers as transdermal substitute.

PubMed

Vashisth, Priya; Srivastava, Amit Kumar; Nagar, Hemant; Raghuwanshi, Navdeep; Sharan, Shruti; Nikhil, Kumar; Pruthi, Parul A; Singh, Rajesh P; Roy, Partha; Pruthi, Vikas

2016-07-01

In order to promote the natural healing process, drug-functionalized nanofibrous transdermal substitute was fabricated using gellan as chief polymer and polyvinyl alcohol (PVA) as supporting polymer via electrospinning technique. These fabricated nanofibers physiochemically mimic the extracellular matrix (ECM) which supports the cell growth. For neo-tissue regeneration in a sterilized environment, amoxicillin (Amx) was entrapped within these nanofibers. Entrapment of Amx in the nanofibers was confirmed by FESEM, FTIR, XRD and TG analysis. In vitro cell culture studies revealed that the fabricated non-cytotoxic nanofibers promoted enhance cell adherence and proliferation of human keratinocytes. A preliminary in vivo study performed on rat model for full thickness skin excision wound demonstrated the prompt re-epithelialization in early phase and quicker collagen deposition in later phases of wound healing in case of Amx-functionalized gellan/PVA nanofibers. Data collectively confirmed the potential usage of gellan based electrospun nanofibers as transdermal substitute for faster skin restoration. Copyright © 2016 Elsevier Inc. All rights reserved.

Synthesis and Preclinical Characterization of a Cationic Iodinated Imaging Contrast Agent (CA4+) and Its Use for Quantitative Computed Tomography of Ex Vivo Human Hip Cartilage.

PubMed

Stewart, Rachel C; Patwa, Amit N; Lusic, Hrvoje; Freedman, Jonathan D; Wathier, Michel; Snyder, Brian D; Guermazi, Ali; Grinstaff, Mark W

2017-07-13

Contrast agents that go beyond qualitative visualization and enable quantitative assessments of functional tissue performance represent the next generation of clinically useful imaging tools. An optimized and efficient large-scale synthesis of a cationic iodinated contrast agent (CA4+) is described for imaging articular cartilage. Contrast-enhanced CT (CECT) using CA4+ reveals significantly greater agent uptake of CA4+ in articular cartilage compared to that of similar anionic or nonionic agents, and CA4+ uptake follows Donnan equilibrium theory. The CA4+ CECT attenuation obtained from imaging ex vivo human hip cartilage correlates with the glycosaminoglycan content, equilibrium modulus, and coefficient of friction, which are key indicators of cartilage functional performance and osteoarthritis stage. Finally, preliminary toxicity studies in a rat model show no adverse events, and a pharmacokinetics study documents a peak plasma concentration 30 min after dosing, with the agent no longer present in vivo at 96 h via excretion in the urine.

Lung imaging of laboratory rodents in vivo

NASA Astrophysics Data System (ADS)

Cody, Dianna D.; Cavanaugh, Dawn; Price, Roger E.; Rivera, Belinda; Gladish, Gregory; Travis, Elizabeth

2004-10-01

We have been acquiring respiratory-gated micro-CT images of live mice and rats for over a year with our General Electric (formerly Enhanced Vision Systems) hybrid scanner. This technique is especially well suited for the lung due to the inherent high tissue contrast. Our current studies focus on the assessment of lung tumors and their response to experimental agents, and the assessment of lung damage due to chemotherapy agents. We have recently installed a custom-built dual flat-panel cone-beam CT scanner with the ability to scan laboratory animals that vary in size from mice to large dogs. A breath-hold technique is used in place of respiratory gating on this scanner. The objective of this pilot study was to converge on scan acquisition parameters and optimize the visualization of lung damage in a mouse model of fibrosis. Example images from both the micro-CT scanner and the flat-panel CT scanner will be presented, as well as preliminary data describing spatial resolution, low contrast resolution, and radiation dose parameters.

Direct peptide bioconjugation/PEGylation at tyrosine with linear and branched polymeric diazonium salts.

PubMed

Jones, Mathew W; Mantovani, Giuseppe; Blindauer, Claudia A; Ryan, Sinead M; Wang, Xuexuan; Brayden, David J; Haddleton, David M

2012-05-02

Direct polymer conjugation at peptide tyrosine residues is described. In this study Tyr residues of both leucine enkephalin and salmon calcitonin (sCT) were targeted using appropriate diazonium salt-terminated linear monomethoxy poly(ethylene glycol)s (mPEGs) and poly(mPEG) methacrylate prepared by atom transfer radical polymerization. Judicious choice of the reaction conditions-pH, stoichiometry, and chemical structure of diazonium salt-led to a high degree of site-specificity in the conjugation reaction, even in the presence of competitive peptide amino acid targets such as histidine, lysines, and N-terminal amine. In vitro studies showed that conjugation of mPEG(2000) to sCT did not affect the peptide's ability to increase intracellular cAMP induced in T47D human breast cancer cells bearing sCT receptors. Preliminary in vivo investigation showed preserved ability to reduce [Ca(2+)] plasma levels by mPEG(2000)-sCT conjugate in rat animal models. © 2012 American Chemical Society

Simultaneously multiparametric spectroscopic monitoring of tissue viability in the brain and small intestine

NASA Astrophysics Data System (ADS)

Tolmasov, Michael; Barbiro-Michaely, Efrat; Mayevsky, Avraham

2007-02-01

Under body O II imbalance, the Autonomic Nervous System is responsible for redistribution of blood flow with preference to the most vital organs (brain, heart), while the less vital organs (intestine, GI tract) are hypoperfused. The aim of this study was to develop and use an animal model for real time monitoring of tissue viability in the brain, and the small intestine, under various levels of oxygen and blood supply. Male Wistar rats were anesthetized, the brain cortex and intestinal serosa were exposed and connected by optical fibers to the Multi-Site Multi-Parametric (MSMP) monitoring system. Tissue blood flow (TBF) and mitochondrial NADH redox state were monitored simultaneously in the two organs. The rats were subjected to short anoxia, 20 minutes hypoxia or epinephrine (2& 8μg/kg I.V.). Under oxygen deficiency, cerebral blood flow (CBF) was elevated, whereas intestinal TBF was reduced. Mitochondrial NADH was significantly elevated in both organs. Systemic injection of Adrenaline showed a dose-depended increase in systemic blood pressure and CBF response whereas, intestinal TBF similarly decreased in both doses. In addition, NADH was elevated (reduced form) in the intestine whereas oxidation was observed in the brain. In conclusion, our preliminary results may imply the ability of using of the MSMP for monitoring non-vital organs in order to detect early changes in the balance between oxygen supply and demand in the body.

Insoluble Dietary Fiber from Pear Pomace Can Prevent High-Fat Diet-Induced Obesity in Rats Mainly by Improving the Structure of the Gut Microbiota.

PubMed

Chang, Shimin; Cui, Xingtian; Guo, Mingzhang; Tian, Yiling; Xu, Wentao; Huang, Kunlun; Zhang, Yuxing

2017-04-28

Supplement of dietary fibers (DF) is regarded as one of the most effective way to prevent and relieve chronic diseases caused by long-term intake of a high-fat diet in the current society. The health benefits of soluble dietary fibers (SDF) have been widely researched and applied, whereas the insoluble dietary fibers (IDF), which represent a higher proportion in plant food, were mistakenly thought to have effects only in fecal bulking. In this article, we proved the anti-obesity and glucose homeostasis improvement effects of IDF from pear pomace at first, and then the mechanisms responsible for these effects were analyzed. The preliminary study by real-time PCR and ELISA showed that this kind of IDF caused more changes in the gut microbiota compared with in satiety hormone or in hepatic metabolism. Further analysis of the gut microbiota by high-throughput amplicon sequencing showed IDF from pear pomace obviously improved the structure of the gut microbiota. Specifically, it promoted the growth of Bacteroidetes and inhibited the growth of Firmicutes. These results are coincident with previous hypothesis that the ratio of Bacteroidetes/Firmicutes is negatively related with obesity. In conclusion, our results demonstrated IDF from pear pomace could prevent high-fat diet-induced obesity in rats mainly by improving the structure of the gut microbiota.

Moderate red-wine consumption partially prevents body weight gain in rats fed a hyperlipidic diet.

PubMed

Vadillo, Montserrat; Bargalló, Montserrat Vadillo; Ardévol, Anna; Grau, Anna Ardévol; Fernández-Larrea, Juan; Fernández-Larrea, Juan de Dios; Pujadas, Gerard; Anguiano, Gerard Pujadas; Bladé, Cinta; Segarra, Maria Cinta Bladé; Salvadó, Maria Josepa; Rovira, Maria Josepa Salvadó; Arola, Lluís; Ferré, Lluia Arola; Blay, Mayte; Olivé, Mayte Blay

2006-02-01

Red wine is a beverage that can exert a broad spectrum of health-promoting actions both in humans and laboratory animal models if consumed moderately. However, information about its effect on body weight is scarce. We have evaluated the effect of moderate red wine consumption on body weight and energy intake in male Zucker lean rats fed a hypercaloric diet for 8 weeks. For this purpose, we used three 5-animal groups: a high-fat diet group (HFD), a high-fat-diet red-wine-drinking group (HFRWD), and a standard diet group (SD). After 8 weeks, the HFRWD group had a lower body weight gain (175.66 +/- 2.78% vs 188.22 +/- 4.83%; P<.05) and lower energy intake (269.45 +/- 4.02 KJ/animal.day vs day vs 300.81 +/- 4.52 KJ/animal.day; P<.05) and had less fat mass at epididymal location respect to the whole body weight (0.014 +/- 0.001 vs 0.017 +/- 0.001; P<.05) than the HFD group. However, the red wine didn't modified the fed efficiency 0.012 +/- 0.001 g/KJ for HFRWD group versus 0.013 +/- 0.001 g/KJ for the HFD one (P=.080). These findings, though preliminary, show that moderate red wine intake can prevent the increase of body weight by modulating energy intake in a rat diet-induced model of obesity.

A novel approach to breast cancer diagnosis via PET imaging of microcalcifications using 18F-NaF

PubMed Central

Wilson, George H.; Gore, John C.; Yankeelov, Thomas E.; Barnes, Stephanie; Peterson, Todd E.; True, Jarrod M.; Shokouhi, Sepideh; McIntyre, J. Oliver.; Sanders, Melinda; Abramson, Vandana; Ngyuen, The-Quyen; Mahadevan-Jansen, Anita; Tantawy, Mohammed N.

2015-01-01

Rationale Current radiological methods for diagnosing breast cancer detect specific morphological features of solid tumors and/or any associated calcium deposits. These deposits originate from an early molecular microcalcification process which consists of two types: type 1 is calcium oxylate (CO) and type II is carbonated calcium hydroxyapetite (HAP). Type I microcalcifications are mainly associated with benign tumors while type II have been shown to be produced, internally, by malignant cells. No current non-invasive in vivo techniques are available for detecting intratumoral microcalcifications. Such a technique would have a significant impact on breast cancer diagnosis and prognosis in preclinical and clinical settings. 18F-NaF PET has been solely used for bone imaging by targeting the bone HAP. In this work, we provide preliminary evidence that 18F-NaF PET imaging can be used to detect breast cancer by targeting the HAP lattice within the tumor microenvironment with high specificity and soft-tissue contrast-to-background ratio, while delineating tumors from inflammation. METHODS Mice were injected with approximately 106 MDA-MB-231 cells subcutaneously and imaged with 18F-NaF PET/CT in a 120 min dynamic sequence when the tumors reached a size of ~250 mm3. Regions-of-interest (ROIs) were drawn around the tumor, muscle, and bone. The concentration of the radiotracer within those ROIs were compared to one another. For comparison to inflammation, rats with inflammatory paws were subjected to 18F-NaF PET imaging. RESULTS Tumor uptake of 18F− was significantly higher (p<0.05) than muscle uptake where the tumor-to-muscle ratio was ~3.5. The presence of type II microcalcification in the MDA-MB-231 cell line was confirmed histologically using alizarin red S and von Kossa staining as well as Raman microspectroscopy. No uptake of 18F− was observed in the rat inflamed tissue. Lack of HAP in the inflamed tissue was verified histologically. CONCLUSIONS This study provides preliminary evidence suggesting that specific targeting of the HAP within the tumor microenvironment with 18F may be able to distinguishing between inflammation and cancer. PMID:24833491

Gastroprotective effect of Senecio candicans DC on experimental ulcer models.

PubMed

Hariprasath, Lakshmanan; Raman, Jegadeesh; Nanjian, Raaman

2012-03-06

Senecio candicans DC (Asteraceae) is used as a remedy for gastric ulcer and stomach pain in the Nilgiris district, Tamil Nadu for which no scientific evidence exists. The present study was performed to evaluate the gastroprotective effects and acute oral toxicity of aqueous leaf extract of Senecio candicans (AESC) in experimental models. The antiulcerogenic activity of AESC was performed in two different ulcer models viz., pylorus-ligated model and ethanol-induced model using Wistar albino rats. Acute toxicity study was also performed to get information on the admissible dose for treatment of ulcer. Preliminary phytochemical screening of AESC was performed to find the active principles present, which are thus responsible for the antiulcerogenic activity. DPPH assay was performed to confirm the antioxidant activity of AESC. The acute toxicity study did not show any mortality up to 2500mg/kg b.w. of AESC. Both the ulcer models showed gastroprotective effect comparable to that of the standard Omeprazole. The results of antioxidant enzymes, histopathology sections, ATPase and mucus content of gastric secretion showed that several mechanisms are involved in the gastroprotective effect. The preliminary phytochemical screening revealed the presence of alkaloids, flavonoids and steroids in AESC. The DPPH assay confirmed the antioxidant activity of AESC. The traditional consumption of AESC for the treatment of gastric ulcer is thus true, the antioxidant constituents present in the extract plays a major role in the gastroprotective activity, but since Senecio species are known for the presence of pyrrolizidine alkaloids, a detailed study in future is required to describe the safe dose for a prolonged period. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

The targets of acetone cyanohydrin neurotoxicity in the rat are not the ones expected in an animal model of konzo.

PubMed

Soler-Martín, Carla; Riera, Judith; Seoane, Ana; Cutillas, Blanca; Ambrosio, Santiago; Boadas-Vaello, Pere; Llorens, Jordi

2010-01-01

Konzo is a neurotoxic motor disease caused by excess consumption of insufficiently processed cassava. Cassava contains the cyanogenic glucoside linamarin, but konzo does not present the known pathological effects of cyanide. We hypothesized that the aglycone of linamarin, acetone cyanohydrin, may be the cause of konzo. This nitrile rapidly decomposes into cyanide and acetone, but the particular exposure and nutrition conditions involved in the emergence of konzo may favor its stabilization and subsequent acute neurotoxicity. A number of preliminary observations were used to design an experiment to test this hypothesis. In the experiment, young female Long-Evans rats were given 10mM acetone cyanohydrin in drinking water for 2 weeks, and then 20mM for 6 weeks. Nutrition deficits associated with konzo were modeled by providing tapioca (cassava starch) as food for the last 3 of these weeks. After this period, rats were fasted for 24h in order to increase endogenous acetone synthesis, and then exposed to 0 (control group) or 50 micromol/kg-h of acetone cyanohydrin for 24h (treated group) through subcutaneous osmotic minipump infusion (n=6/group). Motor activity and gait were evaluated before exposure (pre-test), and 1 and 6 days after exposure. Brains (n=4) were stained for neuronal degeneration by fluoro-jade B. Rats exposed to 50 micromol/kg-h of acetone cyanohydrin showed acute signs of toxicity, but no persistent motor deficits. Two animals showed fluoro-jade staining in discrete thalamic nuclei, including the paraventricular and the ventral reuniens nuclei; one also exhibited labeling of the dorsal endopiriform nucleus. Similar effects were not elicited by equimolar KCN exposure. Therefore, acetone cyanohydrin may cause selective neuronal degeneration in the rat, but the affected areas are not those expected in an animal model of konzo. Copyright (c) 2009 Elsevier Inc. All rights reserved.

Intrapleural polymeric films containing cisplatin for malignant pleural mesothelioma in a rat tumour model: a preliminary study.

PubMed

Ampollini, Luca; Sonvico, Fabio; Barocelli, Elisabetta; Cavazzoni, Andrea; Bilancia, Rocco; Mucchino, Claudio; Cantoni, Anna Maria; Carbognani, Paolo

2010-03-01

This study aims to investigate the effect of intrapleural polymeric films containing cisplatin on the local recurrence of malignant pleural mesothelioma in a rat tumour model. An orthotopic rat recurrence model of malignant pleural mesothelioma was used. Five animals per group were evaluated. Polymeric films (4.5 cm diameter) for the local delivery of anticancer drug were constructed: hyaluronate, chitosan and the combined dual-layer polymers were loaded with cisplatin at a concentration of 100 mgm(-2). Animals without any adjuvant therapy were used as control. Mesothelioma cells were injected subpleurally in the anaesthetised rats. Six days later, a pleural tumour of 5.5mm was resected and a left pneumonectomy and pleural abrasion were performed. Thereafter, the cisplatin-loaded and unloaded films or cisplatin solution were intrapleurally applied, according to randomisation. After 6 days, animals were euthanised and organs harvested for morphological and histological evaluations. The primary endpoint was the volume of tumour recurrence. The secondary endpoints were treatment-related toxicity; cisplatin serum concentration evaluated at different time points; and cisplatin concentration in the pleura measured at autopsy. Analysis of variance (ANOVA) was used for statistical analysis. Bonferroni correction was applied for comparison between all groups. Tumour volume was significantly reduced in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups in comparison to control groups (p=0.001 and p<0.0001, respectively). Animals treated with hyaluronate-chitosan cisplatin had a tumour recurrence significantly lesser than animals treated with cisplatin solution (p=0.003) and hyaluronate cisplatin (p=0.032). No toxicity related to the different treatments was observed. On postoperative days 1 and 2, cisplatin was detected in the serum at a concentration six- and sevenfold significantly higher in the hyaluronate cisplatin and hyaluronate-chitosan cisplatin groups, in comparison to cisplatin solution, and was maintained over time. Cisplatin levels in the pleura were higher in the hyaluronate-chitosan cisplatin group than in all others. Hyaluronate-chitosan cisplatin was significantly effective in reducing tumour recurrence compared with cisplatin solution. Hyaluronate and hyaluronate-chitosan loaded with cisplatin assured significantly higher and more prolonged plasmatic drug concentrations than cisplatin solution without increasing toxicity. Copyright (c) 2009 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Biological Cleavage of the C–P Bond in Perfluoroalkyl Phosphinic Acids in Male Sprague-Dawley Rats and the Formation of Persistent and Reactive Metabolites

PubMed Central

Yeung, Leo W.Y.; Mabury, Scott A.

2017-01-01

Background: Perfluoroalkyl phosphinic acids (PFPiAs) have been detected in humans, wildlife, and various environmental matrices. These compounds have been used with perfluoroalkyl phosphonic acids (PFPAs) as surfactants in consumer products and as nonfoaming additives in pesticide formulations. Unlike the structurally related perfluoroalkyl sulfonic and carboxylic acids, little is known about the biological fate of PFPiAs. Objectives: We determined the biotransformation products of PFPiAs and some pharmacokinetic parameters in a rat model. Methods: Male Sprague-Dawley rats received an oral gavage dose of either C6/C8PFPiA, C8/C8PFPiA, or C8PFPA. Blood was sampled over time, and livers were harvested upon sacrifice. Analytes were quantified using ultra-high-performance liquid chromatography–tandem mass spectrometry or gas chromatography–mass spectrometry. Results: PFPiAs were metabolized to the corresponding PFPAs and 1H-perfluoroalkanes (1H-PFAs), with 70% and 75% biotransformation 2 wk after a single bolus dose for C6/C8PFPiA and C8/C8PFPiA, respectively. This is the first reported cleavage of a C-P bond in mammals, and the first attempt, with a single-dose exposure, to characterize the degradation of any perfluoroalkyl acid. Elimination half-lives were 1.9±0.5 and 2.8±0.8 days for C6/C8PFPiA and C8/C8PFPiA, respectively, and 0.95±0.17 days for C8PFPA. Although elimination half-lives were not determined for 1H-PFAs, concentrations were higher than the corresponding PFPAs 48 h after rats were dosed with PFPiAs, suggestive of slower elimination. Conclusions: PFPiAs were metabolized in Sprague-Dawley rats to form persistent PFPAs as well as 1H-PFAs, which contain a labile hydrogen that may undergo further metabolism. These results in rats produced preliminary findings of the pharmacokinetics and metabolism of PFPiAs, which should be further investigated in humans. If there is a parallel between the disposition of these chemicals in humans and rats, then humans with detectable amounts of PFPiAs in their blood may be undergoing continuous exposure. https://doi.org/10.1289/EHP1841 PMID:29135439

Long-term hippocampal glutamate synapse and astrocyte dysfunctions underlying the altered phenotype induced by adolescent THC treatment in male rats.

PubMed

Zamberletti, Erica; Gabaglio, Marina; Grilli, Massimo; Prini, Pamela; Catanese, Alberto; Pittaluga, Anna; Marchi, Mario; Rubino, Tiziana; Parolaro, Daniela

2016-09-01

Cannabis use has been frequently associated with sex-dependent effects on brain and behavior. We previously demonstrated that adult female rats exposed to delta-9-tetrahydrocannabinol (THC) during adolescence develop long-term alterations in cognitive performances and emotional reactivity, whereas preliminary evidence suggests the presence of a different phenotype in male rats. To thoroughly depict the behavioral phenotype induced by adolescent THC exposure in male rats, we treated adolescent animals with increasing doses of THC twice a day (PND 35-45) and, at adulthood, we performed a battery of behavioral tests to measure affective- and psychotic-like symptoms as well as cognition. Poorer memory performance and psychotic-like behaviors were present after adolescent THC treatment in male rats, without alterations in the emotional component. At cellular level, the expression of the NMDA receptor subunit, GluN2B, as well as the levels of the AMPA subunits, GluA1 and GluA2, were significantly increased in hippocampal post-synaptic fractions from THC-exposed rats compared to controls. Furthermore, increases in the levels of the pre-synaptic marker, synaptophysin, and the post-synaptic marker, PSD95, were also present. Interestingly, KCl-induced [(3)H]D-ASP release from hippocampal synaptosomes, but not gliosomes, was significantly enhanced in THC-treated rats compared to controls. Moreover, in the same brain region, adolescent THC treatment also resulted in a persistent neuroinflammatory state, characterized by increased expression of the astrocyte marker, GFAP, increased levels of the pro-inflammatory markers, TNF-α, iNOS and COX-2, as well as a concomitant reduction of the anti-inflammatory cytokine, IL-10. Notably, none of these alterations was observed in the prefrontal cortex (PFC). Together with our previous findings in females, these data suggest that the sex-dependent detrimental effects induced by adolescent THC exposure on adult behavior may rely on its ability to trigger different region-dependent changes in glutamate synapse and glial cells. The phenotype observed in males is mainly associated with marked dysregulations in the hippocampus, whereas the prevalence of alterations in the emotional sphere in females is associated with profound changes in the PFC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hindlimb Suspension as a Model to Study Ophthalmic Complications in Microgravity Status Report: Optimization of Rat Retina Flat Mounts Staining to Study Vascular Remodeling

NASA Technical Reports Server (NTRS)

Theriot, Corey A.; Zanello, Susana B.

2014-01-01

Preliminary data from a prior tissue-sharing experiment has suggested that early growth response protein-1 (Egr1), a transcription factor involved in various stress responses in the vasculature, is induced in the rat retina after 14 days of hindlimb suspension (HS) and may be evidence that mechanical stress is occurring secondary to the cephalad fluid shift. This mechanical stress could cause changes in oxygenation of the retina, and the subsequent ischemia- or inflammation-driven hypoxia may lead to microvascular remodeling. This microvascular remodeling process can be studied using image analysis of retinal vessels and can be then be quantified by the VESsel GENeration Analysis (VESGEN) software, a computational tool that quantifies remodeling patterns of branching vascular trees and capillary or vasculogenic networks. Our project investigates whether rodent HS is a valid model to study the effects of simulated-weightlessness on ocular structures and their relationship with intracranial pressure (ICP). One of the hypotheses to be tested is that HS-induced cephalad fluid shift is accompanied by vascular engorgement that produces changes in retinal oxygenation, leading to oxidative stress, hypoxia, microvascular remodeling, and cellular degeneration. We have optimized the procedure to obtain flat mounts of rat retina, staining of the endothelial lining in vasculature and acquisition of high quality images suitable for VESGEN analysis. Briefly, eyes were fixed in 4% paraformaldehyde for 24 hours and retinas were detached and then mounted flat on microscope slides. The microvascular staining was done with endothelial cell-specific isolectin binding, coupled to Alexa-488 fluorophore. Image acquisition at low magnification and high resolution was performed using a new Leica SP8 confocal microscope in a tile pattern across the X,Y plane and multiple sections along the Z-axis. This new confocal microscope has the added capability of dye separation using the Linear Unmixing method and allows us to remove the autofluorescence originating from the photoreceptor layer. In summary, we have an improved method for studying the retinal microvasculature that will provide an increase in the quality of images captured and will be applied throughout the various animal cohorts of the recentlyinitiated study that will evaluate rodent HS as a model to study ophthalmic complications in microgravity.

Imaging Nicotine in Rat Brain Tissue by Use of Nanospray Desorption Electrospray Ionization Mass Spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lanekoff, Ingela T.; Thomas, Mathew; Carson, James P.

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 tissuemore » 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.« less

Lateral habenula perturbation reduces default-mode network connectivity in a rat model of depression.

PubMed

Clemm von Hohenberg, Christian; Weber-Fahr, Wolfgang; Lebhardt, Philipp; Ravi, Namasivayam; Braun, Urs; Gass, Natalia; Becker, Robert; Sack, Markus; Cosa Linan, Alejandro; Gerchen, Martin Fungisai; Reinwald, Jonathan Rochus; Oettl, Lars-Lennart; Meyer-Lindenberg, Andreas; Vollmayr, Barbara; Kelsch, Wolfgang; Sartorius, Alexander

2018-03-27

Hyperconnectivity of the default-mode network (DMN) is one of the most widely replicated neuroimaging findings in major depressive disorder (MDD). Further, there is growing evidence for a central role of the lateral habenula (LHb) in the pathophysiology of MDD. There is preliminary neuroimaging evidence linking LHb and the DMN, but no causal relationship has been shown to date. We combined optogenetics and functional magnetic resonance imaging (fMRI), to establish a causal relationship, using an animal model of treatment-resistant depression, namely Negative Cognitive State rats. First, an inhibitory light-sensitive ion channel was introduced into the LHb by viral transduction. Subsequently, laser stimulation was performed during fMRI acquisition on a 9.4 Tesla animal scanner. Neural activity and connectivity were assessed, before, during and after laser stimulation. We observed a connectivity decrease in the DMN following laser-induced LHb perturbation. Our data indicate a causal link between LHb downregulation and reduction in DMN connectivity. These findings may advance our mechanistic understanding of LHb inhibition, which had previously been identified as a promising therapeutic principle, especially for treatment-resistant depression.

Effect of methylmercury on the rat mast cell degranulation

NASA Astrophysics Data System (ADS)

Graevskaya, E. E.; Yasutake, A.; Aramai, R.; Rubin, A. B.

2003-05-01

Methylmercury is the well-known neurotoxicant as weil as a modulator of the immune system. We investigated the effects of MeHg on the rat mast cell degranulation induced by nonimmunological stimuli (the selective liberator of histamine, compound 48/80, and calcium ionophore A23187) both in vivo and in vitro. In 8, 12 and 15 days afterthe final administration of MeHg we observed the suppression of calcium ionophore A23187-and 48/80-induced histamine release, which enhanced with time. In experiments in vitro incubation of peritoneal mast cells with MeHg alone in the dose range 10^{-8} to 10^{-6} did not induce mast cell degranulation, however modified the activation of mast cells by compound 48/80, and calcium ionophore A23187. We observed activation of stimulated secretion by preliminary incubation with low dose of MeHg 10^{-8} M and inhibition by dose of MeHg 10^{-6} M. These results show that MeHg treatment can modify mast cell function in vivo and in vitro and provide insight into the understanding what role this cell has in the pathogenesis of Minamata disease-comlected disorders.

Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas

PubMed Central

Showler, Kaye; Nishimura, Mayumi; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J.; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro

2017-01-01

Abstract The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. PMID:27738081

Influence of the estrus cycle on the evaluation of a vaginal irritation study in intact and ovariectomized rats

PubMed Central

Ishii, Aiko; Ogawa, Bunichiro; Koyama, Tomoko; Nakanishi, Yutaka; Sasaki, Minoru

2017-01-01

When conducting vaginal irritation studies, ovariectomized rats or rabbits are typically used according to practical reports. In the present study, we evaluated the influence of the estrus cycle in a vaginal irritation study using intact rats and ovariectomized rats, which exhibit a late diestrus-like condition, to determine whether intact rats can be useful for evaluating vaginal irritancy. Rats were divided into 4 groups: proestrus, estrus, and metestrus or diestrus in intact rats and ovariectomized rats. All the rats in each group were treated with a vehicle or sodium dodecyl sulfate, as the irritant, in single-dose and 4-day repeat-dose vaginal irritation studies. Each rat’s vagina was examined histopathologically, and the irritation score was calculated using a semiquantitative scoring system. In the single-dose study, the irritation scores for the proestrus or ovariectomized groups treated with sodium dodecyl sulfate were higher than those of the estrus group or metestrus or diestrus group. In the 4-day repeat-dose study, a significant histopathological difference was not found among the intact rats (proestrus, estrus, and metestrus or diestrus groups), and the irritation score range of the intact rats was similar to that of the ovariectomized rats, though the mean score of the intact rats was slightly lower than that of the ovariectomized rats. These results suggest that intact rats might be well suited for 4-day vaginal irritation studies and useful for evaluating vaginal irritancy using not only the mean score, but also individual irritation score ranges, whereas the estrus cycle would need to be identified in single-dose vaginal irritation studies. PMID:28458454

Intranasal mucoadhesive microemulsions of clonazepam: preliminary studies on brain targeting.

PubMed

Vyas, Tushar K; Babbar, A K; Sharma, R K; Singh, Shashi; Misra, Ambikanandan

2006-03-01

The aim of this investigation was to prepare clonazepam microemulsions (CME) for rapid drug delivery to the brain to treat acute status epileptic patients and to characterize and evaluate the performance of CME in vitro and in vivo in rats. The CME were prepared by the titration method and were characterized for globule size and size distribution, zeta potential, and drug content. CME was radiolabeled with (99m)Tc (technetium) and biodistribution of drug in the brain was studied in Swiss albino rats after intranasal and intravenous administrations. Brain scintigraphy imaging in rabbits was also performed to ascertain the uptake of the drug into the brain. Pre and postCME formulation treated human nasal mucosa was subjected to transmission electron microscopy to investigate the mechanism of drug uptake across the nasal mucosa. CME were transparent and stable with mean globule size of 15 +/- 10 nm and zeta potential of -30 mV to -40 mV. (99m)Tc-labeled clonazepam solution ((99m)Tc CS)/ clonazepam microemulsion (CME)/clonazepam mucoadhesive microemulsion (CMME) were found to be stable and suitable for in vivo studies. Brain/blood uptake ratios at 0.50 hour (h) following intranasal CMME, CME, clonazepam solution (CS), and intravenous CME administrations were found to be 0.67, 0.50, 0.48, and 0.13, respectively indicating more effective targeting with intranasal administration and best targeting of the brain with intranasal CMME. Brain/blood ratio at all sampling points up to 8 h following intranasal administration of CMME compared to intravenous was found to be twofold higher indicating larger extent of distribution of the drug in brain. Rabbit brain scintigraphy also showed higher intranasal uptake of the drug into the brain. Transmission electron microscopy revealed significant accretion of CMME within interstitial spaces and paracellular mode of transport due to stretching of the tight junctions present in the nasal mucosa. This investigation demonstrates a more rapid and larger extent of transport of clonazepam into the rat brain with intranasal CMME, which may prove useful in treating acute status epileptics. Copyright 2006 Wiley-Liss, Inc. and the American Pharmacists Association.

Cell Death, Neuronal Plasticity and Functional Loading in the Development of the Central Nervous System

NASA Technical Reports Server (NTRS)

Keefe, J. R.

1985-01-01

Research on the precise timing and regulation of neuron production and maturation in the vestibular and visual systems of Wistar rats and several inbred strains of mice (C57B16 and Pallid mutant) concentrated upon establishing a timing baseline for mitotic development of the neurons of the vestibular nuclei and the peripheral vestibular sensory structures (maculae, cristae). This involved studies of the timing and site of neuronal cell birth and preliminary studies of neuronal cell death in both central and peripheral elements of the mammalian vestibular system. Studies on neuronal generation and maturation in the retina were recently added to provide a mechanism for more properly defining the in utero' developmental age of the individual fetal subject and to closely monitor potential transplacental effects of environmentally stressed maternal systems. Information is given on current efforts concentrating upon the (1) perinatal period of development (E18 thru P14) and (2) the role of cell death in response to variation in the functional loading of the vestibular and proprioreceptive systems in developing mammalian organisms.

Low-Dose Oral Sirolimus and the Risk of Menstrual-Cycle Disturbances and Ovarian Cysts: Analysis of the Randomized Controlled SUISSE ADPKD Trial

PubMed Central

Braun, Matthias; Young, James; Reiner, Cäcilia S.; Poster, Diane; Krauer, Fabienne; Kistler, Andreas D.; Kristanto, Paulus; Wang, Xueqi; Liu, Yang; Loffing, Johannes; Andreisek, Gustav; von Eckardstein, Arnold; Senn, Oliver; Wüthrich, Rudolf P.; Serra, Andreas L.

2012-01-01

Sirolimus has been approved for clinical use in non proliferative and proliferative disorders. It inhibits the mammalian target of rapamycin (mTOR) signaling pathway which is also known to regulate ovarian morphology and function. Preliminary observational data suggest the potential for ovarian toxicity but this issue has not been studied in randomized controlled trials. We reviewed the self-reported occurrence of menstrual cycle disturbances and the appearance of ovarian cysts post hoc in an open label randomized controlled phase II trial conducted at the University Hospital Zürich between March 2006 and March 2010. Adult females with autosomal dominant polycystic kidney disease, an inherited kidney disease not known to affect ovarian morphology and function, were treated with 1.3 to 1.5 mg sirolimus per day for a median of 19 months (N = 21) or standard care (N = 18). Sirolimus increased the risk of both oligoamenorrhea (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.1 to 29) and ovarian cysts (HR 4.4, CI 1.1 to 26); one patient was cystectomized five months after starting treatment with sirolimus. We also studied mechanisms of sirolimus-associated ovarian toxicity in rats. Sirolimus amplified signaling in rat ovarian follicles through the pro-proliferative phosphatidylinositol 3-kinase pathway. Low dose oral sirolimus increases the risk of menstrual cycle disturbances and ovarian cysts and monitoring of sirolimus-associated ovarian toxicity is warranted and might guide clinical practice with mammalian target of rapamycin inhibitors. Trial Registration ClinicalTrials.gov NCT00346918 PMID:23071528

In vivo confirmation of hydration based contrast mechanisms for terahertz medical imaging using MRI

NASA Astrophysics Data System (ADS)

Bajwa, Neha; Sung, Shijun; Garritano, James; Nowroozi, Bryan; Tewari, Priyamvada; Ennis, Daniel B.; Alger, Jeffery; Grundfest, Warren; Taylor, Zachary

2014-09-01

Terahertz (THz) detection has been proposed and applied to a variety of medical imaging applications in view of its unrivaled hydration profiling capabilities. Variations in tissue dielectric function have been demonstrated at THz frequencies to generate high contrast imagery of tissue, however, the source of image contrast remains to be verified using a modality with a comparable sensing scheme. To investigate the primary contrast mechanism, a pilot comparison study was performed in a burn wound rat model, widely known to create detectable gradients in tissue hydration through both injured and surrounding tissue. Parallel T2 weighted multi slice multi echo (T2w MSME) 7T Magnetic Resonance (MR) scans and THz surface reflectance maps were acquired of a full thickness skin burn in a rat model over a 5 hour time period. A comparison of uninjured and injured regions in the full thickness burn demonstrates a 3-fold increase in average T2 relaxation times and a 15% increase in average THz reflectivity, respectively. These results support the sensitivity and specificity of MRI for measuring in vivo burn tissue water content and the use of this modality to verify and understand the hydration sensing capabilities of THz imaging for acute assessments of the onset and evolution of diseases that affect the skin. A starting point for more sophisticated in vivo studies, this preliminary analysis may be used in the future to explore how and to what extent the release of unbound water affects imaging contrast in THz burn sensing.

EFFECT OF ACTIVE ACCUMULATION OF CALCIUM AND PHOSPHATE IONS ON THE STRUCTURE OF RAT LIVER MITOCHONDRIA

PubMed Central

Greenawalt, John W.; Rossi, Carlo S.; Lehninger, Albert L.

1964-01-01

Rat liver mitochondria allowed to accumulate maximal amounts of Ca++ and HPO4 = ions from the suspending medium in vitro during respiration have a considerably higher specific gravity than normal mitochondria and may be easily separated from the latter by isopycnic centrifugation in density gradients of sucrose or cesium chloride. When the mitochondria are allowed to accumulate less than maximal amounts of Ca++ and HPO4 = from the medium, they have intermediate specific gravities which are roughly proportional to their content of calcium phosphate. Maximally "loaded" mitochondria are relatively homogeneous with respect to specific gravity. Correlated biochemical and electron microscopic studies show that Ca++-loaded mitochondria contain numerous dense granules, of which some 85 per cent are over 500 A in diameter. These granules are electron-opaque not only following fixation and staining with heavy metal reagents, but also following fixation with formaldehyde, demonstrating that the characteristic granules in Ca++-loaded mitochondria have intrinsic electron-opacity. The dense granules are almost always located within the inner compartment of the mitochondria and not in the space between the inner and outer membranes. They are frequently located at or near the cristae and they often show electron-transparent "cores." Such granules appear to be made up of clusters of smaller dense particles, but preliminary x-ray diffraction analysis and electron diffraction studies have revealed no evidence of crystallinity in the deposits. The electron-opaque granules decrease in number when the Ca++-loaded mitochondria are incubated with 2,4-dinitrophenol; simultaneously there is discharge of Ca++ and phosphate from the mitochondria into the medium. PMID:14228516

Endothelin-like action of Pausinystalia yohimbe aqueous extract on vascular and renal regional hemodynamics in Sprague Dawley rats.

PubMed

Ajayi, A A; Newaz, M; Hercule, H; Saleh, M; Bode, C O; Oyekan, A O

2003-12-01

The bark of the African tree Pausinystalia yohimbe has been used as a food additive with aphrodisiac and penile erection enhancing properties. The effect of an aqueous extract of P. yohimbe (CCD-X) on renal circulation was assessed in order to test the hypothesis that it possesses additional effects on nitric oxide production and/or endothelin-1 (ET-1)-like actions. In vivo studies with CCD-X in Sprague Dawley rats demonstrated a dose-dependent (1-1000 ng/kg) increase in mean blood pressure (p < 0.001) and an increase in medullary blood flow (MBF) (p < 0.001). Both the pressor action and renal medullary vasodilation were blocked by endothelinA (ETA) receptor antagonist BMS182874 and endothelinB (ETB) receptor antagonist BQ788 in combination. L-Nomega-nitro-l-arginine methyl ester (L-NAME; 10 mg/kg) also inhibited the increase in MBF induced by CCD-X. In vitro studies in isolated perfused kidney and in pressurized renal microvessels confirmed the dose-dependent vasoconstrictor action of this extract. ETA receptor antagonist BQ610 and ETB receptor antagonist BQ788 separately and significantly attenuated the renal vasoconstrictor actions of the extract (p < 0.001 ANOVA). These preliminary observations indicate that, in addition to the alpha-adrenergic antagonist actions that characterize yohimbine, CCD-X possesses endothelin-like actions and affects nitric oxide (NO) production in renal circulation. These findings suggest a strong possibility of post-receptor cross-talk between alpha2-adrenoceptors and endothelin, as well as a direct effect of alpha2-adrenoceptors on renal NO production. (c) 2003 Prous Science

Hypoglycemic effect of basil (Ocimum basilicum) aqueous extract is mediated through inhibition of α-glucosidase and α-amylase activities: an in vitro study.

PubMed

El-Beshbishy, Ha; Bahashwan, Sa

2012-02-01

The present study investigated the in vitro hypoglycemic activity of basil (Ocimum basilicum) aqueous extract. Preliminary phytochemical screening of the extract revealed the presence of reducing sugars, cardiac glycosides, tannins, saponins, glycosides, flavonoids and steroids. The total polyphenols content (TPC), flavonoids content (FC), percentage diphenylpicrylhydrazyl (DPPH( · )) radical inhibition and total antioxidant status (TAS) were estimated. The FC was 41 ± 2.2 rutin/g dry extract, the TPC was 146 ± 5.26 mg catechin/g dry extract and the TAS was 5.12 ± 0.7 mmol/L. The %DPPH( · ) free radical inhibition was 60%, 54%, 49% and 43%, respectively, for different extract concentrations; 20, 18.2, 16.3 and 14.5 mg/ml, respectively. The extract elicited significant dose-dependent pattern against rat intestinal sucrase (RIS; IC(50) = 36.72 mg/ml), rat intestinal maltase (RIM; IC(50) = 21.31 mg/ml) and porcine pancreatic α-amylase (PPA; IC(50) = 42.50 mg/ml) inhibitory activities. The inhibition was greater against maltase compared with sucrase. These effects may be attributed to the high TPC and FC levels. The linear regression analysis revealed strong significant positive correlations between %DPPH( · ) radical inhibition and each of %RIS, %RIM and %PPA inhibiting activity. Also, strong significant positive correlations between %RIS and either %RIM or %PPA inhibition activity were observed. We concluded therefore that basil aqueous extract via antioxidant and possibly α-glucosidase and α-amylase inhibiting activities, offered positive benefits to control diabetes.

Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

PubMed

Kargutkar, Samira; Brijesh, S

2018-04-01

Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

Hepatoprotective activity of punarnavashtak kwath, an Ayurvedic formulation, against CCl4-induced hepatotoxicity in rats and on the HepG2 cell line.

PubMed

Shah, Vaishali N; Shah, Mamta B; Bhatt, Parloop A

2011-04-01

Punarnavashtak kwath (PNK) is a classical Ayurvedic formulation, mentioned in Ayurvedic literature Bhaishajya Ratnavali, for hepatic disorders and asthma. This study investigated the hepatoprotective activity of PNK to validate the traditional use of this formulation. PNK was prepared in the laboratory according to the method given in Ayurvedic literature. Phytochemical screening was performed to determine the presence of phytoconstituents. Hepatoprotective activity was evaluated against CCl(4)-induced hepatotoxicity in rats and by its effect on the HepG2 cell line. Preliminary phytochemical screening revealed the presence of alkaloids, tannins, flavonoids, saponins, and a bitter principle in PNK. Administration of PNK produced significant hepatoprotective effect as demonstrated by decreased levels of serum liver marker enzymes such as aspartate transaminase, serum alanine transaminase, serum alkaline phosphatase, and serum bilirubin and an increase in protein level. Thiopentone-induced sleeping time was also decreased in the PNK-treated animals compared with the CCl(4)-treated group. It also showed antioxidant activity by increase in activity of glutathione, superoxide dismutase, and catalase and by a decrease in thiobarbituric acid reactive substance level compared with the CCl(4)-treated group. Results of a histopathological study also support the hepatoprotective activity of PNK. Investigation carried out on the HepG2 cell line depicted significant increase in viability of cells exposed to PNK as compared with CCl(4)-treated cells. It can be concluded that PNK protects hepatocytes from CCl(4)-induced liver damages due to its antioxidant effect on hepatocytes. An in vitro study on HepG2 cell lines also supports its protective effect.

Distortion product otoacoustic emissions as non-invasive biomarkers and predictors of soman-induced central neurotoxicity: a preliminary study.

PubMed

Job, Agnès; Baille, Valérie; Dorandeu, Frédéric; Pouyatos, Benoît; Foquin, Annie; Delacour, Claire; Denis, Josiane; Carpentier, Pierre

2007-09-05

The organophosphorus nerve agent soman is an irreversible cholinesterase (ChE) inhibitor that can produce long-lasting seizures and brain damage in which the neurotransmitters acetylcholine and glutamate are involved. These same neurotransmitters play key-roles in the auditory function. It was then assumed that exploring the hearing function may provide markers of the central events triggered by soman intoxication. In the present study, distortion product otoacoustic emissions (DPOAEs), a non-invasive audiometric method, were used to monitor cochlear functionality in rats administered with a moderate dose of soman (45 microg/kg). DPOAEs were investigated either 4h or 24h post-challenge. In parallel, the effects of soman on whole blood and brain ChE activity and on brain histology were also studied. The first main result is that DPOAE intensities were significantly decreased 4h post-soman and returned to baseline at 24h. The amplitude changes were well related to the severity of symptoms, with the greatest change being recorded in the rats that survived long-lasting convulsions. The second main result is that baseline DPOAEs recorded 8 days before soman appear to predict the severity of symptoms produced by the intoxication. Indeed, the lowest baseline DPOAEs corresponded to the occurrence of long-lasting convulsions and brain damage and to the greatest inhibition in central ChE. These results thus suggest that DPOAEs represent a promising non-invasive tool to assess and predict the central consequences of nerve agent poisoning. Further investigations will be carried out to assess the potential applications and the limits of this non-invasive method.

The neurotoxic effects of methamphetamine on 5-hydroxytryptamine and dopamine in brain: evidence for the protective effect of chlormethiazole.

PubMed

Green, A R; De Souza, R J; Williams, J L; Murray, T K; Cross, A J

1992-04-01

Studies were undertaken in mice and rats on the neurotoxic effects of methamphetamine on dopaminergic and 5-hydroxytryptaminergic neurones in the brain and the neuroprotective action of chlormethiazole. In initial studies, mice were injected with methamphetamine (5 mg/kg, i.p.) at 2 hr intervals, to a total of 4 times. This procedure produced a 66% loss of striatal dopamine and a 50% loss of tyrosine hydroxylase activity 3 days later. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each dose of methamphetamine, totally prevented the methamphetamine-induced loss of tyrosine hydroxylase activity and partly prevented the loss of dopamine. Phencyclidine (20 mg/kg, i.p.), given in place of chlormethiazole, also prevented the loss of tyrosine hydroxylase. Administration to rats of 4 doses of methamphetamine (15 mg/kg, i.p.) at 3 hr intervals resulted in a 75% loss of striatal dopamine 3 days later and a similar loss of 5-HT and 5-HIAA in cortex and hippocampus. Chlormethiazole (50 mg/kg, i.p.), given 15 min before each injection of methamphetamine, protected against the loss of dopamine and indoleamine content, in the respective regions. Pentobarbital (25 mg/kg, i.p.) also provided substantial protection but diazepam (2.5 mg/kg, i.p.) was without effect. Confirming earlier studies, dizocilpine (1 mg/kg) also provided substantial protection against the methamphetamine-induced neurotoxicity. Preliminary data indicated that chlormethiazole was not neuroprotective because of a hypothermic action. These data therefore demonstrate that chlormethiazole is an effective neuroprotective agent against methamphetamine-induced neurotoxicity and extend the evidence for the possible value of this drug in preventing neurodegeneration.

Air puff-induced 22-kHz calls in F344 rats.

PubMed

Inagaki, Hideaki; Sato, Jun

2016-03-01

Air puff-induced ultrasonic vocalizations in adult rats, termed "22-kHz calls," have been applied as a useful animal model to develop psychoneurological and psychopharmacological studies focusing on human aversive affective disorders. To date, all previous studies on air puff-induced 22-kHz calls have used outbred rats. Furthermore, newly developed gene targeting technologies, which are essential for further advancement of biomedical experiments using air puff-induced 22-kHz calls, have enabled the production of genetically modified rats using inbred rat strains. Therefore, we considered it necessary to assess air puff-induced 22-kHz calls in inbred rats. In this study, we assessed differences in air puff-induced 22-kHz calls between inbred F344 rats and outbred Wistar rats. Male F344 rats displayed similar total (summed) duration of air puff-induced 22 kHz vocalizations to that of male Wistar rats, however, Wistar rats emitted fewer calls of longer duration, while F344 rats emitted higher number of vocalizations of shorter duration. Additionally, female F344 rats emitted fewer air puff-induced 22-kHz calls than did males, thus confirming the existence of a sex difference that was previously reported for outbred Wistar rats. The results of this study could confirm the reliability of air puff stimulus for induction of a similar amount of emissions of 22-kHz calls in different rat strains, enabling the use of air puff-induced 22-kHz calls in inbred F344 rats and derived genetically modified animals in future studies concerning human aversive affective disorders. Copyright © 2015 Elsevier Inc. All rights reserved.

The acute effects of different spironolactone doses on cardiac function in streptozotocin-induced diabetic rats.

PubMed

Vranic, Aleksandra; Simovic, Stefan; Ristic, Petar; Nikolic, Tamara; Stojic, Isidora; Srejovic, Ivan; Zivkovic, Vladimir; Jakovljevic, Vladimir; Djuric, Dusan

2017-11-01

Currently, cardiovascular diseases are the leading cause of global mortality, while diabetes mellitus remains an important cause of cardiovascular morbidity. A recent study showed that patients with diabetes mellitus treated with mineralocorticoid receptor antagonists have improved coronary microvascular function, leading to improved diastolic dysfunction. In this study, we evaluated the influence of acute administration of spironolactone on myocardial function in rats with streptozotocin-induced diabetes mellitus, with special emphasis on cardiodynamic parameters in diabetic rat hearts. The present study was carried out on 40 adult male Wistar albino rats (8 weeks old). Rats were randomly divided into 4 groups (10 animals per group): healthy rats treated with 0.1 μmol/L of spironolactone, diabetic rats treated with 0.1 μmol/L of spironolactone, healthy rats treated with 3 μmol/L of spironolactone, and diabetic rats treated with 3 μmol/L of spironolactone. Different, dose-dependent, acute responses of spironolactone treatment on isolated, working diabetic and healthy rat heart were observed in our study. In healthy rats, better systolic function was achieved with higher spironolactone dose, while in diabetic rats, similar effects of low and high spironolactone dose were observed.

Muscarinic receptor immunoreactivity in the superior salivatory nucleus neurons innervating the salivary glands of the rat.

PubMed

Ueda, Hirotaka; Mitoh, Yoshihiro; Fujita, Masako; Kobashi, Motoi; Yamashiro, Takashi; Sugimoto, Tomosada; Ichikawa, Hiroyuki; Matsuo, Ryuji

2011-07-15

The superior salivatory nucleus (SSN) contains preganglionic parasympathetic neurons to the submandibular and sublingual salivary glands. Cevimeline, a muscarinic acetylcholine receptor agonist, stimulates the salivary glands and is presently used as sialogogue in the treatment of dry mouth. Since cevimeline passes through the blood-brain barrier, it is also able to act on muscarinic acetylcholine receptors in the central nervous system. Our preliminary experiment using the whole-cell patch-clamp technique has shown that cevimeline excites SSN neurons in rat brain slices, suggesting that SSN neurons have muscarinic acetylcholine receptors; however, it is unclear which subtypes of muscarinic acetylcholine receptors exist in SSN neurons. In the present study, we investigated immunohistochemically muscarinic acetylcholine receptor subtypes, M1 receptor (M1R), M2R, M3R, M4R, and M5R in SSN neurons. SSN neurons innervating the salivary glands, retrogradely labeled with a fluorescent tracer from the chorda-lingual nerve, mostly expressed M3R immunoreactivity (-ir) (92.3%) but not M1R-ir. About half of such SSN neurons also showed M2R- (40.1%), M4R- (54.0%) and M5R-ir (46.0%); therefore, it is probable that SSN neurons co-express M3R-ir with at least two of the other muscarinic receptor subtypes. This is the first report to show that SSN neurons contain muscarinic acetylcholine receptors. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Remote effects of extracorporeal shock wave therapy on cutaneous microcirculation.

PubMed

Kisch, Tobias; Sorg, Heiko; Forstmeier, Vinzent; Knobloch, Karsten; Liodaki, Eirini; Stang, Felix; Mailänder, Peter; Krämer, Robert

2015-11-01

Extracorporeal shock wave treatment (ESWT) has proven its clinical benefits in different fields of medicine. Tissue regeneration and healing is improved after shock wave treatment. Even in the case of burn wounds angiogenesis and re-epithelialization is accelerated, but ESWT in extensive burn wounds is impracticable. High energy ESWT influences cutaneous microcirculation at body regions remote from application site. Eighteen Sprague Dawley rats were randomly assigned to two groups and received either high energy ESWT (Group A: total 1000 impulses, 10 J) or placebo shock wave treatment (Group B: 0 impulses, 0 J), applied to the dorsal lower leg of the hind limb. Ten minutes later microcirculatory effects were assessed at the contralateral lower leg of the hind limb (remote body region) by combined Laser-Doppler-Imaging and Photospectrometry. In Group A cutaneous capillary blood velocity was significantly increased by 152.8% vs. placebo ESWT at the remote body location (p = 0.01). Postcapillary venous filling pressure remained statistically unchanged (p > 0.05), while cutaneous tissue oxygen saturation increased by 12.7% in Group A (p = 0.220). High energy ESWT affects cutaneous hemodynamics in body regions remote from application site in a standard rat model. The results of this preliminary study indicate that ESWT might be beneficial even in disseminated and extensive burn wounds by remote shock wave effects and should therefore be subject to further scientific evaluation. Copyright © 2015 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Preliminary Studies of Acute Cadmium Administration Effects on the Calcium-Activated Potassium (SKCa and BKCa) Channels and Na+/K+-ATPase Activity in Isolated Aortic Rings of Rats.

PubMed

Vassallo, Dalton V; Almenara, Camila C P; Broseghini-Filho, Gilson Brás; Teixeira, Ariane Calazans; da Silva, David Chaves F; Angeli, Jhuli K; Padilha, Alessandra S

2018-06-01

Cadmium is an environmental pollutant closely linked with cardiovascular diseases that seems to involve endothelium dysfunction and reduced nitric oxide (NO) bioavailability. Knowing that NO causes dilatation through the activation of potassium channels and Na + /K + -ATPase, we aimed to determine whether acute cadmium administration (10 μM) alters the participation of K + channels, voltage-activated calcium channel, and Na + /K + -ATPase activity in vascular function of isolated aortic rings of rats. Cadmium did not modify the acetylcholine-induced relaxation. After L-NAME addition, the relaxation induced by acetylcholine was abolished in presence or absence of cadmium, suggesting that acutely, this metal did not change NO release. However, tetraethylammonium (a nonselective K + channels blocker) reduced acetylcholine-induced relaxation but this effect was lower in the preparations with cadmium, suggesting a decrease of K + channels function in acetylcholine response after cadmium incubation. Apamin (a selective blocker of small Ca 2+ -activated K + channels-SK Ca ), iberiotoxin (a selective blocker of large-conductance Ca 2+ -activated K + channels-BK Ca ), and verapamil (a blocker of calcium channel) reduced the endothelium-dependent relaxation only in the absence of cadmium. Finally, cadmium decreases Na + /K + -ATPase activity. Our results provide evidence that the cadmium acute incubation unaffected the calcium-activated potassium channels (SK Ca and BK Ca ) and voltage-calcium channels on the acetylcholine vasodilatation. In addition, acute cadmium incubation seems to reduce the Na + /K + -ATPase activity.

Phytochemical analysis, hepatoprotective and antioxidant activity of Alchornea cordifolia methanol leaf extract on carbon tetrachloride-induced hepatic damage in rats.

PubMed

Osadebe, Patience O; Okoye, Festus B C; Uzor, Philip F; Nnamani, Nneka R; Adiele, Ijeoma E; Obiano, Nkemakonam C

2012-04-01

To investigate the hepatoprotective and antioxidant activities of Alchornea cordifolia (A. cordifolia) leaf extract. Various solvent fractions of the methanol extract of the leaf of the plant A. cordifolia Mull. Arg (Fam: Euphorbiaceae) were evaluated for hepatoprotective activity by carbon tetrachloride-induced liver damage in rats. The degree of protection was measured by using biochemical parameters such as serum glutamate oxalate transaminase (SGOT/AST), serum glutamate pyruvate transaminase (SGPT/ALT), alkaline phosphatase (ALP) and total bilirubin. The in vitro antioxidant activity of the extract was also evaluated by the 1, 1-diphenyl- 2-picrylhydrazyl (DPPH) free radical scavenging assay. The extract was subjected to preliminary phytochemical screening. The ethyl acetate and chloroform fractions, at a dose of 300 mg/kg, produced significant (P<0.05) hepatoprotection by decreasing the activities of the serum enzymes and bilirubin while there were marked scavenging of the DPPH free radicals by the fractions. The effects were comparable to those of the standard drugs used for the respective experiments, silymarin and ascorbic acid. Alkaloids, flavonoids, saponins and tannins were detected in the phytochemical screening. From this study, it was concluded that the plant of A. cordifolia possesses hepatoprotective as well as antioxidant activities and these activities reside mainly in the ethyl acetate and acetone fractions of methanol leaf extract. Copyright © 2012 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Metabolism during hypodynamia

NASA Technical Reports Server (NTRS)

Federov, I. V.

1980-01-01

Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

Primary characterization and evaluation of anti ulcerogenic activity of an aqueous extract from callus culture of Cereus peruvianus Mill. (Cactaceae).

PubMed

Jayme, Milena O; Ames, Franciele Q; Bersani-Amado, Ciomar A; Machado, Maria de Fatima P S; Mangolin, Claudete A; Goncalves, Regina A C; de Oliveira, Arildo J B

2015-01-01

In the current study we reported cultivation, extraction procedure, analysis and preliminary characterization of the aqueous extract from Cereus peruvianus callus culture and evaluated its anti ulcerogenic activity in vivo models of experimental ulcers in Wistar rats. The obtained aqueous extract from callus (AC) was dialyzed and subjected to freeze-thaw process, providing a possible polysaccharide. The carbohydrate and protein contents of the aqueous extract were estimated at 53.4% and 0.66%, respectively, composed primarily of galactose, arabinose and galacturonic acid, with minor amounts of glucose. This appeared heterogeneous when analyzed by high-performance size-exclusion chromatography and a multiangle laser light scattering detector (HPSEC-MALLS). The AC was found to be significantly effective against ethanol-induced lesions but was ineffective against indomethacin-induced lesions. The callus culture of C. peruvianus is an alternative source for the synthesis of substances originally produced by plants. The calluses grown indefinitely in vitro under controlled conditions are stable tissues, and the aqueous extract from calluses may be used instead of fully developed plants using the protocols described in this study.

Closure of skin incisions by laser-welding with a combination of two near-infrared diode lasers: preliminary study for determination of optimal parameters

NASA Astrophysics Data System (ADS)

Hu, Liming; Lu, Zhihua; Wang, Biao; Cao, Junsheng; Ma, Xiaobo; Tian, Zhenhua; Gao, Zhijian; Qin, Li; Wu, Xiaodong; Liu, Yun; Wang, Lijun

2011-03-01

Laser welding has the potential to become an effective method for wound closure and healing without sutures. Closure of skin incisions by laser welding with a combination of two near-infrared lasers (980 and 1064 nm), was performed for the first time in this study. One centimeter long, full-thickness incisions were made on the Wistar rat's dorsal skin. The efficiencies of laser-welding with different parameters were investigated. Incision-healing, histology examination, and a tensile strength test of incisions were recorded. Laser welding with the irradiance level of 15.9 W/cm2 for both 980 and 1064-nm lasers and exposure time of 5 s per spot in continuous wave mode yielded a more effective closure and healing with minimal thermal damage, faster recovery, and stronger apposition in comparison with a suturing technique. The conclusion is that skin welding with a combination of two near-infrared diode lasers can be a good candidate for incision closure, and further investigations are in progress for clinical use.

The history behind successful uterine transplantation in humans

PubMed Central

Castellón, Luis Arturo Ruvalcaba; Amador, Martha Isolina García; González, Roberto Enrique Díaz; Eduardo, Montoya Sarmiento Jorge; Díaz-García, César; Kvarnström, Niclas; Bränström, Mats

2017-01-01

This paper aimed to describe the basic aspects of uterine transplant (UTx) research in humans, including preliminary experiences in rodents and domestic species. Studies in rats, domestic species, and non-human primates validated and optimized the UTx procedure in terms of its surgical aspects, immunosuppression, rejection diagnosis, peculiarities of pregnancy in immunosuppressed patients, and patients with special uterine conditions. In animal species, the first live birth from UTx was achieved in a syngeneic mouse model in 2003. Twenty-five UTx procedures have been performed in humans. The first two cases were unsuccessful, but established the need for rigorous research to improve success rates. As a result of a controlled clinical study under a strictly designed research protocol, nine subsequent UTx procedures have resulted in six healthy live births, the first of them in 2014. Further failed UTx procedures have been performed in China, Czech Republic, Brazil, Germany, and the United States, most of which using living donors. Albeit still an experimental procedure in, UTx is the first potential alternative for the treatment of absolute uterine factor infertility (AUFI). PMID:28609280

Closure of skin incisions by laser-welding with a combination of two near-infrared diode lasers: preliminary study for determination of optimal parameters.

PubMed

Hu, Liming; Lu, Zhihua; Wang, Biao; Cao, Junsheng; Ma, Xiaobo; Tian, Zhenhua; Gao, Zhijian; Qin, Li; Wu, Xiaodong; Liu, Yun; Wang, Lijun

2011-03-01

Laser welding has the potential to become an effective method for wound closure and healing without sutures. Closure of skin incisions by laser welding with a combination of two near-infrared lasers (980 and 1064 nm), was performed for the first time in this study. One centimeter long, full-thickness incisions were made on the Wistar rat's dorsal skin. The efficiencies of laser-welding with different parameters were investigated. Incision-healing, histology examination, and a tensile strength test of incisions were recorded. Laser welding with the irradiance level of 15.9 W∕cm(2) for both 980 and 1064-nm lasers and exposure time of 5 s per spot in continuous wave mode yielded a more effective closure and healing with minimal thermal damage, faster recovery, and stronger apposition in comparison with a suturing technique. The conclusion is that skin welding with a combination of two near-infrared diode lasers can be a good candidate for incision closure, and further investigations are in progress for clinical use.

Peroxisome proliferation due to di(2-ethylhexyl) phthalate (DEHP): species differences and possible mechanisms.

PubMed Central

Elcombe, C R; Mitchell, A M

1986-01-01

The exposure of cultured rat hepatocytes to mono(2-ethylhexyl)phthalate (MEHP) for 72 hr resulted in marked induction of peroxisomal enzyme activity (beta-oxidation; cyanide-insensitive palmitoyl CoA oxidase) and concomitant increases in the number of peroxisomes. Similar treatment of cultured guinea pig, marmoset, or human hepatocytes revealed little or no effect of MEHP. In order to eliminate possible confounding influences of biotransformation, the proximate peroxisome proliferator(s) derived from MEHP have been identified. Using cultured hepatocytes these agents were found to be metabolite VI [mono(2-ethyl-5-oxohexyl) phthalate] and metabolite IX [mono(2-ethyl-5-hydroxyhexyl) phthalate]. The addition of these "active" metabolites to cultured guinea pig, marmoset, or human hepatocytes again revealed little effect upon peroxisomes or related enzyme activities (peroxisomal beta-oxidation or microsomal lauric acid hydroxylation). These studies demonstrate a marked species difference in the response of hepatocytes to MEHP-elicited peroxisome proliferation. Preliminary studies have also suggested that peroxisome proliferation due to MEHP may be due to an initial biochemical lesion of fatty acid metabolism. Images FIGURE 4. a FIGURE 4. b PMID:3104023

Preliminary PET/CT Imaging with Somatostatin Analogs [68Ga]DOTAGA-TATE and [68Ga]DOTAGA-TOC.

PubMed

Satpati, Drishty; Shinto, Ajit; Kamaleshwaran, K K; Sarma, Haladhar Dev; Dash, Ashutosh

2017-12-01

Somatostatin receptor positron emission tomography/X-ray computed tomography (SSTR-PET/CT) is a well-established technique for staging and detection of neuroendocrine tumors (NETs). Ga-68-labeled DOTA-conjugated octreotide analogs are the privileged radiotracers for diagnosis and therapeutic monitoring of NETs. Hence, we were interested in assessing the influence of promising, newer variant DOTAGA on the hydrophilicity, pharmacokinetics, and lesion pick-up of somatostatin analogs. Herein, the potential of ([ 68 Ga]DOTAGA, Tyr 3 , Thr 8 ) octreotide ([ 68 Ga]DOTAGA-TATE) and ([ 68 Ga]DOTAGA, Tyr 3 ) octreotide ([ 68 Ga]DOTAGA-TOC) as NET imaging agents has been investigated. Amenability of [ 68 Ga]DOTAGA-(TATE/TOC) to kit-type formulation has been demonstrated. Biodistribution studies were carried out in normal rats at 1 h post-injection (p.i.). [ 68 Ga]DOTAGA-(TATE/TOC) PET/CT scans were carried out in patients (70-170 MBq, 1 h p.i.) with histologically confirmed well-differentiated NETs. [ 68 Ga]DOTAGA-TATE exhibited hydrophilicity similar to [ 68 Ga]DOTA-TATE (log P = -3.51 vs -3.69) whereas [ 68 Ga]DOTAGA-TOC was more hydrophilic than [ 68 Ga]DOTA-TOC (log P = -3.27 vs -2.93). [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE showed almost identical blood and kidney uptake in normal rats whereas significantly fast clearance (p < 0.05) of [ 68 Ga]DOTAGA-TATE was observed from other non-specific organs (liver, lungs, spleen, intestine). [ 68 Ga]DOTAGA-TOC also demonstrated rapid clearance from blood and kidneys (p < 0.05) in comparison to [ 68 Ga]DOTA-TOC. The metastatic lesions in NET patients were well identified by [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTAGA-TOC. The phenomenal analogy was observed between [ 68 Ga]DOTAGA-TATE and [ 68 Ga]DOTA-TATE as well as between [ 68 Ga]DOTAGA-TOC and [ 68 Ga]DOTA-TOC in biodistribution studies in rats. The good lesion detection ability of the two radiotracers indicates their potential as NET imaging radiotracers.

Increasing the efficacy of antitumor glioma vaccines by photodynamic therapy and local injection of allogeneic glioma cells

NASA Astrophysics Data System (ADS)

Christie, Catherine E.; Peng, Qian; Madsen, Steen J.; Uzal, Francisco A.; Hirschberg, Henry

2016-03-01

Immunotherapy of brain tumors involves the stimulation of an antitumor immune response. This type of therapy can be targeted specifically to tumor cells thus sparing surrounding normal brain. Due to the presence of the blood-brain barrier, the brain is relatively isolated from the systemic circulation and, as such, the initiation of significant immune responses is more limited than other types of cancers. The purpose of this study was to show that the efficacy of tumor primed antigen presenting macrophage vaccines could be increased by: (1) PDT of the priming tumor cells, and (2) injection of allogeneic glioma cells directly into brain tumors. Experiments were conducted in an in vivo brain tumor model using Fisher rats and BT4C (allogeneic) and F98 (syngeneic) glioma cells. Preliminary results showed that vaccination alone had significantly less inhibitory effect on F98 tumor growth compared to the combination of vaccination and allogeneic cell (BT4C) injection.

The preliminary evaluation of degradation of substance P(SP) fragment's analogue less than Glu SP6-11 in the subcellular fractions from different areas of rat brain.

PubMed

Turski, W A; Lachowicz, L; Koziołkiewicz, W

1985-01-01

Peptidase(s) activity of different subcellular fractions isolated from cortex, hippocampus, midbrain, thalamus with hypothalamus, cerebellum and medulla oblongata exerted against less than Glu SP6-11 (3H-Phen8) was evaluated in "low-ionic" and similar (in composition) to both extracellular and intracellular conditions. The incubation of less than Glu SP6-11 with different fractions leaves the hexapeptide undegraded in the studied conditions in most cases. Peptidases activity results in the formation of the first of all C-terminal and exceptionally "internal" labelled products. Labelled N-terminal products were not seen. The most effective degradation in vitro of less than Glu SP6-11 takes place, in the majority of cases, in "low ionic" conditions when compared to those similar to extra or intracellular ones. The biggest total (per 1 g of wet mass) and specific activities against less than Glu SP6-11 can be shown in the hippocampus areas.

Alternative wavelengths for sutureless laser microvascular anastomosis: a preliminary study on acute samples.

PubMed

Bass, L S; Oz, M C; Libutti, S K; Treat, M R

1992-06-01

Attempts to improve the speed and patency of microvascular anastomosis with laser-assisted techniques have provided a modest reduction in operative time and comparable success rates. Using sutureless microvascular anastomoses, 30 end-to-end anastomoses were created in the rat carotid artery using the gallium-aluminum-arsenide diode laser (808 nm). Indocyanine green and fibrinogen were applied to enhance tissue absorption of the laser energy and strengthen the bond created. These were compared with previously reported welds using the THC:YAG laser (2150 nm). Mean welding times were 140 and 288 s, and mean bursting pressures immediately after welding were 515 and 400 mmHg for the diode and THC:YAG laser groups, respectively. Histologically, both lateral and vertical spread of thermal damage was limited. Since both lasers create welds of adequate initial strength without stay sutures and are faster and easier to use than existing systems, evaluation of long-term patency would be worthwhile.

Characterization of bone microstructure using photoacoustic spectrum analysis

NASA Astrophysics Data System (ADS)

Feng, Ting; Kozloff, Kenneth M.; Xu, Guan; Du, Sidan; Yuan, Jie; Deng, Cheri X.; Wang, Xueding

2015-03-01

Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and deterioration in microarchitecture. This study investigates the feasibility of characterizing bone microstructure by analyzing the frequency spectrum of the photoacoustic signals from the bone. Modeling and numerical simulation of photoacoustic signals and their frequency-domain analysis were performed on trabecular bones with different mineral densities. The resulting quasilinear photoacoustic spectra were fit by linear regression, from which spectral parameter slope can be quantified. The modeling demonstrates that, at an optical wavelength of 685 nm, bone specimens with lower mineral densities have higher slope. Preliminary experiment on osteoporosis rat tibia bones with different mineral contents has also been conducted. The finding from the experiment has a good agreement with the modeling, both demonstrating that the frequency-domain analysis of photoacoustic signals can provide objective assessment of bone microstructure and deterioration. Considering that photoacoustic measurement is non-ionizing, non-invasive, and has sufficient penetration in both calcified and noncalcified tissues, this new technology holds unique potential for clinical translation.

Comparative study of toxicity of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats.

PubMed

Koizumi, M; Yamamoto, Y; Ito, Y; Takano, M; Enami, T; Kamata, E; Hasegawa, R

2001-12-01

The toxicities of 4-nitrophenol and 2,4-dinitrophenol in newborn and young rats was examined and the susceptibility of newborn rats was analyzed in terms of presumed unequivocally toxic and no observed adverse effect levels (NOAELs). In the 18-day repeated dose newborn rat study, 4-nitrophenol was orally given from Day 4 to Day 21 after birth but did not induce any toxicity up to 160 mg/kg in the main study, although it induced death in one of six males at 160 mg/kg, and three of six males and one of six females at 230 mg/kg in a prior dose-finding study. In the 28-day repeated dose oral toxicity study starting at 6 weeks of age, 4-nitrophenol caused the death of most males and females at 1,000 mg/kg but was not toxic at 400 mg/kg except for male rat-specific renal toxicity. As unequivocally toxic levels were considered to be 230 mg/kg/day in newborn rats and 600 to 800 mg/kg/day in young rats, and NOAELs were 110 mg/kg/day in newborn rats and 400 mg/kg/day in young rats, the susceptibility of the newborn to 4-nitrophenol appears to be 2.5 to 4 times higher than that of young animals. In the newborn rat study of 2,4-dinitrophenol, animals died at 30 mg/kg in the dose-finding study and significant lowering of body and organ weights was observed at 20 mg/kg in the main study. In the 28-day young rat study, clear toxic signs followed by death occurred at 80 mg/kg but there was no definitive toxicity at 20 mg/kg. As unequivocally toxic levels and NOAELs were considered to be 30 and 10 mg/kg/day in newborn rats and 80 and 20 mg/kg/day in young rats, respectively, the toxicity of 2,4-dinitrophenol in newborns again seems to be 2 to 3 times stronger than in young rats. Abnormalities of external development and reflex ontogeny in the newborn were not observed with either chemical. Based on these results, it can be concluded that the toxic response in newborn rats is at most 4 times higher than that in young rats, at least in the cases of 4-nitrophenol and 2,4-dinitrophenol.

An analysis of pharmaceutical experience with decades of rat carcinogenicity testing: support for a proposal to modify current regulatory guidelines.

PubMed

Sistare, Frank D; Morton, Daniel; Alden, Carl; Christensen, Joel; Keller, Douglas; Jonghe, Sandra De; Storer, Richard D; Reddy, M Vijayaraj; Kraynak, Andrew; Trela, Bruce; Bienvenu, Jean-Guy; Bjurström, Sivert; Bosmans, Vanessa; Brewster, David; Colman, Karyn; Dominick, Mark; Evans, John; Hailey, James R; Kinter, Lewis; Liu, Matt; Mahrt, Charles; Marien, Dirk; Myer, James; Perry, Richard; Potenta, Daniel; Roth, Arthur; Sherratt, Philip; Singer, Thomas; Slim, Rabih; Soper, Keith; Fransson-Steen, Ronny; Stoltz, James; Turner, Oliver; Turnquist, Susan; van Heerden, Marjolein; Woicke, Jochen; DeGeorge, Joseph J

2011-06-01

Data collected from 182 marketed and nonmarketed pharmaceuticals demonstrate that there is little value gained in conducting a rat two-year carcinogenicity study for compounds that lack: (1) histopathologic risk factors for rat neoplasia in chronic toxicology studies, (2) evidence of hormonal perturbation, and (3) positive genetic toxicology results. Using a single positive result among these three criteria as a test for outcome in the two-year study, fifty-two of sixty-six rat tumorigens were correctly identified, yielding 79% test sensitivity. When all three criteria were negative, sixty-two of seventy-six pharmaceuticals (82%) were correctly predicted to be rat noncarcinogens. The fourteen rat false negatives had two-year study findings of questionable human relevance. Applying these criteria to eighty-six additional chemicals identified by the International Agency for Research on Cancer as likely human carcinogens and to drugs withdrawn from the market for carcinogenicity concerns confirmed their sensitivity for predicting rat carcinogenicity outcome. These analyses support a proposal to refine regulatory criteria for conducting a two-year rat study to be based on assessment of histopathologic findings from a rat six-month study, evidence of hormonal perturbation, genetic toxicology results, and the findings of a six-month transgenic mouse carcinogenicity study. This proposed decision paradigm has the potential to eliminate over 40% of rat two-year testing on new pharmaceuticals without compromise to patient safety.

A comparison of human exposures to fiberglass with those used in a recent rat chronic inhalation study.

PubMed

Hesterberg, T W; Hart, G A

1994-12-01

In a recent rat inhalation study, 2 years of exposure to high concentrations of fiberglass (FG) resulted in no treatment-related fibrosis or thoracic tumors. To determine the relevancy of this study for human risk assessment, it is important to compare the rat experimental exposure levels with those of humans. Data on human exposures were taken from several studies and included FG manufacturing, installation and removal, and ambient air. FG levels in the rat aerosol were 200,000-fold higher than indoor air, > 2000-fold higher than during FG insulation manufacturing, and > 1000-fold higher than FG batt installation. The rat aerosol was 30-fold more concentrated than the highest human exposure (blowing installation of unbound FG). Rat FG lung burden also vastly exceeded that of FG workers, which was not significantly elevated above nonworker levels. The amount of fibers/mg dry lung for the rat after lifetime exposure was > 4000-fold greater than for the FG worker, average exposure 11 years. Aerosol and lung fiber dimensions in the rat study were comparable to those of human exposures. From these comparisons, it can be concluded that the exposure level in the rat inhalation study was sufficiently, if not excessively, high in comparison to human exposures. Increasing the experimental exposure in the rat studies would not serve to mirror human environmental or occupational exposures.

Strain-related differences after experimental traumatic brain injury in rats.

PubMed

Reid, Wendy Murdock; Rolfe, Andrew; Register, David; Levasseur, Joseph E; Churn, Severn B; Sun, Dong

2010-07-01

The present study directly compares the effects of experimental brain injury in two commonly used rat strains: Fisher 344 and Sprague-Dawley. We previously found that Fisher rats have a higher mortality rate and more frequent seizure attacks at the same injury level than Sprague-Dawley rats. Although strain differences in rats are commonly accepted as contributing to variability among studies, there is a paucity of literature addressing strain influence in experimental neurotrauma. Therefore this study compares outcome measures in two rat strains following lateral fluid percussion injury. Fisher 344 and Sprague-Dawley rats were monitored for changes in physiological measurements, intracranial pressure, and electroencephalographic activity. We further analyzed neuronal degeneration and cell death in the injured brain using Fluoro-Jade-B (FJB) histochemistry and caspase-3 immunostaining. Behavioral studies using the beam walk and Morris water maze were conducted to characterize strain differences in both motor and cognitive functional recovery following injury. We found that Fisher rats had significantly higher intracranial pressure, prolonged seizure activity, increased FJB-positive staining in the injured cortex and thalamus, and increased caspase-3 expression than Sprague-Dawley rats. On average, Fisher rats displayed a greater amount of total recording time in seizure activity and had longer ictal durations. The Fisher rats also had increased motor deficits, correlating with the above results. In spite of these results, Fisher rats performed better on cognitive tests following injury. The results demonstrate that different rat strains respond to injury differently, and thus in preclinical neurotrauma studies strain influence is an important consideration when evaluating outcomes.

Strain-Related Differences after Experimental Traumatic Brain Injury in Rats

PubMed Central

Rolfe, Andrew; Register, David; Levasseur, Joseph E.; Churn, Severn B.; Sun, Dong

2010-01-01

Abstract The present study directly compares the effects of experimental brain injury in two commonly used rat strains: Fisher 344 and Sprague-Dawley. We previously found that Fisher rats have a higher mortality rate and more frequent seizure attacks at the same injury level than Sprague-Dawley rats. Although strain differences in rats are commonly accepted as contributing to variability among studies, there is a paucity of literature addressing strain influence in experimental neurotrauma. Therefore this study compares outcome measures in two rat strains following lateral fluid percussion injury. Fisher 344 and Sprague-Dawley rats were monitored for changes in physiological measurements, intracranial pressure, and electroencephalographic activity. We further analyzed neuronal degeneration and cell death in the injured brain using Fluoro-Jade-B (FJB) histochemistry and caspase-3 immunostaining. Behavioral studies using the beam walk and Morris water maze were conducted to characterize strain differences in both motor and cognitive functional recovery following injury. We found that Fisher rats had significantly higher intracranial pressure, prolonged seizure activity, increased FJB-positive staining in the injured cortex and thalamus, and increased caspase-3 expression than Sprague-Dawley rats. On average, Fisher rats displayed a greater amount of total recording time in seizure activity and had longer ictal durations. The Fisher rats also had increased motor deficits, correlating with the above results. In spite of these results, Fisher rats performed better on cognitive tests following injury. The results demonstrate that different rat strains respond to injury differently, and thus in preclinical neurotrauma studies strain influence is an important consideration when evaluating outcomes. PMID:20392137

Safety assessment of recombinant green fluorescent protein orally administered to weaned rats.

PubMed

Richards, Harold A; Han, Chung-Ting; Hopkins, Robin G; Failla, Mark L; Ward, William W; Stewart, C Neal

2003-06-01

Several proposed biotechnological applications of green fluorescent protein (GFP) are likely to result in its introduction into the food supply of domestic animals and humans. We fed pure GFP and diets containing transgenic canola expressing GFP to young male rats for 26 d to evaluate the potential toxicity and allergenicity of GFP. Animals (n = 8 per group) were fed either AIN-93G (control), control diet plus 1.0 mg of purified GFP daily, modified control diet with 200 g/kg canola (Brassica rapa cv Westar), or control diet with 200 g/kg transgenic canola containing one of two levels of GFP. Ingestion of GFP did not affect growth, food intake, relative weight of intestine or other organs, or activities of hepatic enzymes in serum. Comparison of the amino acid sequence of GFP to known food allergens revealed that the greatest number of consecutive amino acid matches between GFP and any food allergen was four, suggesting the absence of common allergen epitopes. Moreover, GFP was rapidly degraded during simulated gastric digestion. These data indicate that GFP is a low allergenicity risk and provide preliminary indications that GFP is not likely to represent a health risk.

Intraperitoneal injection of neuropeptide Y (NPY) alters neurotrophin rat hypothalamic levels: Implications for NPY potential role in stress-related disorders.

PubMed

Gelfo, Francesca; De Bartolo, Paola; Tirassa, Paola; Croce, Nicoletta; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

2011-06-01

Neuropeptide Y (NPY) is a 36-amino acid peptide which exerts several regulatory actions within peripheral and central nervous systems. Among NPY actions preclinical and clinical data have suggested that the anxiolytic and antidepressant actions of NPY may be related to its antagonist action on the hypothalamic-pituitary-adrenal (HPA) axis. The neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins involved in the growth, survival and function of neurons. In addition to this, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has been proposed. To characterize the effect of NPY on the production of neurotrophins in the hypothalamus we exposed young adult rats to NPY intraperitoneal administration for three consecutive days and then evaluated BDNF and NGF synthesis in this brain region. We found that NPY treatment decreased BDNF and increased NGF production in the hypothalamus. Given the role of neurotrophins in the hypothalamus, these findings, although preliminary, provide evidence for a role of NPY as inhibitor of HPA axis and support the idea that NPY might be involved in pathologies characterized by HPA axis dysfunctions. Copyright © 2011 Elsevier Inc. All rights reserved.

Cardiovascular effects of equinatoxin III from the sea anemone Actinia equina (L.).

PubMed

Suput, D; Frangez, R; Bunc, M

2001-09-01

Equinatoxin III is the most hemolytic, and the least lethal of the three basic proteins isolated from the sea anemone Actinia equina (L.). Its LD50 in mice is 83 microg/kg. Preliminary results on Wistar rats have suggested cardiorespiratory arrest as a putative cause of death, but the mechanism of its action has not yet been studied. So far only equinatoxin II has been investigated more thoroughly. As equinatoxin II is less lythic, but more toxic, than equinatoxin III (its LD50 in mice=35 microg/kg), it may be assumed that haemolysis with a consequent rise in plasma potassium level is not the major factor in the lethality of equinatoxins. To assess the relative contribution of hyperkalemia in the lethality of the toxin in rat, the effects of equinatoxin III were compared to the effects of hyperkalemia caused by the injection of KCl giving the same final concentration of K+ in the plasma as that observed after an i.v. injection of 3LD50 of equinatoxin III. As coronary vasoconstriction may be an important mechanism of the cardiotoxic action of equinatoxins, the effect of EqT III on isolated porcine coronary arteries was studied by measurements of smooth muscle tension in the presence of 1-100 nM equinatoxin III. The results revealed that animals survive the elevated K+ plasma concentration caused by an i.v. application of KCl. This suggests that equinatoxin III induced haemolysis is not the major mechanism of equinatoxin III lethality. However, equinatoxin III increases the potassium induced contractions of coronary smooth muscle for 289+/-29%, suggesting that coronary vasoconstriction may be an important factor in the cardiotoxic effects of equinatoxin III.

Phagosomal pH and glass fiber dissolution in cultured nasal epithelial cells and alveolar macrophages: a preliminary study.

PubMed Central

Johnson, N F

1994-01-01

The dissolution rate of glass fibers has been shown to be pH sensitive using in vitro lung fluid simulant models. The current study investigated whether there is a difference in phagosomal pH (ppH) between rat alveolar macrophages (AM) and rat nasal epithelial cells (RNEC) and whether such a difference would influence the dissolution of glass fibers. The ppH was measured in cultured AM and RNEC using flow cytometric, fluorescence-emission rationing techniques with fluorescein-labeled, amorphous silica particles. Glass fiber dissolution was determined in AM and RNEC cultured for 3 weeks with fast dissolving glass fibers (GF-A) or slow dissolving ones (GF-B). The mean diameters of GF-A were 2.7 microns and of GF-B, 2.6 microns, the average length of both fibers was approximately 22 to 25 microns. Dissolution was monitored by measuring the length and diameter of intracellular fibers and estimating the volume, assuming a cylindrical morphology. The ppH of AM was 5.2 to 5.8, and the ppH of RNEC was 7.0 to 7.5. The GF-A dissolved more slowly in RNEC than in AM, and no dissolution was evident in either cell type with GF-B. The volume loss with GF-A after a 3-week culture with AM was 66% compared to 45% for cultured RNEC. These results are different from those obtained using in vitro lung fluid-simulant models where dissolution is faster at higher pH. This difference suggests that dissolution rates of glass fibers in AM should not be applied to the dissolution of fibers in epithelial cells. Images Figure 1. a Figure 1. b Figure 2. a Figure 2. b Figure 3. a Figure 3. b PMID:7882965

Effects of buprenorphine in the adrenal, thyroid, and cytokine intra-operative responses in a rat model (Rattus norvegicus): a preliminary study

PubMed Central

Félix, Nuno M; Leal, Rodolfo O; Goy-Thollot, I; Walton, Ronald S; Gil, Solange A; Mateus, Luísa M; Matos, Ana S; Niza, Maria M R E

2017-01-01

Objective(s): Buprenorphine is a common analgesic in experimental research, due to effectiveness and having few side-effects, including a limited influence in the immune and endocrine systems. However, how buprenorphine affects cytokine levels and the adrenal and thyroid response during general anesthesia and surgery is incompletely understood. This study aimed to assess whether buprenorphine modulated significantly those responses in rats submitted to general anesthesia, mechanical ventilation, and surgical insertion of intravascular catheters. Materials and Methods: Animals were anesthetized with isoflurane, mechanically ventilated, and surgically instrumented for carotid artery and the femoral vein catheter placement. The test group (n=16), received buprenorphine subcutaneously before surgery, whereas the control group (n=16) received normal saline. Blood sampling to determine plasma levels of adrenocorticotropic hormone (ACTH), corticosterone (CS), total thyroxine (TT4), total triiodothyronine (TT3), thyroid-stimulating hormone (TSH), TNF-α, IL6, IL10, TNF-α, IL6, and IL10 mRNA was performed at 10 min after completion of all surgical procedures and at 90, 150, 240, and 300 min thereafter, with the animals still anesthetized and with mechanical ventilation. Results: Buprenorphine-treated animals had higher levels of ACTH, CS, and TT4 at several time points (P<0.05) and TSH and TT3 at all-time points (P<0.05). They also had increased IL10, TNF-α, and IL10 mRNA levels. Conclusion: In this model, buprenorphine significantly modulated the intra-operative cytokine and endocrine response to anesthesia, mechanical ventilation, and surgical placement of intravascular catheters. The mechanism and significance of these findings remain undetermined. Researchers should be aware of these effects when considering the use of buprenorphine for analgesic purposes. PMID:28804607

The enhanced value of combining conventional and 'omics' analyses in early assessment of drug-induced hepatobiliary injury

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ellinger-Ziegelbauer, Heidrun, E-mail: heidrun.ellinger-ziegelbauer@bayerhealthcare.com; Adler, Melanie; Amberg, Alexander

2011-04-15

The InnoMed PredTox consortium was formed to evaluate whether conventional preclinical safety assessment can be significantly enhanced by incorporation of molecular profiling ('omics') technologies. In short-term toxicological studies in rats, transcriptomics, proteomics and metabolomics data were collected and analyzed in relation to routine clinical chemistry and histopathology. Four of the sixteen hepato- and/or nephrotoxicants given to rats for 1, 3, or 14 days at two dose levels induced similar histopathological effects. These were characterized by bile duct necrosis and hyperplasia and/or increased bilirubin and cholestasis, in addition to hepatocyte necrosis and regeneration, hepatocyte hypertrophy, and hepatic inflammation. Combined analysis ofmore » liver transcriptomics data from these studies revealed common gene expression changes which allowed the development of a potential sequence of events on a mechanistic level in accordance with classical endpoint observations. This included genes implicated in early stress responses, regenerative processes, inflammation with inflammatory cell immigration, fibrotic processes, and cholestasis encompassing deregulation of certain membrane transporters. Furthermore, a preliminary classification analysis using transcriptomics data suggested that prediction of cholestasis may be possible based on gene expression changes seen at earlier time-points. Targeted bile acid analysis, based on LC-MS metabonomics data demonstrating increased levels of conjugated or unconjugated bile acids in response to individual compounds, did not provide earlier detection of toxicity as compared to conventional parameters, but may allow distinction of different types of hepatobiliary toxicity. Overall, liver transcriptomics data delivered mechanistic and molecular details in addition to the classical endpoint observations which were further enhanced by targeted bile acid analysis using LC/MS metabonomics.« less

Effects of Local Administration of Boric Acid on Posterolateral Spinal Fusion with Autogenous Bone Grafting in a Rodent Model.

PubMed

Kömürcü, Erkam; Özyalvaçlı, Gülzade; Kaymaz, Burak; Gölge, Umut Hatay; Göksel, Ferdi; Cevizci, Sibel; Adam, Gürhan; Ozden, Raif

2015-09-01

Spinal fusion is among the most frequently applied spinal surgical procedures. The goal of the present study was to evaluate whether the local administration of boric acid (BA) improves spinal fusion in an experimental spinal fusion model in rats. Currently, there is no published data that evaluates the possible positive effects if the local administration of BA on posterolateral spinal fusion. Thirty-two rats were randomly divided into four independent groups: no material was added at the fusion area for group 1; an autogenous morselized corticocancellous bone graft was used for group 2; an autogenous morselized corticocancellous bone graft with boric acid (8.7 mg/kg) for group 3; and only boric acid was placed into the fusion area for group 4. The L4-L6 spinal segments were collected at week 6, and the assessments included radiography, manual palpation, and histomorphometry. A statistically significant difference was determined between the groups with regard to the mean histopathological scores (p = 0.002), and a paired comparison was made with the Mann-Whitney U test to detect the group/groups from which the difference originated. It was determined that only the graft + BA practice increased the histopathological score significantly with regard to the control group (p = 0.002). Whereas, there was no statistically significant difference between the groups in terms of the manual assessment of fusion and radiographic analysis (respectively p = 0.328 and p = 0.196). This preliminary study suggests that BA may clearly be useful as a therapeutic agent in spinal fusion. However, further research is required to show the most effective dosage of BA on spinal fusion, and should indicate whether BA effects spinal fusion in the human body.

Hydroethanolic extract of the inner stem bark of Cedrela odorata has low toxicity and reduces hyperglycemia induced by an overload of sucrose and glucose.

PubMed

Giordani, Morenna Alana; Collicchio, Thiago Carvalho Mamede; Ascêncio, Sergio Donizeti; Martins, Domingos Tabajara de Oliveira; Balogun, Sikiru Olaitan; Bieski, Isanete Geraldini Costa; da Silva, Leilane Aparecida; Colodel, Edson Moleta; de Souza, Roberto Lopes; de Souza, Damiana Luiza Pereira; de França, Suélem Aparecida; Andrade, Claudia Marlise Balbinotti; Kawashita, Nair Honda

2015-03-13

Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata. The inner stem bark extract of Cedrela odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from 10 to 5000 mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500 mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500 mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma. The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose of the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but reduced the triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity. Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases and glucose transporter inhibitors and antioxidant property. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Evaluation of the effects of pulsed wave LLLT on tibial diaphysis in two rat models of experimental osteoporosis, as examined by stereological and real-time PCR gene expression analyses.

PubMed

Mohsenifar, Zhaleh; Fridoni, Mohammadjavad; Ghatrehsamani, Mahdi; Abdollahifar, Mohammad-amin; Abbaszadeh, Hojjatallah; Mostafavinia, Atarodalsadat; Fallahnezhad, Somaye; Asghari, Mohammadali; Bayat, Saba; Bayat, Mohammad

2016-05-01

Osteoporosis (OP) and osteoporotic fracture are major public health issues for society; the burden for the affected individual is also high. Previous studies have shown that pulsed wave low-level laser therapy (PW LLLT) has osteogenic effects. This study intended to evaluate the impacts of PW LLLT on the cortical bone of osteoporotic rats' tibias in two experimental models, ovariectomized and dexamethasone-treated. We divided the rats into four ovariectomized induced OP (OVX-d) and four dexamethasone-treated (glucocorticoid-induced OP, GIOP) groups. A healthy (H) group of rats was considered for baseline evaluations. At 14 weeks following ovariectomy, we subdivided the OVX-d rats into the following groups: (i) control which had OP, (ii) OVX-d rats treated with alendronate (1 mg/kg), (iii) OVX-d rats treated with LLLT, and (iv) OVX-d rats treated with alendronate and PW LLLT. The remaining rats received dexamethasone over a 5-week period and were also subdivided into four groups: (i) control rats treated with intramuscular (i.m.) injections of distilled water (vehicle), (ii) rats treated with subcutaneous alendronate injections (1 mg/kg), (iii) laser-treated rats, and (iv) rats simultaneously treated with laser and alendronate. The rats received alendronate for 30 days and underwent PW LLLT (890 nm, 80 Hz, 0.972 J/cm(2)) three times per week during 8 weeks. Then, the right tibias were extracted and underwent a stereological analysis of histological parameters and real-time polymerase chain reaction (RT-PCR). A significant increase in cortical bone volume (mm(3)) existed in all study groups compared to the healthy rats. There were significant decreases in trabecular bone volume (mm(3)) in all study groups compared to the group of healthy rats. The control rats with OP and rats from the vehicle group showed significantly increased osteoclast numbers compared to most other groups. Alendronate significantly decreased osteoclast numbers in osteoporotic rats. Concurrent treatments (compounded by PW LLLT and alendronate) produce the same effect on osteoporotic bone.

The rat: a laboratory model for studies of the diving response

PubMed Central

Gan, Qi; Juric, Rajko

2010-01-01

Underwater submersion in mammals induces apnea, parasympathetically mediated bradycardia, and sympathetically mediated peripheral vasoconstriction. These effects are collectively termed the diving response, potentially the most powerful autonomic reflex known. Although these physiological responses are directed by neurons in the brain, study of neural control of the diving response has been hampered since 1) it is difficult to study the brains of animals while they are underwater, 2) feral marine mammals are usually large and have brains of variable size, and 3) there are but few references on the brains of naturally diving species. Similar responses are elicited in anesthetized rodents after stimulation of their nasal mucosa, but this nasopharyngeal reflex has not been compared directly with natural diving behavior in the rat. In the present study, we compared hemodynamic responses elicited in awake rats during volitional underwater submersion with those of rats swimming on the water's surface, rats involuntarily submerged, and rats either anesthetized or decerebrate and stimulated nasally with ammonia vapors. We show that the hemodynamic changes to voluntary diving in the rat are similar to those of naturally diving marine mammals. We also show that the responses of voluntary diving rats are 1) significantly different from those seen during swimming, 2) generally similar to those elicited in trained rats involuntarily “dunked” underwater, and 3) generally different from those seen from dunking naive rats underwater. Nasal stimulation of anesthetized rats differed most from the hemodynamic variables of rats trained to dive voluntarily. We propose that the rat trained to dive underwater is an excellent laboratory model to study neural control of the mammalian diving response, and also suggest that some investigations may be done with nasal stimulation of decerebrate preparations to decipher such control. PMID:20093670

The characteristics of wild rat (Rattus spp.) populations from an inner-city neighborhood with a focus on factors critical to the understanding of rat-associated zoonoses.

PubMed

Himsworth, Chelsea G; Jardine, Claire M; Parsons, Kirbee L; Feng, Alice Y T; Patrick, David M

2014-01-01

Norway and black rats (Rattus norvegicus and Rattus rattus) are among the most ubiquitous urban wildlife species and are the source of a number of zoonotic diseases responsible for significant human morbidity and mortality in cities around the world. Rodent ecology is a primary determinant of the dynamics of zoonotic pathogens in rodent populations and the risk of pathogen transmission to people, yet many studies of rat-associated zoonoses do not account for the ecological characteristics of urban rat populations. This hinders the development of an in-depth understanding of the ecology of rat-associated zoonoses, limits comparability among studies, and can lead to erroneous conclusions. We conducted a year-long trapping-removal study to describe the ecological characteristics of urban rat populations in an inner-city neighborhood of Vancouver, Canada. The study focused on factors that might influence the ecology of zoonotic pathogens in these populations and/or our understanding of that ecology. We found that rat population density varied remarkably over short geographical distances, which could explain observed spatial distributions of rat-associated zoonoses and have implications for sampling and data analysis during research and surveillance. Season appeared to influence rat population composition even within the urban environment, which could cause temporal variation in pathogen prevalence. Body mass and bite wounds, which are often used in epidemiologic analyses as simple proxies for age and aggression, were shown to be more complex than previously thought. Finally, we found that factors associated with trapping can determine the size and composition of sampled rat population, and thus influence inferences made about the source population. These findings may help guide future studies of rats and rat-associated zoonoses.

The Characteristics of Wild Rat (Rattus spp.) Populations from an Inner-City Neighborhood with a Focus on Factors Critical to the Understanding of Rat-Associated Zoonoses

PubMed Central

Himsworth, Chelsea G.; Jardine, Claire M.; Parsons, Kirbee L.; Feng, Alice Y. T.; Patrick, David M.

2014-01-01

Norway and black rats (Rattus norvegicus and Rattus rattus) are among the most ubiquitous urban wildlife species and are the source of a number of zoonotic diseases responsible for significant human morbidity and mortality in cities around the world. Rodent ecology is a primary determinant of the dynamics of zoonotic pathogens in rodent populations and the risk of pathogen transmission to people, yet many studies of rat-associated zoonoses do not account for the ecological characteristics of urban rat populations. This hinders the development of an in-depth understanding of the ecology of rat-associated zoonoses, limits comparability among studies, and can lead to erroneous conclusions. We conducted a year-long trapping-removal study to describe the ecological characteristics of urban rat populations in an inner-city neighborhood of Vancouver, Canada. The study focused on factors that might influence the ecology of zoonotic pathogens in these populations and/or our understanding of that ecology. We found that rat population density varied remarkably over short geographical distances, which could explain observed spatial distributions of rat-associated zoonoses and have implications for sampling and data analysis during research and surveillance. Season appeared to influence rat population composition even within the urban environment, which could cause temporal variation in pathogen prevalence. Body mass and bite wounds, which are often used in epidemiologic analyses as simple proxies for age and aggression, were shown to be more complex than previously thought. Finally, we found that factors associated with trapping can determine the size and composition of sampled rat population, and thus influence inferences made about the source population. These findings may help guide future studies of rats and rat-associated zoonoses. PMID:24646877

The long pursued Holy Grail of the true "alcoholic" rat.

PubMed

Gessa, Gian Luigi

2016-08-15

An anthology of microdialysis and electrophysiological studies on ethanol effect on mesolimbic dopaminergic neurons is presented. The usefulness of rats with innate preference for ethanol, such as the Sardinian alcohol-preferring (sP), in studying ethanol rewarding and reinforcing effects is signaled. The generation of the long sought "alcoholics rat" from sP rats is announced. Rats of the sP line avoid the shortcomings of using rats non selected for ethanol preference. Copyright © 2016. Published by Elsevier B.V.

Ethanol intake and sup 3 H-serotonin uptake I: A study in Fawn-Hooded rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Daoust, M.; Compagnon, P.; Legrand, E.

1991-01-01

Ethanol intake and synaptosomal {sup 3}H-serotonin uptake were studied in male Fawn-Hooded and Sprague-Dawley rats. Fawn-Hooded rats consumed more alcohol and more water than Sprague-Dawley rats. Plasma alcohol levels of Sprague-Dawley rats were not detectable but were about 5 mg/dl in Fawn-Hooded rats. Ethanol intake increased the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex, but not in thalamus. In Fawn-Hooded rats, serotonin uptake (Vmax) was higher than in Sprague-Dawley rats cortex. Ethanol intake reduced the Vmax of serotonin uptake in Fawn-Hooded rats in hippocampus and cortex. In cortex, the carrier affinity for serotonin was increased inmore » alcoholized Fawn-Hooded rats. These results indicate that synaptosomal {sup 3}H-serotonin uptake is affected by ethanol intake. In Fawn-Hooded rats, high ethanol consumption is associated with high serotonin uptake. In rats presenting high serotonin uptake, alcoholization reduces {sup 3}H-serotonin internalization in synaptosomes, indicating a specific sensitivity to alcohol intake of serotonin uptake system.« less

Effects of parsley (Petroselinum crispum) on the liver of diabetic rats: a morphological and biochemical study.

PubMed

Bolkent, S; Yanardag, R; Ozsoy-Sacan, O; Karabulut-Bulan, O

2004-12-01

Parsley is used by diabetics in Turkey to reduce blood glucose. The present study aims to investigate both the morphological and biochemical effects of parsley on liver tissue. Rat hepatocytes were examined by light and electron microscopy. Degenerative changes were observed in the hepatocytes of diabetic rats. These degenerative changes were significantly reduced or absent in the hepatocytes of diabetic rats treated with parsley. Blood glucose levels, alanine transaminase and alkaline phosphatase were observed to be raised in diabetic rats. Diabetic rats treated with parsley demonstrated significantly lower levels of blood glucose, alanine transaminase and alkaline phosphatase. The present study suggests that parsley demonstrates a significant hepatoprotective effect in diabetic rats. 2004 John Wiley & Sons, Ltd.

Comparative study of kanamycin sulphate microparticles and nanoparticles for intramuscular administration: preparation in vitro release and preliminary in vivo evaluation.

PubMed

Mustafa, Sanaul; Devi, V Kusum; Pai, Roopa S

2016-11-01

Kanamycin sulphate (KS) is a Mycobacterium tuberculosis protein synthesis inhibitor. KS is polycationic, a property responsible for KS poor oral absorption half-life (2.5 h) and rapid renal clearance, which results in serious nephrotoxicity/ototoxicity. The current study aimed to develop KS-loaded PLGA vitamin-E-TPGS microparticles (MPs) and nanoparticles (NPs) to reduce the dosing frequency and dose-related adverse effect. In vitro release was sustained up to 10 days for KS PLGA-TPGS MPs and 13 days for KS PLGA-TPGS NPs in phosphate-buffered saline (PBS) pH 7.4. The in vivo pharmacokinetic test in Wistar rats showed that the AUC 0-∞ of KS PLGA-TPGS NPs (280.58 μg/mL*min) was about 1.62-fold higher than that of KS PLGA-TPGS MPs (172.30 μg/mL*min). Further, in vivo protein-binding assay ascribed 1.20-fold increase in the uptake of KS PLGA-TPGS NPs through the alveolar macrophage (AM). The studies, therefore, could provide another useful tool for successful development of KS MPs and NPs.

Gravitational Biology: The Rat Model

NASA Technical Reports Server (NTRS)

1997-01-01

In this session, Session JP3, the discussion focuses on the following topics: Morphology of brain, pituitary and thyroid in the rats exposed to altered gravity; Biochemical Properties of B Adrenoceptors After Spaceflight (LMS-STS78) or Hindlimb Suspension in Rats; Influence of Hypergravity on the Development of Monoaminergic Systems in the Rat Spinal Cord; A Vestibular Evoked Potentials (VsEPs) Study of the Function of the Otolith Organs in Different Head Orientations with respect to Earth Gravity Vector in the Rat; Quantitative Observations on the Structure of Selected Proprioceptive Components in Adult Rats that Underwent About Half of their Fetal Development in Space; Effects of a Nine-Day Shuttle Mission on the Development of the Neonatal Rat Nervous System, A Behavioral Study; Muscle Atrophy Associated to Microgravity in Rat, Basic Data For Countermeasures; Simulated Weightlessness by Unloading in the Rat, Results of a Time Course Study of Biochemical Events Occurring During Unloading and Lack of Effect of a rhBNP-2 Treatment on Bone Formation and Bone Mineral Content in Unloading Rats; and Cytological Mechanism of the Osteogenesis Under Microgravity Conditions.

High-Moisture Diet for Laboratory Rats: Complete Blood Counts, Serum Biochemical Values, and Intestinal Enzyme Activity

NASA Technical Reports Server (NTRS)

Battles, August H.; Knapka, Joseph T.; Stevens, Bruce R.; Lewis, Laura; Lang, Marie T.; Gruendel, Douglas J.

1991-01-01

Rats were fed an irradiated high-moisture diet (KSC-25) with or without access to a water bottle. Physiologic values were compared between these two groups and a group of rats fed a purified diet. Hematologic and serum biochemical values, urine specific gravity, and intestinal enzyme activities were determined from samples collected from the three groups of rats. Sprague Dawley rats (n=32) fed the irradiated high-moisture diet with or without a water bottle were the test animals. Rats (n=16) fed an irradiated purified diet and water provided via a water bottle were the control group. The purified diet formulation, modified AIN-76A, is a commonly used purified diet for laboratory rodents. All rats remained alert and healthy throughout the study. A comparison of the physiologic values of rats in this study with reported normal values indicated that all of the rats in the study were in good health. Significant differences (P less than 0.05) of the physiologic values from each rat group are reported.

A Two-Year Ecological Study of Norway Rats (Rattus norvegicus) in a Brazilian Urban Slum.

PubMed

Panti-May, Jesús A; Carvalho-Pereira, Ticiana S A; Serrano, Soledad; Pedra, Gabriel G; Taylor, Josh; Pertile, Arsinoê C; Minter, Amanda; Airam, Vladimir; Carvalho, Mayara; Júnior, Nivison N; Rodrigues, Gorete; Reis, Mitermayer G; Ko, Albert I; Childs, James E; Begon, Mike; Costa, Federico

2016-01-01

The Norway or brown rat (Rattus norvegicus) is among the most ubiquitous of rodents. However, the lack of studies describing Norway rat populations from tropical areas have limited our understanding regarding their demography and seasonal dynamics. In this study, we describe seasonal pattern in the abundance, reproductive parameters, and morphometrics of Norway rat populations in Salvador, Brazil. Rodents were trapped over four seasonal trapping periods (2013-2014) from three valleys. A total of 802 Norway rats were trapped over the course of the study over 7653 trap-nights. Norway rat abundance was high, but there was no significant differences between seasons. The reproductive parameters (e.g. frequency of pregnant and lactating females) did not show statistical differences between seasons. Female rats collected in the rainy season were heavier and older than females from the dry season. Salvador rats had a high incidence of pregnancy and birth rate (estimated birth rate of 79 young per year) compared to previous studies. The information generated is critical for the understanding of the ecology of Norway rat, the main reservoir of Leptospira in Salvador. However, future studies examining the effect of rodent control programs aimed at reducing populations, and determining rates of recovery, will further clarify our understanding of population dynamics.

A Two-Year Ecological Study of Norway Rats (Rattus norvegicus) in a Brazilian Urban Slum

PubMed Central

Panti-May, Jesús A.; Carvalho-Pereira, Ticiana S. A.; Serrano, Soledad; Pedra, Gabriel G.; Taylor, Josh; Pertile, Arsinoê C.; Minter, Amanda; Airam, Vladimir; Carvalho, Mayara; Júnior, Nivison N.; Rodrigues, Gorete; Reis, Mitermayer G.; Ko, Albert I.; Childs, James E.; Begon, Mike; Costa, Federico

2016-01-01

The Norway or brown rat (Rattus norvegicus) is among the most ubiquitous of rodents. However, the lack of studies describing Norway rat populations from tropical areas have limited our understanding regarding their demography and seasonal dynamics. In this study, we describe seasonal pattern in the abundance, reproductive parameters, and morphometrics of Norway rat populations in Salvador, Brazil. Rodents were trapped over four seasonal trapping periods (2013–2014) from three valleys. A total of 802 Norway rats were trapped over the course of the study over 7653 trap-nights. Norway rat abundance was high, but there was no significant differences between seasons. The reproductive parameters (e.g. frequency of pregnant and lactating females) did not show statistical differences between seasons. Female rats collected in the rainy season were heavier and older than females from the dry season. Salvador rats had a high incidence of pregnancy and birth rate (estimated birth rate of 79 young per year) compared to previous studies. The information generated is critical for the understanding of the ecology of Norway rat, the main reservoir of Leptospira in Salvador. However, future studies examining the effect of rodent control programs aimed at reducing populations, and determining rates of recovery, will further clarify our understanding of population dynamics. PMID:27015422

The Presence Of Rat And House Sanitation Associated With Leptospira sp. Bacterial Infection In Rats (A Cross Sectional Study In Semarang, Central Java Province, Indonesia)

NASA Astrophysics Data System (ADS)

Setiyani, Endang; Martini, Martini; Saraswati, Lintang Dian

2018-02-01

The Gajah Mungkur sub-district in Semarang, Indonesia had highest leptospirosis cases (reported in human with seven infected and one dead) in 2015. The purpose of this study was to analyze the association between house sanitation and density of rats with Leptospira sp. infection in rats. The study design was cross sectional observational analytic. The number of 308 trapswere placed in study sites over three consecutive nights afterwards. Every houses were placed with four traps, inside and outside. Trapped rats were anesthetized with atropine dose from 0.02 to 0.05 mg/kg body weight of rats continued with Ketamine HCL dose of 50-100 mg/kg body weight of rats by injecting in the thick thigh muscle of it. After that, identification of rats by species and gender then continues with surgery in which a kidney sample was taken to confirm the presence of bacteria Leptospirasp using PCR techniques. The trap installed in 77 houses which later had further observation on house sanitation which includes the existence of a pile of used goods, food storage, garbage can, and the presence of the ceiling, windows and other ventilation.Data was analyzed using distribution frequency and bivariate chi-square test. We had 100 rats captured with live traps as the samples.The proportion of Rattusnorvegicuswas 27% (14.8% positive Leptospira sp.infection) and Rattustanezumi 73% (11%positive Leptospira sp.infection). The proportion of male and female rats were almost equal. The statistic test result was significant between the density of rats (p = 0.0001, OR 12.833, 95%CI: 1.565-105.261) and sex of rats (p = 0.019, OR 0.095, 95%CI: 0.012-0.769) with Leptospira sp. infection in rats. The number of rats may increase the infection of Leptospirasp., especially female rats and poor condition of house sanitation. It is recommended to improve house sanitation and regularly trapping rats.

Analysis of genes involved in the PI3K/Akt pathway in radiation- and MNU-induced rat mammary carcinomas.

PubMed

Showler, Kaye; Nishimura, Mayumi; Daino, Kazuhiro; Imaoka, Tatsuhiko; Nishimura, Yukiko; Morioka, Takamitsu; Blyth, Benjamin J; Kokubo, Toshiaki; Takabatake, Masaru; Fukuda, Maki; Moriyama, Hitomi; Kakinuma, Shizuko; Fukushi, Masahiro; Shimada, Yoshiya

2017-03-01

The PI3K/AKT pathway is one of the most important signaling networks in human breast cancer, and since it was potentially implicated in our preliminary investigations of radiation-induced rat mammary carcinomas, our aim here was to verify its role. We included mammary carcinomas induced by the chemical carcinogen 1-methyl-1-nitrosourea to determine whether any changes were radiation-specific. Most carcinomas from both groups showed activation of the PI3K/AKT pathway, but phosphorylation of AKT1 was often heterogeneous and only present in a minority of carcinoma cells. The negative pathway regulator Inpp4b was significantly downregulated in both groups, compared with in normal mammary tissue, and radiation-induced carcinomas also showed a significant decrease in Pten expression, while the chemically induced carcinomas showed a decrease in Pik3r1 and Pdk1. Significant upregulation of the positive regulators Erbb2 and Pik3ca was observed only in chemically induced carcinomas. However, no genes showed clear correlations with AKT phosphorylation levels, except in individual carcinomas. Only rare carcinomas showed mutations in PI3K/AKT pathway genes, yet these carcinomas did not exhibit stronger AKT phosphorylation. Thus, while AKT phosphorylation is a common feature of rat mammary carcinomas induced by radiation or a canonical chemical carcinogen, the mutation of key genes in the pathways or permanent changes to gene expression of particular signaling proteins do not explain the pathway activation in the advanced cancers. Although AKT signaling likely facilitates cancer development and growth in rat mammary carcinomas, it is unlikely that permanent disruption of the PI3K/AKT pathway genes is a major causal event in radiation carcinogenesis. © The Author 2016. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Xenotransplantation of uterine leiomyoma in Wistar rats: a pilot study.

PubMed

Sousa, Willane Bandeira de; Garcia, João Batista Santos; Nogueira Neto, João; Furtado, Pablo Gustavo Ribeiro; Anjos, Jonhnathan Adriano Araújo dos

2015-07-01

To evaluate whether xenografts derived from hysterectomized patients would implant successfully and lead to uterine leiomyoma in Wistar rats. This experimental study examined six female Wistar rats implanted with uterine leiomyoma obtained from patients who underwent hysterectomies at the gynecological surgery service of the HUUFMA. The rats were divided into two groups. Group I consisted of three rats in which the uterine leiomyoma had been implanted in the parietal peritoneum, and group II consisted of three rats in which the uterine leiomyoma was implanted in the subcutaneous tissue. The immunosuppressant mycophenolate mofetil (MMF) was administered orally by gavage (at a dose of 40 mg/kg of body weight) to prevent transplant rejection starting 15 days before the transplant and continuing throughout the entire experiment. After four weeks, necrosis and neovascularization were evaluated histologically in both groups and were classified as either absent or present. Lymphocytic inflammatory infiltration was also examined and classified as mild, moderate or intense (by hematoxylin and eosin staining), and fibrosis was classified as grade I-III (by Masson's trichrome staining). Necrosis was absent from all three rats in group I and was observed in only one rat from group II. Neovascularization was present in two rats from group I and in only one rat from group II. The lymphocytic inflammatory infiltrate was mild in two rats and moderate in one rat from group I, and it was moderate in two rats and intense in one rat from group II. Two rats from group 1 exhibited grade III fibrosis, and one rat presented grade I fibrosis. In group II, two rats presented grade I fibrosis and one rat had grade II fibrosis. When necrosis and neovascularization were evaluated as variables, group I demonstrated greater evidence of successful implantation when compared to group II, indicating that the peritoneal implantation technique produces better results than the subcutaneous approach (p=0.039). This study demonstrates that the xenotransplantation of uterine leiomyoma into the parietal peritoneum is more effective than the xenotransplantation of uterine leiomyoma into the subcutaneous tissue, and it describes a promising new model for the study of leiomyoma in vivo. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics.

PubMed

Hunt, Pamela S; Barnet, Robert C

2015-09-01

Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5g/kg/day ethanol on postnatal days (PD) 4-9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as 'gap filling' completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis of gene expression profiles in tympanic membrane following perforation using PCR Array in rats--preliminary investigation.

PubMed

Hassmann-Poznańska, Elżbieta; Taranta, Andrzej; Bialuk, Izabela; Poznańska, Maria; Zajączkiewicz, Hanna; Winnicka, Maria Małgorzata

2013-10-01

The goal of this work was to identify genes, known to be involved in the skin wound healing, that express differentially in the healthy and injured tympanic membrane (TM), and designate the molecules potentially beneficial for treatment of TM perforation. The molecular mechanisms controlling the course of TM regeneration are far from being elucidated. Twenty rats had their tympanic membranes perforated, while four served as a control. Animals were sacrificed on either days 1, 2, 3, 5 and 10 post injury, and TMs were immediately dissected and frozen in liquid nitrogen. Total TM RNA was isolated and reversely transcribed. qPCR was performed using Rat Wound Healing RT(2) Profiler PCR Array (QIAGEN) containing primers for 84 genes. Statistically significant changes in the expression of 42 genes were found in various stages of TM healing. The increased expression of genes taking part in the inflammatory reaction (interleukin 6, granulocyte and macrophage chemotactic proteins) was observed from day 2. The expression of several genes of extracellular matrix components and their remodeling enzymes was also changed. Among growth factor genes: Vegfa, Igf1 and Hbegf showed increased expression at the beginning of the healing process, while Hgf expression was highest on day 3. Several changes in the expression of genes involved in remodeling of extracellular matrix point to important role of connective tissue in TM healing. The molecules accelerating this process, like HbEGF and HGF, seem to be good candidates for further evaluation of their possible use in clinical treatment. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

An Animal Model of Fetal Alcohol Spectrum Disorder: Trace Conditioning as a Window to Inform Memory Deficits and Intervention Tactics

PubMed Central

Hunt, Pamela S.; Barnet, Robert C.

2014-01-01

Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5 g/kg/day ethanol on postnatal days (PD) 4–9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as ‘gap filling’ completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions. PMID:25477227

78 FR 8410 - Thiacloprid; Pesticide Tolerances

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-06

...) were noted in dog, rat, and mouse studies. Increased prostate weight and prostatic hypertrophy were... acetylcholine receptors. In the neurotoxicity studies in rats, there was a reduction in motor and locomotor... uterine tumors in rats, thyroid follicular adenomas in rat and ovarian tumors in mice. A cancer slope...

Three-dimensional dynamics of temperature fields in phantoms and biotissue under IR laser photothermal therapy using gold nanoparticles and ICG dye

NASA Astrophysics Data System (ADS)

Akchurin, Georgy G.; Garif, Akchurin G.; Maksimova, Irina L.; Skaptsov, Alexander A.; Terentyuk, Georgy S.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Tuchin, Valery V.

2010-02-01

We describe applications of silica (core)/gold (shell) nanoparticles and ICG dye to photothermal treatment of phantoms, biotissue and spontaneous tumor of cats and dogs. The laser irradiation parameters were optimized by preliminary experiments with laboratory rats. Three dimensional dynamics of temperature fields in tissue and solution samples was measured with a thermal imaging system. It is shown that the temperature in the volume region of nanoparticles localization can substantially exceed the surface temperature recorded by the thermal imaging system. We have demonstrated effective optical destruction of cancer cells by local injection of plasmon-resonant gold nanoshells and ICG dye followed by continuous wave (CW) diode laser irradiation at wavelength 808 nm.

Preparation, crystallization and preliminary X-ray diffraction analysis of two intestinal fatty-acid binding proteins in the presence of 11-(dansylamino)undecanoic acid

PubMed Central

Laguerre, Aisha; Wielens, Jerome; Parker, Michael W.; Porter, Christopher J. H.; Scanlon, Martin J.

2011-01-01

Fatty-acid binding proteins (FABPs) are abundantly expressed proteins that bind a range of lipophilic molecules. They have been implicated in the import and intracellular distribution of their ligands and have been linked with metabolic and inflammatory responses in the cells in which they are expressed. Despite their high sequence identity, human intestinal FABP (hIFABP) and rat intestinal FABP (rIFABP) bind some ligands with different affinities. In order to address the structural basis of this differential binding, diffraction-quality crystals have been obtained of hIFABP and rIFABP in complex with the fluorescent fatty-acid analogue 11-(dansylamino)undecanoic acid. PMID:21301109

Surface labeling of Pneumocystis carinii from in vitro culture

DOE Office of Scientific and Technical Information (OSTI.GOV)

Radding, J.A.; Armstrong, M.Y.; Bogucki, M.S.

1989-01-01

Pneumocystis carinii is an opportunistic pathogen of man, carried as a commensal in healthy subjects. It frequently causes a fatal pneumonia in the immunosuppressed host. It is a major complication of HIV-1 infection in man (AIDS). Using surface radioiodination of rat-derived P. carinii trophozoites obtained from in vitro culture, a major surface glycoprotein (gp120) has been identified. The glycoprotein exhibits adherent behavior similar to that of the intact organism. Purification of gp120 by conventional methods was unsuccessful as the glycoprotein irreversibly bound to numerous column matrices. A combination of gel chromatography and hydroxyapatite chromatography in sodium dodecylsulfate was utilized tomore » purify the glycoprotein. Some preliminary characterization of the glycoprotein is presented.« less

Retinal and choroidal imaging in vivo using integrated photoacoustic microscopy and optical coherence tomography

NASA Astrophysics Data System (ADS)

Tian, Chao; Zhang, Wei; Nguyen, Van Phuc; Huang, Ziyi; Wang, Xueding; Paulus, Yannis M.

2018-02-01

Most reported photoacoustic ocular imaging work to date uses small animals, such as mice and rats, the eyes of which are small and less than one-third the size of a human eye, which poses a challenge for clinical translation. Here we achieved chorioretinal imaging of larger animals, i.e. rabbits, using a dual-modality photoacoustic microscopy (PAM) and optical coherence tomography (OCT) system. Preliminary experimental results in living rabbits demonstrate that the PAM can noninvasively visualize depth-resolved retinal and choroidal vessels using a safe laser exposure dose; and the OCT can finely distinguish different retinal layers, the choroid, and the sclera. This reported work might be a major step forward in clinical translation of photoacoustic microscopy.

Influence of endogenous opiates on the hypotensive action of taurine in DOCA-salt rats.

PubMed

Sato, Y; Fujita, T

1988-12-01

We studied the role of endogenous opiate activation in the hypotensive action of taurine, a sulphur amino acid, in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Previous work had shown that supplementation with 1% taurine reduced blood pressure when given after DOCA-salt hypertension had been established. In the present study, in conscious rats, intraperitoneal injection of naloxone, an opiate antagonist, increased blood pressure in taurine-supplemented DOCA-salt rats, but not in DOCA-salt rats or vehicle-treated control rats. These results suggest that activation of an endogenous opiate might contribute to the hypotensive action of taurine in DOCA-salt hypertensive rats.

Interim results of two-year toxicological studies in rats of vinylidene chloride incorporated in the drinking water or administered by repeated inhalation

PubMed Central

Rampy, L. W.; Quast, J. F.; Humiston, C. G.; Balmer, M. F.; Schwetz, B. A.

1977-01-01

Male and female Sprague-Dawley rats were exposed to vinylidene chloride (VDC) orally or by inhalation in 2-year toxicological studies. Interim results are included in this report. VDC was given in the drinking water at mean ± S.D. concentrations of 0, 68 ± 13, 106 ± 22, and 220 ± 35 ppm which produced mean ± S.D. dosage levels of 0, 5.9 ± 0.6, 10.0 ± 1.2, and 19.3 ± 2.7 mg/kg for male rats and 0, 7.5 ± 0.4, 12.6 ± 1.1, and 25.6 ± 2.4 mg/kg for female rats. Forty-eight rats/sex/VDC level and 80 rats/sex in the control group were used in the 2-year study with an interim kill of an additional 10 rats/sex/level at 90 days. In the inhalation study, rats were exposed to 0, 10, or 40 ppm of VDC vapor 6 hr/day, 5 days/week for 5 weeks, after which the exposure levels were changed to 0, 25, and 75 ppm of VDC. Exposure continued for a total of 18 months and the rats held for observation an additional 6 months. Interim kills occurred at 1, 6 and 12 months. A separate 90-day study using 20 rats/sex/level was conducted at 0, 25, and 75 ppm of VDC vapor. There were 86 rats/sex/level in the 2-year portion of the study. The parameters monitored were: body weight, food and water consumption (drinking water study only), hematology, clinical chemistries, cytogentics of bone marrow cells (inhalation study only), mortality, terminal organ weights, and gross and histopathology. Based on interim kills and gross pathologic observations, the main conclusions are: increased cytoplasmic vacuolation of hepatocytes was seen in the livers of rats given 200 ppm VDC in drinking water or 25 or 75 ppm VDC vapor by inhalation; based on gross tumor count, tumor incidence in VDC-exposed rats was not greater than controls. PMID:612457

Allograft en bloc vagino-utero-ovarian avascular transplant versus autograft implantation in rats.

PubMed

Salehian, Mohammad-Taghi; Salehian, Arash; Mossaffa, Nariman; Hadian, Mehrnaz; Eghtesadi-Araghi, Payam

2008-12-01

The aim of this study was to compare the results of an allograft en bloc vagino-uteroovarian avascular transplant with those of autograft implantation in rats. Thirty-four inbred adult virgin female Albino rats (age range, 10 - 12 weeks) were divided into 2 groups: the control group (autograft, n=11) and the study group (en bloc vagino-utero-ovariectomy, n=23). In the study group, the uterus and adnexa and the ovaries of the donor rat were transplanted to the recipient animal. Twenty-five to 30 days after that procedure, all rats were killed, and the samples were assessed histopathologically. No immunosuppressive drugs were used. Ten rats died during the postoperative period. In 16 rats, the transplanted system had survived completely at the conclusion of the study. In each of the study groups, complete survival of the uterus and ovaries was noted in 8 rats (34.8% in the study group and 72.8% in the control group). In all rats except 1, histopathologic examination did not reveal any signs of the classic criteria for tissue rejection reaction. The lack of revascularization, nonspecific signs of inflammation, and the presence of large granular lymphocytes and natural killer cells were reported. Our data indicated that the outcome of both allograft and homograft avascular en bloc transplant of vagino-utero-ovariectomy in rats was successful, and that immunologic rejection did not seem to have an important role in those procedures.

Object similarity affects the perceptual strategy underlying invariant visual object recognition in rats

PubMed Central

Rosselli, Federica B.; Alemi, Alireza; Ansuini, Alessio; Zoccolan, Davide

2015-01-01

In recent years, a number of studies have explored the possible use of rats as models of high-level visual functions. One central question at the root of such an investigation is to understand whether rat object vision relies on the processing of visual shape features or, rather, on lower-order image properties (e.g., overall brightness). In a recent study, we have shown that rats are capable of extracting multiple features of an object that are diagnostic of its identity, at least when those features are, structure-wise, distinct enough to be parsed by the rat visual system. In the present study, we have assessed the impact of object structure on rat perceptual strategy. We trained rats to discriminate between two structurally similar objects, and compared their recognition strategies with those reported in our previous study. We found that, under conditions of lower stimulus discriminability, rat visual discrimination strategy becomes more view-dependent and subject-dependent. Rats were still able to recognize the target objects, in a way that was largely tolerant (i.e., invariant) to object transformation; however, the larger structural and pixel-wise similarity affected the way objects were processed. Compared to the findings of our previous study, the patterns of diagnostic features were: (i) smaller and more scattered; (ii) only partially preserved across object views; and (iii) only partially reproducible across rats. On the other hand, rats were still found to adopt a multi-featural processing strategy and to make use of part of the optimal discriminatory information afforded by the two objects. Our findings suggest that, as in humans, rat invariant recognition can flexibly rely on either view-invariant representations of distinctive object features or view-specific object representations, acquired through learning. PMID:25814936

Effects of alpha lipoic acid on acrylamide-induced hepatotoxicity in rats.

PubMed

Al-Qahtani, F A; Arafah, M; Sharma, B; Siddiqi, N J

2017-07-31

Acrylamide (ACR) is a neurotoxicant, reproductive toxicant, and carcinogen in animal species.  It is used in many industries and has been found to form naturally in foods cooked at high temperatures. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant whose therapeutic effect has been related to its antioxidant activity.  This study was carried out to study the protective effect of alpha lipoic acid on acrylamide induced perturbations in rat liver.  Four groups of rats were studied viz., control rats, acrylamide treated rats, alpha lipoic acid treated rats, and alpha lipoic acid plus acrylamide treated rats. ACR and ALA treatment alone and together caused a signifi-cant increase in hepatic reduced glutathione content while a decrease in hepatic ascorbic content was observed when compared to control group.  ALA pretreatment of acrylamide exposed rats caused no a signifi-cant alteration in superoxide dismutase activity but resulted in a tendency towards restoration of glutathione peroxidase and catalase activity to near normal levels.  Gel electrophoresis showed fragmentation of DNA in the treated groups.  The dose of ALA used in the present study afforded partial restoration of oxidative indices altered by ACR in rat liver.

Surgical anatomy of the liver, hepatic vasculature and bile ducts in the rat.

PubMed

Martins, Paulo Ney Aguiar; Neuhaus, Peter

2007-04-01

The rat is the most used experimental model in surgical research. Virtually all procedures in clinical liver surgery can be performed in the rat. However, the use of the rat model in liver surgery is limited by its small size and limited knowledge of the liver anatomy. As in humans, the rat liver vasculature and biliary system have many anatomical variations. The development of surgical techniques, and the study of liver function and diseases require detailed knowledge of the regional anatomy. The objective of this study was to describe and illustrate systematically the surgical anatomy of the rat liver to facilitate the planning and performance of studies in this animal. Knowledge of the diameter and length of liver vessels is also important for the selection of catheters and perivascular devices. Twelve Wistar rat livers were dissected using a surgical microscope. Hepatic and extrahepatic anatomical structures were measured under magnification with a millimeter scale. In this study, we describe the rat liver topographical anatomy, compare it with the human liver and review the literature. Increased knowledge of the rat liver anatomy and microsurgical skills permit individualized dissection, parenchymal section, embolization and ligature of vascular and biliary branches.

Composition of Muscle Fiber Types in Rat Rotator Cuff Muscles.

PubMed

Rui, Yongjun; Pan, Feng; Mi, Jingyi

2016-10-01

The rat is a suitable model to study human rotator cuff pathology owing to the similarities in morphological anatomy structure. However, few studies have reported the composition muscle fiber types of rotator cuff muscles in the rat. In this study, the myosin heavy chain (MyHC) isoforms were stained by immunofluorescence to show the muscle fiber types composition and distribution in rotator cuff muscles of the rat. It was found that rotator cuff muscles in the rat were of mixed fiber type composition. The majority of rotator cuff fibers labeled positively for MyHCII. Moreover, the rat rotator cuff muscles contained hybrid fibers. So, compared with human rotator cuff muscles composed partly of slow-twitch fibers, the majority of fast-twitch fibers in rat rotator cuff muscles should be considered when the rat model study focus on the pathological process of rotator cuff muscles after injury. Gaining greater insight into muscle fiber types in rotator cuff muscles of the rat may contribute to elucidate the mechanism of pathological change in rotator cuff muscles-related diseases. Anat Rec, 299:1397-1401, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

76 FR 47529 - Port Access Route Study: In the Waters of Montauk Channel and Block Island Sound

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-05

.... ACTION: Notice of availability of Preliminary Study Recommendations with request for comments. SUMMARY: The Coast Guard announces the availability of Preliminary Study Recommendations of a Port Access Route... study area. Preliminary recommendations indicate that marine transportation safety would be enhanced...

High-peak-power microwave pulses: effects on heart rate and blood pressure in unanesthetized rats.

PubMed

Jauchem, J R; Frei, M R

1995-10-01

Exposure sources capable of generating high-peak-power microwave pulses, with relatively short pulse widths, have recently been developed. Studies of the effect of these sources on the cardiovascular systems of animals have not been reported previously. We exposed 14 unanesthetized male Sprague-Dawley rats to 10 high-peak-power microwave pulses generated by a transformer-energized megawatt pulsed output (TEMPO) microwave source, at frequencies ranging from 1.2-1.8 GHz. Peak power densities were as high as 51.6 kW/cm2. At 14 d prior to irradiation, the animals were implanted with chronic aortic cannulae. With appropriate shielding of the transducer, blood pressure recordings were obtained during microwave pulsing. In a preliminary series of exposures at 1.7-1.8 GHz (peak power density 3.3-6.5 kW/cm2), an immediate but transient increase in mean arterial blood pressure (significant) and decrease in heart rate (non-significant) were observed. A loud noise was associated with each pulse produced by the TEMPO; this factor was subsequently attenuated. In a second series of exposures at 1.2-1.4 GHz (peak power density 14.6-51.6 kW/cm2), there were no significant changes in mean arterial blood pressure or heart rate during microwave exposure. The earlier significant increase in blood pressure that occurred during microwave exposure appeared to be related to the sharp noise produced by the TEMPO source. After appropriate sound attenuation, there were no significant effects of exposure to the microwave pulses.

Interstitial photodynamic therapy and glioblastoma: light fractionation study on a preclinical model: preliminary results

NASA Astrophysics Data System (ADS)

Leroy, Henri-Arthur; Vermandel, Maximilien; Tétard, Marie-Charlotte; Lejeune, Jean-Paul; Mordon, Serge; Reyns, Nicolas

2015-03-01

Background Glioblastoma is a high-grade cerebral tumor with local recurrence and poor outcome. Photodynamic therapy (PDT) is a local treatment based on the light activation of a photosensitizer (PS) in the presence of oxygen to form cytotoxic species. Fractionation of light delivery may enhance treatment efficiency by restoring tissue oxygenation. Objectives To evaluate the efficiency of light fractionation using MRI imaging, including diffusion and perfusion, compared to histological data. Materials and Methods Thirty-nine "Nude" rats were grafted with human U87 cells into the right putamen. After PS precursor intake (5-ALA), an optic fiber was introduced into the tumor. The rats were randomized in three groups: without illumination, with monofractionated illumination and the third one with multifractionated light. Treatment effects were assessed with early MRI including diffusion and perfusion sequences. The animals were eventually sacrificed to perform brain histology. Results On MRI, we observed elevated diffusion values in the center of the tumor among treated animals, especially in multifractionated group. Perfusion decreased around the treatment site, all the more in the multifractionated group. Histology confirmed our MRI findings, with a more extensive necrosis and associated with a rarified angiogenic network in the treatment area, after multifractionated PDT. However, we observed more surrounding edema and neovascularization in the peripheral ring after multifractionated PDT. Conclusion Fractionated interstitial PDT induced specific tumoral lesions. The multifractionated scheme was more efficient, inducing increased tumoral necrosis, but it also caused significant peripheral edema and neovascularization. Diffusion and perfusion MRI imaging were able to predict the histological lesions.