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Sample records for 14-day range-finding study

  1. ACUTE, 14-DAY REPEATED DOSING, AND 90-DAY SUBCHRONIC TOXICITY STUDIES OF POTASSIUM PICLORAM (JOURNAL VERSION)

    EPA Science Inventory

    Potassium picloram was administered either by gavage (acute studies) or in drinking water to male and female Sprague-Dawley derived rats (14-day and 90-day studies). The acute oral LD50 was 950 mg/kg (812-1120) for males and 686 mg/kg (599-786) for females. Depression, prostratio...

  2. A 14-day ground-based hypokinesia study in nonhuman primates: A compilation of results

    NASA Technical Reports Server (NTRS)

    Kazarian, L.; Cann, C. E.; Parfitt, M.; Simmons, D.; Morey-Holton, E.

    1981-01-01

    A 14 day ground based hypokinesia study with rhesus monkeys was conducted to determine if a spaceflight of similar duration might affect bone remodeling and calcium homeostatis. The monkeys were placed in total body casts and sacrificed either immediately upon decasting or 14 days after decasting. Changes in vertebral strength were noted and further deterioration of bone strength continued during the recovery phase. Resorption in the vertebrae increased dramatically while formation decreased. Cortical bone formation was impaired in the long bones. The immobilized animals showed a progressive decrease in total serum calcium which rebounded upon remobilization. Most mandibular parameters remained unchanged during casting except for retardation of osteon birth or maturation rate and density distribution of matrix and mineral moieties.

  3. Ocular Outcomes Evaluation in a 14-Day Head-Down Bed Rest Study

    PubMed Central

    Taibbi, Giovanni; Cromwell, Ronita L.; Zanello, Susana B.; Yarbough, Patrice O.; Ploutz-Snyder, Robert J.; Godley, Bernard F.; Vizzeri, Gianmarco

    2014-01-01

    Introduction We evaluated ocular outcomes in a 14-day head-down tilt (HDT) bed rest (BR) study designed to simulate the effects of microgravity on the human body. Methods Healthy subjects were selected using NASA standard screening procedures. Standardized NASA BR conditions were implemented (e.g., strict sleep-wake cycle, standardized diet, 24-hour-a-day BR, continuous video monitoring). Subjects maintained a 6° HDT position for 14 consecutive days. Weekly ophthalmological examinations were performed in the sitting (pre/post-BR) and HDT (in-bed phase) positions. Equivalency tests with optimal-alpha techniques evaluated pre/post-BR differences in best-corrected visual acuity (BCVA), spherical equivalent, intraocular pressure (IOP), Spectral-domain OCT retinal nerve fiber layer thickness (RNFLT), optic disc and macular parameters. Results 16 subjects (12 men and 4 women) were enrolled. Nearly all ocular outcomes were within our predefined clinically relevant thresholds following HDTBR, except near BCVA (pre/post-BR mean difference: −0.06 logMAR), spherical equivalent (−0.30 D), Tonopen XL IOP (+3.03 mmHg) and Spectralis OCT average (+1.14 μm), temporal-inferior (+1.58 μm) and nasal-inferior RNFLT (+3.48 μm). Modified Amsler grid, red dot test, confrontational visual field and color vision were within normal limits throughout. No changes were detected on stereoscopic color fundus photography. Discussion A few functional and structural changes were detected after 14-day HDTBR, notably an improved BCVA possibly due to learning effect and RNFL thickening without signs of optic disc edema. In general, 6° HDTBR determined a small non-progressive IOP elevation, which returned to baseline levels post-BR. Further studies with different BR duration and/or tilt angle are warranted to investigate microgravity-induced ophthalmological changes. PMID:25245897

  4. Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

    NASA Technical Reports Server (NTRS)

    Cromwell, R. L.; Zanello, S. B.; Yarbough, P. O.; Taibbi, G.; Vizzeri, G.

    2011-01-01

    /D) ratio. For all measures, there was no significant difference between subject groups for pre-bed rest testing. Post bed rest values also remained similar between groups. Comparison of pre- to post bed rest testing within each group did not demonstrate any statistical differences. These preliminary results from 14-day bed rest studies suggest that the combination of exercise and horizontal bed rest as compared to 6 degrees HDT bed rest did not produce differences in the ocular response with regard to IOP and optic disc parameters. The ocular measures reported here only included pre- and post bed rest time points. Further investigation is needed to examine both the acute response and long term adaptation of structural and functional ocular parameters in the bed rest platform and determine its usefulness for studying spaceflight phenomena. From a clinical perspective, the ability to study ocular responses in the controlled environment of the bed rest platform can provide valuable information for the care of patients restricted to bed rest.

  5. Comparison of Ocular Outcomes in Two 14-Day Bed Rest Studies

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita L.; Zanello, S. B.; Yarbough, P. O.; Tabbi, G.; Vizzeri, G.

    2012-01-01

    Reports of astronauts' visual changes have raised concern about ocular health during long-duration spaceflight. Some of these findings include globe flattening with hyperopic shifts, choroidal folds, optic disc edema, retinal nerve fiber layer (RNFL) thickening, and cotton wool spots. While the etiology remains unknown, it is hypothesized that, in predisposed individuals, hypertension in the brain may follow cephalad fluid shifts during spaceflight. This possible mechanism of ocular changes may also apply to analogous cases of idiopathic intracranial hypertension (IIH) or pseudotumor cerebri on Earth patients. Head-down t ilt (HDT) bed rest is a spaceflight analog that induces cephalad fluid shifts. Previous studies of the HDT position demonstrated body fluid shifts associated with changes in intraocular pressure (IOP) but the conditions of bed rest varied among experiments, making it difficult to compare data and draw conclusions. For these reasons, vision evaluation of bed rest subjects was implemented for NASA bed rest studies since 2010, in an attempt to monitor vision health in subjects subjected to bed rest. Vision monitoring is thus currently performed in all NASA-conducted bed rest campaigns

  6. Dried blood spot analysis of donepezil in support of a GLP 3-month dose-range finding study in rats.

    PubMed

    Meier-Davis, Susan R; Meng, Min; Yuan, Weiwei; Diehl, Lisa; Arjmand, Fatima M; Lucke, Rebecca M; Huang, Betsy; Wen, Jianye; Shudo, Jutaro; Nagata, Tetsuto

    2012-01-01

    Donepezil hydrochloride is a reversible acetyl cholinesterase inhibitor approved for Alzheimer disease treatment. As an alternate therapy, a donepezil hydrochloride transdermal patch is in development. Recommended nonclinical safety studies include a 3-month Good Laboratory Practice (GLP) dose-range finding (DRF) study prior to conducting the 2-year dermal carcinogenicity study in rats. Demonstration of systemic exposure is necessary to interpret the in vivo data. Previous nonclinical reports supporting oral dosing have utilized liquid chromatography tandem mass spectrometry (LC/MS/MS) to quantify donepezil concentrations in plasma. Smaller species with limited blood volumes do not allow serial sampling to derive the full pharmacokinetic profile from a single animal. Therefore, the option of another analytical method requiring decreased sample volumes is desirable as it would decrease the required number of animals while obtaining the complete profile. The dried blood spot (DBS) technique allows drug level measurement from a few microliters; however, the method is still not widely utilized in GLP studies. Because donepezil plasma levels are known by the oral route, DBS was used to bridge the previous oral data and to support a 13-week GLP DRF study for repeated topical application in rats, comparing oral administration with 4 topical formulations. The DBS method was validated and demonstrated robustness and reproducibility for application to the DRF study. The assay results were comparable to a previously reported plasma LC/MS/MS assay-derived pharmacokinetic profile and provided justification for selection of the topical formulation and dose levels for the subsequent dermal carcinogenicity study. PMID:22705881

  7. Rifabutin-based 10-day and 14-day triple therapy as a third-line and fourth-line regimen for Helicobacter pylori eradication: A pilot study

    PubMed Central

    Mori, Hideki; Matsuzaki, Juntaro; Tsugawa, Hitoshi; Fukuhara, Seiichiro; Miyoshi, Sawako; Hirata, Kenro; Seino, Takashi; Matsushita, Misako; Nishizawa, Toshihiro; Masaoka, Tatsuhiro; Kanai, Takanori

    2015-01-01

    Background and aim This prospective randomized study was designed to assess the efficacy of 10-day and 14-day rifabutin-based triple therapy as a third- or fourth-line rescue therapy. Methods Patients who failed first- and second-line eradication therapy were enrolled. H. pylori was isolated from gastric biopsy specimens and the rpoB mutation status, a factor of resistance to rifamycins, and minimum inhibitory concentrations (MICs) of rifabutin and amoxicillin were determined. Enrolled patients were randomly assigned to receive 10-day or 14-day eradication therapy with esomeprazole (20 mg, 4 times a day (q.i.d.)), amoxicillin (500 mg, q.i.d.), and rifabutin (300 mg, once a day (q.d.s.)). Poor compliance was defined as intake of <80% of study drugs. Successful H. pylori eradication was confirmed using a [13C] urea breath test or a stool antigen test, 12 weeks after the end of therapy. Results Twelve patients were assigned to the 10-day group, and 17, to the 14-day group. Intention-to-treat and per-protocol analyses of eradication rates were 83.3% and 81.8% for the 10-day group and 94.1% and 91.7% for the 14-day group, respectively. All patients with rpoB mutation-positive strains (n = 3) showed successful eradication, irrespective of the regimen received. Therapy was stopped due to adverse events in 8.3% and 29.3% of patients in the 10-day and 14-day groups, respectively. Conclusion Both the 10-day and 14-day therapies were effective as rescue regimens. In particular, the 14-day therapy resulted in successful eradication in over 90% of patients, but the 10-day treatment may be enough to obtain a successful eradication rate, considering the tolerability of therapy. PMID:27403304

  8. Efficacy of 7-Day and 14-Day Triple Therapy Regimens for the Eradication of Helicobacter pylori: A Comparative Study in a Cohort of Romanian Patients

    PubMed Central

    Arama, Stefan Sorin; Tiliscan, Catalin; Negoita, Cristina; Croitoru, Alexandru; Arama, Victoria; Mihai, Carmen Marina; Pop, Florinel

    2016-01-01

    Objective. This study compared the eradication rates of of Helicobacter pylori (HP) infection by a 7-day and 14-day anti-HP regimen. Materials and Methods. An open, randomized, prospective study was performed to evaluate the response to anti-HP treatment in adult HP-positive patients following a 7-day course (Regimen A) of a proton pump inhibitor in association with clarithromycin and amoxicillin compared to a 14-day course (Regimen B). Gastric biopsies were performed at baseline and two months after anti-HP treatment. Results. Seventy-eight patients aged 18–64 years (28 males, 50 females) diagnosed with HP infection were included. Fifty-two (66.7%) patients received Regimen B and 26 (33.3%) Regimen A. The overall eradication rate was 70.5%. Better treatment response (p < 0.01) was seen in Regimen B (44/52, 84.2% versus 11/26, 42.3%). Significant improvement in histological features was seen in regimen B. There has been significant overall reduction in endoscopic aspects of gastric and duodenal lesions in both regimens. Younger patients ≤35 years had a better response to Regimen B. Better treatment response was seen in women, urban residents, and those with tertiary level of education in both groups. Conclusion. 14-day anti-HP regimen offered a significant better overall eradication of HP in study population. PMID:26858750

  9. Randomized dose-ranging study of the 14-day early bactericidal activity of bedaquiline (TMC207) in patients with sputum microscopy smear-positive pulmonary tuberculosis.

    PubMed

    Diacon, Andreas H; Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M

    2013-05-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies. PMID:23459487

  10. Randomized Dose-Ranging Study of the 14-Day Early Bactericidal Activity of Bedaquiline (TMC207) in Patients with Sputum Microscopy Smear-Positive Pulmonary Tuberculosis

    PubMed Central

    Dawson, Rodney; Von Groote-Bidlingmaier, Florian; Symons, Gregory; Venter, Amour; Donald, Peter R.; Conradie, Almari; Erondu, Ngozi; Ginsberg, Ann M.; Egizi, Erica; Winter, Helen; Becker, Piet; Mendel, Carl M.

    2013-01-01

    Bedaquiline is a new antituberculosis agent targeting ATP synthase. This randomized, double-blinded study enrolling 68 sputum smear-positive pulmonary tuberculosis patients evaluated the 14-day early bactericidal activity of daily doses of 100 mg, 200 mg, 300 mg, and 400 mg bedaquiline, preceded by loading doses of 200 mg, 400 mg, 500 mg, and 700 mg, respectively, on the first treatment day and 100 mg, 300 mg, 400 mg, and 500 mg on the second treatment day. All groups showed activity with a mean (standard deviation) daily fall in log10 CFU over 14 days of 0.040 (0.068), 0.056 (0.051), 0.077 (0.064), and 0.104 (0.077) in the 100-mg, 200-mg, 300-mg, and 400-mg groups, respectively. The linear trend for dose was significant (P = 0.001), and activity in the 400-mg dose group was greater than that in the 100-mg group (P = 0.014). All of the bedaquiline groups showed significant bactericidal activity that was continued to the end of the 14-day evaluation period. The finding of a linear trend for dose suggests that the highest dose compatible with safety considerations should be taken forward to longer-term clinical studies. PMID:23459487

  11. Evaluation of safety margins of Chenopodium album seed decoction: 14-day subacute toxicity and microbicidal activity studies

    PubMed Central

    2011-01-01

    Background Sperm immobilizing activity and plausible mechanism of action of Chenopodium album seed decoction (CAD) have been elucidated in our earlier studies. The present study has been carried out to explore the safety standards of CAD along with microbicidal properties as prerequisite for its use as a topically applicable vaginal contraceptive. Methods The safety standards of CAD were assessed by a) Hemolytic index determination using rabbit erythrocytes, to set the doses of the other experiments, b) Dermal irritancy test using refined version of Draize scoring system on rabbits, c) Possible effect on local tissues and reproductive performance in female rats after fourteen daily single dose application, d) PCNA staining- to evaluate the effect of CAD on vaginal tissue proliferation, e) TUNEL assay- to examine its ability to induce in situ apoptosis in the vaginal tissue sections of the treated animals, and f) Microbicidal activity- to explore the effect of CAD on the growth of Lactobacillus acidophilus and Candida albicans. Results In vitro irritation studies on rabbit erythrocytes revealed the hemolytic index of CAD to be 8.2 mg/ml. The dermal irritation test showed it to be a non-irritant even at higher doses. Intra vaginal application of CAD in rat vagina for 14 consecutive days caused slight reversible inflammation on vaginal epithelial cells at doses as high as 82 mg/ml. However, at this dose level it neither had any adverse effect on vaginal tissue proliferation nor did it cause in situ apoptosis as evident from PCNA staining and TUNEL assay. Fertility and fecundity were restored 4-15 days after withdrawal of CAD application. At dose level 10 times that of its spermicidal MEC (minimum effective concentration), CAD did not block the growth of Lactobacillus, although the size of individual colony was marginally reduced. However, growth of the pathogenic fungus Candida albicans was completely inhibited with 20 mg/ml of CAD. Conclusion The overall result

  12. Association Between Cardiovascular and Intraocular Pressure Changes in a 14-Day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

    NASA Technical Reports Server (NTRS)

    Cromwell, Ronita; Zanello, Susana; Yarbough, Patrice; Ploutz-Snyder, Robert; Taibbi, Giovanni; Vizzeri, Gianmarco

    2013-01-01

    Visual symptoms and intracranial pressure increase reported in astronauts returning from long duration missions in low Earth-orbit are thought to be related to fluid shifts within the body due to microgravity exposure. Because of this possible relation to fluid shifts, studies conducted in head-down tilt (HDT) bed rest are being monitored for potential changes in ocular health. These measures will also serve to determine whether HDT is a suitable ground-based analog to model subclinical cardiovascular and ocular changes that could shed light on the etiology of the VIIP syndrome observed in spaceflight. Sixteen healthy normotensive (12M, 4F, age range 29-54 years), non-smoker and normal weight subjects, volunteered to participate in a 14 day 6 deg head HDT study conducted at the NASA Flight Analogs Research Unit (FARU). This facility provides standard bed rest conditions (diet, wake/sleep time, time allowed in sunlight) during the time that the subjects stay at the FARU. Cardiovascular parameters were obtained in supine posture at BR-5, BR+0, and BR+3 and ocular monitoring was performed weekly. Intraocular pressure (IOP) increased from pre-bed rest BR-3) to the third day into bed rest (BR+3). Values reached a plateau towards the end of the bed rest phase (BR10) and decreased within the first three days of recovery (BR+2) returning to levels comparable to baseline at BR-3. As expected, most cardiovascular parameters were affected by 14 days of HDT bed rest. Plasma volume decreased as a result of bed rest but recovered to baseline levels by BR+3. Indications of cardiovascular deconditioning included increase in both systolic and diastolic blood pressure and heart rate, and a decrease in stroke volume and cardiac output between BR-5 and BR+3. Due to the experimental design of this study, we were not able to test the hypothesis that fluid shifts might be involved in the IOP increase during the bed rest phase, since cardiovascular measures were not available for those

  13. Miniaturization of cytotoxicity tests for concentration range-finding studies prior to conducting the pH 6.7 Syrian hamster embryo cell-transformation assay.

    PubMed

    Plöttner, Sabine; Käfferlein, Heiko U; Brüning, Thomas

    2013-08-15

    The Syrian hamster embryo (SHE) cell-transformation assay (SHE assay) is a promising alternative method to animal testing for the identification of potential carcinogens in vitro. Prior to conducting the SHE assay the appropriate concentration range for each test chemical must be established, with a maximum concentration causing approximately 50% cytotoxicity. Concentration range-finding is done in separate experiments, which are similar to the final SHE assay but with less replicates and more concentrations. Here we present an alternative for the cytotoxicity testing by miniaturization of the test procedure by use of 24-well plates and surpluses from feeder-cell preparations as target cells. In addition, we integrated the photometry-based neutral red (NR) assay. For validation of the assay, incubations with dimethyl sulf-oxide, p-phenylenediamine-2HCl, aniline, o-toluidine-HCl, 2,4-diaminotoluene, and 2-naphthylamine were carried out in the miniaturized approach and compared with the standard procedure in terms of calculating the relative plating efficiencies (RPEs). To directly compare both methods, concentrations that produced 50% cytotoxicity (IC50) were calculated. Excellent associations were observed between the number of colonies and NR uptake. For all test substances a concentration-dependent, concomitant decrease of NR uptake in the miniaturized approach and RPEs in the standard test was observed after a 7-day incubation. The results from both test setups showed a comparable order of magnitude and the IC50 values differed by a factor <2 (1.4-1.9), depending on the substance in question. Overall, the miniaturized approach should be considered an improved alternative for cytotoxicity testing in the SHE assay, as it saves valuable SHE cells and speeds-up the time, to obtain test results more rapidly. PMID:23830925

  14. 14 Days to Have Your Say

    ERIC Educational Resources Information Center

    Peterson, Andrea; Haulgren, Frank

    2010-01-01

    During spring quarter 2008, the Western Washington University (WWU) Libraries established an interactive bloglike environment called "14 Days to Have Your Say" with the intention of gathering new ideas and feedback about the libraries from the university community. The environment was developed as a fairly simple Drupal site. The project was open…

  15. Nutrition Composition and Single, 14-Day and 13-Week Repeated Oral Dose Toxicity Studies of the Leaves and Stems of Rubus coreanus Miquel.

    PubMed

    Om, Ae-Son; Song, Yu-Na; Noh, GeonMin; Kim, HaengRan; Choe, JeongSook

    2016-01-01

    The leaves and stems of the plant Rubus coreanus Miquel (RCMLS) are rich in vitamins, minerals and phytochemicals which have antioxidant, anti-hemolytic, anti-inflammatory, anti-fatigue and anti-cancer effects. However, RCMLS is not included in the Korean Food Standards Codex due to the lack of safety assurance concerning RCMLS. We evaluated single and repeated oral dose toxicity of RCMLS in Sprague-Dawley rats. RCMLS did not induce any significant toxicological changes in both male and female rats at a single doses of 2500 mg/kg/day. Repeated oral dose toxicity studies showed no adverse effects in clinical signs, body weight, food consumption, ophthalmic examination, urinalysis, hematology, serum biochemistry, necropsy findings, organ weight, and histopathology at doses of 625, 1250, and 2500 mg/kg/day. The LD50 and LOAEL of RCMLS might be over 2500 mg/kg body weight/day and no target organs were identified. Therefore, this study revealed that single and repeated oral doses of RCMLS are safe. PMID:26760987

  16. Optical Range-Finding from Image Focus

    NASA Astrophysics Data System (ADS)

    Weckler, Paul Reese

    Scope of the study. Much of the labor-intensive work in agriculture consists of reaching out, grasping an object, and then placing the object in a desired position. This repetitious work exploits the unsurpassed hand-eye coordination in human beings. Substitution of machines for manual labor will require simulation of human hand-eye coordination. Most robots in agricultural applications will need the ability to recognize and manipulate three-dimensional objects. With present technology, this requirement makes agricultural robotic systems uneconomical, except for special applications. A method for gauging the distance from a video camera to an object of interest was investigated. By using a calibrated camera-lens system, range was related to focus. Optimum focus of the image was determined by maximizing the high -frequency content of the Fourier transform of the object image. The Walsh-Hadamard transform was investigated as an alternative focusing function. Software was developed to determine optimum image focus and control a motorized camera lens. Findings and conclusions. Range values from the video camera to target objects were calculated by the system. Calculated values were compared with measured distances. Differences between calculated and actual distance averaged less than 0.5%. The Walsh-Hadamard transform provided focus information comparable to the Fourier transform. Using double precision floating-point arithmetic, the Walsh-Hadamard transform executed more than three times faster than the Fourier transform. Distance values calculated using the Walsh -Hadamard transform differed from values calculated with the Fourier transform by less than 1%. This system used a passive, non-triangulation technique to obtain the distance from the machine vision camera to the object of interest. A passive non-triangulation system was the simplest image acquisition requirements, since it does not require a second camera, structured lighting, camera movement, or time

  17. A Phase II Study of a Dose-Density Regimen With Fluorouracil, Epirubicin, and Cyclophosphamide on Days 1 and 4 Every 14 Days With Filgrastim Support Followed by Weekly Paclitaxel in Women With Primary Breast Cancer

    PubMed Central

    Pietri, Elisabetta; Andreis, Daniele; Fabbri, Francesca; Menna, Cecilia; Schirone, Alessio; Kopf, Barbara; Rocca, Andrea; Amadori, Dino

    2015-01-01

    Background. Recent evidence shows that use of anthracycline and taxane adjuvant chemotherapy and dose-dense regimens, consisting of more frequent administration of the drugs, have improved outcomes for breast cancer patients. In this study, we evaluated administration of an epirubicin-based regimen with paclitaxel in a sequential, dose-dense schedule as adjuvant treatment for patients with high-risk primary breast cancer. Methods. In a phase II Simon two-stage design study, we evaluated the feasibility of a modified fluorouracil, epirubicin, and cyclophosphamide (FEC) regimen at high dose intensity (fluorouracil 500 mg/m2 i.v. on days 1 and 4, epirubicin 60 mg/m2 i.v. on days 1 and 4, and cyclophosphamide 500 mg/m2 i.v. on days 1 and 4; all drugs were administered every 14 days for 3 cycles) with granulocyte colony-stimulating factor support followed by dose-intense weekly paclitaxel 100 mg/m2 for 8 cycles. In 11 patients with breast cancer following quadrantectomy (n = 8) or modified radical mastectomy (n = 3), any grade 3 (G3) or higher nonhematologic toxicity (excluding alopecia, nausea or vomiting, and bone pain, which might be a consequence of the administration of filgrastim) and adherence to the scheduled dose-dense treatment (deliverability) were monitored with the purpose of enrolling an additional 27 patients in the case of a satisfying toxicity profile and deliverability of the planned treatment (at least 7 patients completing the treatment). Results. Five of 11 patients experienced G3 or higher nonhematologic toxicity during the FEC regimen. We did not observe G3 or higher nonhematologic toxicity related to paclitaxel treatment. In particular, three patients experienced G3 fatigue, one patient had G3 oral mucositis, three patients had G3 hypokalemia, one patient had G3 syncope, one patient had G3 transaminitis (alanine aminotransferase), one patient experienced G4 pulmonary thromboembolism, and 1 patient had a G3 breast infection. Four of 11 patients

  18. An automatic 14-day paste diet feeder for animals

    NASA Technical Reports Server (NTRS)

    Vasques, Marilyn; Mulenburg, Jerry; Gundo, Dan; Griffith, Jon

    1994-01-01

    During a centrifuge experiment, any interruption that requires stopping the centrifuge may influence the results. Centrifuges often must be stopped for animal maintenance (food, water and waste removal), especially in cases of timed feedings. To eliminate the need for stopping the centrifuge while still providing timed feeding, an automatic paste diet feeder was developed. The feeder is based on a constant volume concept and can deliver a predetermined amount of paste diet at specified time intervals. This unit was supported by water delivery and waste collection systems. The entire system performed reliably and maintained the animals well for a continuous centrifugation experiment of 14 days.

  19. EPO modulation in a 14-days undersea scuba dive.

    PubMed

    Revelli, L; Vagnoni, S; D'Amore, A; Di Stasio, E; Lombardi, C P; Storti, G; Proietti, R; Balestra, C; Ricerca, B M

    2013-10-01

    Erythropoiesis is affected during deep saturation dives. The mechanism should be related to a downregulation of serum Erythropoietin (s-EPO) concentration or to a toxic effect of the hyperbaric hyperoxia. We evaluated s-EPO and other haematological parameters in 6 scuba divers before, during and after a 14-days guinness saturation dive (8-10 m). Athletes were breathing air at 1.8-2 ATA, under the control of a team of physicians. Serum parameters were measured before diving (T0) and: 7 days (T1), 14 days (T2) after the beginning of the dive and 2 h (T3) and 24 h (T4) after resurfacing. Hgb, and many other haematological parameters did not change whereas Ht, s-EPO, the ratio between s-EPO predicted and that observed and reticulocytes (absolute, percent) declined progressively from T0 to T3. At T4 a significant rise in s-EPO was observed. Hgb did not vary but erythropoiesis seemed to be affected as s-EPO and reticulocyte counts showed. All these changes were statistically significant. The experiment, conducted in realistic conditions of dive length, oxygen concentration and pressure, allows us to formulate some hypotheses about the role of prolonged hyperbarism on erythropoiesis. The s-EPO rise, 24 h after resurfacing, is clearly documented and related to the "Normobaric Oxygen Paradox". This evidence suggests interesting hypotheses for new clinical applications such as modulation of s-EPO production and Hgb content triggered by appropriate O₂ administration in pre-surgical patients or in some anemic disease. PMID:23670359

  20. Subchronic toxicity studies on 1,3,5-trinitrobenzene, 1,3-dinitrobenzene, and tetryl in rats. 14-day toxicity evaluation of n-methyl-n, 2,4,6-tetranitroaniline in Fischer 344 rats. Final report

    SciTech Connect

    Reddy, T.V.

    1994-05-01

    Subacute toxic effects of Tetryl in male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of Tetryl (0, 500, 1250, 2000, 2500 and 5000 mg/kg diet) for fourteen days. The average daily Tetryl doses consumed were 32, 82, 130, 178 and 374 for females and 31, 80, 121, 170 and 350 for males. Food and water consumption were not significantly altered. Final body weight was reduced in only the high dose males while relative organ weights were significantly changed in this same dose group involving the liver (females), kidneys (males), and spleen (males). Hematology and clinical chemistry studies indicated increased values relating to reticulocytes (females) and methemoglobin (females and males) in high and mid dose groups while total protein and albumin were significantly increased in all groups except the 50 mg/kg female group. Alkaline phosphatase was decreased in these same female groups. The only histopathological change noted which was considered meaningful was a mild increase in hyaline droplet deposition in male kidneys in all dose groups.

  1. NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation?

    NASA Technical Reports Server (NTRS)

    Crucian, B. E.; Stowe, R. P.; Mehta, S. K.; Chouker, A.; Feuerecker, M.; Quiriarte, H.; Pierson, D. L.; Sams, C. F.

    2011-01-01

    This poster paper reviews the use of 14 day undersea missions as a possible analog for short duration spaceflight for the study of immune system dysregulation. Sixteen subjects from the the NASA Extreme Enviro nment Mission Operations (NEEMO) 12, 13 and 14 missions were studied for immune system dysregulation. The assays that are presented in this poster are the Virleukocyte subsets, the T Cell functions, and the intracellular/secreted cytokine profiles. Other assays were performed, but are not included in this presntation.

  2. Rat soleus muscle fiber responses to 14 days of spaceflight and hindlimb suspension

    NASA Technical Reports Server (NTRS)

    Ohira, Yoshi; Jiang, Bian; Roy, Roland R.; Oganov, V.; Il'ina-Kakueva, E. I.; Marini, J. F.; Edgerton, V. R.

    1992-01-01

    Morphological and enzymatic responses in fibers of different types were studied in rats after 14 days of spaceflight onboard Cosmos 2044 or hindlimb suspension. Fibers were classified as fast-twitch, slow-twitch, or both fast- and slow-twitch on the basis of the type of myosin heavy chains (MHC). Data obtained indicate that during the 14 days of spaceflight or suspension the protein profiles of 9-14 percents of the slow-twitch fibers reconfigured from typical slow-twitch toward fast switch fibers, while all fibers were dramatically losing total protein. These results were consistent with the data obtained from Cosmos 1887 and Skylab 3. It is suggested that effects of spaceflight on skeletal muscle can be attributed to a dramatic reduction in the level and/or pattern of loading.

  3. [A 14-day-old boy with jaundice and apnoea].

    PubMed

    Smerud, Ole-Jørgen Olsøy; Solevåg, Anne Lee; Hansen, Thor Willy Ruud; Grønn, Morten

    2015-12-15

    We describe an infant who was readmitted from home at 14 days of age with jaundice and a history of apnoea and episodes of retrocollis/opisthotonos. He had been only mildly jaundiced on discharge from the maternity clinic at 2 days of age. The total serum bilirubin (TSB) on admission was 542 µmol/L, and the infant was treated intensively with triple phototherapy and exchange transfusion. In contrast to what is recommended in Norwegian national guidelines for management of neonatal jaundice, the parents had apparently neither received oral nor written information about jaundice and its follow-up at the time of discharge from maternity. They therefore contacted their child healthcare centre when they had questions about jaundice, though the national guidelines specifically state that follow-up for neonatal jaundice during the first 2 weeks of life is the responsibility of the birth hospital. Inappropriate advice resulted in delayed referral, and the child has been diagnosed with chronic kernicterus, probably the first such case in Norway since national guidelines were formalised in 2006. Genetic work-up disclosed compound heterozygosity for Crigler-Najjar syndrome type I, to the best of our knowledge the first instance of this disorder ever to have been diagnosed in Norway. The incidence of kernicterus is Norway is much lower than in other industrialised countries. This is most likely due to national guidelines for management of neonatal jaundice, which place the responsibility for management and follow-up of jaundice with the birth hospital during the crucial first 2 weeks of life. This case report reminds us that tragedies may occur when guidelines are disregarded. PMID:26674039

  4. Human Habitation in a Lunar Electric Rover During a 14-Day Field Trial

    NASA Technical Reports Server (NTRS)

    Litaker, Harry, Jr.; Thompson, Shelby; Howard, Robert, Jr.

    2010-01-01

    Various military and commercial entities, as well as the National Aeronautics and Space Administration (NASA), have conducted space cabin confinement studies. However, after an extensive literature search, only one study was found using a simulated lunar rover (LUNEX II), under laboratory conditions, with a crew of two for an eighteen day lunar mission. Forty-three years later, NASA human factors engineers conducted a similar study using the Lunar Electric Rover (LER) in a dynamic real-world lunar simulation at the Black Point Lava Flow in Arizona. The objective of the study was to obtain human-in-the-loop performance data on the vehicle s interior volume with respect to human-system interfaces, crew accommodations, and habitation over a 14-day mission. Though part of a larger study including 212 overall operational elements, this paper will discuss only the performance of fifty different daily habitational elements within the confines of the vehicle carried out by two male subjects. Objective timing data and subjective questionnaire data were collected. Results indicate, much like the LUNEX II study, the LER field study suggest that a crew of two was able to maintain a satisfactory performance of tasks throughout the 14-day field trail within a relative small vehicle volume.

  5. Single-dose oral toxicity of fermented rice extracts (FREs): a 14-day observation.

    PubMed

    Choi, Jae-Suk; Kim, Joo-Wan; Kim, Ki-Young; Ku, Sae-Kwang; Sohn, Jae Hak

    2014-01-01

    The aim of present research was to determine the acute oral toxicity of fermented rice extracts (FREs), in female and male ICR mice. To investigate the toxicity and identify target organs, FREs were orally administered once to male and female ICR mice at doses of 0 (vehicle control), 500, 1000, or 2000 mg/kg body weight (BW). Effects on mortality, BW, and clinical signs were monitored over 14 days, including changes in the weights and histopathological characteristics of 14 organs, as described in the Korea Food and Drug Administration (KFDA) Guidelines (2009-116, 2009). No treatment-related mortality was observed during the 14-day observation period in either gender. In addition, no FRE-related change was observed in BW or organ weight (OW), clinical indicators, or histopathological findings in this study. Our results suggest that the FRE is non-toxic in mice and is therefore likely to be safe for clinical use. The approximate LD and LD50 in mice after single oral dose of FRE are greater than 2000 mg/kg in female and male ICR mice. Additionally, no specific target organ or negative clinical indicator was detected in this study. PMID:24374435

  6. Report of 14-day bedrest simulation of Skylab

    NASA Technical Reports Server (NTRS)

    Johnson, P. C. (Compiler); Mitchell, C. (Compiler)

    1976-01-01

    Part one of a two-phase bedrest project in which the physiological effects of weightlessness were simulated is presented. The project was designed to approximate the medical testing and dietary control of Skylab. The test period included a three week pre-flight period, a two week bedrest period and a two week post-flight period. The test subjects ate measured amounts of the Skylab diet and drank deionized water to recreate the metabolic balance studies of Skylab. The medical testing program, pre- and postbedrest, was similar to that of Skylab including: lower body negative pressure testing the orthostatic intolerance noted after both spaceflights and bedrest, bicycle ergometry testing the cardiovascular response to graded exercise, postural equilibrium, vestibular studies and electromyograms. Fluid and electrolyte shifts and balance were documented with intake and output records and radionuclide studies. The subjects were observed by a psychiatrist who watched for signs of mental stress in the test environment and changes in mental status.

  7. The 14-day repeated dose liver micronucleus test with methapyrilene hydrochloride using young adult rats.

    PubMed

    Inoue, Kenji; Ochi, Akimu; Koda, Akira; Wako, Yumi; Kawasako, Kazufumi; Doi, Takaaki

    2015-03-01

    The repeated dose liver micronucleus (RDLMN) assay using young adult rats has the potential to detect genotoxic hepatocarcinogens that can be integrated into a general toxicity study. The assay methods were thoroughly validated by 19 Japanese facilities. Methapyrilene hydrochloride (MP), known to be a non-genotoxic hepatocarcinogen, was examined in the present study. MP was dosed orally at 10, 30 and 100mg/kg/day to 6-week-old male Crl:CD (SD) rats daily for 14 days. Treatment with MP resulted in an increase in micronucleated hepatocytes (MNHEPs) with a dosage of only 100mg/kg/day. At this dose level, cytotoxicity followed by regenerative cell growth was noted in the liver. These findings suggest that MP may induce clastogenic effects indirectly on the liver or hepatotoxicity of MP followed by regeneration may cause increase in spontaneous incidence of MNHEPs. PMID:24768639

  8. Effect of 14 days of bed rest on urine metabolite excretion and plasma enzyme levels

    NASA Technical Reports Server (NTRS)

    Pace, N.; Grunbaum, B. W.; Kodama, A. M.; Rahlmann, D. F.; Newsom, B. D.

    1974-01-01

    After 1 week of ambulatory base-line measurement, a group of 8 men 19-26 years of age remained continuously recumbent for 14 days. Studies were continued for 1 week following the prolonged recumbency. Urine excretion rates for a number of constituents were determined 2 days before bed rest, on day 14 of bed rest, and day 6 after bed rest. Blood plasma samples were also obtained at these times, and analyzed for several enzymes. On day 14 of bed rest significant increases were observed in urine excretion of total osmotically-active substances, magnesium, calcium, phosphate, creatinine, hydroxyproline, and 17-OH corticosteroids. A decrease occurred in urinary glucose excretion. Plasma levels of alkaline phosphatase and LDH-3 were depressed, while plasma GPT was elevated. Many of these changes persisted on day 6 after bed rest, and are interpreted as concomitants of the disuse atrophy of the musculoskeletal system that characterizes prolonged bed rest and weightlessness.

  9. Local versus whole-body sweating adaptations following 14 days of traditional heat acclimation.

    PubMed

    Poirier, Martin P; Gagnon, Daniel; Kenny, Glen P

    2016-08-01

    The purpose of this study was to examine if local changes in sweat rate following 14 days of heat acclimation reflect those that occur at the whole-body level. Both prior to and following a 14-day traditional heat acclimation protocol, 10 males exercised in the heat (35 °C, ∼20% relative humidity) at increasing rates of heat production equal to 300 (Ex1), 350 (Ex2), and 400 (Ex3) W·m(-2). A 10-min recovery period followed Ex1, while a 20-min recovery period separated Ex2 and Ex3. The exercise protocol was performed in a direct calorimeter to measure whole-body sweat rate and, on a separate day, in a thermal chamber to measure local sweat rate (LSR), sweat gland activation (SGA), and sweat gland output (SGO) on the upper back, chest, and mid-anterior forearm. Post-acclimation, whole-body sweat rate was greater during each exercise bout (Ex1: 14.3 ± 0.9; Ex2: 17.3 ± 1.2; Ex3: 19.4 ± 1.3 g·min(-1), all p ≤ 0.05) relative to pre-acclimation (Ex1: 13.1 ± 0.6; Ex2: 15.4 ± 0.8; Ex3: 16.5 ± 1.3 g·min(-1)). In contrast, only LSR on the forearm increased with acclimation, and this increase was only observed during Ex2 (Post: 1.32 ± 0.33 vs. Pre: 1.06 ± 0.22 mg·min(-1)·cm(-2), p = 0.03) and Ex3 (Post: 1.47 ± 0.41 vs. Pre: 1.17 ± 0.23 mg·min(-1)·cm(-2), p = 0.05). The greater forearm LSR post-acclimation was due to an increase in SGO, as no changes in SGA were observed. Overall, these data demonstrate marked regional variability in the effect of heat acclimation on LSR, such that not all local measurements of sweat rate reflect the improvements observed at the whole-body level. PMID:27467216

  10. Effect of a 14-day hindlimb suspension on beta-adrenoreceptors in rats.

    PubMed

    Bouzeghrane, F; Somody, L; Gallo-Bona, N; Gauquelin-Koch, G; Gharib, C; Fagette, S

    1999-05-01

    Exposure to long-term simulated microgravity exhibits reduced sympathetic nervous system activity. This study tested the hypothesis that the hypersensitivity of adrenoreceptors would explain partly many other features of the hemodynamic consequences of return from space. The biochemical properties of the beta adrenoreceptors (betaAR) were determined using 125I-cyanopindolol (125I-CYP) binding in three rat groups: (1) The first experimental group consisted of 24 h-restrained orthostatic rats in the horizontal position, to test the early effect of the attachment to the suspension device; (2) the second experimental group consisted of 24 h-restrained antiorthostatic rats, to test the early effect of the suspension; (3) the third experimental group consisted of 14 day-restrained antiorthostatic rats, to test the long term effect of the suspension. The study was performed in two organs involved in blood pressure regulation, i.e. the heart (atria and ventricles were separated) and kidneys. The Scatchard analysis of 125I-cyanopindolol binding in both organs indicated no significant alterations in the dissociation constant (Kd) and the maximum binding capacity (Bmax) in the three experimental groups. These results do not allow the conclusion about the SNS adaptation pattern to simulated microgravity. Thus, the hypothesis that betaAR are involved in the cardiovascular adaptation to simulated microgravity is not verified in this model where, as a matter of fact, cardiovascular deconditioning is not verified even if this model is widely used. PMID:10390061

  11. Changes in prevalence of subjective fatigue during 14-day 6° head-down bed rest

    NASA Astrophysics Data System (ADS)

    Hirayanagi, Kaname; Natsuno, Toyoki; Shiozawa, Tomoki; Yamaguchi, Nobuhisa; Watanabe, Yoriko; Suzuki, Satomi; Iwase, Satoshi; Mano, Tadaaki; Yajima, Kazuyoshi

    2009-06-01

    The present study examines the prevalence of subjective fatigue in young healthy males during 14 days of 6° head-down bed rest (HDBR) by using a multidimensional questionnaire. Forty-one subjects completed the Subjective Fatigue Scale questionnaire to assess the fatigue-related complaints and symptoms. The questionnaire is composed of three sections, with 10 items each. The sections measured drowsiness and dullness (Section 1), difficulty in concentration (Section 2), and the projection of physical disintegration (Section 3). The subjects answered simple questions between 1400 and 1700 on 6 measurement days before and during the HDBR period. The prevalence rate of low back pain was markedly high (80.5%) on the second day and more than 50% in the first half of the HDBR period, and any complaints related to either a lack of sleep or a deterioration in the quality of sleep continued until the end of the HDBR period. Our findings may be useful in developing preventive strategies against physical and mental fatigue associated with prolonged HDBR, horizontal bed rest, and microgravity environments.

  12. Evidence for increased beta-adrenoreceptor responsiveness induced by 14 days of simulated microgravity in humans

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Polet, J. L.; Engelke, K. A.; Hoffler, G. W.; Lane, L. D.; Blomqvist, C. G.; Eckberg, D. L. (Principal Investigator)

    1997-01-01

    We studied hemodynamic responses to alpha- and beta-receptor agonists in eight healthy men before and after 14 days of 6 degrees head-down tilt (HDT) to test the hypothesis that increased adrenoreceptor responsiveness is induced by prolonged exposure to simulated microgravity. Steady-state infusions of isoproterenol (Iso) at rates of 0.005, 0.01, and 0.02 microgram.kg-1.min-1 were used to assess beta 1- and beta 2-adrenoreceptor responsiveness. Infusions of phenylephrine (PE) at rates of 0.25, 0.50, and 1.00 microgram.kg-1.min-1 were used to assess responsiveness of alpha 1-vascular adrenoreceptors. Slopes calculated from linear regressions between Iso and PE doses and changes in beat-to-beat heart rate, blood pressure, and leg vascular resistance (occlusion plethysmography) for each subject were used as an index of alpha- and beta-adrenoreceptor responsiveness. HDT increased the slopes of heart rate (1,056 +/- 107 to 1,553 +/- 83 beats micrograms-1.kg-1.min-1; P = 0.014) and vasodilation (-469 +/- 111 to -1,446 +/- 309 peripheral resistance units.microgram-1.kg-1.min-1; P = 0.0224) to Iso infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that simulated microgravity causes selective increases in beta 1- and beta 2-adrenoreceptor responsiveness without affecting alpha 1-vascular adrenoreceptor responses.

  13. Glycogen depletion and resynthesis during 14 days of chronic low-frequency stimulation of rabbit muscle.

    PubMed

    Prats, C; Bernal, C; Cadefau, J A; Frias, J; Tibolla, M; Cussó, R

    2002-10-10

    Electro-stimulation alters muscle metabolism and the extent of this change depends on application intensity and duration. The effect of 14 days of chronic electro-stimulation on glycogen turnover and on the regulation of glycogen synthase in fast-twitch muscle was studied. The results showed that macro- and proglycogen degrade simultaneously during the first hour of stimulation. After 3 h, the muscle showed net synthesis, with an increase in the proglycogen fraction. The glycogen content peaked after 4 days of stimulation, macroglycogen being the predominant fraction at that time. Glycogen synthase was determined during electro-stimulation. The activity of this enzyme was measured at low UDPG concentration with either high or low Glu-6-P content. Western blots were performed against glycogen synthase over a range of stimulation periods. Activation of this enzyme was maximum before the net synthesis of glycogen, partial during net synthesis, and low during late synthesis. These observations suggest that the more active, dephosphorylated and very low phosphorylated forms of glycogen synthase may participate in the first steps of glycogen resynthesis before net synthesis is observed, while partially phosphorylated forms are most active during glycogen elongation. PMID:12383944

  14. Fiber size and myosin phenotypes of selected rhesus lower limb muscles after a 14-day spaceflight

    NASA Technical Reports Server (NTRS)

    Roy, R. R.; Zhong, H.; Bodine, S. C.; Pierotti, D. J.; Talmadge, R. J.; Barkhoudarian, G.; Kim, J.; Fanton, J. W.; Kozlovskaya, I. B.; Edgerton, V. R.

    2000-01-01

    Muscle biopsies were taken from the rhesus (Macaca mulatta) soleus (Sol, a slow ankle extensor), medial gastrocnemius (MG, a fast ankle extensor), tibialis anterior (TA, a fast ankle flexor), and vastus lateralis (VL, a fast knee extensor) muscles in vivarium controls (n=5) before and after either a 14-day spaceflight (Bion 11, n=2) or a 14-day ground-based flight simulation (n=3). Myosin heavy chain (MHC) composition (gel electrophoresis), fiber type distribution (immunohistochemistry), and fiber size were determined. Although there were no significant changes, each muscle showed trends towards adaptation.

  15. Short Term (14 Days) Consumption of Insoluble Wheat Bran Fibre-Containing Breakfast Cereals Improves Subjective Digestive Feelings, General Wellbeing and Bowel Function in a Dose Dependent Manner

    PubMed Central

    Lawton, Clare L.; Walton, Jenny; Hoyland, Alexa; Howarth, Elaine; Allan, Peter; Chesters, David; Dye, Louise

    2013-01-01

    This study investigated whether increasing insoluble (predominantly wheat bran) fibre over 14 days improves subjective digestive feelings, general wellbeing and bowel function. A single centre, multi-site, open, within subjects design with a 14 day non-intervention (baseline) monitoring period followed by a 14 day fibre consumption (intervention) period was performed. 153 low fibre consumers (<15 g/day AOAC 985.29) completed a daily symptom diary for 14 days after which they consumed one bowl of ready-to-eat breakfast cereal containing at least 5.4 g fibre (3.5 g from wheat bran) for 14 days and completed a daily symptom diary. Significant improvements were demonstrated in subjective perception of bowel function (e.g., ease of defecation) and digestive feelings (bloating, constipation, feeling sluggish and digestive discomfort). Significant improvements were also found in subjective perception of general wellbeing (feeling less fat, more mentally alert, slim, happy and energetic whilst experiencing less stress, mental and physical tiredness, difficulty concentrating and fewer headaches). In general, improvements in study outcomes increased with increasing cereal/fibre consumption. However, consuming an additional minimum 5.4 g of fibre (3.5 g wheat bran) per day was shown to deliver measurable and significant benefits for digestive health, comfort and wellbeing. Encouraging consumption of relatively small amounts of wheat bran could also provide an effective method of increasing overall fibre consumption. PMID:23609776

  16. Evidence for Increased Beta-Adrenoreceptor Responsiveness Induced by 14 Days of Simulated Microgravity in Humans

    NASA Technical Reports Server (NTRS)

    Convertino, Victor A.; Polet, Jill L.; Engelke, Keith A.; Hoffler, G. W.; Lane, Lynda D.

    1996-01-01

    We studied hemodynamic responses to alpha and beta receptor agonists in 8 healthy men ( 38+- 2 yrs) before and after 14 days of 6 degree head-down tilt (HDT) to test the hypothesis that increased adrenergic responsiveness is induced by prolonged exposure to microgravity. Immediately following a 30-min baseline period, a steady-state infusion of isoproterenol (ISO) was used to assess beta 1- and beta 2-adrenergic responsiveness. ISO was infused at three graded constant rates of 0.005, 0.01 and 0.02 ug/kg/min. After heart rate and blood pressure had been allowed to return to baseline levels following ISO infusion graded infusion of phenylephrine (PE) was used to assess responsiveness of alpha I-vascular receptors. PE was infused at three graded constant rates of 0.25, 0.50 and 1.00 ug/kg/min. Each infusion interval for both drugs was 9 min. During the infusions, constant monitoring of beat-to-beat blood pressure and heart rate was performed and leg blood flow was measured with occlusion plethysmography at each infusion level. The slopes calculated from linear regressions between ISO and PE doses and changes in heart rate, blood pressure, and leg vascular resistance for each subject were used to represent alpha- and beta- adrenoreceptor responsiveness. Fourteen days HDT increased the slopes of heart rate (1056 +- 107 to 1553 +- 83 beats/ug/kg/min; P= 0.014) and vasodilation (-469ft +- 111 to -l446 +- 309 PRU/ug/kg/min; P =0.0224) to ISO infusion. There was no alteration in blood pressure or vascular resistance responses to PE infusion after HDT. Our results provide evidence that microgravity causes selective increases in beta 1- and beta 2-adrenergic responsiveness without affecting alpha 1-vascular responses.

  17. Biomedical analysis of rat body hair after hindlimb suspension for 14 days

    NASA Astrophysics Data System (ADS)

    Terada, Masahiro; Kawano, Fuminori; Ishioka, Noriaki; Higashibata, Akira; Majima, Hideyuki J.; Yamazaki, Takashi; Watanabe-Asaka, Tomomi; Niihori, Maki; Nakao, Reiko; Yamada, Shin; Mukai, Chiaki; Ohira, Yoshinobu

    2012-04-01

    The levels of 26 minerals in rat body hair were analyzed in control and hindlimb-suspended Wistar Hannover rats (n=5 each). We quantified the levels of 22 minerals in this experiment. However, we were unable to measure the levels of 4 minerals (Be, V, Cd, and Hg) quantitatively because they were below the limit of detection. Of the 22 quantified, the levels of 19 minerals were not significantly different between control and hindlimb-suspended groups. The levels of 3 minerals (Pb, Cr, and Al) tended to be higher in the hindlimb-suspended group than in the control group; however, this difference was not significant. The concentrations of 3 other minerals (I, K, and Mg) were significantly different between the 2 groups. The iodine (I) level was 58.2% higher in the hindlimb-suspended group than in the control group (P<0.05). Potassium (K) and magnesium (Mg) levels were 55.2% and 20.4% lower, respectively, in the experimental group (P<0.05 in both cases). These results indicate that a physiological change in mineral metabolism resulting from physical or mental stress, such as hindlimb suspension, is reflected in body hair. The Japan Aerospace Exploration Agency (JAXA) has initiated a human research study to investigate the effects of long-term space flight on gene expression and mineral metabolism by analyzing hair samples of astronauts who stayed in the International Space Station (ISS) for 6 months. We believe that hindlimb suspension for 14 days can simulate the effects of an extremely severe environment, such as space flight, because the hindlimb suspension model elicits a rapid physiological change in skeletal muscle, bone, and fluid shift even in the short term. These results also suggest that we can detect various effects on the body by analyzing the human scalp hair shaft.

  18. Flexible range finding applied to 3D surface synthesis: A pseudo-trinocular approach

    NASA Astrophysics Data System (ADS)

    Hong, Tongminh

    An important area in machine vision and computer graphics is surface modeling, which involves the issue of data acquisition. A new range finding system is proposed which exploits perspective invariance (cross ratio), the targeting capability of structural lighting (slide projector), and epipolar planes' geometry (trinocular strategy). The system allows a fully autonomous calibration process and is highly efficient in terms of speed and accuracy. The system eliminates the ambiguity in disparity matching experienced in stereopsis, the extra image processing encountered in the trinocular system, the tedious reorganization of range data into a rectangular domain for surface modeling, and the scanning process of most active range finders that are not suitable for moving objects. Research described includes the development of several new camera calibration techniques, reformulation of the epipolar lines geometry method, and a rigorous study of the orientation constraints of the sensors (cameras and projector) in order to enhance the robustness of the vision system. The superiority of this new pseudo trinocular approach over the active structural lighting method and the passive binocular and/or trinocular techniques is convincing. It is believed that the proposed range finder has considerable potential for surface modeling.

  19. Detecting laser-range-finding signals in surveying converter lining based on wavelet transform

    NASA Astrophysics Data System (ADS)

    Li, Hongsheng; Yang, Xiaofei; Shi, Tielin; Yang, Shuzi

    1998-08-01

    The precision of the laser range finding subsystem has important influences on the performances of the whole measurement system applied to survey the steelmaking converter lining erosion state. In the system, the object of laser beams is some rough lighting surfaces in high temperature. the laser range finding signals to reach the microcomputer system would be submerged in intense disturb environments. Common laser range finding devices could not work normally. This paper presents a method based on the wavelet transform to test solving the problem. The idea of this method includes encoding the measuring signals, decomposing the encoded received signals of components in different frequency scales and time domains by the wavelet transform method, extracting the features of encoded signals according to queer points to confirm the arrival of signals, and accurately calculating out the measured distances. In addition, the method is also helpful to adopt some digital filter algorithms in time. It could make further in improvement on the precision.

  20. Adaptations of young adult rat cortical bone to 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Vanderby, R., Jr.; Martinez, D. A.; Ashman, R. B.; Ulm, M. J.; Grindeland, R. E.; Durnova, G. N.; Kaplanskii, A.

    1992-01-01

    To determine whether mature humeral cortical bone would be modified significantly by an acute exposure to weightlessness, adult rats (110 days old) were subjected to 14 days of microgravity on the COSMOS 2044 biosatellite. There were no significant changes in peak force, stiffness, energy to failure, and displacement at failure in the flight rats compared with ground-based controls. Concentrations and contents of hydroxyproline, calcium, and mature stable hydroxylysylpyridinoline and lysylpyridinoline collagen cross-links remained unchanged after spaceflight. Bone lengths, cortical and endosteal areas, and regionl thicknesses showed no significant differences between flight animals and ground controls. The findings suggest that responsiveness of cortical bone to microgravity is less pronounced in adult rats than in previous spaceflight experiments in which young growing animals were used. It is hypothesized that 14 days of spaceflight may not be sufficient to impact the biochemical and biomechanical properties of cortical bone in the mature rat skeleton.

  1. Integrated Resistance and Aerobic Training Maintains Cardiovascular and Skeletal Muscle Fitness During 14 Days of Bed Rest

    NASA Technical Reports Server (NTRS)

    Ploutz-Snyder, Lori; Goetchius, Elizabeth; Crowell, Brent; Hackney, Kyle; Wickwire, Jason; Ploutz-Snyder, Robert; Snyder, Scott

    2012-01-01

    Background: Known incompatibilities exist between resistance and aerobic training. Of particular importance are findings that concurrent resistance and aerobic training reduces the effectiveness of the resistance training and limits skeletal muscle adaptations (example: Dudley & Djamil, 1985). Numerous unloading studies have documented the effectiveness of resistance training alone for the maintenance of skeletal muscle size and strength. However the practical applications of those studies are limited because long ]duration crew members perform both aerobic and resistance exercise throughout missions/spaceflight. To date, such integrated training on the International Space Station (ISS) has not been fully effective in the maintenance of skeletal muscle function. Purpose: The purpose of this study was to evaluate the efficacy of high intensity concurrent resistance and aerobic training for the maintenance of cardiovascular fitness and skeletal muscle strength, power and endurance over 14 days of strict bed rest. Methods: 9 subjects (8 male and 1 female; 34.5 +/- 8.2 years) underwent 14 days of bed rest with concurrent training. Resistance and aerobic training were integrated as shown in table 1. Days that included 2 exercise sessions had a 4-8 hour rest between exercise bouts. The resistance training consisted of 3 sets of 12 repetitions of squat, heel raise, leg press and hamstring curl exercise. Aerobic exercise consisted of periodized interval training that included 30 sec, 2 min and 4 min intervals alternating by day with continuous aerobic exercise.

  2. Optimal Culture Incubation Time in Orthopedic Device-Associated Infections: a Retrospective Analysis of Prolonged 14-Day Incubation

    PubMed Central

    Wahl, Peter; Fracheboud, Dominique; Gautier, Emanuel

    2014-01-01

    Accurate diagnosis of orthopedic device-associated infections can be challenging. Culture of tissue biopsy specimens is often considered the gold standard; however, there is currently no consensus on the ideal incubation time for specimens. The aim of our study was to assess the yield of a 14-day incubation protocol for tissue biopsy specimens from revision surgery (joint replacements and internal fixation devices) in a general orthopedic and trauma surgery setting. Medical records were reviewed retrospectively in order to identify cases of infection according to predefined diagnostic criteria. From August 2009 to March 2012, 499 tissue biopsy specimens were sampled from 117 cases. In 70 cases (59.8%), at least one sample showed microbiological growth. Among them, 58 cases (82.9%) were considered infections and 12 cases (17.1%) were classified as contaminations. The median time to positivity in the cases of infection was 1 day (range, 1 to 10 days), compared to 6 days (range, 1 to 11 days) in the cases of contamination (P < 0.001). Fifty-six (96.6%) of the infection cases were diagnosed within 7 days of incubation. In conclusion, the results of our study show that the incubation of tissue biopsy specimens beyond 7 days is not productive in a general orthopedic and trauma surgery setting. Prolonged 14-day incubation might be of interest in particular situations, however, in which the prevalence of slow-growing microorganisms and anaerobes is higher. PMID:24153117

  3. NASA 14 Day Undersea Missions: A Short-Duration Spaceflight Analog for Immune System Dysregulation

    NASA Technical Reports Server (NTRS)

    Crucian, B. E.; Stowe, R. P.; Mehta, S. K.; Quiriarte, H.; Pierson, D. L.; Sams, C. F.

    2010-01-01

    BACKGROUND Spaceflight-associated immune dysregulation (SAID) occurs during spaceflight and may represent specific clinical risks for exploration-class missions. An appropriate ground analog for spaceflight-associated immune dysregulation would offer a platform for ground-evaluation of various potential countermeasures. This study evaluated the NASA Undersea Mission Operations ( NEEMO ), consisting of 14 day undersea deployment at the Aquarius station, as an analog for SAID. Sixteen Aquanauts from missions NEEMO-12, 13 and 14 participated in the study. RESULTS Mid-mission alterations leukocyte distribution occurred, including granulocytosis and elevations in central-memory CD8+ T-cells. General T cell function was reduced during NEEMO missions in roughly 50% of subjects. Secreted cytokines profiles were evaluated following whole blood stimulation with CD3/CD28 (T cells) or LPS (monocytes). T cell production of IFNg, IL-5, IL-10, IL-2, TNFa and IL-6 were all reduced before and during the mission. Conversely, monocyte production of TNFa, IL-10, IL-6, IL-1b and IL-8 were elevated during mission, moreso at the MD-14 timepoint. Antibodies to Epstein-Barr virus (EBV) viral capsid antigen and early antigen were increased in approximately 40% of the subjects. Changes in EBV tetramer-positive CD8+ T-cells exhibited a variable pattern. Antibodies against Cytomegalovirus (CMV) were marginally increased during the mission. Herpesvirus reactivation was determined by PCR. EBV viral load was generally elevated at L-6. Higher levels of salivary EBV were found during the NEEMO mission than before and after as well as than the healthy controls. No VZV or CMV was found in any pre, during and after NEEMO mission or control samples. Plasma cortisol was elevated at L-6. CONCLUSION Unfortunately, L-6 may be too near to mission start to be an appropriate baseline measurement. The general immune changes in leukocyte distribution, T cell function, cytokine production, virus specific

  4. Comparison of soleus muscles from rats exposed to microgravity for 10 versus 14 days

    NASA Technical Reports Server (NTRS)

    Staron, R. S.; Kraemer, W. J.; Hikida, R. S.; Reed, D. W.; Murray, J. D.; Campos, G. E.; Gordon, S. E.

    1998-01-01

    The effects of two different duration space-flights on the extent of atrophy, fiber type composition, and myosin heavy chain (MHC) content of rat soleus muscles were compared. Adult male Fisher rats (n=12) were aboard flight STS-57 and exposed to 10 days of microgravity and adult ovariectomized female Spraque-Dawley rats (n=12) were aboard flight STS-62 for 14 days. Soleus muscles were bilaterally removed from the flight and control animals and frozen for subsequent analyses. Muscle wet weights, fiber types (I, IC, IIC, and IIA), cross-sectional area, and MHC content were determined. Although a significant difference was found between the soleus wet weights of the two ground-based control groups, they were similar with regard to MHC content (ca 90% MHCI and ca 10% MHCIIa) and fiber type composition. Unloading of the muscles caused slow-to-fast transformations which included a decrease in the percentage of type I fibers and MHCI, an increase in fibers classified as type IC, and the expression of two fast myosin heavy chains not found in the control rat soleus muscles (MHCIId and MHCIIb). Although the amount of atrophy (ca 26%) and the extent of slow-to-fast transformation (decrease in the percentage of MHCI from 90% to 82.5%) in the soleus muscles were similar between the two spaceflights, the percentages of the fast MHCs differed. After 14 days of spaceflight, the percentage of MHCIIa was significantly lower and the percentages of MHCIId and MHCIIb were significantly higher than the corresponding MHC content of the soleus muscles from the 10-day animals. Indeed, MHCIId became the predominant fast MHC after 14 days in space. These data suggest fast-to-faster transformations continued during the longer spaceflight.

  5. +Gz tolerance in man after 14-day bedrest periods with isometric and isotonic exercise conditioning

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Haines, R. F.; Sandler, H.; Bernauer, E. M.; Morse, J. T.; Armbruster, R.; Sagan, L.; Van Beaumont, W.

    1975-01-01

    The effects of isometric and isotonic exercise training on post-bedrest +Gz tolerance were determined. In general, 14-day bedrest resulted in a significant loss of Gz tolerance, as previously discovered. At 2.1 Gz, neither the isometric nor the isotonic exercises regimens resulted in a significant increase in post-bedrest Gz tolerance. However, following isometric exercise, restoration of about half the tolerance decrement occurred at 3.2 Gz and 3.8 Gz. Possible reasons for this partial restoration of tolerance are put forward.

  6. Changes in recruitment of Rhesus soleus and gastrocnemius muscles following a 14 day spaceflight

    NASA Technical Reports Server (NTRS)

    Hodgson, J. A.; Bodine-Fowler, S. C.; Roy, R. R.; De Leon, R. D.; De Guzman, C. P.; Koslovskaia, I.; Sirota, M.; Edgerton, V. R.

    1991-01-01

    The effect of microgravity on the recruitment patterns of the soleus, gastrocnemius, and tibialis-anterior muscles was investigated by comparing electromyograms (EMGs) of these muscles of Rhesus monkeys implanted with EMG electrodes, taken before and after a 14-day flight on board Cosmos 2044. It was found that the EMG amplitude values in the soleus muscle decreased after the spaceflight but returned to normal values over the 2-wk recovery period. The medial amplitudes of gastrocnemius and tibialis anterior were not changed by flight. Joint probability density distributions displayed changes after flight in both the soleus and gastrocnemius muscles, but not in tibialis anterior.

  7. Effect of high sodium intake during 14 days of bed-rest on acid-base balance

    NASA Astrophysics Data System (ADS)

    Frings, P.; Baecker, N.; Heer, M.

    Lowering mechanical load like in microgravity is the dominant stimulus leading to bone loss However high dietary sodium intake is also considered as a risk factor for osteoporosis and thereby might exacerbate the microgravity induced bone loss In a metabolic balance non bed-rest study we have recently shown that a very high sodium intake leads to an increased bone resorption most likely because of a mild metabolic acidosis Frings et al FASEB J 19 5 A1345 2005 To test if mild metabolic acidosis also occurs during immobilization we examined the effect of increased dietary sodium on bone metabolism and acid-base balance in eight healthy male test subjects mean age 26 25 pm 3 49 years body weight 77 98 pm 4 34 kg in our metabolic ward during a 14-day head-down tilt HDT bed-rest study The study was designed as a randomized crossover study with two study periods Each period was divided into three parts 4 ambulatory days with 200 mmol sodium intake 14 days of bed-rest with either 550 mmol or 50 mmol sodium intake and 3 recovery days with 200 mmol sodium intake The sodium intake was altered by variations in dietary sodium chloride content Blood pH P CO2 and P O2 were analyzed in fasting morning fingertip blood samples several times during the entire study Bicarbonate HCO 3 - and base excess BE were calculated according to the Henderson-Hasselbach equation Preliminary results in the acid-base balance from the first study period 4 subjects with 550 mmol and 4 subjects with 50 mmol sodium intake strongly

  8. Hemodynamics, renal function, plasma renin, and aldosterone in man after 5 to 14 days of bedrest

    NASA Technical Reports Server (NTRS)

    Melada, G. A.; Goldman, R. H.; Luetscher, J. A.; Zager, P. G.

    1975-01-01

    Continuous bedrest for 5 to 14 days had no significant effect on resting heart rate, blood pressure, or cardiac output in six normal men. Head-up tilt induced greater tachycardia in 5 of 6 patients after bed rest than in the control period. Propranolol diminished both tachycardia and the incidence of hypotension and faintness in upright posture. Plasma volume fell, extracellular fluid volume increased, and plasma renin activity was significantly elevated following bedrest. Unusually large increases in plasma renin followed head-up tilt or administration of isoproterenol during bedrest and after resuming normal activity. During bedrest, plasma aldosterone was often increased in the early morning. It is concluded that after bedrest, upright posture evokes strong beta-adrenergic activity as well as exaggerated metabolic and circulatory responses which can be reduced or abolished by the beta-adrenergic blocker, propranolol.

  9. Self-Reported Recovery from 2-Week 12-Hour Shift Work Schedules: A 14-Day Follow-Up

    PubMed Central

    Merkus, Suzanne L.; Holte, Kari Anne; Huysmans, Maaike A.; van de Ven, Peter M.; van Mechelen, Willem; van der Beek, Allard J.

    2015-01-01

    Background Recovery from fatigue is important in maintaining night workers' health. This study compared the course of self-reported recovery after 2-week 12-hour schedules consisting of either night shifts or swing shifts (i.e., 7 night shifts followed by 7 day shifts) to such schedules consisting of only day work. Methods Sixty-one male offshore employees—20 night workers, 16 swing shift workers, and 25 day workers—rated six questions on fatigue (sleep quality, feeling rested, physical and mental fatigue, and energy levels; scale 1–11) for 14 days after an offshore tour. After the two night-work schedules, differences on the 1st day (main effects) and differences during the follow-up (interaction effects) were compared to day work with generalized estimating equations analysis. Results After adjustment for confounders, significant main effects were found for sleep quality for night workers (1.41, 95% confidence interval 1.05–1.89) and swing shift workers (1.42, 95% confidence interval 1.03–1.94) when compared to day workers; their interaction terms were not statistically significant. For the remaining fatigue outcomes, no statistically significant main or interaction effects were found. Conclusion After 2-week 12-hour night and swing shifts, only the course for sleep quality differed from that of day work. Sleep quality was poorer for night and swing shift workers on the 1st day off and remained poorer for the 14-day follow-up. This showed that while working at night had no effect on feeling rested, tiredness, and energy levels, it had a relatively long-lasting effect on sleep quality. PMID:26929834

  10. Daily Supine LBNP Treadmill Exercise Maintains Upright Exercise Capacity During 14 Days of Bed Rest

    NASA Technical Reports Server (NTRS)

    Ertl, Andy C.; Watenpaugh, D. E.; Hargens, Alan R.; Fortney, S. M.; Lee, S. M. C.; Ballard, R. E.; William, J. M.

    1996-01-01

    Exposure to microgravity or bed rest reduces upright exercise capacity. Exercise modes, durations, and intensities which will effectively and efficiently counteract such deconditioning are presently unresolved. We that daily supine treadmill interval training with lower body negative pressure (LBNP) would prevent reduction in upright exercise capacity during 14 days of 6 deg. head-down bed rest (BR). Eight healthy male subjects underwent two 14 day BR protocols separated by 3 months. In a crossover design, subjects either remained at strict BR or performed 40 min of daily exercise consisting of supine walking and running at intensities varying from 40-80% of pre-BR upright peak oxygen uptake (VO2). LBNP during supine exercise was used to provide 1.0 to 1.2 times body weight of footward force. An incremental upright treadmill test to measure submaximal and peak exercise responses was given pre- and post-BR. In the non-exercise condition, peak VO2 and time to exhaustion were reduced 16 +/- 4% and 10 +/- 1% (p less than 0.05), respectively, from pre-BR. With LBNP exercise these variables were not significantly different (NS) from pre-BR. During submaximal treadmill speeds after BR, heart rate was higher (11 +/- 11 bpm, p less than 0.05) and respiratory exchange ratio was elevated (p less than 0.05) in the no exercise condition. Both were maintained at pre-BR levels in the LBNP exercise condition (NS from pre-BR). Since this supine treadmill interval training with addition of LBNP maintained upright exercise responses and capacity during BR, this countermeasure may also be effective during space flight.

  11. Range-finding in squid using retinal deformation and image blur.

    PubMed

    Chung, Wen-Sung; Marshall, Justin

    2014-01-20

    Squid and other cephalopods catch prey with remarkable speed and precision [1]. Before the strike occurs, they encounter the difficult task of judging an object's distance and size in the contrast-poor world of the mid-water environment [1-4]. Here we describe a solution to this common problem underwater, where a large portion of a squid's dorso-temporal retina is intentionally blurred. This apparently counter-adaptive 'retinal bump' is combined with a vertical bobbing behavior that scans objects of interest from focused to defocused retinal regions. The image focus differential changes sharply at precisely the distance equivalent to tentacle length and enables the squid, Sepioteuthis lessoniana, to capture prey. This unique range-finding mechanism is an adaptation to hunting, defense, and object size identification in an environment where the depth cues found on land are less reliable. PMID:24456975

  12. Thyroid hormones improve cardiac function and decrease expression of pro-apoptotic proteins in the heart of rats 14 days after infarction.

    PubMed

    de Castro, Alexandre Luz; Fernandes, Rafael Oliveira; Ortiz, Vanessa D; Campos, Cristina; Bonetto, Jéssica H P; Fernandes, Tânia R G; Conzatti, Adriana; Siqueira, Rafaela; Tavares, Angela Vicente; Schenkel, Paulo Cavalheiro; Belló-Klein, Adriane; da Rosa Araujo, Alex Sander

    2016-02-01

    Apoptosis is a key process associated with pathological cardiac remodelling in early-phase post-myocardial infarction. In this context, several studies have demonstrated an anti-apoptotic effect of thyroid hormones (TH). The aim of this study was to evaluate the effects of TH on the expression of proteins associated with the apoptotic process 14 days after infarction. Male Wistar rats (300-350 g) (n = 8/group) were divided into four groups: Sham-operated (SHAM), infarcted (AMI), sham-operated + TH (SHAMT) and infarcted + TH (AMIT). For 12 days, the animals received T3 and T4 [2 and 8 µg/(100 g day)] by gavage. After this, the rats were submitted to haemodynamic and echocardiographic analysis, and then were sacrificed and the heart tissue was collected for molecular analysis. Statistical analyses included two-way ANOVA with Student-Newman-Keuls post test. Ethics Committee number: 23262. TH administration prevented the loss of ventricular wall thickness and improved cardiac function in the infarcted rats 14 days after the injury. AMI rats presented an increase in the pro-apoptotic proteins p53 and JNK. The hormonal treatment prevented this increase in AMIT rats. In addition, TH administration decreased the Bax:Bcl-2 ratio in the infarcted rats. TH administration improved cardiac functional parameters, and decreased the expression of pro-apoptotic proteins 14 days after myocardial infarction. PMID:26659365

  13. Automation of a reclaimer using global and local range-finding systems

    NASA Astrophysics Data System (ADS)

    Ahn, Hyun S.; Choi, Chin T.; Lee, Kwan H.; Ha, Yeong-Ho

    1996-02-01

    A reclaimer is used to dig raw material from a pile and transfer it to the blast furnaces in a steel making company. We propose a range finding vision system consisting of global and local range finders to fully automate the reclaimer. A global range sensor attached to the top of the reclaimer enables scanning more than 270 degrees and detecting a three dimensional profile of a pile. The sensor uses Ladar containing a range finder and one axis scan mirror. We added a motor to rotate Ladar for another axis scanning. A height map is obtained from the acquired range data by geometric transformation. Linear interpolation is applied between neighboring range data pixels because the initial height map is represented as a group of sparsely shaped points. By thresholding and edge following, we can calculate the optimal job path which avoids overload and maximizes digging efficiency. A local range finder attached at the end of the boom detects range data between the pile and bucket. The world coordinates are computed by three-dimensional translation and rotation of local range data. The local range data is used for renewing the height map after picking up some part of the pile. In this way, we obtain pile management and reclaimer automation.

  14. Attenuated thermoregulatory sweating and cutaneous vasodilation after 14-day bed rest in humans.

    PubMed

    Michikami, Daisaku; Kamiya, Atsunori; Fu, Qi; Iwase, Satoshi; Mano, Tadaaki; Sunagawa, Kenji

    2004-01-01

    We investigated the effect of head-down bed rest (HDBR) for 14 days on thermoregulatory sweating and cutaneous vasodilation in humans. Fluid intake was ad libitum during HDBR. We induced whole body heating by increasing skin temperature for 1 h with a water-perfused blanket through which hot water (42 degrees C) was circulated. The experimental room was air-conditioned (27 degrees C, 30-40% relative humidity). We measured skin blood flow (chest and forearm), skin temperatures (chest, upper arm, forearm, thigh, and calf), and tympanic temperature. We also measured sweat rate by the ventilated capsule method in which the skin area for measurement was drained by dry air conditioned at 27 degrees C under similar skin temperatures in both trials. We calculated cutaneous vascular conductance (CVC) from the ratio of skin blood flow to mean blood pressure. From tympanic temperature-sweat rate and -CVC relationships, we assessed the threshold temperature and sensitivity as the slope response of variables to a given change in tympanic temperature. HDBR increased the threshold temperature for sweating by 0.31 degrees C at the chest and 0.32 degrees C at the forearm, whereas it reduced sensitivity by 40% at the chest and 31% at the forearm. HDBR increased the threshold temperature for cutaneous vasodilation, whereas it decreased sensitivity. HDBR reduced plasma volume by 11%, whereas it did not change plasma osmolarity. The increase in the threshold temperature for sweating correlated with that for cutaneous vasodilation. In conclusion, HDBR attenuated thermoregulatory sweating and cutaneous vasodilation by increasing the threshold temperature and decreasing sensitivity. HDBR increased the threshold temperature for sweating and cutaneous vasodilation by similar magnitudes, whereas it decreased their sensitivity by different magnitudes. PMID:12949026

  15. AICAR treatment for 14 days normalizes obesity-induced dysregulation of TORC1 signaling and translational capacity in fasted skeletal muscle.

    PubMed

    Drake, Joshua C; Alway, Stephen E; Hollander, John M; Williamson, David L

    2010-12-01

    The aim of this study was to determine the effect of 14 days of 5-aminoimidazole-4-carboxamide-1β-4-ribofuranoside (AICAR) treatment on mammalian target of rapamycin (mTOR) signaling and mTOR-regulated processes (i.e., translation initiation) in obese mouse skeletal muscle. Our hypothesis was that daily treatment (14 days) with AICAR would normalize obesity-induced alterations in skeletal muscle mTOR signaling and mTOR-regulated processes to lean levels and positively affect muscle mass. Fourteen-week-old male, lean (L; 31.3 g body wt) wild-type and ob/ob (O; 59.6 g body wt) mice were injected with the AMP-activated kinase (AMPK) activator AICAR (A) at 0.5 mg·g body wt(-1)·day(-1) or saline control (C) for 14 days. At 24 h after the last injection (including a 12-h fast), all mice were killed, and the plantar flexor complex muscle (gastrocnemius, soleus, and plantaris) was excised for analysis. Muscle mass was lower in OC (159 ± 12 mg) than LC, LA, and OA (176 ± 10, 178 ± 9, and 166 ± 16 mg, respectively) mice, independent of a body weight change. A decrease in obese muscle mass corresponded with higher muscle cross section staining intensity for lipid and glycogen, higher blood glucose and insulin levels, and lower nuclear-enriched fractions for peroxisome proliferator-activated receptor-γ coactivator-1α protein expression in OC skeletal muscle, which was normalized with AICAR treatment. AMPK and acetyl-cocarboxylase phosphorylation was reduced in OC mice and augmented by AICAR treatment in OA mice. Conversely, OC mice displayed higher activation of downstream targets (S6 kinase-1 and ribosomal protein S6) of mTOR and lower raptor-associated mTOR than LC mice, which were reciprocally altered after 14 days of AICAR treatment. Dysregulation of translational capacity was improved in OA mice, as assessed by sucrose density gradient fractionation of ribosomes, total and ribosome-associated RNA content, eukaryotic initiation factor 4F complex formation, and

  16. Neurobehavioral Toxicity of a Repeated Exposure (14 Days) to the Airborne Polycyclic Aromatic Hydrocarbon Fluorene in Adult Wistar Male Rats

    PubMed Central

    Peiffer, Julie; Cosnier, Frédéric; Grova, Nathalie; Nunge, Hervé; Salquèbre, Guillaume; Decret, Marie-Josèphe; Cossec, Benoît; Rychen, Guido; Appenzeller, Brice M. R.; Schroeder, Henri

    2013-01-01

    Fluorene is one of the most abundant polycyclic aromatic hydrocarbons in air and may contribute to the neurobehavioral alterations induced by the environmental exposure of humans to PAHs. Since no data are available on fluorene neurotoxicity, this study was conducted in adult rats to assess the behavioral toxicity of repeated fluorene inhalation exposure. Male rats (n = 18/group) were exposed nose-only to 1.5 or 150 ppb of fluorene 6 hours/day for 14 consecutive days, whereas the control animals were exposed to non-contaminated air. At the end of the exposure, animals were tested for activity and anxiety in an open-field and in an elevated-plus maze, for short-term memory in a Y-maze, and for spatial learning in an eight-arm maze. The results showed that the locomotor activity and the learning performances of the animals were unaffected by fluorene. In parallel, the fluorene-exposed rats showed a lower level of anxiety than controls in the open-field, but not in the elevated-plus maze, which is probably due to a possible difference in the aversive feature of the two mazes. In the same animals, increasing blood and brain levels of fluorene monohydroxylated metabolites (especially the 2-OH fluorene) were detected at both concentrations (1.5 and 150 ppb), demonstrating the exposure of the animals to the pollutant and showing the ability of this compound to be metabolized and to reach the cerebral compartment. The present study highlights the possibility for a 14-day fluorene exposure to induce some specific anxiety-related behavioral disturbances, and argues in favor of the susceptibility of the adult brain when exposed to volatile fluorene. PMID:23977039

  17. Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans

    NASA Technical Reports Server (NTRS)

    Wilson, Thad E.; Shibasaki, Manabu; Cui, Jian; Levine, Benjamin D.; Crandall, Craig G.

    2003-01-01

    This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and

  18. Nocturnal Hypoxia Exposure With Simulated Altitude For 14 Days Does Not Significantly Alter Working Memory or Vigilance in Humans

    PubMed Central

    Thomas, Robert Joseph; Tamisier, Renaud; Boucher, Judith; Kotlar, Yana; Vigneault, Kevin; Weiss, J. Woodrow; Gilmartin, Geoffrey

    2007-01-01

    Study Objectives: To assess the effect of 2 weeks of nocturnal hypoxia exposure using simulated altitude on attention and working memory in healthy adult humans. Design: Prospective experimental physiological assessment. Setting: General Clinical Research Center. Participants: Eleven healthy, nonsmoking, subjects (7 men, 4 women). The subjects had a mean age of 27 ± 1.5 years and body mass index of 23 ± 0.9 kg/m2 Interventions: Subjects were exposed to 9 hours of continuous hypoxia from 2200 to 0700 hours in an altitude tent. Acclimatization was accomplished by graded increases in “altitude” over 3 nights (7700, 10,000 and 13,000 feet), followed by 13,000 feet for 13 consecutive days (FIO2 0.13). Measurements and Results: Polysomnography that included airflow measurements with a nasal cannula were done at baseline and during 3 time points across the protocol (nights 3, 7, and 14). Attention (10-minute Psychomotor Vigilance Task) and working memory (10-minute verbal 2-back) were assessed at baseline and on day 4, 8, 9, and 15. Nocturnal hypoxia was documented using endpoints of minimum oxygen saturation, oxygen desaturation index, and percentage of total sleep time under 90% and 80%. Total sleep time was reduced, stage 1 sleep was increased, and both obstructive and nonobstructive respiratory events were induced by altitude exposure. There was no difference in subjective mood, attention, or working memory. Conclusions: Two weeks of nocturnal continuous hypoxia in an altitude tent did not induce subjective sleepiness or impair objective vigilance and working memory. Caution is recommended in the extrapolation to humans the effects of hypoxia in animal models. Citation: Thomas RJ; Ramisier R; Boucher J; Kotlar Y; Vigneault K; Weiss JW; Gilmartin G. Nocternal hypoxia exposure with simulated altitude for 14 days does not significantly alter working memory or vigilance in humans. SLEEP 2007;30(9):1195-1203. PMID:17910391

  19. Range-Finding Risk Assessment of Inhalation Exposure to Nanodiamonds in a Laboratory Environment

    PubMed Central

    Koivisto, Antti J.; Palomäki, Jaana E.; Viitanen, Anna-Kaisa; Siivola, Kirsi M.; Koponen, Ismo K.; Yu, Mingzhou; Kanerva, Tomi S.; Norppa, Hannu; Alenius, Harri T.; Hussein, Tareq; Savolainen, Kai M.; Hämeri, Kaarle J.

    2014-01-01

    This study considers fundamental methods in occupational risk assessment of exposure to airborne engineered nanomaterials. We discuss characterization of particle emissions, exposure assessment, hazard assessment with in vitro studies, and risk range characterization using calculated inhaled doses and dose-response translated to humans from in vitro studies. Here, the methods were utilized to assess workers’ risk range of inhalation exposure to nanodiamonds (NDs) during handling and sieving of ND powder. NDs were agglomerated to over 500 nm particles, and mean exposure levels of different work tasks varied from 0.24 to 4.96 µg·m−3 (0.08 to 0.74 cm−3). In vitro-experiments suggested that ND exposure may cause a risk for activation of inflammatory cascade. However, risk range characterization based on in vitro dose-response was not performed because accurate assessment of delivered (settled) dose on the cells was not possible. Comparison of ND exposure with common pollutants revealed that ND exposure was below 5 μg·m−3, which is one of the proposed exposure limits for diesel particulate matter, and the workers’ calculated dose of NDs during the measurement day was 74 ng which corresponded to 0.02% of the modeled daily (24 h) dose of submicrometer urban air particles. PMID:24840353

  20. Pharmacokinetics and dose-range finding toxicity of a novel anti-HIV active integrase inhibitor.

    PubMed

    Nair, Vasu; Okello, Maurice; Mishra, Sanjay; Mirsalis, Jon; O'Loughlin, Kathleen; Zhong, Yu

    2014-08-01

    Integration of viral DNA into human chromosomal DNA catalyzed by HIV integrase represents the "point of no return" in HIV infection. For this reason, HIV integrase is considered a crucial target in the development of new anti-HIV therapeutic agents. We have discovered a novel HIV integrase inhibitor 1, that exhibits potent antiviral activity and a favorable metabolism profile. This paper reports on the pharmacokinetics and toxicokinetics of compound 1 and the relevance of these findings with respect to further development of this integrase-targeted antiviral agent. Oral administration of compound 1 in Sprague Dawley rats revealed rapid absorption. Drug exposure increased with increasing drug concentration, indicative of appropriate dose-dependence correlation. Compound 1 exhibited suitable plasma half-life, extensive extravascular distribution and acceptable bioavailability. Toxicity studies revealed no compound-related clinical pathology findings. There were no changes in erythropoietic, white blood cell or platelet parameters in male and female rats. There was no test-article related change in other clinical chemistry parameters. In addition, there were no detectable levels of bilirubin in the urine and there were no treatment-related effects on urobilinogen or other urinalysis parameters. The preclinical studies also revealed that the no observed adverse effect level and the maximum tolerated dose were both high (>500mg/kg/day). The broad and significant antiviral activity and favorable metabolism profile of this integrase inhibitor, when combined with the in vivo pharmacokinetic and toxicokinetic data and their pharmacological relevance, provide compelling and critical support for its further development as an anti-HIV therapeutic agent. PMID:24821255

  1. Evaluation of Arecoline Hydrobromide Toxicity after a 14-Day Repeated Oral Administration in Wistar Rats

    PubMed Central

    Niu, Jianrong; Zhou, Xuzheng; Li, Jianyong; Li, Bing

    2015-01-01

    A subchronic toxicity test was conducted in rats on the basis of a previous acute toxicity test to evaluate the safety of arecoline hydrobromide (Ah), to systematically study its pharmacological effects and to provide experimental support for a safe clinical dose. Eighty rats were randomly divided into four groups: a high-dose group (1000 mg/kg), medium-dose group (200 mg/kg), low-dose group (100mg/kg) and blank control group. The doses were administered daily via gastric lavage for 14 consecutive days. There were no significant differences in the low-dose Ah group compared to the control group (P>0.05) with regard to body weight, organ coefficients, hematological parameters and histopathological changes. The high-dose of Ah influenced some of these parameters, which requires further study. The results of this study indicated that a long-term, continuous high dose of Ah was toxic. However, it is safe to use Ah according to the clinically recommended dosing parameters. The level of Ah at which no adverse effects were observed was 100 mg/kg/day under the present study conditions. PMID:25880067

  2. Antiorthostatic suspension for 14 days does not diminish the oxidative response of neutrophils in mice

    NASA Technical Reports Server (NTRS)

    Smolen, J. E.; Fossett, M. C.; Joe, Y.; Prince, J. E.; Priest, E.; Kanwar, S.; Smith, C. W.

    2000-01-01

    The effects of long-term spaceflight on inflammatory responses have not been well-studied in either humans or animals. It is thus important to determine if the functions of immune and inflammatory cells are altered in models of spaceflight. One such animal model is antiorthostatic suspension (AOS), in which the experimental animal is subjected to a head-down tilt that mimics both the stress and the cephalad fluid shift experienced in spaceflight. A previous study reported that the peritoneal neutrophils from mice experiencing AOS generated less superoxide than unsuspended controls. We expanded on this study using several different stimuli and measuring the oxidative response of murine neutrophils in a variety of ways. These responses included the rate, lag period, and dose/response characteristics for superoxide generation, FACS analysis with dihydrodichlorofluorescein as a substrate, and a chemiluminescence response with luminol as a substrate. We also examined phagocytosis of three different microorganisms. While some effects of orthostatic suspension (attributable to the stress of the apparatus) were observed, no clear effects of AOS on oxidative function of the peritoneal neutrophils were seen.

  3. +Gz tolerance in man after 14-day bedrest periods with isometric and isotonic exercise conditioning.

    PubMed

    Greenleaf, J E; Bernauer, E M; Morse, J T; Sandler, H; Armbruster, R; Sagan, L; van Beaumont, W

    1975-05-01

    The purpose of this study was to determine the effects of isometric or isotonic exercise training on post-bedrest +Gz tolerance. Seven male volunteers, 19-22 years, underwent accelerations of +2.1 Gz (740 s), +3.2 Gz (327 s), and +3.8 Gz (312 s) in a selected, randomized order; the ramp to peak acceleration was 1.8 G/min. The centrifugation runs were terminated by loss of central vision (blackout) to a white light with a luminance of 3.15 times 10-5 log candle/cm-2 (0.092 ft-lambert). The study began with a 14-d ambulatory control period, followed by three 14-d bedrest periods (each separated by a 21-d recovery period) and then a final week of recovery. During the ambulatory periods, the subjects exercised on a bicycle ergometer at 50% of their maximal oxygen uptake (max VO2) for 1 h/d. During two of the three bedrest periods, the subjects performed in the supine position one of two routines, either isometric exercise (21% of max leg extension force for 1 min followed by 1-min rest) or isotonic exercise (68% of max VO2) for 0.5 in the morning and afternoon. During the third bedrest period, no exercise was performed. In general +Gz tolerance was reduced by 24% to 35% (p less than or equal to 0.05) after bedrest. Compared with control values, there were significant reductions in average tolerance times after bedrest with no exercise and isotonic exercise at all G levels. With isometric exercise, there was a significant decrease in tolerance at 2.1 Gz but not at 3.2 Gz or 3.8 Gz, even though the latter tolerances were reduced 15.6% and 10.0%, respectively. Both exercise regimens maintained tolerance at levels equal to or above that obtained with no exercise. Compared with control values, average tolerances were lower (p less than or equal to 0.05) after the two recovery periods between the bedrest periods (minus 24% to minus 26% at 3.2 Gz and 3.8 Gz), indicating that 3 weeks of ambulation was not sufficient time for full recovery from the deconditioning induced in

  4. KIC 7668647: a 14 day beaming sdB+WD binary with a pulsating subdwarf

    NASA Astrophysics Data System (ADS)

    Telting, J. H.; Baran, A. S.; Nemeth, P.; Østensen, R. H.; Kupfer, T.; Macfarlane, S.; Heber, U.; Aerts, C.; Geier, S.

    2014-10-01

    The recently discovered subdwarf B (sdB) pulsator KIC 7668647 is one of the 18 pulsating sdB stars detected in the Kepler field. It features a rich g-mode frequency spectrum, with a few low-amplitude p-modes at short periods. This makes it a promising target for a seismic study aiming to constrain the internal structure of this star, and of sdB stars in general. We use new ground-based low-resolution spectroscopy, and the near-continuous 2.88 year Kepler light curve, to reveal that KIC 7668647 consists of a subdwarf B star with an unseen white-dwarf companion with an orbital period of 14.2 d. An orbit with a radial-velocity amplitude of 39 km s-1 is consistently determined from the spectra, from the orbital Doppler beaming seen by Kepler at 163 ppm, and from measuring the orbital light-travel delay of 27 s by timing of the many pulsations seen in the Kepler light curve. The white dwarf has a minimum mass of 0.40 M⊙. We use our high signal-to-noise average spectra to study the atmospheric parameters of the sdB star, and find that nitrogen and iron have abundances close to solar values, while helium, carbon, oxygen and silicon are underabundant relative to the solar mixture. We use the full Kepler Q06-Q17 light curve to extract 132 significant pulsation frequencies. Period-spacing relations and multiplet splittings allow us to identify the modal degree ℓ for the majority of the modes. Using theg-mode multiplet splittings we constrain the internal rotation period at the base of the envelope to 46-48 d as a first seismic result for this star. The few p-mode splittings may point at a slightly longer rotation period further out in the envelope of the star. From mode-visibility considerations we derive that the inclination of the rotation axis of the sdB in KIC 7668647 must be around ~60°. Furthermore, we find strong evidence for a few multiplets indicative of degree 3 ≤ ℓ ≤ 8, which is another novelty in sdB-star observations made possible by Kepler. Based on

  5. A 14-day elemental diet is highly effective in normalizing the lactulose breath test.

    PubMed

    Pimentel, Mark; Constantino, Tess; Kong, Yuthana; Bajwa, Meera; Rezaei, Abolghasem; Park, Sandy

    2004-01-01

    Treatment of small intestinal bacterial overgrowth is frustrated by the low efficacy of antibiotics. Elemental diets have been shown to reduce enteric flora. In this study, we evaluate the ability of an elemental diet to normalize the lactulose breath test (LBT) in IBS subjects with abnormal breath test findings. Consecutive subjects with IBS and abnormal LBT suggesting the presence of bacterial overgrowth underwent a 2-week exclusive elemental diet. The diet consisted of Vivonex Plus (Novartis Nutrition Corp., Minneapolis, MN) in a quantity based on individual caloric requirement. On day 15 (prior to solid food), subjects returned for a follow-up breath test and those with an abnormal LBT were continued on the diet for an additional 7 days. The ability of an elemental diet to normalize the LBT was determined for days 15 and 21. A chart review was then conducted to evaluate any clinical benefit 1 month later. Of the 93 subjects available for analysis, 74 (80%) had a normal LBT on day 15 of the elemental diet. When those who continued to day 21 were included, five additional patients normalized the breath test (85%). On chart review, subjects who successfully normalized their breath test had a 66.4 +/- 36.1% improvement in bowel symptoms, compared to 11.9 +/- 22.0% in those who failed to normalize (P < 0.001). An elemental diet is highly effective in normalizing an abnormal LBT in IBS subjects, with a concomitant improvement in clinical symptoms. PMID:14992438

  6. Increased beta-adrenergic responsiveness induced by 14 days exposure to simulated microgravity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Polet, J. L.; Engelke, K. A.; Hoffler, G. W.; Lane, L. D.; Blomqvist, C. G.

    1995-01-01

    Increased sensitivity of end-organ responses to neuroendocrine stimuli as a result of prolonged exposure to the relative inactivity of microgravity has recently been hypothesized. This notion is based on the inverse relationship between circulating norepinephrine and beta-adrenoreceptor sensitivity. The beta-adrenoreceptor activity is reduced in individuals who have elevated plasma norepinephrine as a result of regular exposure to upright posture and physical exercise. In contrast, adrenoreceptor hypersensitivity has been reported in patients with dysautonomias in which circulating catecholamines are absent or reduced. Taken together, these studies and the observation that circulating plasma norepinephrine has been reduced during spaceflight and in groundbased simulations of microgravity prompt the suggestion that adrenoreceptor hypersensitivity may be a consequence of the adaptation to spaceflight. We conducted an experiment designed to measure cardiovascular responses to adrenoreceptor agonists in human subjects before and after prolonged exposure to 6 deg head-down tilt (HDT) to test the hypothesis that adaptation to microgravity increases adrenoreceptor responsiveness, and that this adaptation is associated with reduced levels of circulating norepinephrine.

  7. [The dendritic spines of the pyramidal neurons in layer V of the rat sensorimotor cortex following a 14-day space flight].

    PubMed

    Belichenko, P V; Krasnov, I B

    1991-11-01

    There was made a quantitative study of the influence of 14 days space flight ("Kosmos-2044") on dendritic spine (DS) density of the layer V pyramidal neurons of rat sensomotor cortex. There was found an increase of the number of apical DS lying in the layers III-IV in the flight group only. Number of DS on oblique dendrites was increased in the III-IV cortical layers both in the flight and tail-suspended rats. There was also an increase in the number of DS on basal dendrites in all experimental groups. Obtained data are compared with similar 7 days flight results ("Kosmos-1667") and other data of nervous tissue plasticity in weightlessness. PMID:1810500

  8. Computerized spatial navigation training during 14 days of bed rest in healthy older adult men: Effect on gait performance.

    PubMed

    Marusic, Uros; Kavcic, Voyko; Giordani, Bruno; Gerževič, Mitja; Meeusen, Romain; Pišot, Rado

    2015-06-01

    Prolonged physical inactivity or bed rest (BR) due to illness or other factors can result in significant declines in physical health and even cognitive functions. Based on random selection, 7 healthy older adult men received computerized spatial navigation training, while 8 served as active controls during 14-day BR. Greater post-BR declines were seen in normal and complex (dual-task) walking for the control as compared to intervention group, suggesting that computerized spatial navigation training can successfully moderate detrimental BR effects. Findings underline the generalization of cognitive-based intervention to the motor domain and potentially support their use to supplement BR interventions (e.g., exercise and nutrition). PMID:25938245

  9. 14-day prulifloxacin treatment of acute uncomplicated cystitis in women with recurrent urinary tract infections: a prospective, open-label, pilot trial with 6-month follow-up.

    PubMed

    Cai, T; Mazzoli, S; Nesi, G; Boddi, V; Mondaini, N; Bartoletti, R

    2009-11-01

    Recurrent urinary tract infections (UTI) are very common in otherwise healthy young women, and can have a very negative social and economic impact. In order to evaluate the tolerability and efficacy of a 14-day course of prulifloxacin orally administered once daily, 51 young female patients, attending the same STD center between may and June 2007 for symptoms of cystitis, with a history of recurrent UTI and urine culture positive for uropathogens, were enrolled in this prospective study. Microbiological and clinical efficacy was tested over three follow-up visits at 1, 3 and 6 months. Quality of life (QoL) was measured and the impact of prulifloxacin in modifying the Lactobacillus vaginal flora was also evaluated. At baseline, the pathogens most commonly isolated were Enterococcus faecalis (43.2%) and Escherichia coli (27.5%). 41 of the 51 women, (80.3%) had Lactobacillus spp. in vaginal samples at baseline. microbiological results at follow-up examinations were as follows: after 1 month, 47 patients were recurrence-free and 4 had recurrence; after 3 months, 41 were recurrence-free, while 6 reported recurrence; finally, after 6 months, 36 were recurrence-free and 5 had recurrence. A statistically significant difference was reported between the QoL questionnaire mean scores at baseline (0.63), 1 (0.77), 3 (0.77) and 6 months (0.78) after treatment (all p<0.001). the vaginal swab cultures demonstrated that Lactobacillus spp. flora was maintained in 38 out of the 41 (92.6%) patients who had positive vaginal swab sample at baseline. in conclusion, a 14-day administration of prulifloxacin 600 mg is a safe, well tolerated and effective treatment for the management of UTI in young women. PMID:19933045

  10. Transversal Stiffness and Beta-Actin and Alpha-Actinin-4 Content of the M. Soleus Fibers in the Conditions of a 3-Day Reloading after 14-Day Gravitational Unloading

    PubMed Central

    Ogneva, I. V.

    2011-01-01

    The aim of the work was to analyze the structural changes in different parts of the sarcolemma and contractile apparatus of muscle fibers by measuring their transversal stiffness by atomic force microscopy in a three-day reloading after a 14-day gravity disuse, which was carried out by hind-limbs suspension. The object of the study was the soleus muscle of the Wistar rat. It was shown that after 14 days of disuse, there was a reduction of transversal stiffness of all points of the sarcolemma and contractile apparatus. Readaptation for 3 days leads to complete recovery of the values of the transversal stiffness of the sarcolemma and to partial value recovery of the contractile apparatus. The changes in transversal stiffness of sarcolemma correlate with beta-actin and alpha-actinin-4 in membrane protein fractions. PMID:21941432

  11. Troposphere delay modeling using ray-traced delays around Tsukuba during a 14-days typhoon period in September 2007

    NASA Astrophysics Data System (ADS)

    Pany, A.; Boehm, J.; Hobiger, T.; Schuh, H.

    2009-04-01

    Accurate modeling of the tropospheric delay of microwave signals is of great importance for space geodetic techniques, such as Very Long Baseline Interferometry (VLBI) and the Global Navigation Satellite Systems (GNSS). In state-of-the-art VLBI analysis tropospheric zenith delays are estimated using mapping functions, and gradients are applied in order to account for azimuthal asymmetries. Monte Carlo simulations carried out within the International VLBI Service for Geodesy and Astrometry (IVS) to design the next generation VLBI system, VLBI2010, have clearly shown that the tropospheric delay is the limiting factor in VLBI analysis and that a simple gradient model, as currently applied, might be insufficient for VLBI2010 which will provide a much higher observation density. The Japan Meteorological Agency (JMA) provides high resolution numerical weather models. With KARAT, the Kashima Ray-Tracing Tools, we computed tropospheric slant delays around the VLBI site in Tsukuba for a 14-days typhoon period in September 2007. The resolution of these ray-traced delays is 1° in both azimuth and elevation, and three hours in time. The delays exhibit significant azimuthally asymmetric characteristics. We fit spherical harmonic functions of different degrees and orders to the ray-traced delays in order to test their ability of modeling the spatial structures of the troposphere, and we investigate whether further continuation of the continued fraction form, i.e. estimating more coefficients, might improve troposphere modeling.

  12. Increasing the operating distance of a phase-shift laser range-finding system by using an active reflector

    NASA Astrophysics Data System (ADS)

    Hu, Pengcheng; Yu, Liang; Mei, Jianting; Tan, Jiubin

    2015-12-01

    A new phase-shift laser ranging method is developed by combining the conventional phase-shift ranging and the concept of transponder, in which the passive mirror in a phase-shift laser range-finding system is replaced with an active reflector whose light source power is the same as that at the measurement terminal. As a result, the power of the returned light is inversely proportional to the 2nd instead of the 4th power of the distance being measured. Section 3 indicate that by using the active reflector, the operating distance is dramatically increased without increasing the laser power or lens aperture. With a transmitted power of 20 mW and an aperture of 100 mm, the operating distance increased from 1.5 km to 9.4 km, and a 15-fold range gain can be forecasted for a transmitted power of 1 W. This strongly confirms the suitability of the developed phase-shift method with an active reflector for measuring longer distances.

  13. Alterations in glomerular and tubular dynamics at 1 and 14 days simulated microgravity and after acute return to orthostasis

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.; Mendonca, Margarida M.

    1995-01-01

    Head-down tilt (HDT) is utilized to simulate microgravity and produces a cephalad fluid shift, which results in alterations in fluid and electrolyte balance. These changes in volume homeostasis are due, in part, to alterations in multiple volume control mechanisms in which renal function is a major participant. We have previously demonstrated that glomerular filtration rate increases early in HDT and eventually returns to values not different from non-tilt measurements. This early increase in glomerular filtration rate was also demonstrated during days 2 and 8 of the SLS-1 mission. However, urine flow and electrolyte excretion does not parallel the alternations in glomerular filtration rate and the site of this change in nephron fluid reabsorption pattern has not been previously examined. Through determination of the location of alterations in tubular fluid reabsorption within the nephron, a more detailed hypothesis can be forwarded as to which specific neuro-humoral agents participating in control or renal function in microgravity conditions. the importance of this type of examination is that measurements in circulating neuro-humoral agents and urinary excretion patterns alone are not accurate predictors of how renal functional response may alter to head-down tilt or other models of simulated weightlessness. To examine this issue, renal micropuncture techniques were utilized in Munich-Wistar rats submitted 24 hour and 14 day head-down tilt, measuring all the determinants of glomerular ultrafiltration and obtaining data regarding segmental tubular fluid reabsorption. Following these measurements, the rats were returned to an orthostatic position and after 60 minutes, the measurements were repeated.

  14. A Randomised Trial of empiric 14-day Triple, five-day Concomitant, and ten-day Sequential Therapies for Helicobacter pylori in Seven Latin American Sites

    PubMed Central

    Greenberg, E. Robert; Anderson, Garnet L.; Morgan, Douglas R.; Torres, Javier; Chey, William D.; Bravo, Luis Eduardo; Dominguez, Ricardo L.; Ferreccio, Catterina; Herrero, Rolando; Lazcano-Ponce, Eduardo C.; Meza-Montenegro, Mercedes María; Peña, Rodolfo; Peña, Edgar M.; Salazar-Martínez, Eduardo; Correa, Pelayo; Martínez, María Elena; Valdivieso, Manuel; Goodman, Gary E.; Crowley, John J.; Baker, Laurence H.

    2011-01-01

    Summary Background Evidence from Europe, Asia, and North America suggests that standard three-drug regimens of a proton pump inhibitor plus amoxicillin and clarithromycin are significantly less effective for eradicating Helicobacter pylori (H. pylori) infection than five-day concomitant and ten-day sequential four-drug regimens that include a nitroimidazole. These four-drug regimens also entail fewer antibiotic doses and thus may be suitable for eradication programs in low-resource settings. Studies are limited from Latin America, however, where the burden of H. pylori-associated diseases is high. Methods We randomised 1463 men and women ages 21–65 selected from general populations in Chile, Colombia, Costa Rica, Honduras, Nicaragua, and Mexico (two sites) who tested positive for H. pylori by a urea breath test (UBT) to: 14 days of lansoprazole, amoxicillin, and clarithromycin (standard therapy); five days of lansoprazole, amoxicillin, clarithromycin, and metronidazole (concomitant therapy); or five days of lansoprazole and amoxicillin followed by five of lansoprazole, clarithromycin, and metronidazole (sequential therapy). Eradication was assessed by UBT six–eight weeks after randomisation. Findings In intention-to-treat analyses, the probability of eradication with standard therapy was 82·2%, which was 8·6% higher (95% adjusted CI: 2·6%, 14·5%) than with concomitant therapy (73·6%) and 5·6% higher (95% adjusted CI: −0·04%, 11·6%) than with sequential therapy (76·5%). In analyses limited to the 1314 participants who adhered to their assigned therapy, the probabilities of eradication were 87·1%, 78·7%, and 81·1% with standard, concomitant, and sequential therapies, respectively. Neither four-drug regimen was significantly better than standard triple therapy in any of the seven sites. Interpretation Standard 14-day triple-drug therapy is preferable to five-day concomitant or ten-day sequential four-drug regimens as empiric therapy for H. pylori

  15. Quantitative changes of GABA-immunoreactive cells in the hindlimb representation of the rat somatosensory cortex after 14-day hindlimb unloading by tail suspension

    NASA Technical Reports Server (NTRS)

    D'Amelio, F.; Fox, R. A.; Wu, L. C.; Daunton, N. G.

    1996-01-01

    The present study was aimed at evaluating quantitatively gamma-aminobutyric acid (GABA) immunoreactivity in the hindlimb representation of the rat somatosensory cortex after 14 days of hindlimb unloading by tail suspension. A reduction in the number of GABA-immunoreactive cells with respect to the control animals was observed in layer Va and Vb. GABA-containing terminals were also reduced in the same layers, particularly those terminals surrounding the soma and apical dendrites of pyramidal cells in layer Vb. On the basis of previous morphological and behavioral studies of the neuromuscular system of hindlimb-suspended animals, it is suggested that the unloading due to hindlimb suspension alters afferent signaling and feedback information from intramuscular receptors to the cerebral cortex due to modifications in the reflex organization of hindlimb muscle groups. We propose that the reduction in immunoreactivity of local circuit GABAergic neurons and terminals is an expression of changes in their modulatory activity to compensate for the alterations in the afferent information.

  16. Does negative affect mediate the relationship between daily PTSD symptoms and daily alcohol involvement in female rape victims? Evidence from 14 days of interactive voice response assessment.

    PubMed

    Cohn, Amy; Hagman, Brett T; Moore, Kathleen; Mitchell, Jessica; Ehlke, Sarah

    2014-03-01

    The negative reinforcement model of addiction posits that individuals may use alcohol to reduce negative affective (NA) distress. The current study investigated the mediating effect of daily NA on the relationship between daily PTSD symptoms and same-day and next-day alcohol involvement (consumption and desire to drink) in a sample of 54 non-treatment-seeking female rape victims who completed 14 days of interactive voice response assessment. The moderating effect of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also examined. Multilevel models suggested that NA mediated the relationship between PTSD and same-day, but not next-day alcohol involvement. NA was greater on days characterized by more severe PTSD symptoms, and alcohol consumption and desire to drink were greater on days characterized by higher NA. Furthermore, daily PTSD symptoms and NA were more strongly associated with same-day (but not next-day) alcohol consumption and desire to drink for women with an AUD than without. Results suggest that NA plays an important role in female rape victims' daily alcohol use. Differences between women with and without an AUD indicate the need for treatment matching to subtypes of female rape victims. PMID:24731112

  17. Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

    NASA Technical Reports Server (NTRS)

    Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

    2002-01-01

    The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

  18. Does negative affect mediate the relationship between daily PTSD symptoms and daily alcohol involvement in female rape victims? Evidence from 14 days of interactive voice response assessment

    PubMed Central

    Cohn, Amy; Hagman, Brett T.; Moore, Kathleen; Mitchell, Jessica; Ehlke, Sarah

    2014-01-01

    The negative reinforcement model of addiction posits that individuals may use alcohol to reduce with negative affective (NA) distress. The current study investigated the mediating effect of daily NA on the relationship between daily PTSD symptoms and same-day and next-day alcohol involvement (consumption and desire to drink) in a sample of 54 non-treatment-seeking female rape victims who completed 14 days of interactive voice response assessment. The moderating effect of lifetime alcohol use disorder diagnosis (AUD) on daily relationships was also examined. Multilevel models suggested that NA mediated the relationship between PTSD and same-day, but not next-day alcohol involvement. NA was greater on days characterized by more severe PTSD symptoms, and alcohol consumption and desire to drink were greater on days characterized by higher NA. Further, daily PTSD symptoms and NA were more strongly associated with same-day (but not next-day) alcohol consumption and desire to drink for women with an AUD than without. Results suggest that NA plays an important role in female rape victims’ daily alcohol use. Differences between women with and without an AUD indicate the need for treatment matching to sub-types of female rape victims. PMID:24731112

  19. Multiparametric temporal analysis of the Caco-2/TC7 demonstrated functional and differentiated monolayers as early as 14 days of culture.

    PubMed

    Zeller, Perrine; Bricks, Thibault; Vidal, Guillaume; Jacques, Sébastien; Anton, Pauline M; Leclerc, Eric

    2015-05-25

    Reducing the differentiation period for obtaining an in vitro intestinal barrier model is required to reduce the duration and cost for drug screening assays. In this frame, the Caco-2/TC7 subclone differentiation state was investigated from day 0 (D0) to day 32 (D32). As such, the expression of 45 genes (including cell junction, cell polarization, cell functionality, drug transport and metabolism genes) was followed throughout the 32 days. In parallel, the monolayer polarization and the formation of the cellular junctions were characterized by the immuno-staining of occludin, claudin-1 and actin proteins. The cell monolayer permeability was analyzed via transepithelial electric resistance measurements and paracellular transport of Lucifer Yellow. The P-gp efflux efficiency was assessed by rhodamine 123 transport. Alkaline phosphate activity was quantified to assess the cell differentiation. Three stages of differentiation were observed using the clustering of principal component analysis of the RTqPCR data and the overall assays. From D0 to D10, cells were in a proliferation stage and under-differentiated; from D14 to D21 a stable differentiation stage was reached; from D25 to D32 the epithelium seemed to enter into a post-differentiated stage. This study demonstrates that Caco-2/TC7 cells are functional and ready for use in drug screening permeability assays from 14 days in culture when compared with conventional 21 days for Caco-2 cells. In addition, this study provides a refined set of data allowing temporal and multi scale investigations, due to the intracellular kinetics and mRNA levels that can be correlated with membrane protein kinetics and functional extracellular activities. Therefore, shorter time in culture combined with a better knowledge of the cells during the time in culture will in turn help to improve the quality and cost of Caco-2/TC7 assays for drug development. PMID:25725134

  20. Rapid molecular detection of inducible macrolide resistance in Mycobacterium chelonae and M. abscessus strains: a replacement for 14-day susceptibility testing?

    PubMed

    Hanson, Kimberly E; Slechta, E Susan; Muir, Haleina; Barker, Adam P

    2014-05-01

    The erm(41) gene causes inducible macrolide resistance in Mycobacterium abscessus but not Mycobacterium chelonae. erm(41) sequencing of 285 M. abscessus and 45 M. chelonae isolates was compared to 14-day susceptibility; agreement percentages were 98.9% and 100%, respectively. Extended incubation may not be necessary for M. chelonae, and the erm(41) genotype is a useful adjunct for M. abscessus. PMID:24554745

  1. Planktonic and biofilm community characterization and Salmonella resistance of 14-day old chicken cecal microflora derived continuous-flow cultures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    These studies were initiated to compare the composition of GIT bacterial communities in birds during the transition period in age where their susceptibility to Salmonella shifts to resistance. One of the challenges to developing probiotics is to develop an efficacious culture of minimal diversity, ...

  2. Improvement of the lung function of horses with heaves by treatment with a botanical preparation for 14 days.

    PubMed

    Anour, R; Leinker, S; van den Hoven, R

    2005-12-01

    The effects of an oral preparation containing a mixture of extracts from yellow gentian, garden sorrel, cowslip, verbena and common elder on the lung function of nine horses suffering from heaves were determined in a longitudinal crossover study. The horses were divided at random into a group of five (group 1) and a group of four (group 2). The horses in group 1 were each given 15 tablets of the preparation twice daily, while the horses in group 2 were left untreated. Fourteen days later, the horses in group 2 were given the same course of treatment while the horses in group 1 were left untreated. On being subjected to a histamine inhalation provocation test, five of eight horses tested appeared to be hyperresponsive to histamine. The treatment decreased the histamine sensitivity of three of them; it also caused a significant decrease in maximal intrapleural pressure difference of all the horses. The treatment had no significant effects on the clinical signs, the mucociliary activity or the cytology of the bronchoalveolar lavage fluid of the horses. PMID:16326966

  3. Nutritional status changes in humans during a 14-day saturation dive: the NASA Extreme Environment Mission Operations V project.

    PubMed

    Smith, Scott M; Davis-Street, Janis E; Fesperman, J Vernell; Smith, Myra D; Rice, Barbara L; Zwart, Sara R

    2004-07-01

    Ground-based analogs of spaceflight are an important means of studying physiologic and nutritional changes associated with space travel, and the NASA Extreme Environment Mission Operations V (NEEMO) is such an analog. To determine whether saturation diving has nutrition-related effects similar to those of spaceflight, we conducted a clinical nutritional assessment of the NEEMO crew (4 men, 2 women) before, during, and after their 14-d saturation dive. Blood and urine samples were collected before, during, and after the dive. The foods consumed by the crew were typical of the spaceflight food system. A number of physiologic changes were observed, during and after the dive, that are also commonly observed during spaceflight. Hemoglobin and hematocrit were lower (P < 0.05) after the dive. Transferrin receptors were significantly lower immediately after the dive. Serum ferritin increased significantly during the dive. There was also evidence indicating that oxidative damage and stress increased during the dive. Glutathione peroxidase and superoxide dismutase decreased during and after the dive (P < 0.05). Decreased leptin during the dive (P < 0.05) may have been related to the increased stress. Subjects had decreased energy intake and weight loss during the dive, similar to what is observed during spaceflight. Together, these similarities to spaceflight provide a model to use in further defining the physiologic effects of spaceflight and investigating potential countermeasures. PMID:15226467

  4. Nutritional status changes in humans during a 14-day saturation dive: the NASA Extreme Environment Mission Operations V project

    NASA Technical Reports Server (NTRS)

    Smith, Scott M.; Davis-Street, Janis E.; Fesperman, J. Vernell; Smith, Myra D.; Rice, Barbara L.; Zwart, Sara R.

    2004-01-01

    Ground-based analogs of spaceflight are an important means of studying physiologic and nutritional changes associated with space travel, and the NASA Extreme Environment Mission Operations V (NEEMO) is such an analog. To determine whether saturation diving has nutrition-related effects similar to those of spaceflight, we conducted a clinical nutritional assessment of the NEEMO crew (4 men, 2 women) before, during, and after their 14-d saturation dive. Blood and urine samples were collected before, during, and after the dive. The foods consumed by the crew were typical of the spaceflight food system. A number of physiologic changes were observed, during and after the dive, that are also commonly observed during spaceflight. Hemoglobin and hematocrit were lower (P < 0.05) after the dive. Transferrin receptors were significantly lower immediately after the dive. Serum ferritin increased significantly during the dive. There was also evidence indicating that oxidative damage and stress increased during the dive. Glutathione peroxidase and superoxide dismutase decreased during and after the dive (P < 0.05). Decreased leptin during the dive (P < 0.05) may have been related to the increased stress. Subjects had decreased energy intake and weight loss during the dive, similar to what is observed during spaceflight. Together, these similarities to spaceflight provide a model to use in further defining the physiologic effects of spaceflight and investigating potential countermeasures.

  5. Effect of a 14-day course of systemic corticosteroids on the hypothalamic-pituitary-adrenal-axis in patients with acute exacerbation of chronic obstructive pulmonary disease

    PubMed Central

    Schuetz, Philipp; Christ-Crain, Mirjam; Schild, Ursula; Süess, Erika; Facompre, Michael; Baty, Florent; Nusbaumer, Charly; Brutsche, Martin; Müller, Beat

    2008-01-01

    Background As supra-physiological intake of corticosteroids is a well known risk factor for the development of adrenal insufficiency, we investigated the function of the hypothalamic-pituitary-adrenal (HPA) axis during a 14-day course of systemic corticosteroids in patients with acute exacerbation of chronic obstructive pulmonary disease using clinical and laboratory measures. Methods A systematic clinical and laboratory assessment including measurement of basal cortisol levels and the response to low dose (1 μg) ACTH stimulation was performed in nine patients before, on the first and the last day of treatment, as well as 2, 7 and 21 days after corticosteroid withdrawal. Results At baseline, all nine patients had normal responses to 1 μg ACTH. On the first day of steroid treatment, 78% had a blunted peak cortisol response. This percentage increased to 89% after 14 days of steroid treatment. 78%, 33% and 33% of the patients had a blunted cortisol response to ACTH 2, 7, and 21 days after corticosteroid withdrawal, respectively. ROC curve analysis revealed that only basal cortisol concentrations (AUC 0.89), but not ACTH concentrations (AUC 0.49) or clinical signs (AUC 0.47) were predictive of an impaired function of the HPA axis. Basal cortisol levels of > 400 and < 150 nmol/l were 96% and 100% sensitive for a normal or pathological response to the ACTH stimulation test, respectively. Conclusion Immediate and prolonged suppression of the HPA axis is a common finding in otherwise asymptomatic patients undergoing systemic steroid treatment for acute exacerbation of chronic obstructive pulmonary disease and can reliably be assessed with the low-dose ACTH test. PMID:18221550

  6. A range finding protocol to support design for transcriptomics experimentation: examples of in-vitro and in-vivo murine UV exposure.

    PubMed

    Bruning, Oskar; Rodenburg, Wendy; van Oostrom, Conny T; Jonker, Martijs J; de Jong, Mark; Dekker, Rob J; Rauwerda, Han; Ensink, Wim A; de Vries, Annemieke; Breit, Timo M

    2014-01-01

    In transcriptomics research, design for experimentation by carefully considering biological, technological, practical and statistical aspects is very important, because the experimental design space is essentially limitless. Usually, the ranges of variable biological parameters of the design space are based on common practices and in turn on phenotypic endpoints. However, specific sub-cellular processes might only be partially reflected by phenotypic endpoints or outside the associated parameter range. Here, we provide a generic protocol for range finding in design for transcriptomics experimentation based on small-scale gene-expression experiments to help in the search for the right location in the design space by analyzing the activity of already known genes of relevant molecular mechanisms. Two examples illustrate the applicability: in-vitro UV-C exposure of mouse embryonic fibroblasts and in-vivo UV-B exposure of mouse skin. Our pragmatic approach is based on: framing a specific biological question and associated gene-set, performing a wide-ranged experiment without replication, eliminating potentially non-relevant genes, and determining the experimental 'sweet spot' by gene-set enrichment plus dose-response correlation analysis. Examination of many cellular processes that are related to UV response, such as DNA repair and cell-cycle arrest, revealed that basically each cellular (sub-) process is active at its own specific spot(s) in the experimental design space. Hence, the use of range finding, based on an affordable protocol like this, enables researchers to conveniently identify the 'sweet spot' for their cellular process of interest in an experimental design space and might have far-reaching implications for experimental standardization. PMID:24823911

  7. Effects of 14 days of spaceflight and nine days of recovery on cell body size and succinate dehydrogenase activity of rat dorsal root ganglion neurons

    NASA Technical Reports Server (NTRS)

    Ishihara, A.; Ohira, Y.; Roy, R. R.; Nagaoka, S.; Sekiguchi, C.; Hinds, W. E.; Edgerton, V. R.

    1997-01-01

    The cross-sectional areas and succinate dehydrogenase activities of L5 dorsal root ganglion neurons in rats were determined after 14 days of spaceflight and after nine days of recovery. The mean and distribution of the cross-sectional areas were similar to age-matched, ground-based controls for both the spaceflight and for the spaceflight plus recovery groups. The mean succinate dehydrogenase activity was significantly lower in spaceflight compared to aged-matched control rats, whereas the mean succinate dehydrogenase activity was similar in age-matched control and spaceflight plus recovery rats. The mean succinate dehydrogenase activity of neurons with cross-sectional areas between 1000 and 2000 microns2 was lower (between 7 and 10%) in both the spaceflight and the spaceflight plus recovery groups compared to the appropriate control groups. The reduction in the oxidative capacity of a subpopulation of sensory neurons having relatively large cross-sectional areas immediately following spaceflight and the sustained depression for nine days after returning to 1 g suggest that the 0 g environment induced significant alterations in proprioceptive function.

  8. Association Between Cardiovascular and Intraocular Pressure Changes in a 14-day 6 deg Head Down Tilt (HDT) Bed Rest Study: Possible Implications in Retinal Anatomy

    NASA Technical Reports Server (NTRS)

    Cromwell, R. L.; Zanello, S. B.; Yarbough, P. O.; Ploutz-Snyder, R.; Taibbi, G.; Brewer, J. L.; Vizzeri, G.

    2013-01-01

    Mean IOP significantly increased while at 6deg HDT and returned towards pre-bed rest values upon leaving bed rest. While mean IOP increased during bed rest, it remained within the normal limits for subject safety. A diuretic shift and cardiovascular deconditioning occurs during in-bed rest, as expected. There was no demonstrable correlation between the largest change in IOP (pre/post) and cardiovascular measure changes (pre/post). Additional mixed effects linear regression modeling may reveal some subclinical physiological changes that might assist in describing the VIIP syndrome pathophysiology.

  9. Integrating laser-range finding, electronic compass measurements and GPS to rapidly map vertical changes in volcanic stratigraphy and constrain unit thicknesses and volumes: two examples from the northern Cordilleran volcanic province

    NASA Astrophysics Data System (ADS)

    Nogier, M.; Edwards, B. R.; Wetherell, K.

    2005-12-01

    We present preliminary results of laser-range finding-GPS surveys from two separate locations in northern British Columbia, in the south-central northern Cordilleran volcanic province: Hoodoo Mountain volcano and Craven Lake cone. This technique, described in detail below, is appropriate for rapidly measuring changes in vertical thicknesses of units that either would be difficult or impossible to measure by most other techniques. The ability to accurately measure thicknesses of geologic units in otherwise difficult-to-access locations will aide in generating better quantitative estimates of deposit geometries and eruption volumes. Such data is particularly important for constraining quantitative models of magma production and eruption dynamics. The deposits of interest in this study comprised at least partly inaccessible, largely pyroclastic units, although the technique could be used to map any vertical surfaces. The first field location was the northern side of Hoodoo Mountain volcano (56deg47'23.72'N/131deg17'36.97'W/1208m-asl), where a sequence of welded to unwelded, trachytic-phonolitic tephra was deposited in a paleovalley. This deposit is informally referred to as the Pointer Ridge deposit, and it comprises at least 7 distinct subunits. The horizontal limit of the exposures is approximately 1.5km, and the vertical limit is approximately 250m. Three different GPS base stations were used to map the lateral and vertical variations in the deposit. The second field location is north of Craven Lake (56deg54'44.55'N/129deg21'42.17'W/1453m-asl), along Craven Creek, where a sequence of basaltic tephra is overlain by pillow lava and glacial diamicton. This exposure is 200m long and approximately 30m high, much smaller than the area mapped at Hoodoo Mountain. The basaltic tephra appears to comprise 4 distinct sequences (measured thicknesses vary from 3-4m) not including the overlying pillow lava (measured thickness varies from 2 to 10m), and measurements of the

  10. Vehicle Based Laser Range Finding in Crops

    PubMed Central

    Ehlert, Detlef; Adamek, Rolf; Horn, Hans-Juergen

    2009-01-01

    Laser rangefinders and laser scanners are widely used for industrial purposes and for remote sensing. In agriculture information about crop parameters like volume, height, and density can support the optimisation of production processes. In scientific papers the measurement of these parameters by low cost laser rangefinders with one echo has been presented for short ranges. Because the cross section area of the beam increases with the measuring range, it can be expected that laser rangefinders will have a reduced measuring accuracy in small sized crops and when measuring far distances. These problems are caused by target areas smaller than the beam and by the beam striking the edges of crop objects. Lab tests under defined conditions and a real field test were performed to assess the measuring properties under such difficult conditions of a chosen low cost sensor. Based on lab tests it was shown that the accuracy was reduced, but the successful use of the sensor under field conditions demonstrated the potential to meet the demands for agricultural applications, Insights resulting from investigations made in the paper contribute to facilitating the choice or the development of laser rangefinder sensors for vehicle based measurement of crop parameters for optimisation of production processes. PMID:22412333

  11. Absence of Change in Total Daily Energy Expenditure (EE(sub TD)) in Young and Mature Rats During 14 Days of Hypergravity

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Moran, M. M.; Stein, T. P.; Hoban-Higgins, T. M.; Fuller, P.; Fuller, C. A.; Dalton, Bonnie P. (Technical Monitor)

    1999-01-01

    Effect of age on the response of EE(sub TD) to an increase in gravity was assessed in young (Y; 1.5 month old) and mature (M; 8 month old) Sprague-Dawley rats. Rats were implanted with transmitters to monitor activity, and metabolism was determined by the double labeled water technique. Daily food intake was measured. For each age, rats (n=8 per treatment) were exposed to centrifugation at 2G, or remained at 1G. There was a difference in EE(sub TD) between age groups, 182 plus or minus 11 and 143 plus or minus 5 kcal/kg/day in Y and M, respectively. This difference was attributed in part to a lower activity level in M animals, 48% of Y rats. After day 6 there was no effect on EE(sub TD) of exposure to 2G, or on food intake per 100g BW. Prior studies show a 20% increase in resting EE with hypergravity. In our study the level of activity was reduced to 41% of 1G in both age groups during 2G. For Y at 1G resting EE accounted for 78% of the EE(sub TD) and activity 22%, while at 2G resting EE was 96% of EE(sub TD) and activity 4%. M rats had similar changes. Independent of age, with exposure to hypergravity EE(sub TD) is maintained by behavioral changes.

  12. Addition of clidinium-C to the 14-day proton-pump inhibitor-based triple therapy for Helicobacter pylori eradication

    PubMed Central

    Seyyedmajidi, Mohammadreza; Homapoor, Saba; Zanganeh, Elahe; Dadjou, Mohammad; Eskandari Nejad, Shahab; Tajik Galayeri, Mohammad Hadi; Vafaeimanesh, Jamshid

    2016-01-01

    Background: Triple therapy with a proton pump inhibitor and two antibiotics in Helicobacter pylori (HP) eradication is widely accepted, but this combination fails in a considerable number of cases. The aim of this study was to assess the effect of clidinium-C addition on HP eradication and to investigate the efficacy and safety of clidinium-C in prevention of drugs' side effects. Methods: A total of 200 histopathologically confirmed HP positive peptic ulcer enrolled in this study which were randomly assigned to two treatment groups: OAC (20 mg omeprazole bid, 1000 mg amoxicillin bid and 500 mg clarithromycin bid) and OAC + clidinium-C. The effect of treatment and adverse effects were compared 6 weeks after completion of treatment. A13C-urea breath test was performed to confirm HP eradication. Results: A total of 184 patients (90 in group A and 94 in group B) completed the treatment protocols. HP eradication was achieved in 71.1% in OAC versus 72.3% in OCA+clidinium-C, (P=0.73). The frequencies of abdominal pain and stool abnormality, among the side effects recorded during the therapy period, were significantly lower in group B (OCA+clidinium-C) (P=0.01 and P=0.001, respectively). Conclusion: Addition of clidinium-C to OCA triple therapy decreases abdominal pain and frequency of stool abnormalities without affecting HP eradication rate. Based on these findings addition of clidinium-C may increase patient's compliance. PMID:27386057

  13. Psychological Symptoms Before and After a 14-Day Initial Inpatient Treatment in Tuberculosis Patients Compared with Their Primary Caregivers and Healthy Controls

    PubMed Central

    Emami, Habib; Modarressi, Taher; Najmi, Kosar; Radmand, Golnar; Tabarsi, Payam; Richter, Jörg

    2015-01-01

    Background: Tuberculosis (TB) is one of the most challenging public health burdens in the world. Recent research demonstrated high prevalence of mental disorders in TB patients and their caregivers. The purpose of this study was to assess mental health of TB patients and their caregivers in Iran before and after a two-week inpatient treatment and to determine the prevalence of psychological problems in these groups. Materials and Methods: A standardized questionnaire (SCL-90) was used to assess psychological symptoms in 146 hospitalized TB patients and their caregivers (n=89). Furthermore, the scores of both target groups were compared with those of a group of healthy individuals (n=85). Results: The mean scores before the start of the initial treatment of the patients were significantly lower for paranoid ideation (P=0.038) and hostility (P= 0.046), and the scores of depression (P=0.046) and somatization (P=0.001) were significantly higher than those of the healthy individuals. The patients scored significantly higher than the caregivers on depression (0.047) and somatization (P< 0.001), whereas the caregivers scored higher than the healthy individuals on paranoid ideation (P= 0.044) and hostility (P= 0.034). Multiple linear regression showed that age, educational level and marital status were factors affecting the mental health of TB patients and their caregivers. The variance in psychological symptoms of the patients was between 10% (paranoid ideation) and 27% (hostility) of the variance in the symptoms of their caregivers. Conclusion: Tuberculosis control and treatment programs should not only address issues like continued respiratory symptoms, but should also focus on mental health in TB patients and their caregivers. PMID:26858764

  14. Follicular populations and luteal function in dairy heifers treated with a controlled internal drug release insert for 14 days as a method to synchronize the estrous cycle before prostaglandin F₂α treatment and artificial insemination.

    PubMed

    Escalante, R C; Poock, S E; Lucy, M C

    2013-06-01

    Progesterone-containing controlled internal drug release (CIDR) inserts are used to synchronize the estrous cycle before PGF2α is administered for timed AI (14dCIDR-PGF2α program). The program, initially designed for beef cattle, was recently shown to be efficacious in dairy heifers. We hypothesized that the 14-d CIDR treatment would synchronize the estrous cycle in dairy heifers and result in a uniformly sized corpus luteum (CL) and largest follicle (LF) at the time of PGF2α treatment. Holstein (n=110) or Holstein × Guernsey (n=4) dairy heifers were assigned to 2 treatments: (1) 14dCIDR-PGF2α [CIDR in for 14 d, CIDR out for 16d, PGF2α and AI after observed estrus (n=57)] or (2) control [PGF2α and AI after observed estrus (n=57)]. Regardless of treatment, additional PGF2α injections were administered at 14-d intervals to heifers that were not seen in estrus. Ovarian ultrasonography and blood sampling were done on d 0 (CIDR administered), 14 (day CIDR removed), 19 (5d after CIDR removed), 30 (PGF2α administered), and 44 (second PGF2α dose administered to heifers that were not detected in estrus after the first PGF2α). Compared with control (untreated), more CIDR-treated heifers were categorized as having a small CL (≤ 9.9 mm) and large LF (15.0-19.9 mm) on d 14 (CIDR removal) and, as expected, a greater percentage of CIDR-treated heifers were in estrus during the 5d after the CIDR removal compared with control heifers (75.4 vs. 22.8%, respectively). On d 19, the CIDR-treated heifers had apparently ovulated based on disappearance of LF and appearance of small CL. On d 30 (PGF2α administration), 89% of 14dCIDR-PGF2α heifers had CL that were ≥ 20 mm in diameter compared with 55% for control. Presence of larger CL on d 30 was associated with greater concentrations of plasma progesterone in 14dCIDR-PGF2α compared with control (10.5 ± 0.5 vs. 5.0 ± 0.6 ng/mL, respectively). The percentages of heifers with LF in the smallest category (≤ 9.9 mm) tended

  15. [Close-range retinoscopy using integrated optic range finding].

    PubMed

    Kulnig, W

    1983-12-01

    A new type of retinoscope is described which permits all the theoretical advantages of close-range retinoscopy to be exploited in practice thanks to an integrated rangefinder which employs the coincident-image principle. PMID:6668884

  16. Exercise thermoregulation after 14 days of bed rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Reese, R. D.

    1980-01-01

    The effects of bed rest and exercise training during bed rest on body temperature and thermoregulatory responses at rest and during exercise are investigated. Seven male subjects underwent three two-week periods of bed rest during which isometric, isotonic, or no exercises were performed, separated by two ambulatory control periods and preceded by a two-week control period, during which they exercised regularly. Rectal and mean skin temperatures and sweating responses were determined during 70-min submaximal supine exercise during the bed rest and recovery periods. Measurements reveal a reduction in basal oral temperature during the control-recovery periods, with a relatively constant level during bed rest periods, and a significant increase in the rectal temperature elavation brought on by exercise following all three bed-rest regimes. It is concluded that the excessive increase in rectal temperature could be influenced by changes in skin heat conductance or the inhibition of sweating.

  17. Safety studies of l-alanyl-l-glutamine (l-AG).

    PubMed

    Oda, S; Mullaney, T; Bowles, A J; Durward, R; Lynch, B; Sugimura, Y

    2008-03-01

    The safety of l-alanyl-l-glutamine (l-AG) derived by fermentation using a recombinant Escherichia coli strain containing the l-amino acid alpha-ligase gene from Bacillus subtilis, was assessed in acute and subchronic toxicity studies in the rat. l-AG was tested in vitro in a bacterial reverse mutation assay and in a chromosome aberration assay. l-AG was not acutely toxic when administered to Sprague-Dawley rats by gavage at 2000mg/kg bw. In a 14-day range-finding study, l-AG at up to 5% in the diet was without effect. In the 13-week dietary study, there were no toxicologically significant differences between the treated groups (1.0, 3.0 and 5.0% l-AG) and the controls (0% and 5% l-AG produced via a different method) with respect to body weight gain, feed consumption, feed efficiency, or the results of ophthalmological, haematological, clinical chemistry, and urinalysis evaluations. Three of 10 high-dose males had mild testicular changes, however, these were of exactly the same nature and severity as those that occur spontaneously, and were considered unlikely to be treatment-related. The NOAEL in both males and females was established as the highest dose tested at 3129 and 3601mg/kg bw/day, respectively (5.0% in the diet). There was no evidence of genotoxicity of l-AG in the Ames assay or in the in vitro CHL cell chromosome aberration study. PMID:18082299

  18. To Study or to Sleep? The Academic Costs of Extra Studying at the Expense of Sleep

    ERIC Educational Resources Information Center

    Gillen-O'Neel, Cari; Huynh, Virginia W.; Fuligni, Andrew J.

    2013-01-01

    This longitudinal study examined how nightly variations in adolescents' study and sleep time are associated with academic problems on the following day. Participants ("N" = 535, 9th grade M[subscript age] = 14.88) completed daily diaries every day for 14 days in 9th, 10th, and 12th grades. Results suggest that regardless of how much a student…

  19. High sensitivity 1.06 micron optical receiver for precision laser range finding. [YAG laser design

    NASA Technical Reports Server (NTRS)

    Scholl, F. W.; Harris, J. S., Jr.

    1977-01-01

    Aluminum gallium antimonide avalanche photodiodes with average gain of 10, internal quantum efficiency of greater than 60%, capacitance less than 0.2pf, and dark current of less than 1 micron were designed and fabricated for use in a low noise optical receiver suitable for 2 cm accuracy rangefinding. Topics covered include: (1) design of suitable photodetector structures; (2) epitaxial growth of AlGaSb devices; (3) fabrication of photodetectors; and (4) electro-optics characterization.

  20. Data acquisition and analysis of range-finding systems for spacing construction

    NASA Technical Reports Server (NTRS)

    Shen, C. N.

    1981-01-01

    For space missions of future, completely autonomous robotic machines will be required to free astronauts from routine chores of equipment maintenance, servicing of faulty systems, etc. and to extend human capabilities in hazardous environments full of cosmic and other harmful radiations. In places of high radiation and uncontrollable ambient illuminations, T.V. camera based vision systems cannot work effectively. However, a vision system utilizing directly measured range information with a time of flight laser rangefinder, can successfully operate under these environments. Such a system will be independent of proper illumination conditions and the interfering effects of intense radiation of all kinds will be eliminated by the tuned input of the laser instrument. Processing the range data according to certain decision, stochastic estimation and heuristic schemes, the laser based vision system will recognize known objects and thus provide sufficient information to the robot's control system which can develop strategies for various objectives.

  1. HUMORAL AND CELL-MEDIATED IMMUNE STATUS OF MICE EXPOSED TO TRANS-1,2-DICHLORO ETHYLENE

    EPA Science Inventory

    The study assessed possible adverse immunological effects of trans-1,2-dichloroethylene (DCE) on random-bred CD-1 mice following 14 and 90 days of exposure. A 14-day range-finding study was performed on male mice by gavage at doses 1/10 and 1/100 the LD50 (210 and 21 mg/kg). No a...

  2. CARCINOGENIC POTENTIAL OF ROTENONE. PHASE I: DIETARY ADMINISTRATION TO HAMSTERS

    EPA Science Inventory

    Studies were performed to evaluate the potential carcinogenicity rotenone in the Syrian Golden hamster. Several ancillary range-finding studies were carried out including 14-day feeding trials and a reproduction experiment. The latter experiment indicated that rotenone at a level...

  3. Effects of rehydration on +Gz tolerance after 14-days' bed rest.

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Van Beaumont, W.; Bernauer, E. M.; Haines, R. F.; Sandler, H.; Staley, R. W.; Young, H. L.; Yusken, J. W.

    1973-01-01

    Investigation of the magnitude of reduction in human tolerance to centrifugation following 2 weeks of bed rest with moderate daily exercise. The degree of hypovolemia associated with these exposures is assessed, and the possibility to improve or to return to control levels the tolerance to acceleration forces acting in the head-to-foot direction through rehydration prior to acceleration is explored.

  4. +Gz tolerance after 14 days bed rest and the effects of rehydration.

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Van Beaumont, W.; Bernauer, E. M.; Haines, R. F.; Sandler, H.; Young, H. L.; Yusken, J. W.

    1972-01-01

    Measurement of the reduction in centrifugation tolerance after two weeks of bedrest with moderate daily exercise, with an attempt to determine if rehydration improves +Gz tolerance. There were significant reductions in +Gz tolerance during bedrest periods at three acceleration levels. Rehydration resulted in a significant increase in tolerance at 2.1G but it did not restore tolerance to control levels. Rehydration did not affect tolerance at 3.2G and 3.8G.

  5. Effects of exercise on fluid exchange and body composition in man during 14-day bed rest

    NASA Technical Reports Server (NTRS)

    Greenleaf, J. E.; Bernauer, E. M.; Juhos, L. T.; Young, H. L.; Morse, J. T.; Staley, R. W.

    1977-01-01

    A description is presented of an investigation in which body composition, fluid intake, and fluid and electrolyte losses were measured in seven normal, healthy men during three 2-wk bed-rest periods, separated by two 3-wk recovery periods. During bed rest the subjects remained in the horizontal position continuously. During the dietary control periods, body mass decreased significantly with all three regimens, including no exercise, isometric exercise, and isotonic excercise. During bed rest, body mass was essentially unchanged with no exercise, but decreased significantly with isotonic and isometric exercise. With one exception, there were no statistically significant changes in body density, lean body mass, or body fat content by the end of each of the three bed-rest periods.

  6. 4 CFR 7.5 - Adverse actions: Suspensions for 14 days or less.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Section 7.5 Accounts GOVERNMENT ACCOUNTABILITY OFFICE PERSONNEL SYSTEM PERSONNEL RELATIONS AND SERVICES... writing and to furnish affidavits and other documentary evidence in support of the answer; (3) Be... therefor, and any order effecting the suspension, together with any supporting material, shall...

  7. TOXICOLOGY OF TRANS-1,2-DICHLOROETHYLENE IN THE MOUSE

    EPA Science Inventory

    Trans-1,2-dichloroethylene (DCE) was administered to male and female CD-1 mice in order to evaluate its effects on standard toxicological parameters. Following an acute LD50 determination (2122 mg/kg in males and 2391 mg/kg in females) and a 14-day range-finding study, a 90-day d...

  8. Voucher-Based Contingent Reinforcement of Smoking Abstinence among Methadone-Maintained Patients: A Pilot Study

    ERIC Educational Resources Information Center

    Dunn, Kelly E.; Sigmon, Stacey C.; Thomas, Colleen S.; Heil, Sarah H.; Higgins, Stephen T.

    2008-01-01

    This study evaluated the efficacy of a contingency management (CM) intervention to promote smoking cessation in methadone-maintained patients. Twenty participants, randomized into contingent (n = 10) or noncontingent (n = 10) experimental conditions, completed the 14-day study. Abstinence was determined using breath carbon monoxide and urine…

  9. 14 Days of supplementation with blueberry extract shows anti-atherogenic properties and improves oxidative parameters in hypercholesterolemic rats model.

    PubMed

    Ströher, Deise Jaqueline; Escobar Piccoli, Jacqueline da Costa; Güllich, Angélica Aparecida da Costa; Pilar, Bruna Cocco; Coelho, Ritiéle Pinto; Bruno, Jamila Benvegnú; Faoro, Debora; Manfredini, Vanusa

    2015-01-01

    The effects of supplementation with blueberry (BE) extract (Vaccinium ashei Reade) for 14 consecutive days on biochemical, hematological, histopathological and oxidative parameters in hypercholesterolemic rats were investigated. After supplementation with lyophilized extract of BE, the levels of total cholesterol, low-density lipoprotein cholesterol and triglycerides were decreased. Histopathological analysis showed significant decrease (p < 0.05) of aortic lesions in hypercholesterolemic rats. Oxidative parameters showed significant reductions (p < 0.05) in oxidative damage to lipids and proteins and an increase in activities of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. The BE extract showed an important cardioprotective effect by the improvements in the serum lipid profile, antioxidant system, particularly in reducing oxidative stress associated with hypercholesterolemia and anti-atherogenic effect in rats. PMID:26171628

  10. Fluid compartment and renal function alterations in the rat during 7 and 14 day head down tilt

    NASA Technical Reports Server (NTRS)

    Tucker, Bryan J.

    1991-01-01

    Exposure to conditions of microgravity for any extended duration can modify the distribution of fluid within the vascular and interstitial spaces, and eventually intracellular volume. Whether the redistribution of fluid and resetting of volume homeostasis mechanisms is appropriate for the long term environmental requirements of the body in microgravity remains to be fully defined. The event that initiates the change in fluid volume homeostasis is the cephalad movement of fluid which potentially triggers volume sensors and stretch receptors (atrial stretch with the resulting release of atrial natriuretic peptide) and suppresses adrenergic activity via the carotid and aortic arch baroreceptors. All these events act in concert to reset blood and interstitial volume to new levels, which in turn modify the renin-angiotensin system. All these factors have an influence on the kidney, the end organ for fluid volume control. How the fluid compartment volume changes interrelate with alterations in renal functions under conditions of simulated microgravity is the focus of the present investigation which utilizes 25-30 deg head-down tilt in the rat.

  11. PRESTORAGE LEUKOREDUCTION ABROGATES THE DETRIMENTAL EFFECT OF AGING ON PACKED RED CELLS TRANSFUSED AFTER TRAUMA: A PROSPECTIVE COHORT STUDY

    PubMed Central

    Phelan, Herb A.; Eastman, Alexander L.; Aldy, Kim; Carroll, Elizabeth A.; Nakonezny, Paul A.; Jan, Tiffany; Howard, Jessi L.; Chen, Yixiao; Friese, Randall S.; Minei, Joseph P.

    2011-01-01

    Background We sought to prospectively duplicate our retrospective findings showing prestorage leukoreduction (PS-LR) blunts the detrimental effect of aging on banked packed red blood cells (PRBCs) transfused after injury. Methods Over 19 months, trauma patients transfused > 4 units PRBCs and surviving at least 24 hours were followed. The age of each unit was collected. Results The cohort consisted of 153 patients. All models showed no association between advancing blood age and the likelihood of developing multiorgan dysfunction syndrome (MODS) or infections regardless of whether mean age of blood was analyzed as a continuous variable, as a percentage of blood received which was <14 days old, or as a dichotomized value above or below 14 days old. Conclusions This prospective study duplicates our retrospective findings of an abrogation of the detrimental effects of advancing mean PRBC age on outcomes after trauma by performing PS-LR. PMID:21924400

  12. Improved Outcome with Early Rifampicin Combination Treatment in Methicillin-Sensitive Staphylococcus aureus Bacteraemia with a Deep Infection Focus – A Retrospective Cohort Study

    PubMed Central

    Forsblom, Erik; Ruotsalainen, Eeva; Järvinen, Asko

    2015-01-01

    Introduction Rifampicin has been used as adjunctive therapy in Staphylococcus aureus bacteraemia (SAB) with a deep infection focus. However, data for prognostic impact of rifampicin therapy is unestablished including the optimal initiation time point. We studied the impact of rifampicin therapy and the optimal initiation time for rifampicin treatment on prognosis in methicillin-sensitive S. aureus bacteraemia with a deep infection. Methods Retrospective, multicentre study in Finland including 357 SAB patients with a deep infection focus. Patients with alcoholism, liver disease or patients who died within 3 days were excluded. Patients were categorised according to duration of rifampicin therapy and according to whether rifampicin was initiated early (within 7 days) or late (7 days after) after the positive blood cultures. Primary end point was 90 days mortality. Results Twenty-seven percent of patients received no rifampicin therapy, 14% received rifampicin for 1-13 days whereas 59% received rifampicin ≥14 days. The 90 day mortality was; 26% for patients treated without rifampicin, 16% for rifampicin therapy of any length and 10% for early onset rifampicin therapy ≥14 days. Lack of rifampicin therapy increased (OR 1.89, p=0.026), rifampicin of any duration decreased (OR 0.53, p=0.026) and rifampicin therapy ≥14 days with early onset lowered the risk for a fatal outcome (OR 0.33, p<0.01) during 90 days follow-up. Conclusion Rifampicin adjunctive therapy for at least 14 days and initiated within 7 days of positive blood culture associated with improved outcome among SAB patients with a deep infection. PMID:25874546

  13. A Prospective Randomized Experimental Study to Investigate the Eradication Rate of Endometriosis after Surgical Resection versus Aerosol Plasma Coagulation in a Rat Model

    PubMed Central

    Rothmund, Ralf; Scharpf, Marcus; Tsaousidis, Christos; Planck, Constanze; Enderle, Markus Dominik; Neugebauer, Alexander; Kroeker, Kristin; Nuessle, Daniela; Fend, Falko; Brucker, Sara; Kraemer, Bernhard

    2016-01-01

    Purpose To investigate the eradication rate of endometriosis after surgical resection (SR) vs. thermal ablation with aerosol plasma coagulation (AePC) in a rat model. Methods In this prospective, randomized, controlled, single-blinded animal study endometriosis was induced on the abdominal wall of 34 female Wistar rats. After 14 days endometriosis was either removed by SR or ablated by AePC. 14 days later the rats were euthanized to evaluate the eradication rate histopathologically. Intervention times were recorded. Results Eradication rate of endometriosis after 14 days did not significantly differ between AePC and SR (p=0.22). Intervention time per endometrial lesion was 22.1 s for AePC and 51.8 s for SR (p<0.0001). Conclusions This study compares the eradication rate of the new aerosol plasma coagulation device versus standard surgical resection of endometriosis in a rat model. Despite being a thermal method, AePC showed equality towards SR regarding eradication rate but with significantly shorter intervention time. PMID:26941579

  14. Studies on preweaning piglet diarrhoea.

    PubMed

    Driesen, S J; Carland, P G; Fahy, V A

    1993-07-01

    The aim of this study was to determine the cause and risk factors involved in preweaning piglet diarrhoea. Faecal samples from 2380 diarrhoeic piglets, 5 to 30 days of age, were examined for enteropathogens. Isospora suis oocysts were detected in 53.8% of samples, Escherichia coli in 18.2% and rotavirus in 16.9%. I suis had the widest distribution, being present on 70.9% of 151 piggeries. The onset of diarrhoea occurred mainly between 7 and 14 days (77.5%), peaking at 10 days. Records of 4086 litters from two intensive piggeries were analysed and showed no seasonal variation or effect of sow parity on the incidence of piglet diarrhoea. I suis was the most common enteropathogen associated with diarrhoea in piglets from 5 days of age until weaning. PMID:8368968

  15. Herpes simplex virus 2 meningitis: a retrospective cohort study.

    PubMed

    Miller, Stephanie; Mateen, Farrah J; Aksamit, Allen J

    2013-04-01

    Herpes simplex virus 2 is a leading cause of viral meningitis and the most commonly recognized infectious cause of benign, recurrent meningitis. We report a retrospective, observational cohort study of patients with herpes simplex virus type 2 (HSV-2) meningitis, confirmed by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). The terms "herpes simplex," "meningitis," or "encephalitis" were searched in the medical records system of the Mayo Clinic in Rochester, Minnesota (1995-2008). Patients were included if they had a clinical diagnosis of meningitis and HSV-2 detected by PCR in the CSF. There were 28 patients with 33 episodes identified (83 % female; mean age at presentation of meningitis 36 years, range 17-53; mean time to HSV2 detection from symptom onset 3 days, range 0-6; history of genital herpes 23 %). No patient took oral antiviral treatment at the time of presentation. Episodes were most likely to include headache (100 %), photophobia (47 %), self-reported fever (45 %), meningismus (44 %), and nausea and/or vomiting (29 %). CSF at the time of meningitis was notable for elevated protein (mean 156 g/dL, range 60-258) and white cell count (mean 504 cells/μL, range 86-1,860) with normal glucose (mean 54 mg/dL, range 32-80). Mollaret cells were never detected. Neuroimaging was most often normal (83 %) when performed, although some cases showed nonspecific (14 %) or meningeal changes (3 %). There was no consistent relationship to genital herpes. The duration of treatment with intravenous acyclovir ranged from 3 to 14 days for the first meningitic episode (daily dose range from 500 to 1,000 mg and total dose range from 500 mg q8h for 3 days to 800 mg q8h for 14 days). For subsequent episodes, the duration of treatment of intravenous acyclovir ranged from less than 1 to 14 days (total dose range from 1,390 mg for 1 day to 900 mg q8h for 10 days). The dose of valacyclovir ranged from 500 mg once daily to 500 mg four times daily. The median duration

  16. Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.

    PubMed

    Nakano, Masahiko; Takahashi, Hisaaki; Koura, Seiko; Chung, Catherine; Tafazoli, Shahrzad; Roberts, Ashley

    2014-10-01

    The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study. PMID:24995591

  17. Comparative study of 6-APA production by free and agar immobilized bacteria in nutrient broth culture.

    PubMed

    Dolui, A K; Das, S

    2011-04-01

    In the present study different bacterial samples were isolated from soil of different places of Dibrugarh and screened for biotransformation ability to produce 6-Aminopenicillanic acid. Among ten isolated bacterial samples, three gram positive bacterial samples designated as AKDD-2, AKDD-4 and AKDD-6 showed the production of 6-APA from penicillin G. Assessment of production of 6-APA after incubation in penicillin G (2 mg/ml) by three different samples separately in free and agar immobilization state was done by HPLC analysis. Reusability of immobilized cells was found successful up to 14 days. PMID:21614893

  18. Lunar Outpost Life Support Trade Studies

    NASA Astrophysics Data System (ADS)

    Ewert, Michael; Barta, Daniel J.; Lange, Kevin; Anderson, Molly

    Engineering trade-off studies of life support system architecture and technology options were conducted for potential lunar surface mission scenarios within NASA's Constellation Program. The scenarios investigated are based largely on results of the NASA Lunar Architecture Team (LAT) Phase II study. In particular, the possibility of "Hosted Sortie" missions, the high cost of power during eclipse periods, and the potential to reduce life support consumables through scavenging, in-situ resources, and alternative EVA technologies were all examined. These trade studies were performed within the Systems Integration, Modeling and Analysis (SIMA) element of NASA's Exploration Life Support (ELS) technology development project. The tools and methodology used in the study are described briefly, followed by a discussion of mission scenarios, life support technology options and results presented in terms of "equivalent system mass" for various regenerative life support technologies and architectures. Three classes of repeated or extended lunar surface missions were investigated in this study along with several life support resource scenarios for each mission class. Individual mission durations of 14 days, 90 days and 180 days were considered with 10 missions assumed for each at a rate of 2 missions per year. The 14-day missions represent a class of "Hosted Sortie" missions where a pre-deployed and potentially mobile habitat provides life support for multiple crews at one or more locations. The 90-day and 180-day missions represent lunar outpost expeditions with a larger fixed habitat. The 180-day missions assume continuous human presence and must provide life support through eclipse periods of up to 122 hours while the 90-day missions are planned for best-case periods of nearly continuous sunlight. This paper investigates system optimization within the assumptions of each scenario and addresses how the scenario selected drives the life support system to different designs

  19. Lunar Outpost Life Support Trade Studies

    NASA Technical Reports Server (NTRS)

    Lange, Kevin E.; Anderson, Molly S.; Ewert, Michael K.; Barta, Daniel J.

    2008-01-01

    Engineering trade-off studies of life support system architecture and technology options were conducted for potential lunar surface mission scenarios within NASA's Constellation Program. The scenarios investigated are based largely on results of the NASA Lunar Architecture Team (LAT) Phase II study. In particular, the possibility of Hosted Sortie missions, the high cost of power during eclipse periods, and the potential to reduce life support consumables through scavenging, in-situ resources, and alternative EVA technologies were all examined. These trade studies were performed within the Systems Integration, Modeling and Analysis (SIMA) element of NASA's Exploration Life Support (ELS) technology development project. The tools and methodology used in the study are described briefly, followed by a discussion of mission scenarios, life support technology options and results presented in terms of equivalent system mass for various regenerative life support technologies and architectures. Three classes of repeated or extended lunar surface missions were investigated in this study along with several life support resource scenarios for each mission class. Individual mission durations of 14 days, 90 days and 180 days were considered with 10 missions assumed for each at a rate of 2 missions per year. The 14-day missions represent a class of Hosted Sortie missions where a pre-deployed and potentially mobile habitat provides life support for multiple crews at one or more locations. The 90-day and 180-day missions represent lunar outpost expeditions with a larger fixed habitat. The 180-day missions assume continuous human presence and must provide life support through eclipse periods of up to 122 hours while the 90-day missions are planned for best-case periods of nearly continuous sunlight. This paper investigates system optimization within the assumptions of each scenario and addresses how the scenario selected drives the life support system to different designs

  20. Brexpiprazole Alters Monoaminergic Systems following Repeated Administration: an in Vivo Electrophysiological Study

    PubMed Central

    Mansari, Mostafa El; Bundgaard, Christoffer; Blier, Pierre

    2016-01-01

    Background: Brexpiprazole was recently approved as adjunctive therapy for depression and treatment of schizophrenia in adults. To complement results from a previous study in which its acute effects were characterized, the present study assessed the effect of repeated brexpiprazole administration on monoaminergic systems. Methods: Brexpiprazole (1mg/kg, subcutaneous) or vehicle was administered once daily for 2 and 14 days. Single-unit electrophysiological recordings from noradrenaline neurons in the locus coeruleus, serotonin neurons in the dorsal raphe nucleus, dopaminergic neurons in the ventral tegmental area, and pyramidal neurons in the hippocampus CA3 region were obtained in adult male Sprague-Dawley rats under chloral hydrate anesthesia within 4 hours after final dosing. Results: Brexpiprazole blunted D2 autoreceptor responsiveness, while firing activity of ventral tegmental area dopaminergic neurons remained unaltered. Brexpiprazole increased the firing rate of locus coeruleus noradrenaline neurons and increased noradrenaline tone on α2-adrenergic receptors in the hippocampus. Administration of brexpiprazole for 2 but not 14 days increased the firing rate of serotonin neurons in the dorsal raphe nucleus. In the hippocampus, serotonin1A receptor blockade significantly disinhibited pyramidal neurons after 2- and 14-day brexpiprazole administration. In contrast, no significant disinhibition occurred after 24-hour washout or acute brexpiprazole. Conclusions: Repeated brexpiprazole administration resulted in a marked occupancy of D2 autoreceptors, while discharge activity of ventral tegmental area dopaminergic neurons remained unaltered. Brexpiprazole enhanced serotonergic and noradrenergic tone in the hippocampus, effects common to antidepressant agents. Together, these results provide further insight in the neural mechanisms by which brexpiprazole exerts antidepressant and antipsychotic effects. PMID:26428352

  1. Histomorphometric study of alveolar bone healing in rats fed a boron-deficient diet.

    PubMed

    Gorustovich, Alejandro A; Steimetz, Tammy; Nielsen, Forrest H; Guglielmotti, María B

    2008-04-01

    Bone healing after tooth extraction in rats is a suitable experimental model to study bone formation. Thus, we performed a study to determine the effects of boron (B) deficiency on bone healing by using this model. The first lower right molar of weanling Wistar rats was extracted under anesthesia. The animals were divided into two groups: +B (adequate; 3 mg B/kg diet), and -B (boron-deficient; 0.07 mg/kg diet). The animals in both groups were killed in groups of 10 at 7 and 14 days after surgery. The guidelines of the NIH for the care and use of laboratory animals were observed. The mandibles were resected, fixed, decalcified, and embedded in paraffin. Buccolingually oriented sections were obtained at the level of the mesial alveolus and used for histometric evaluations. Total alveolar volume (TAV) and trabecular bone volume per total volume (BV/TV) in the apical third of the alveolus were determined. Percentages of osteoblast surface (ObS), eroded surface (ES), and quiescent surface (QS) were determined. No statistical significant differences in food intake and body weight were observed. Histomorphometric evaluation found -B rats had 36% and 63% reductions in BV/TV at 7 and 14 days, respectively. When compared with +B rats, -B rats had significant reductions (57% and 87%) in ObS concomitantly with increases (120% and 126%) in QS at 7 and 14 days, respectively. The findings show that boron deficiency results in altered bone healing because of a marked reduction in osteogenesis. PMID:18361451

  2. Biomimetic fiber assembled gradient hydrogel to engineer glycosaminoglycan enriched and mineralized cartilage: An in vitro study.

    PubMed

    Mohan, Neethu; Wilson, Jijo; Joseph, Dexy; Vaikkath, Dhanesh; Nair, Prabha D

    2015-12-01

    The study investigated the potential of electrospun fiber assembled hydrogel, with physical gradients of chondroitin sulfate (CS) and sol-gel-derived bioactive glass (BG), to engineer hyaline and mineralized cartilage in a single 3D system. Electrospun poly(caprolactone) (PCL) fibers incorporated with 0.1% w/w of CS (CSL) and 0.5% w/w of CS (CSH), 2.4% w/w of BG (BGL) and 12.5% w/w of BG (BGH) were fabricated. The CS showed a sustained release up to 3 days from CSL and 14 days from CSH fibers. Chondrocytes secreted hyaline like matrix with higher sulfated glycosaminoglycans (sGAG), collagen type II and aggrecan on CSL and CSH fibers. Mineralization was observed on BGL and BGH fibers when incubated in simulated body fluid for 14 days. Chondrocytes cultured on these fibers secreted a mineralized matrix that consisted of sGAG, hypertrophic proteins, collagen type X, and osteocalcin. The CS and BG incorporated PCL fiber mats were assembled in an agarose-gelatin hydrogel to generate a 3D hybrid scaffold. The signals in the fibers diffused and generated continuous opposing gradients of CS (chondrogenic signal) and BG (mineralization) in the hydrogel. The chondrocytes were encapsulated in hybrid scaffolds; live dead assay at 48 h showed viable cells. Cells maintained their phenotype and secreted specific extracellular matrix (ECM) in response to signals within the hydrogel. Continuous opposing gradients of sGAG enriched and mineralized ECM were observed surrounding each cell clusters on gradient hydrogel after 14 days of culture in response to the physical gradients of raw materials CS and BG. A construct with gradient mineralization might accelerate integration to subchondral bone during in vivo regeneration. PMID:26014103

  3. Prehospital risk factors of mortality and impaired consciousness after severe traumatic brain injury: an epidemiological study

    PubMed Central

    2014-01-01

    Background Severe traumatic brain injury (TBI) is a significant health concern and a major burden for society. The period between trauma event and hospital admission in an emergency department (ED) could be a determinant for secondary brain injury and early survival. The aim was to investigate the relationship between prehospital factors associated with secondary brain injury (arterial hypotension, hypoxemia, hypothermia) and the outcomes of mortality and impaired consciousness of survivors at 14 days. Methods A multicenter, prospective cohort study was performed in dedicated trauma centres of Switzerland. Adults with severe TBI (Abbreviated Injury Scale score of head region (HAIS) >3) were included. Main outcome measures were death and impaired consciousness (Glasgow Coma Scale (GCS) ≤13) at 14 days. The associations between risk factors and outcome were assessed with univariate and multivariate regression models. Results 589 patients were included, median age was 55 years (IQR 33, 70). The median GCS in ED was 4 (IQR 3-14), with abnormal pupil reaction in 167 patients (29.2%). Median ISS was 25 (IQR 21, 34). Three hundred seven patients sustained their TBI from falls (52.1%) and 190 from a road traffic accidents (32.3%). Median time from Out-of-hospital Emergency Medical Service (OHEMS) departure on scene to arrival in ED was 50 minutes (IQR 37-72); 451 patients had a direct admission (76.6%). Prehospital hypotension was observed in 24 (4.1%) patients, hypoxemia in 73 (12.6%) patients and hypothermia in 146 (24.8%). Prehospital hypotension and hypothermia (apart of age and trauma severity) was associated with mortality. Prehospital hypoxemia (apart of trauma severity) was associated with impaired consciousness; indirect admission was a protective factor. Conclusion Mortality and impaired consciousness at 14 days do not have the same prehospital risk factors; prehospital hypotension and hypothermia is associated with mortality, and prehospital hypoxemia with

  4. Changes observed in the thymus and lymph nodes 14 days after exposure to BVDV field strains of enhanced or typical virulence in neonatal calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Clinical presentation following uncomplicated acute infection with bovine viral diarrhea viruses (BVDV) ranges from clinically unapparent to severe (including hemorrhagic disease and death) depending on the strain virulence. Regardless of clinical presentation, BVDV infection of cattle results in i...

  5. Experiment K-6-02. Biomedical, biochemical and morphological alterations of muscle and dense, fibrous connective tissues during 14 days of spaceflight

    NASA Technical Reports Server (NTRS)

    Vailas, A.; Zernicke, R.; Grindeland, R.; Kaplanski, A.

    1990-01-01

    Findings on the connective tissue response to short-term space flight (12 days) are discussed. Specifically, data regarding the biochemical, biomechanical and morphological characteristics of selected connective tissues (humerus, vertebral body, tendon and skeletal muscle) of growing rats is given. Results are given concerning the humerus cortical bone, the vertebral bone, nutritional effects on bone biomechanical properties, and soft tense fiber connective tissue response.

  6. Translocation of Campylobacter and Salmonella to the spleen and liver/gallbladder in 7 and 14 day old broiler chicks following oral gavage

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Day-of-hatch broilers were obtained from a commercial hatchery and orally gavaged with 0.10mL of either 103 or 106 cells of a marker strain of Campylobacter coli (CC) or Salmonella Typhimurium (ST). At one and two wk after inoculation 10 broilers from the control and each treatment group were human...

  7. 4 CFR 7.6 - Adverse actions: Removal, suspension for more than 14 days, reduced in grade, reduced in pay or...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Adverse actions: Removal, suspension for more than 14... proposed under this section is entitled to— (1) At least 30 days' advance written notice, unless there is... by an attorney or other representative; and (4) A written decision and the specific reasons...

  8. L-Arginine supplementation 0.5% of diet during the last 90 days of gestation and 14 days postpartum reduced uterine fluid accumulation in the broodmare.

    PubMed

    Mesa, A M; Warren, L K; Sheehan, J M; Kelley, D E; Mortensen, C J

    2015-08-01

    L-Arginine is an essential amino acid in many species that has been shown to influence reproduction. However, in horses a dose of 1% L-arginine of total dietary intake impaired absorption of other amino acids, whereas a dose of 0.5% did not. The objectives of this experiment were to evaluate postpartum parameters on mares supplemented with 0.5% L-arginine through the last 90d of gestation and 14d postpartum. Sixteen light-horse mares were randomly divided in two groups: 8 mares supplemented with 0.5% L-arginine and 8 mares fed an isonitrogenous equivalent. Gestation length, days to uterine clearance and days to first ovulation were compared. Uterine body depth, diameter of uterine horns, and length of largest pocket of uterine fluid were recorded daily via transrectal ultrasound. Measurements of foal weight, height, and cannon bone circumference were recorded for 9 weeks. Arginine treatment had no effect on gestation length (P=0.58). Supplemented mares cleared fluid quicker postpartum (6.8±0.53d; P=0.026) compared to control (9.0±0.38d). Mares supplemented with L-arginine had smaller diameter of fluid present in the postpartum uterus (P≤0.05). Days to first postpartum ovulation were not affected by treatment nor any influence on uterine involution. Finally, treatment had no effect on any foal's measured parameters. L-Arginine supplementation fed at 0.5% of daily intake during the last 90d of gestation and early postpartum in mares decreased uterine fluid accumulation, yet did not appear to have any effect on any other parameters measured. PMID:26036908

  9. Difluprednate 0.05% Versus Prednisolone Acetate 1% for Endogenous Anterior Uveitis: A Phase III, Multicenter, Randomized Study

    PubMed Central

    Sheppard, John D.; Toyos, Melissa M.; Kempen, John H.; Kaur, Paramjit; Foster, C. Stephen

    2014-01-01

    Purpose. Endogenous anterior uveitis (AU), when untreated, may lead to vision loss. This study compared the safety and efficacy of difluprednate versus prednisolone acetate for the treatment of this condition. Methods. This phase III, double-masked, noninferiority study randomized patients with mild to moderate endogenous AU to receive difluprednate 0.05% (n = 56) four times daily, alternating with vehicle four times daily, or prednisolone acetate 1% (n = 54) eight times daily. The 14-day treatment period was followed by a 14-day dose-tapering period and a 14-day observation period. The primary efficacy end point was change in anterior chamber cell grade (range, 0 for ≤1 cell to 4 for >50 cells) from baseline to day 14. Results. At day 14, the mean change in anterior chamber cell grade with difluprednate was noninferior to that with prednisolone acetate (−2.2 vs. −2.0, P = 0.16). The proportions of difluprednate-treated patients versus prednisolone acetate–treated patients demonstrating complete clearing of anterior chamber cells at day 3 were 13.0% vs. 2.1% (P = 0.046) and at day 21 were 73.9% vs. 63.8% (P = 0.013). A significant between-group difference in the mean IOP increase was seen at day 3 (2.5 mm Hg for difluprednate-treated patients and 0.1 mm Hg for prednisolone acetate–treated patients, P = 0.0013) but not at other time points. The mean IOP values in both groups remained less than 21 mm Hg throughout the study. Conclusions. Difluprednate 0.05% four times daily is well tolerated and is noninferior to prednisolone acetate 1% eight times daily for the treatment of endogenous AU. (ClinicalTrials.gov number, NCT01201798.) PMID:24677110

  10. Novel protective mechanisms of antidepressants against 3-nitropropionic acid induced Huntington's-like symptoms: a comparative study.

    PubMed

    Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

    2011-10-01

    Huntington's disease (HD) is characterized by progressive degeneration of neurons in the striatum, cortex and other parts of the brain, causing motor and cognitive dysfunction. 3-Nitropropionic acid (3-NP) is a well-known mycotoxin that significantly induces motor dysfunction in animals. Studies suggested the involvement of oxidative stress and nitric oxide mechanisms in HD pathogenesis. Clinical reports have also indicated the neuroprotective potential of antidepressants. Therefore, the present study has been designed to elucidate and compare the mechanistic role of different antidepressants (sertraline, venlafaxine, imipramine and trazodone) and their interaction with nitric oxide modulators if any, against 3-NP-induced neurotoxicity. Systemic 3-NP (10 mg/kg) administration for 14 days significantly reduced locomotor activity, body weight, motor coordination, oxidative defense and impaired mitochondrial complex enzyme activities in the striatum. Sertraline, venlafaxine, imipramine and trazodone treatments significantly improved behavioral, oxidative defense and mitochondrial complex enzyme activities as compared with the 3-NP-treated group. Systemic L-arginine (50 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly attenuated their protective effect. Similarly, L-nitro-arginine methyl ester (L-NAME) (10 mg/kg) pretreatment with sub-effective dose of sertraline (10 mg/kg), venlafaxine (10 mg/kg), imipramine (10 mg/kg) and trazodone (10 mg/kg) for 14 days significantly potentiated their protective effects which were significant as compared with their effect alone, respectively. The results of the present study suggest that a nitric oxide mechanism might be involved in their protective effect against 3-NP-induced neurotoxicity. PMID:20305041

  11. Joint US/USSR study: Comparison of effects of horizontal and head-down bed rest

    NASA Technical Reports Server (NTRS)

    Sandler, Harold; Grigoriev, Anatoli I.

    1990-01-01

    An account is given of the results of the first joint U.S./U.S.S.R. bed rest study. The study was accomplished in two parts: A soviet part (May to June 1979) and an American part (July to August 1979). Both studies were conducted under identical conditions and provided a basis for comparison of physiologic reactions and standardizing procedures and methods. Each experiment consisted of three periods: 14 days of pre-bed rest control, 7 days of bed rest, and a 10 to 14 day recovery period. Ten males participated in each study, with five subjects experiencing horizontal bed rest and five subjects a -6 deg head-down body position. Biochemical and hormonal measurements were made of blood and urine, with particular attention to electrolyte metabolism and kidney function; cardio-pulmonary changes at rest and exercise; influence of Lower Body Negative Pressure (LBNP); and incremental exercise using a bicyle ergometer while supine and sitting. Expected moderate changes were noted to occur for various physiologic parameters. Clinical evidence pointed to the fact that head-down bed rest when compared to horizontal conditions more closely matched the conditions seen after manned spaceflight. For the most part, statistically significant differences between the two body positions were not observed.

  12. EFFECTS OF CHLOROFORM IN THE DRINKING WATER OF RATS AND MICE: NINETY-DAY SUBACUTE TOXICITY STUDY

    EPA Science Inventory

    This research was initiated to provide toxicologic and range finding data sufficient for setting dose levels for the chronic phase testing of chloroform in drinking water of male Osborne-Mendel rats and female B6C3F1 mice. A 90-day subchronic study was designed to investigate the...

  13. Sequential alternate administration of tamoxifen and medroxyprogesterone acetate in advanced breast cancer: clinical-biological randomized study.

    PubMed

    De Lena, M; Tommasi, S; Schittulli, F; Lorusso, V; Paradiso, A

    1990-04-30

    From January 1985 to September 1988, 60 women with advanced breast cancer were randomized in two arms to receive: A) tamoxifen (TAM) (20 mg/die) until progression or B) TAM (20 mg/die for 14 days) then medroxyprogesterone acetate (MPA) (1500 mg/die p.o. for 14 days) followed by 7 days of wash-out before repeating the TAM/MPA treatment. All patients were post-menopausal, previously untreated with hormone therapy, and with tumor receptor status determined immediately before randomization; all had objectively evaluable lesions. In order to verify hormone receptor variations due to the antiestrogen, when possible a second biopsy was performed after the initial 14 day cycle of TAM. Thirty-one and 29 patients were included respectively in arms A and B. Objective regression (CR + PR) was observed in 58% of group A and 75% of group B, with CR in 11% and 23%, respectively. Differences were not statistically significant. Median time to progression was 12 months for group A and 9 for group B. Overall survival has not yet been reached in group A while it was 34 months for patients of group B. Metrorrhagia was observed in two cases of group A and in 6 of group B, and thrombophlebitis in 1 and 3 cases, respectively. The second biopsy confirmed a clear increase of PgR content in 8/11 cases (75%). Plasma level variations of TAM, N-desmethyl TAM and MPA were checked at various intervals on 3 patients of group B, and confirmed that our schedule is able to produce a drug wash-out period for tumor cells. In conclusion, our study demonstrated that while the manipulation of hormone receptors seems possible, results indicating better overall survival and time to progression were not obtained with alternate sequential TAM-MPA therapy. PMID:2139523

  14. Long life feasibility study for the shuttle infrared telescope facility

    NASA Technical Reports Server (NTRS)

    1985-01-01

    A study was conducted to assess the feasibility of designing an Infrared Telescope of the 1 meter class which would operate effectively as a Shuttleborne, 14-day Spacelab payload and then be adapted with little modification to work as a 6 month Space station or free flyer payload. The optics configuration and requirements from a previous study were used without modification. In addition, an enhancement to 2 year mission lengths was studied. The cryogenic system selected was a hybrid design with an internal solid Hydrogen tank at 8 Kelvin and an internal superfluid tank at 2K. In addition to the cryogenic design, a detailed look at secondary mirror actuators for chopping, focus and decenter was conducted and analysis and cryo test reported.

  15. Short-term efficacy of calcium fructoborate on subjects with knee discomfort: a comparative, double-blind, placebo-controlled clinical study

    PubMed Central

    Pietrzkowski, Zbigniew; Phelan, Michael J; Keller, Robert; Shu, Cynthia; Argumedo, Ruby; Reyes-Izquierdo, Tania

    2014-01-01

    Calcium fructoborate (CFB) at a dose of 110 mg twice per day was previously reported to improve knee discomfort during the first 14 days of treatment. In this study, 60 participants with self-reported knee discomfort were randomized into two groups receiving CFB or placebo. Initial levels of knee discomfort were evaluated by Western Ontario and McMaster Universities Arthritis Index (WOMAC) and McGill Pain Questionnaire (MPQ) scores at the beginning of the study and also at 7 and 14 days after treatment. Results showed that supplementation with CFB significantly improved knee discomfort in the study subjects; significant reductions of mean within-subject change in WOMAC and MPQ scores were observed for the CFB group compared to the placebo group at both 7 and 14 days after treatment. Estimated treatment differences for the MPQ score were −5.8 (P=0.0009) and −8.9 (P<0.0001) at Day 7 and 14, respectively. Estimated differences for the WOMAC score were −5.3 (P=0.06) and −13.73 (P<0.0001) at Day 7 and 14, respectively. Negative values indicate greater reductions in reported discomfort. On both Day 7 and Day 14, the trend was toward greater improvement in the CFB group. The placebo group did not exhibit any change in the WOMAC and MPQ scores. In conclusion, supplementation with 110 mg CFB twice per day was associated with improving knee discomfort during the 2 weeks of intake. PMID:24940052

  16. Field study of coccidial and rotaviral diarrhoea in unweaned piglets.

    PubMed

    Roberts, L; Walker, E J

    1982-01-01

    A study of diarrhoea in unweaned piglets was carried out in nine herds, with special reference to the enteropathogenic agents which could be demonstrated. Coccidial (Isospora suis) and rotaviral infections were both identified, either singly or in combination. More extensive studies of I suis infection were undertaken in two of the herds and it was found that diarrhoea occurred most commonly in five- to 14-day-old piglets. Piglets with I suis infection were not necessarily diarrhoeic but grew poorly compared to uninfected piglets. I suis infection in litters correlated with oocyst excretion in sows. In herds with I suis infection, amprolium and monensin were used in the sow ration to achieve control, and in one herd oral dosing of piglets with amprolium in the first three or four days of life was carried out. PMID:6278696

  17. The Efficacy of Oral Melatonin in Improving Sleep in Cancer Patients with Insomnia: A Randomized Double-Blind Placebo-Controlled Study

    PubMed Central

    Kurdi, Madhuri S; Muthukalai, Sindhu Priya

    2016-01-01

    Background: The natural hormone melatonin has sleep inducing properties. Insomnia in cancer patients is common. So far, melatonin has been seldom tried for the improvement of sleep in patients with malignancies. Keeping this in mind, we planned and conducted a double-blind study to test the efficacy of melatonin in promoting sleep in patients with malignancies suffering from insomnia. Objective: To assess the hypnotic efficacy of oral melatonin in cancer patients with insomnia. Materials and Methods: After Ethical Committee approval, 50 patients (age range 20-65 years) from our pain clinic NIVARANE who met the Diagnostic and Statistical Manual of Mental Disorders 4th edition criteria for primary insomnia were randomized to receive melatonin 3 mg or placebo at 7 pm orally every day for 14 days from our pharmacist. After 1, 7, 14 days, the patients were reviewed with the Athens insomnia scale oral questionnaire to document the subjective sleep quality. The patients and we, the investigators were blinded to the study drug. Results: There were 2 drop outs (one from each group) as they failed to complete visit on day 14. Significant differences in favor of melatonin treatment were found in clinically relevant improvements in insomnia (46.53%; P = 0.00001 vs. 11.30%; P = 0.1026) There was improvement in sleep from 1 to 7 days (19.91%; P = 0.00001 vs. 0.98%; P = 0.2563). More significant improvements were seen between 7 and 14 days (33.24%; P = 0.00001 vs. 10.42%; P = 0.1469). Conclusion: We conclude that daily intake of oral melatonin 2 h before bedtime improves sleep induction and quality in cancer patients with insomnia. PMID:27559258

  18. Adipogenesis and aldosterone: a study in lean tryptophan-depleted rats.

    PubMed

    Pokusa, Michal; Hlavacova, Natasa; Csanova, Agnesa; Franklin, Michael; Zorad, Stefan; Jezova, Daniela

    2016-07-01

    Next to epithelial tissues, mineralocorticoid receptors are also expressed in adipose tissue and are involved in the process of adipogenesis. Mineralocorticoid receptors in adipose tissue are likely to be activated mainly by glucocorticoids. The aim of the present study was to test the hypothesis that the processes related to adipogenesis are modified under the conditions associated with high circulating aldosterone. We have made advantage of a model of depression based on tryptophan depletion in which we have previously demonstrated that the elevation of serum aldosterone precedes that of corticosterone. Sixty adult female Sprague-Dawley rats were fed either a low tryptophan diet or control diet for 4 (elevation of aldosterone only), 7 and 14 days (broader neuroendocrine activation) respectively. Gene expression of several adipogenic factors, CD31, interleukin-6, adiponectin, resistin and leptin were evaluated. Levels of mRNAs coding for adipogenic, angiogenic and inflammatory factors in adipose tissue were elevated at 4 and 7 days of tryptophan depletion. Additionally, gene expression of aldosterone sensing 11-β-hydroxysteroid dehydrogenase 2 and mineralocorticoid receptors were elevated. All changes disappeared at 14 days of tryptophan depletion. Synchronously an increase of adipose tissue mass was observed. Although direct evidence is not provided, observed changes in gene expression may be related to the action of aldosterone on mineralocorticoid receptors. Our findings represent the first data on any changes in gene expression in adipose tissue in animal models of depression. PMID:27253873

  19. Further absorption studies with the anti-diarrhoeal agent ethacridine lactate in the dog.

    PubMed

    Rising, T J; Fromson, J M; Johnson, P

    1978-01-01

    2-Ethoxy-6,9-diaminoacridine lactate (ethacridine lactate, Rivanol, Metifex) has been administered orally to the dog once daily for 14 days, tritium labelled matterial having been given on days 1 and 14. The extent and rates of urinary excretion of radioactivity and the peak plasma levels and total radioactivity half-lives following the radiolabelled doses on days 1 and 14 were essentially the same. There was no significant change following multiple dosing in the level of urinary acridine-like material as determined fluorimetrically, which compared to approximately 0.01% of the dose found in the 0--24 h urine. It was concluded that, following oral administration of 3H-ethacridine lactate (5 mg/kg), less than 0.1% of the dose is absorbed as acridine-like material. Multiple dosing for 14 days does not alter this very low degree of oral absorption. In a separate study tritiated ethacridine lactate (30 microgram/kg) was administered i.v. to the dog. Approximately 84% of the radioactivity was eliminated in the 0--72 h post dose period, the majority of it being excreted via the faeces. There was a rapid loss of radioactivity from the plasma, followed by a long terminal phase in which acridine-like material was estimated to have a half-life of about 15 h. PMID:581939

  20. Engineering Analysis Studies for Preliminary Design of Lightweight Cryogenic Hydrogen Tanks in UAV Applications

    NASA Technical Reports Server (NTRS)

    Sullivan, Roy M.; Palko, Joseph L.; Tornabene, Robert T.; Bednarcyk, Brett A.; Powers, Lynn M.; Mital, Subodh K.; Smith, Lizalyn M.; Wang, Xiao-Yen J.; Hunter, James E.

    2006-01-01

    A series of engineering analysis studies were conducted to investigate the potential application of nanoclay-enhanced graphite/epoxy composites and polymer cross-linked silica aerogels in cryogenic hydrogen storage tank designs. This assessment focused on the application of these materials in spherical tank designs for unmanned aeronautic vehicles with mission durations of 14 days. Two cryogenic hydrogen tank design concepts were considered: a vacuum-jacketed design and a sandwiched construction with an aerogel insulating core. Analyses included thermal and structural analyses of the tank designs as well as an analysis of hydrogen diffusion to specify the material permeability requirements. The analyses also provided material property targets for the continued development of cross-linked aerogels and nanoclay-enhanced graphite/epoxy composites for cryogenic storage tank applications. The results reveal that a sandwiched construction with an aerogel core is not a viable design solution for a 14-day mission. A vacuum-jacketed design approach was shown to be far superior to an aerogel. Aerogel insulation may be feasible for shorter duration missions. The results also reveal that the application of nanoclay-enhanced graphite/epoxy should be limited to the construction of outer tanks in a vacuum-jacketed design, since a graphite/epoxy inner tank does not provide a significant weight savings over aluminum and since the ability of nanoclay-enhanced graphite/epoxy to limit hydrogen permeation is still in question.

  1. [Metis Study Tour Report.

    ERIC Educational Resources Information Center

    Human Resources Development Authority, Edmonton (Alberta).

    A 14-day tour by field workers was designed to obtain a minimum of information for purposes of policy making by the Indian Association of Alberta. The principal Metis centers in the Province of Alberta were visited, and interviews were conducted in Edmonton with government and private agencies. Fact and opinion are intermingled throughout this…

  2. Immunofluorescence studies of disseminated Hantaan virus infection of suckling mice.

    PubMed Central

    Kurata, T; Tsai, T F; Bauer, S P; McCormick, J B

    1983-01-01

    Hantaan virus, the etiological agent of Korean hemorrhagic fever, was inoculated intracerebrally or intraperitoneally into suckling mice, and the course of the infection was followed by infectivity titration and immunofluorescence studies. Mice became ill and were moribund by 13 to 14 days postinfection. In mice inoculated either intracerebrally or intraperitoneally, virus antigen was present in brain, heart, lungs, liver, and kidney. Less consistently, specific fluorescence was observed in spleen, pituitary gland, thymus, lymph nodes, adrenal, pancreas, salivary glands, trigeminal ganglia, adipose tissue, intestine, and muscle. In all of these tissues, the primary target of infection was the capillary endothelium. In mice inoculated intracerebrally, virus antigen was present mainly in choroid plexus, hippocampal nuclei, and meninges, but in mice inoculated intraperitoneally, central nervous system infection was marked by antigen accumulation in cortical nuclei and thalamus. Images PMID:6134678

  3. A randomized clinical study of the heated lidocaine/tetracaine patch versus subacromial corticosteroid injection for the treatment of pain associated with shoulder impingement syndrome

    PubMed Central

    Radnovich, Richard; Trudeau, Jeremiah; Gammaitoni, Arnold R

    2014-01-01

    Background Treatment for pain due to shoulder impingement syndrome (SIS) typically begins conservatively with nonsteroidal anti-inflammatory drugs and physical therapy and can include subacromial injection of corticosteroids, particularly in patients unresponsive to conservative measures. The heated lidocaine/tetracaine (HLT) patch has been reported to reduce SIS pain in a small case series. Methods This was a prospective, randomized, open-label clinical trial in which adult patients with SIS pain lasting at least 14 days, with an average intensity of ≥4 on a 0–10 scale (0= no pain, 10= worst pain) were randomized to treatment with the HLT patch or a single subacromial injection of triamcinolone acetonide (10 mg). Patients in the HLT patch group applied a single HLT patch to the shoulder for 4 hours twice daily, with a 12-hour interval between treatments during the first 14 days, and could continue to use the patch on an as-needed basis (up to twice daily) during the second 14-day period. No treatment was allowed in the final 14-day period. At baseline and at days 14, 28, and 42, patients rated their pain and pain interference with specific activities (0–10 scale). Results Sixty patients enrolled in the study (average age =51 years, range 18–75, n=21 female). Average pain scores declined from 6.0±1.6 at baseline to 3.5±2.4 at day 42 in the HLT patch group (n=29, P<0.001) and from 5.6±1.2 to 3.2±2.6 in the injection group (n=31, P<0.001). Similar improvements were seen in each group for worst pain; pain interference with general activity, work, or sleep; and range of motion. No significant between-group differences were seen for any pain or pain interference scores at any time point. Conclusion These results suggest that short-term, noninvasive treatment with the HLT patch has similar efficacy to subacromial corticosteroid injections for the treatment of pain associated with SIS. PMID:25525385

  4. Phase II, Randomized, Placebo-controlled, 90-day Study of Emixustat HCL in Geographic Atrophy Associated with Dry Age-Related Macular Degeneration

    PubMed Central

    Dugel, Pravin U.; Novack, Roger L.; Csaky, Karl G.; Richmond, Preston P.; Birch, David G.; Kubota, Ryo

    2015-01-01

    Purpose This study assessed the safety, tolerability, and pharmacodynamics of emixustat hydrochloride (ACU-4429), a novel visual cycle modulator, in subjects with geographic atrophy (GA) associated with dry age-related macular degeneration (AMD). Methods Subjects were randomly assigned to oral emixustat (2, 5, 7, or 10 mg once daily) or placebo (3:1 ratio) for 90 days. Recovery of rod photoreceptor sensitivity following a photobleach was measured by electroretinography. Safety evaluations included analysis of adverse events (AEs) and ophthalmic examinations. Results Seventy-two subjects (54 emixustat, 18 placebo) were evaluated. Emixustat suppressed rod photoreceptor sensitivity in a dose-dependent manner. Suppression plateaued by Day 14, and was reversible within 7-14 days after drug cessation. No systemic AEs of concern were noted. Dose-related ocular AEs (chromatopsia, 57% emixustat vs. 17% placebo; and delayed dark adaptation, 48% emixustat vs. 6% placebo) were mild to moderate, and the majority resolved on study or within 7-14 days after study drug cessation. Conclusions In this phase II study, emixustat produced a dose-dependent, reversible effect on rod function, and an ocular AE profile that is consistent with the proposed mechanism of action. These results support further testing of emixustat for the treatment of GA associated with dry AMD. PMID:25932553

  5. Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats.

    PubMed

    Asanuma, Fumiko; Miyata, Hiroto; Iwaki, Yoshinobu; Kimura, Masaaki; Matsumoto, Kiyoshi

    2010-03-01

    This study attempted to prove our hypothesis that a short-term toxicity study, using a 4-day dosing regimen as an example, is suitable for evaluating myelotoxicity in rats. We compared the hematological, bone marrow cytological and histopathological results of 5-fluorouracil (5-FU) treated and pair-feeding groups after a 4-day administration period. Several experimental groups were defined for this 4-day study as well as for our previously reported 14-day study (Miyata et al., 2009); these included 5-FU treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Although severe reductions in body weight gain and food consumption were reported in the 14-day study, only slight reductions were observed in the 4-day study. In the 4-day study, a decrease in blood reticulocytes and a decreasing trend of marrow erythroid cells were only observed in the FU18 group, and no effects were observed in the pair-feeding groups. The erythroblastic changes observed in this 4-day study were thought to reflect the direct influence of 5-FU administration. Since concerns regarding the influence of secondary changes related to undernutrition were minimized in the 4-day study, it was thought to clarify the direct influence of 5-FU administration on erythroblastic cells. Thus, a 4-day study protocol might be helpful for distinguishing secondary changes related to undernutrition. PMID:22272009

  6. [Felbinac gel for treatment of localized extra-articular rheumatic diseases--a multicenter, placebo controlled, randomized study].

    PubMed

    Bolten, W

    1991-01-01

    281 patients with extra-articular rheumatic disorders (enthesiopathy, bursitis, tendinosis, fibrositis) and moderate or severe localized pain during rest or movement in shoulder, neck, elbow or knee were randomized into groups and treated for 14 days in a double blind study with either 1 g Felbinac Gel 3% (biphenyl acetic acid) three times daily (N = 142) or with the gel formulation only (N = 139). In 50% of the patients treated with Felbinac Gel compared to 29% of the placebo treated patients (p = 0.001), the investigator assessed the global therapeutic success to be good or very good. The magnitude of complaints judged on the basis of a visual analogous scale by patients and doctor showed a significant improvement in pain reduction during rest or activity after 14 days of treatment in the Felbinac group. The rheumatic complaints diminished equally according to patient judgement in both treatment groups and the concomitant use of paracetamol was low in both groups. No significant side-effects or changes in laboratory parameters were observed during therapy. Felbinac Gel therefore is suitable for a low-risk topical therapy of soft tissue rheumatic disorders. PMID:1872042

  7. Short-term toxicity study of ST-20 (NSC-741804) by oral gavage in Sprague-Dawley rats.

    PubMed

    Terse, Pramod S; Johnson, Jerry D; Hawk, Michael A; Ritchie, Glenn D; Ryan, Michael J; Vasconcelos, Daphne Y; Contos, Denise A; Perrine, Susan P; Peggins, James O; Tomaszewski, Joseph E

    2011-06-01

    ST-20 (sodium 2,2-dimethylbutyrate) is a potential therapeutic agent for treatment of β-thalassemia and sickle cell disease. A subchronic oral toxicity study was conducted in Sprague-Dawley rats (10/sex/dose) at gavage dosages of 0 (vehicle control), 200, 600, or 1,000 mg/kg, once daily for up to 15 days followed by a 14-day recovery. Ataxia (females), rough coat/thin appearance (males), and decreased body weights were observed at 1,000 mg/kg. Functional observational battery (FOB) deficits were observed more frequently in females and included decreased body tone, rectal temperature, emotional reactivity, neuromotor-neuromuscular activity (as exhibited by a deficit in visual/tactile placing accuracy, ataxia, hind limb dragging, and decreased grip strength), and rearing. ST-20 caused a decrease in WBC/RBC counts and RBC parameters; increase in reticulocytes and red cell inclusion bodies; decrease in total protein, globulin, and glucose; and increase in AG ratio. Micronucleated polychromatic erythrocytes of the bone marrow increased significantly in males at 1,000 mg/kg. Mean liver and kidney weights increased, and hepatocellular hypertrophy was observed in males at 1,000 mg/kg. Toxicologic findings were fully recovered during the 14-day recovery period. In conclusion, the no-observed adverse effect level for FOB and general toxicity was 200 mg/kg following gavage administration of ST-20 for up to 15 consecutive days. PMID:21558467

  8. Location of injected polymethylmethacrylate microspheres influences the onset of late adverse effects: an experimental and histopathologic study

    PubMed Central

    de Jesus, Luciano Henrique; de Campos Hildebrand, Laura; Martins, Manoela Domingues; da Rosa, Francinne Miranda; Danilevicz, Chris Krebs; Sant’Ana Filho, Manoel

    2015-01-01

    Polymethylmethacrylate (PMMA) has been widely used in the correction of wrinkles because of its long-lasting cosmetic improvements. However, side effects and complications may occur, and its clinical appearance on the oral mucosa can be similar to that of inflammatory or neoplastic disease. The aim of this research was to compare the clinical and histopathologic responses to PMMA injected by two different methods. Twenty-two rats received an injection of PMMA using the tunneling technique (gold standard), with subcutaneous deposition of the filler in the face, or a variation of the technique with transcutaneous submucosal deposition of the filler in the cheek. The tissue reaction was analyzed clinically every 24 hours during the first week, then once a week for the following 3 months. Histologic evaluation was based on the local inflammatory response to the filler. No clinical changes were observed during the initial evaluation period (0–14 days). After 14 days, only the submucosal group showed extra-oral enlargement (n=4, 18.2%). Histopathologic analysis revealed nodule formation in four animals (18.2%) in the submucosal group, with no nodules observed in the subcutaneous group. The data obtained in this study demonstrate that the technique used to deliver the filler may influence the risk of adverse reactions. PMID:26346665

  9. Part 2: A field study of enhanced remediation of Toluene in the vadose zone using a nutrient solution

    USGS Publications Warehouse

    Tindall, J.A.; Weeks, E.P.; Friedel, M.

    2005-01-01

    The objective of this study was to test the effectiveness of a nitrate-rich nutrient solution and hydrogen peroxide (H2O2) to enhance in-situ microbial remediation of toluene in the unsaturated zone. Three sand-filled plots were tested in three phases (each phase lasting approximately 2 weeks). During the control phase, toluene was applied uniformly via sprinkler irrigation. Passive remediation was allowed to occur during this phase. A modified Hoagland nutrient solution, concentrated in 150 L of water, was tested during the second phase. The final phase involved addition of 230 moles of H2O2 in 150 L of water to increase the available oxygen needed for aerobic biodegradation. During the first phase, measured toluene concentrations in soil gas were reduced from 120 ppm to 25 ppm in 14 days. After the addition of nutrients during the second phase, concentrations were reduced from 90 ppm to about 8 ppm within 14 days, and for the third phase (H 2O2), toluene concentrations were about 1 ppm after only 5 days. Initial results suggest that this method could be an effective means of remediating a contaminated site, directly after a BTEX spill, without the intrusiveness and high cost of other abatement technologies such as bioventing or soil-vapor extraction. However, further tests need to be completed to determine the effect of each of the BTEX components. ?? Springer 2005.

  10. Screening study for repeated dose and reproductive/developmental toxicity of rubber accelerator, N,N-dicyclohexyl-2-benzothiazolesulfenamide, in rats.

    PubMed

    Ema, Makoto; Ito, Yoshihiko; Matsumoto, Mariko; Hirose, Akihiko; Kamata, Eiichi

    2007-01-01

    A screening study for a vulcanization accelerator N,N-dicyclohexyl-2-benzothiazole-sulfenamide (DCBS) was performed in rats. Rats were given DCBS by gavage daily at 0, 6, 25, 100, or 400 mg/kg. Males were dosed for a total of 44 days beginning 14 days before mating. Females were dosed for a total of 40-51 days beginning 14 days before mating to day 3 of lactation. Toxicologic changes were significantly noted only at 400 mg/kg. Three females died. An increased incidence of females showing decreased locomotor activity, soil of the lower abdominal fur, and reddish tears was observed. A lowered body weight was found in males and females. Increased urinary ketones and serum inorganic phosphorus and decreased serum glutamate pyruvate transaminase in males were found. Increased absolute and relative weights of the kidneys in males and decreased absolute weight of the thymus in both sexes were noted. Significant fatty degeneration of the renal tubular epithelia, vacuolation of the adrenocortical cells, and atrophy of the spleen were observed in females. Significant decreases in the gestation index, numbers of corpura lutea, implantations, pups born and pups born alive, live birth index, and viability index were detected. It is concluded that the No Observed Adverse Effect Levels (NOAELs) for repeat dose and reproductive/developmental toxicity are 100 mg kg-1 day-1 in this screening study. PMID:17613004

  11. Evaluation of electrical stimulation for ischemic wound therapy: a feasibility study using the lapine wound model.

    PubMed

    Morris, Kimberly A; McGee, Michael F; Jasper, John J; Bogie, Kath M

    2009-04-01

    Chronic wounds are a major secondary complication for many people with impaired mobility. Electrical stimulation (ES) has been recommended as a adjunctive therapy, however optimal treatment paradigms have not been established. Our group seeks to determine the basic mechanisms underlying ES wound therapy, an area where understanding is currently limited. A feasibility study was carried out to develop the Ahn/Mustoe lapine wound model for systematic investigation of the effects of electrical stimulation on ischemic wound therapy. A standardized surgical procedure incorporated a hybrid stimulation system comprising an implantable mini-stimulator and surface electrodes, with creation of repeatable ischemic wounds. Twenty mature male New Zealand white rabbits (3 kg weight) were employed to evaluate the effects of two empirically selected stimulation paradigms applied continuously for 7-21 days, using each animal as its own control. Outcomes measures included transcutaneous blood gas levels, histology, total RNA content and analysis of alpha2 (I) collagen (COL-I), type IV collagen (COL-IV), alpha1 (V) collagen (COL-V), and vascular endothelial growth factor (VEGF) expression using real-time quantitative PCR. All markers for stimulated wounds showed increased activity relative to non-stimulated control wounds between 7 and 14 days following injury, with peak activity at 14 days. By 21 days post-injury, all activity had returned to near baseline level. VEGF and COL-IV levels were found to be significantly higher for pattern A (110 mus pulse width) compared to pattern B (5 mus pulse width) at 14 days, implying that pattern A may be more effective at promoting angiogenesis. All wounds were fully re-epithelialized by 10 days post-injury. Both COL-I and COL-V showed statistically significant (P < 0.05) increased activity between day 7 and day 14 for pattern A, potentially indicating a continued effect on matrix remodeling. The early closure of all wounds implies that the

  12. Mootrala Karma of Kusha [Imperata cylindrica Beauv.] and Darbha [Desmostachya bipinnata Stapf.] - A comparative study.

    PubMed

    Shah, Niti T; Pandya, Tarulata N; Sharma, Parameshwar P; Patel, Bhupesh R; Acharya, Rabinarayan

    2012-07-01

    Kusha (Imperata cylindrica Beauv.) and Darbha (Desmostachya bipinnata Stapf.) are enlisted among Trinapanchamoola, which is a well-known diuretic and are individually enumerated in the Mootravirechaneeya Dashemani. The article deals with the evaluation and comparison of the individual Mootrala (diuretic) action of the two drugs in healthy volunteers. In this study, 29 healthy volunteers were divided into three groups administered with Darbha Moola Churna, Kusha Moola Churna, and placebo in each group for 14 days. The volunteers were subjected to evaluation of diuretic activity by maintaining the daily total input-output charts during the course of the study. The volunteers were advised to consume a minimum 2 l of water daily. Results show that Darbha and Kusha leaded to a percentage increase in urine volume as compared to placebo group, but the result was statistically insignificant. PMID:23723646

  13. Mouse Single Oral Dose Toxicity Study of DHU001, a Polyherbal Formula

    PubMed Central

    Roh, Seong-Soo

    2010-01-01

    This study was conducted to obtain acute information of the oral dose toxicity of DHU001, a polyherbal formula in male and female mice. In order to calculated 50% lethal dose (LD50) and approximate lethal dose (LD) , test material was once orally administered to male and female ICR mice at dose levels of 2000, 1000, 500, 250 and 0 (vehicle control) ml/kg (body weight) . The mortality and changes on body weight, clinical signs, gross observation, organ weight and histopathology of principle organs were monitored 14 days after treatment with DHU001. We could not find any mortalities, DHU001 treatment-related clinical signs, changes on the body and organ weights, gross and histopathological findings. The results obtained in this study suggest that LD50 and approximate LD in mice after single oral dose of DHU001 were considered over 2000 mg/kg in both female and male mice. PMID:24278506

  14. Mootrala Karma of Kusha [Imperata cylindrica Beauv.] and Darbha [Desmostachya bipinnata Stapf.] - A comparative study

    PubMed Central

    Shah, Niti T.; Pandya, Tarulata N.; Sharma, Parameshwar P.; Patel, Bhupesh R.; Acharya, Rabinarayan

    2012-01-01

    Kusha (Imperata cylindrica Beauv.) and Darbha (Desmostachya bipinnata Stapf.) are enlisted among Trinapanchamoola, which is a well-known diuretic and are individually enumerated in the Mootravirechaneeya Dashemani. The article deals with the evaluation and comparison of the individual Mootrala (diuretic) action of the two drugs in healthy volunteers. In this study, 29 healthy volunteers were divided into three groups administered with Darbha Moola Churna, Kusha Moola Churna, and placebo in each group for 14 days. The volunteers were subjected to evaluation of diuretic activity by maintaining the daily total input–output charts during the course of the study. The volunteers were advised to consume a minimum 2 l of water daily. Results show that Darbha and Kusha leaded to a percentage increase in urine volume as compared to placebo group, but the result was statistically insignificant. PMID:23723646

  15. [Effectiveness and tolerance of the C3 convertase inhibitor, N-acetyl-aspartyl-magnesium glutamate with anti-allergic action. Results of a double-blind study].

    PubMed

    Gastpar, H; Kiehn, R; Sieger, C; Weibel, M A

    1989-02-01

    N-Acetyl-aspartyl magnesium glutamate (Rhinaaxia, NAAGA) is a topically active antiallergic dipeptide. The compound acts in two different ways. On the one hand NAAGA inhibits the mast cell-degranulation, on the other hand this compound blocks the activation of the C3-convertase, subsequently followed by a blocked cleavage of the fragments C3a and C5a, respectively. 20 patients suffering from pollinosis were treated for 2 weeks according to a randomized double-blind placebo-controlled study. Besides subjective complaints nasal obstruction was objectively documented via rhinomanometria. 9 out of 10 patients under placebo had to use the rescue drug tritoqualine, a histidine decarboxylase inhibitor, compared to none in the verum group (p less than 0.01). After 14 days of treatment with NAAGA the nasal peak flow rate increased by 21.5 l/min and 21.8 l/min in the tritoqualine/placebo group, respectively (not significant). Nasal obstruction improved statistically significantly after 7 and 14 days of treatment in both groups. Tolerance was reported to be good in either group. PMID:2659002

  16. Maternal-fetal immunoglobulin transport: Studies on the binding, internalization, and release of IgG by chick yolk sac tissue and cultured cells

    SciTech Connect

    Donaldson, J.G.

    1988-01-01

    Immunoglobulin G (IgG) is transported from the yolk across the endodermal cells of the yolk sac and into the fetal circulation during chick embryonic development, thus providing the chick with passive immunity until it becomes immunocompetent. Saturable, Fc-specific receptors are present on the endodermal cells and are believed to mediate this transfer. In this study, IgG receptors were shown to be present on the yolk sac endodermal cells throughout the 21 days of development, although most of the transport occurs during the last 3 days prior to hatching. Fluorescently conjugated IgG was internalized by a receptor mechanism into small apical vesicles in yolk sac endoderm throughout, but cells from 19 day yolk sacs internalized more conjugate than those from 14 day yolk sacs. This was confirmed and quantitated by assaying the internalization of {sup 125}I-IgG into yolk sac tissue. IgG was internalized by a receptor mediated mechanism, reaching a steady state level after 1 to 2 hours. Although both ages of yolk sac tissue possessed the same number of surface IgG receptors, as measured by equilibrium binding assays at 4{degree}C, 19 day yolk sac had the capacity to internalize six times as much IgG by a receptor mechanism as 14 day yolk sac.

  17. Confirmatory double-blind, parallel-group, placebo-controlled study of efficacy and safety of edaravone (MCI-186) in amyotrophic lateral sclerosis patients

    PubMed Central

    Itoyama, Yasuto; Sobue, Gen; Tsuji, Shoji; Aoki, Masashi; Doyu, Manabu; Hamada, Chikuma; Kondo, Kazuoki; Yoneoka, Takatomo; Akimoto, Makoto; Yoshino, Hiide

    2014-01-01

    n Our objective was to confirm the efficacy and safety of edaravone in amyotrophic lateral sclerosis (ALS) patients. We conducted a 36-week confirmatory study, consisting of 12-week pre-observation period followed by 24-week treatment period. Patients received placebo or edaravone i.v. infusion over 60 min for the first 14 days in cycle 1, and for 10 of the first 14 days during cycles 2 to 6. The efficacy primary endpoint was changed in the revised ALS functional rating scale (ALSFRS-R) scores during the 24-week treatment. Patients were treated with placebo (n = 104) and edaravone (n = 102). Changes in ALSFRS-R during the 24-week treatment were −6.35 ± 0.84 in the placebo group (n = 99) and −5.70 ± 0.85 in the edaravone group (n = 100), with a difference of 0.65 ± 0.78 (p = 0.411). Adverse events amounted to 88.5% (92/104) in the placebo group and 89.2% (91/102) in the edaravone group. In conclusion, the reduction of ALSFRS-R was smaller in the edaravone group than in the placebo group, but efficacy of edaravone for treatment of ALS was not demonstrated. Levels and frequencies of reported adverse events were similar in the two groups. PMID:25286015

  18. Clinical efficacy and safety of a short regimen of azithromycin sequential therapy vs standard cefuroxime sequential therapy in the treatment of community-acquired pneumonia: an international, randomized, open-label study.

    PubMed

    Kuzman, I; Daković-Rode, O; Oremus, M; Banaszak, A M

    2005-12-01

    An international, randomized, open-label, comparative study was undertaken in order to assess the efficacy and safety of azithromycin and cefuroxime, short sequential vs standard sequential therapy, respectively, in the treatment of patients with community-acquired pneumonia (CAP). 180 adult patients were included in the study. 89 patients received azithromycin 500 mg intravenously (i.v.) once daily for 1-4 days followed by azithromycin 500 mg orally once daily for 3 days. 91 patients received cefuroxime 1.5 g i.v. three times daily for 1-4 days followed by cefuroxime axetil 500 mg orally twice daily for 7 days. Clinical efficacy was achieved in 67/82 (81.7%) patients treated with azithromycin, and in 73/89 (82.0%) patients treated with cefuroxime. The mean duration of total (i.v. and oral) therapy was significantly shorter for the azithromycin group than for the cefuroxime group (6.2 days vs 10.1 days). Adverse events were recorded in 38.2% of patients treated with azithromycin, and in 29.7% of patients treated with cefuroxime (p = 0.20). Shorter sequential i.v.-to-oral azithromycin therapy of patients with CAP was as effective as standard sequential i.v.-to-oral cefuroxime therapy. PMID:16433194

  19. Ultrastructural features of masseter muscle exhibiting altered occlusal relationship - a study in a rodent model

    SciTech Connect

    Lisboa, Marcio V.; Aciole, Gilberth T. S.; Oliveira, Susana C. P. S.; Marques, Aparecida M. C.; Pinheiro, Antonio L. B.; Santos, Jean N.; Baptista, Abrahao F.; Aguiar, Marcio C.

    2010-05-31

    The role of occlusion on Tempormandibular Disorders (TMD) is still unclear, mainly regarding muscular function. The aim of this study was to evaluate the occlusion highlights on masseter ultra morphology. Twenty Wistar rats were randomly divided in four groups: 10 for control group, 10 for occlusal alteration group (CCO). Rats underwent unilateral amputation of the left inferior and superior molar cusps to simulate an occlusal wear situation. The rats of control group had no occlusal wear. Half of the animals of each group was sacrificed in 14 days after the occlusal consuming and half 30 days after the occlusal consuming. The masseter muscles ipsilateral to the amputated molars were excised and processed for light microscopy, electron microscopy. The light microscopy did not show differences between the groups. The electron microscopy was able to detect a degree of intracellular damage in muscle fibers of CCO group: swollen mitochondria with disrupted cristae and cleared matrix, signs of hypercontraction of I bands and myofibril disorganization.

  20. Preclinical animal acute toxicity studies of new developed MRI contrast agent based on gadolinium

    NASA Astrophysics Data System (ADS)

    Nam, I. F.; Zhuk, V. V.

    2015-04-01

    Acute toxicity test of new developed MRI contrast agent based on disodium salt of gadopentetic acid complex were carried out on Mus musculus and Sprague Dawley rats according to guidelines of preclinical studies [1]. Groups of six animals each were selected for experiment. Death and clinical symptoms of animals were recorded during 14 days. As a result the maximum tolerated dose (MTD) for female mice is 2.8 mM/kg of body weight, male mice - 1.4 mM/kg, female rats - 2.8 mM/kg, male rats - 5.6 mM/kg of body weight. No Observed Adverse Effect Dose (NOAEL) for female mice is 1.4 mM/kg, male mice - 0.7 mM/kg, male and female rats - 0.7 mM/kg. According to experimental data new developed MRI contrast agent based on Gd-DTPA complex is low-toxic.

  1. Comparative study of the effects of two bleaching agents on oral microbiota.

    PubMed

    Alkmin, Yara Tardelli; Sartorelli, Renata; Flório, Flávia Martão; Basting, Roberta Tarkany

    2005-01-01

    This study evaluated the in vivo effects of bleaching agents containing 10% carbamide peroxide (Platinum/Colgate) or 7.5% hydrogen peroxide (Day White 2Z/Discus Dental) on mutans Streptococcus during dental bleaching. The products were applied on 30 volunteers who needed dental bleaching. In each volunteer, one of the two bleaching agents was used on both dental arches one hour a day for three weeks. Analysis of the bacterial counts was made by collecting saliva before (baseline values), during (7 and 21 days) bleaching treatments and 14 days posttreatment. The Friedman non-parametric analysis (alpha=0.05) found no differences in microorganism counts at different times for each group for both agents (p>0.05). The Mann Whitney nonparametric test (alpha=0.05) showed no differences in micro-organism counts for both agents (p>0.05). Different bleaching agents did not change the oral cavity mutans Streptococcus counts. PMID:16130860

  2. Ultrastructural features of masseter muscle exhibiting altered occlusal relationship—a study in a rodent model

    NASA Astrophysics Data System (ADS)

    Lisboa, Marcio V.; Aciole, Gilberth T. S.; Oliveira, Susana C. P. S.; Marques, Aparecida M. C.; Baptista, Abrahão F.; Pinheiro, Antonio L. B.; Aguiar, Marcio C.; Santos, Jean N.

    2010-05-01

    The role of occlusion on Tempormandibular Disorders (TMD) is still unclear, mainly regarding muscular function. The aim of this study was to evaluate the occlusion highlights on masseter ultra morphology. Twenty Wistar rats were randomly divided in four groups: 10 for control group, 10 for occlusal alteration group (CCO). Rats underwent unilateral amputation of the left inferior and superior molar cusps to simulate an occlusal wear situation. The rats of control group had no occlusal wear. Half of the animals of each group was sacrificed in 14 days after the occlusal consuming and half 30 days after the occlusal consuming. The masseter muscles ipsilateral to the amputated molars were excised and processed for light microscopy, electron microscopy. The light microscopy did not show differences between the groups. The electron microscopy was able to detect a degree of intracellular damage in muscle fibers of CCO group: swollen mitochondria with disrupted cristae and cleared matrix, signs of hypercontraction of I bands and myofibril disorganization.

  3. Toxicological Study of Ocimum sanctum Linn Leaves: Hematological, Biochemical, and Histopathological Studies

    PubMed Central

    Gautam, M. K.; Goel, R. K.

    2014-01-01

    The present study was aimed to study the acute and subacute toxicity studies with orally administered 50% ethanolic leaves extract of Ocimum sanctum Linn (OSE). In acute toxicity tests, four groups of mice (n = 6/group/sex) were orally treated with doses of 200, 600, and 2000 mg/kg, and general behavior, adverse effects, and mortality were recorded for up to 14 days. In subacute toxicity study, rats received OSE by gavage at the doses of 200, 400, and 800 mg/kg/day (n = 6/group/sex) for 28 days, and biochemical, hematological, and histopathological changes in tissues (liver, kidney, spleen, heart, and testis/ovary) were determined. OSE did not produce any hazardous symptoms or death and CNS and ANS toxicities in the acute toxicity test. Subacute treatment with OSE did not show any change in body weight, food and water consumption, and hematological and biochemical profiles. In addition, no change was observed both in macroscopic and microscopic aspects of vital organs in rats. Our result showed that Ocimum sanctum extract could be safe for human use. PMID:24616736

  4. Clinical study of the stunned myocardium.

    PubMed

    Sone, T; Tsuboi, H; Sassa, H

    1991-09-01

    Clinical features of 37 cases of stunned myocardium were studied. Mean duration of asynergy was 22.6 +/- 15.7 days. In all 11 cases of unstable angina without any significant serum creatine kinase leakage, the duration of asynergy was within 14 days. Related coronary lesions were reperfused (spontaneously or by interventional therapy) to TIMI grade II or higher. Transient Q waves were observed in 39% of all cases. Negative T waves tended to be prolonged, and persisted after disappearance of asynergy in 74% of all cases. 201Tl uptake in the stunned area varied widely between individual cases (ranging from "absent" to "normal"), although it became normal in all cases in the chronic stage. Mal-distribution of 99mTc-pyrophosphate (PYP) to the endocardial side of the stunned area was observed in 33%. In 186 cases of acute coronary syndrome, we studied whether or not reversibility of ischemia-disturbed myocardium could be predicted by simultaneous dual isotope SPECT, and found that 201Tl-uptake in the chronic stage significantly improved in the region showing absence of 99mTc-PYP accumulation or maldistribution of 99mTc-PYP to the endocardial side, while reversibility of the region showing transmural 99mTc-PYP accumulation and a dought pattern was poor. Ischemia-associated myocardial damage recovered to various degrees, and dual isotope SPECT was useful in evaluating the reversibility of such damage already at the acute stage. PMID:1834873

  5. Establishing a rat model for the study of vitamin K deficiency.

    PubMed

    Mi, Yanni; Xiao, Xue; Liu, Dongzheng; Ping, Nana; Zhu, Yanbing; Li, Bo; Long, Lihui; Cao, Yongxiao

    2016-04-01

    The main vitamin K-deficient model, minidose warfarin, is different from the pathological mechanism of vitamin K deficiency, which is a shortage of vitamin K. The objective of this study was to establish a new method of vitamin K-deficient model combining a vitamin K-deficient diet with the intragastrical administration of gentamicin in rats. The clotting was assayed by an automated coagulation analyser. The plasma PIVKA-II was assayed by ELISA. The vitamin K status was detected by an HPLC-fluorescence system. In the diet- and gentamicin-induced vitamin K-deficient 14-day group, the rats had undetected vitamin K1 and vitamin K2 in the liver and a prolonged APTT. In the 21-day group, there was also a prolonged PT and a decrease of the FIX activities. In the 28-day group, the undetected vitamin K1 and vitamin K2, the prolonged PT and APTT, and the decrease of the FII, FVII, FIX, and FX activities prompted the suggestion that there were serious deficiencies of vitamin K and vitamin K-dependent coagulation in rats. It is suggested that the diet- and gentamicin-induced vitamin K-deficient 14-day or 21-day model can be used for studies related to the status of vitamin K. The vitamin K-deficient 28-day model can be applied to research involving both the status of vitamin K and of vitamin K-dependent coagulation. In conclusion, the combination of a vitamin K-deficient diet with the administration of gentamicin results in a useful model of vitamin K-deficieny. PMID:27256579

  6. [Building of defects of the bladder wall by membrane, created on the basis of type I collagen (an experimental study)].

    PubMed

    Kamalov, A A; Mksimov, V A; Kirpatovskiĭ, V I; Kudriavtsev, Iu V; Karpov, V K; Tokarev, F K; Kamalov, D M; Burov, V N; Okhobotov, D A

    2012-01-01

    Experimental study was performed on 24 Chinchilla rabbits, which underwent resection of the bladder with building of defect by membrane "Collost", created on the basis of type I collagen. The functional state of the bladder in situ was assessed by infusion cystomanometry during repeated surgery at 7, 14 day and at 1, 3, 6 months, and at 1 and 1.5 years. It is found that developing detrusor pressure during bladder contractions was decreased by 10 times in the first week of the study; it was in line with the subcompensation after 3 months, and was restored at 6 month. At 1 and 1.5 years, increase of cumulative function of bladder while saving detrusor pressure was observed. Dilating cystoplastics using biopolymer "Collost" provides good long-term functional results. PMID:23379236

  7. Comparative study of desoximetasone ointment 0.25% versus fluocinonide ointment 0.05% in patients with psoriasis.

    PubMed

    1985-01-01

    In a multicenter, investigator-blind study, desoximetasone ointment 0.25% was compared with fluocinonide ointment 0.05% in the treatment of patients with psoriasis. Evaluations were made before treatment and after 4, 7, and 14 days of treatment. Both drugs were shown to be safe and effective. Desoximetasone was significantly superior to fluocinonide in improving severity scores from baseline for thickening (days 7 and 14) and erythema (day 14); in numbers of subjects cleared of thickening (day 4); in overall evaluation ratings as compared to baseline (day 14); and in number of patients receiving an overall evaluation of excellent. No side effects were reported for either treatment group during the study. PMID:3914368

  8. Long-term scar quality in burns with three distinct healing potentials: A multicenter prospective cohort study.

    PubMed

    Goei, Harold; van der Vlies, Cornelis H; Hop, M Jenda; Tuinebreijer, Wim E; Nieuwenhuis, Marianne K; Middelkoop, Esther; van Baar, Margriet E

    2016-07-01

    The laser Doppler imager is used in cases of indeterminate burn depth to accurately predict wound healing time at an early stage. The laser Doppler imager classifies burns into three estimated healing potentials as follows: high, <14 days; intermediate, 14-21 days; and low, >21 days. At this time, the relationship between these healing potentials and long-term scar quality is unknown. The objective of this study was to determine the long-term scar quality of burns with three distinct healing potentials. The secondary objectives were to compare treatment strategies in intermediate wounds, to study the effect of the timing of surgery on low healing potential wounds and to identify predictors of reduced scar quality. Hence, in a prospective cohort study, scar quality was determined in patients whose burns were assessed with laser Doppler imaging. Scar Quality was assessed with objective and subjective measurement tools, including overall scar quality (Patient and Observer Scar Assessment Scale) as a primary outcome and color and elasticity parameters. A total of 141 patients (>19 months postburn) with 216 scars were included. Wounds with high and intermediate healing potential did not significantly differ regarding scar quality. Wounds with a low healing potential had a significantly lower scar quality. Analysis of 76 surgically treated low healing potential wounds showed no significant differences in the primary outcome regarding the timing of surgery (≤14 days vs. >14). Predictors of reduced long-term scar quality were darker skin type and multiple surgeries. In conclusion, scar quality was strongly related to the healing potential category. Scar quality was very similar in high and intermediate healing potential wounds. No positive effects were found on scar quality or on healing time in surgically treated wounds with intermediate healing potential, advocating a conservative approach. Further studies should focus on the optimal timing of surgery in low healing

  9. Performance of Dutch Children on the Bayley III: A Comparison Study of US and Dutch Norms

    PubMed Central

    Steenis, Leonie J. P.; Verhoeven, Marjolein; Hessen, Dave J.; van Baar, Anneloes L.

    2015-01-01

    Background The Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) are frequently used to assess early child development worldwide. However, the original standardization only included US children, and it is still unclear whether or not these norms are adequate for use in other populations. Recently, norms for the Dutch version of the Bayley-III (The Bayley-III-NL) were made. Scores based on Dutch and US norms were compared to study the need for population-specific norms. Methods Scaled scores based on Dutch and US norms were compared for 1912 children between 14 days and 42 months 14 days. Next, the proportions of children scoring < 1-SD and < -2 SD based on the two norms were compared, to identify over- or under-referral for developmental delay resulting from non-population-based norms. Results Scaled scores based on Dutch norms fluctuated around values based on US norms on all subtests. The extent of the deviations differed across ages and subtests. Differences in means were significant across all five subtests (p < .01) with small to large effect sizes (ηp2) ranging from .03 to .26). Using the US instead of Dutch norms resulted in over-referral regarding gross motor skills, and under-referral regarding cognitive, receptive communication, expressive communication, and fine motor skills. Conclusions The Dutch norms differ from the US norms for all subtests and these differences are clinically relevant. Population specific norms are needed to identify children with low scores for referral and intervention, and to facilitate international comparisons of population data. PMID:26267907

  10. Effect of Commonly Used Beverage, Soft Drink, and Mouthwash on Force Delivered by Elastomeric Chain: A Comparative In Vitro Study

    PubMed Central

    Kumar, Kiran; Shetty, Sharath; Krithika, M J; Cyriac, Bobby

    2014-01-01

    Background: The objective was to evaluate and compare the effect of Coca-Cola®, tea, Listerine® mouthwash on the force delivered by elastomeric chain in vitro. Materials and Methods: Four specimen groups (distilled water, Coca-Cola®, tea, Listerine® mouthwash) with a total sample size of 480 specimens. A specimen is described as a four link grey close elastomeric chain. Jigs, each with a series of pins set 25 mm apart, was used to hold stretched elastomeric chains at a constant length. These jigs allowed for complete submersion of the elastomeric chain in a water bath throughout the test period, as well as the dipping of elastomeric chains in respective control and test solutions. For 60 s, twice a day, groups were exposed to the respective solutions, the two daily exposure was separated by 9 h and force measurements were taken at six time points during the experiment, that is, 1 h, 24 h, 7 days, 14 days, 21 days, and 28 days. Force measurements were made by Instron machine by a single blinded examiner with the help of a second examiner. Results: It was found out that there was highly significant difference between groups control, Coca-Cola®, Listerine®, and tea as well as there was highly significant (p < 0.01) between time periods. Group versus time was also highly significant (p < 0.01). For all groups substantial amount of force decay occurred until 7 days. The control group reached plateau between 7 and 14 days and then suddenly decreased from 14 days to 28 days. The Coca-Cola® and the Listerine® group reached a plateau between 7 and 21 days then decrease between 21 and 28 days. The tea group showed plateau phase between 7 and 28 days. After 28 days in the control group, 25% force decay occurred while the test groups force decay of 30-50% occurred. Conclusion: Coca-Cola®, Listerine® mouthwash, and tea cause an increase in force decay of elastomeric chains over time. Tea caused highest force decay followed by Listerine® and Coca-Cola® when compared

  11. Folate bioavailability from foods rich in folates assessed in a short term human study using stable isotope dilution assays.

    PubMed

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2015-01-01

    Different sources of folate may have different bioavailability and hence may impact the standard definition of folate equivalents. In order to examine this, a short term human study was undertaken to evaluate the relative native folate bioavailabilities from spinach, Camembert cheese and wheat germs compared to pteroylmonoglutamic acid as the reference dose. The study had a single-centre, randomised, four-treatment, four-period, four-sequence, cross-over design, i.e. the four (food) items to be tested (referred to as treatments) were administered in sequences according to the Latin square, so that each experimental treatment occurred only once within each sequence and once within each study period. Each of the 24 subjects received the four experimental items separated by a 14-day equilibrium phase and received a pteroylmonoglutamic acid supplement for 14 days before the first testing and between the testings for saturation of body pools. Folates in test foods, plasma and urine samples were determined by stable isotope dilution assays, and in urine and plasma, the concentrations of 5-methyltetrahydrofolate were evaluated. Standard non-compartmental methods were applied to determine the biokinetic parameters C(max), t(max) and AUC from baseline corrected 5-methyltetrahydrofolate concentrations within the interval from 0 to 12 hours. The variability of AUC and C(max) was moderate for spinach and oral solution of pteroylmonoglutamic acid but high for Camembert cheese and very high for wheat germs. The median t(max) was lowest for spinach, though t(max) showed a high variability among all treatments. When comparing the ratio estimates of AUC and C(max) for the different test foods, highest bioavailability was found for spinach followed by that for wheat germs and Camembert cheese. The results underline the dependence of folate bioavailability on the type of food ingested. Therefore, the general assumption of 50% bioavailability as the rationale behind the definition of

  12. Antithrombotic properties of rafigrelide: a phase 1, open-label, non-randomised, single-sequence, crossover study.

    PubMed

    Balasubramaniam, K; Viswanathan, G; Dragone, J; Grose-Hodge, R; Martin, P; Troy, S; Preston, P; Zaman, A G

    2014-07-01

    Platelets play a central role in atherothrombotic events. We investigated the effect of a novel platelet-lowering agent, rafigrelide, on thrombus formation and characteristics. In this phase 1, open-label, non-randomised, single-sequence, crossover study, healthy male volunteers received rafigrelide for 14 days (Period 1). Following a ≥6-week washout period, they then received rafigrelide + acetylsalicylic acid (ASA) for 14 days (Period 2). Thrombus formation was assessed ex vivo using the Badimon perfusion chamber, and thrombus characteristics were assessed using thromboelastography. A total of 15 volunteers were enrolled in the study and were assigned to Panel A or Panel B, which had different schedules of assessments. In Panel A, after treatment with rafigrelide alone (Period 1), mean (± standard deviation) platelet count was reduced from 283 (± 17) × 10⁹/l at Day 1, to 125 (± 47) × 10⁹/l at Day 14 (n=6) and thrombus area reduced under high and low shear conditions. Reductions in thrombus area under high shear conditions correlated with reductions in platelet count (r²=0.11, p=0.022; n=12). Rafigrelide treatment prolonged clot formation time and reduced clot strength. The addition of ASA to rafigrelide (Period 2) had no additional effect on platelet count or thrombus area under high or low shear conditions. Similar results were seen in Panel B for all parameters. The most common adverse events (≥3 participants per period) were thrombocytopenia and headache. While confirming the platelet-lowering effects of rafigrelide, this early phase study also indicates that rafigrelide has antithrombotic properties under both high and low shear conditions. PMID:24553755

  13. Uptake of silica covered Quantum Dots into living cells: Long term vitality and morphology study on hyaluronic acid biomaterials.

    PubMed

    D'Amico, Michele; Fiorica, Calogero; Palumbo, Fabio Salvatore; Militello, Valeria; Leone, Maurizio; Dubertret, Benoit; Pitarresi, Giovanna; Giammona, Gaetano

    2016-10-01

    Quantum Dots (QDs) are promising very bright and stable fluorescent probes for optical studies in the biological field but water solubility and possible metal bio-contamination need to be addressed. In this work, a simple silica-QD hybrid system is prepared and the uptake in bovine chondrocytes living cells without any functionalization of the external protective silica shield is demonstrated. Moreover, long term treated cells vitality (up to 14days) and the transfer of silica-QDs to the next cell generations are here reported. Confocal fluorescence microscopy was also used to determine the morphology of the so labelled cells and the relative silica-QDs distribution. Finally, we employ silica-QD stained chondrocytes to characterize, as proof of concept, hydrogels obtained from an amphiphilic derivative of hyaluronic acid (HA-EDA-C18) functionalized with different amounts of the RGD peptide. PMID:27287118

  14. [Restoration of the quality of life by eliminating and prevention of heartburn by alginate: results of multicenter study "VIA APIA"].

    PubMed

    Lazebnik, L B; Bordin, D S; Masharova, A A; Dzhulaĭ, G S; Butov, M A; Abdulkhakov, R A; Eremina, E Iu; Tarasova, L V; Safonova, O V; Firsova, L D; Kozhurina, T S

    2010-01-01

    Was conducted a muIticenter study VIA APIA, in which the impact of gaviscon forte (suspension) on symptoms, general state and quality of life of 148 patients (male 53, female 95, age 42.9 +/- 15.6) with gastroesophageal reflux disease (GERD) were investigated. The patients had undergone clinical evaluation of dynamics of GERD symptoms (Likert scale), general state (Visual Analogue Scale, questionnaire SAN) and quality of life (SF-36). It was shown that 14-days treatment with gaviscon forte provided symptoms relief in 84.5% patients and conducted improvement of general state and quality of life. Gaviscon forte recommended as drug of choice in initial treatment for the first time visited patient with heartburn before endoscopy and for pathogenetic treatment of typical reflux syndrome. PMID:20731169

  15. A scanning electron microscopic study of in vitro toxicity of ethylene-oxide-sterilized bone repair materials.

    PubMed

    Zislis, T; Martin, S A; Cerbas, E; Heath, J R; Mansfield, J L; Hollinger, J O

    1989-01-01

    Polylactic acid (PLA) and polyglycolic acid (PGA) have been under investigation for use in the management of hard- and soft-tissue wounds. Current research has included the incorporation of osteo-inductive substances into a PLA-PGA copolymer alloplastic implant material for enhancement of the healing of osseous defects. Conventional methods of sterilization--such as dry heat, steam heat, or 60Co--tend either to destroy or attenuate osteo-inductive activity and alter polymer biodegradation. Ethylene oxide (EO) gas sterilization is currently being tested as an alternate method. This study examined the relationship of EO-induced cytotoxicity to the length of time of polymer aeration following EO sterilization. Three groups of copolymer implant discs were studied: (1) 50:50 PLA-PGA copolymer, (2) PLA-PGA polymer with hydroxyapatite (HA), and (3) PLA-PGA with autolyzed, antigen-extracted (AA) bone particles. Polymer discs, as well as particulate HA and AA bone controls, were sterilized with EO for 12 hours. Following periods of two weeks, one week, one day, or no subsequent vacuum aeration, samples were placed into 24-well culture plates. A suspension of human fibroblasts was added to each well. Cell growth and attachment were permitted for 24 hours. Medium was then removed, and solutions for cell fixation, buffer washing, and dehydration were added to each well. SEM examination revealed changes in cell growth with increasing periods of aeration suggestive of increasing cell vitality. Cells growing on discs having no aeration were small, round, and lobulated, whereas those of seven to 14 days' aeration were more numerous, and flattened with many microvilli, pseudopodia, and dendritic processes, features consistent with normal cell morphology. These results suggest that EO-sterilized polymer implants should be aerated for least seven to 14 days prior to surgical use. PMID:2561372

  16. In liver transplantation, T tube bile represents total bile flow: physiological and scintigraphic studies on biliary secretion of organic anions.

    PubMed

    Lenzen, R; Bähr, A; Eichstädt, H; Marschall, U; Bechstein, W O; Neuhaus, P

    1999-01-01

    The present study was performed to clarify the recovery of hepatocellular uptake and the biliary secretion of bile acids during the first 14 days after orthotopic liver transplantation (OLT) and to determine the fraction of bile flow appearing outside through the T tube and entering the duodenum. Therefore, we determined primary and secondary bile acids in bile samples obtained from the T tube at day 5 after OLT, while the T tube was permanently open, and at days 10 and 14 after OLT, i.e., 4 and 9 days after closure of the T tube, respectively, thus restoring enterohepatic bile acid circulation. In addition, we performed hepatobiliary scintigraphy using technetium 99m-labeled [2,4,6 trimethyl-3-bromo]imino-diacetic acid (technetium 99m-BRIDA) in 12 patients between days 4 and 17 after OLT. Chromatographic analyses of biliary bile acids showed no secondary bile acids during the first 5 days after OLT, as opposed to 10 and 14 days after OLT when enterohepatic circulation was restored. Eleven patients with an uncomplicated postoperative course after OLT showed a significantly reduced hepatic uptake and biliary secretion of 99mTc-BRIDA during the first days after OLT with progressive recovery. One patient with an acute allograft rejection episode showed almost no uptake and only minimal secretion. The bile fraction appearing outside through the inserted T tube represented 94.6% +/- 6.2% of the injected 99mTc-BRIDA. We conclude that OLT results in markedly impaired hepatocellular uptake and biliary secretion of organic anions. Simultaneously, bile acid synthesis is significantly reduced, which, in addition, diminishes bile secretion of the graft. We show that T tube bile is a valid tool for bile physiological studies in patients in whom transplantation was successfully performed. PMID:9873086

  17. Circadian Behavioral Study: LED vs Cool White Fluorescent - 0.1, 1, 10, 40, 80 lux. Part 2

    NASA Technical Reports Server (NTRS)

    Holley, Daniel C.; Syrkin, N.; Mele, G.

    2000-01-01

    Currently, the light source most commonly used in animal habitat lighting is cool white fluorescent (CWF) light. It was the objective of this study to evaluate a novel LED light source for use in animal habitat lighting by comparing its effectiveness to CWF light in producing and maintaining a normal circadian entrainment. The LED and CWF lights had similar spectral power distributions. Sprague-Dawley rats (175-350 g) were kept individually in metabolic cages, under a strict lighting control: 4 days of acclimation at 12:12 LD, 14 days of 12:12 LD, 14 days of 24:0 LD (free-run), and finally 12:12 LD. Food and water were provided ad libitum. Three behavioral parameters were monitored continuously: gross locomotor activity, drinking, and feeding. Combined mean free run periods (tau) were (mean +/- SEM): 24.6 +/- 0.1 and 24.7 +/- 0.2 at 0.1 lux, 25.5 +/- 0.1 and 25.7 +/- 0.1 at 1.0 lux, 25.3 +/- 0.2 and 25.4 +/- 0.2 at 10 lux, 25.8 +/- 0.1 and 25.9 +/- 0.1 at 40 lux, and 25.9 +/- 0.1 and 25.9 +/- 0.1 at 80 lux, CWF and LED respectively. ANOVA found a significant effect (p < 0.05) due to light level, but no difference in tau between rats exposed to constant CWF light and rats exposed to constant LED light. This study has shown that LED light can produce the same entrainment pattern as a conventional CWT light at similar intensities (0.1, 1, 10, 40, and 80 lux). LED light sources may be a suitable replacement for conventional light sources used in animal habitat lighting while providing many mechanical and economical advantages.

  18. A study of the temporal variability of atrazine in private well water. Part I: Study design, implementation, and database development

    USGS Publications Warehouse

    Lorber, M.; Johnson, K.; Kross, B.; Pinsky, P.; Burmeister, L.; Thurman, M.; Wilkins, A.; Hallberg, G.

    1997-01-01

    In 1988, the Iowa Department of Natural Resources, along with the University of Iowa conducted the Statewide Rural Well Water Survey, commonly known as SWRL. A total of 686 private rural drinking water wells was selected by use of a probability sample and tested for pesticides and nitrates. Sixty-eight of these wells, the '10% repeat' wells, were additionally sampled in October, 1990 and June, 1991. Starting in November, 1991, the University of Iowa, with sponsorship from the United States Environmental Protection Agency, revisited these wells to begin a study of the temporal variability of atrazine and nitrates in wells. Other wells, which had originally tested positive for atrazine in SWRL but were not in the 10% repeat population, were added to the study population. Temporal sampling for a year-long period began in February of 1992 and concluded in January of 1993. All wells were sampled monthly, one subset was sampled weekly, and a second subset was sampled for 14-day consecutive periods. Two unique aspects of this study were the use of an immunoassay technique to screen for triazines before gas chromatography/mass spectrometry (GC/MS) analysis and quantification of atrazine, and the use of well owners to sample the wells. A total of 1771 samples from 83 wells are in the final data base for this study. This paper reviews the study design, the analytical methodologies, and development of the data base. A companion paper discusses the analysis of the data from this survey.

  19. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study

    PubMed Central

    Morton, Allison C.; Rothman, Alexander M. K.; Greenwood, John P.; Gunn, Julian; Chase, Alex; Clarke, Bernard; Hall, Alistair S.; Fox, Keith; Foley, Claire; Banya, Winston; Wang, Duolao; Flather, Marcus D.; Crossman, David C.

    2015-01-01

    Aims Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. Methods and results A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31–29.64); placebo group, 43.5 mg day/L (31.15–60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32–0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65–4.62): placebo; 2.21 mg/L (1.67–2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. Conclusion IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. Clinical Trial Registration EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB. PMID:25079365

  20. Study of high explosives in soil for holding determination

    SciTech Connect

    Tappan, B.C.; Campbell, M.S.

    1997-12-31

    A holding time is a regulated amount of time that a sample can be stored before analysis. The holding times that are now used for high explosives (HE) in soil and extracts are the EPA holding times set for semi-volatile organics. These holding times are 14 days at 4 C before sample extraction and 40 days before extract analysis. A previous study on Eastern U.S. soils found that actual decomposition in storage varies for different compounds and different soils, however, no studies prior to this have been performed on Los Alamos soils. The soil samples were spiked with an HE solution of HMX, RDX, TNT, TNB, 2,4-DNT, 2,6-DNT, 4-Am-2,6-DNT, 2-Am-4,6-DNT, Tetryl, NB, 1,3-DNB, 2-NT, 3-NT, and 4-NT, plus two surrogates 3,4-DNT and MNA. A total of five soil types were studied, four uncontaminated and one field contaminated. From the results of the study, it is clear that the EPA holding time now assigned to soils containing high explosives is much too long when analyzing for nitroaromatics, but sufficient when analyzing for HMX and RDX.

  1. DISTRESS AND PTSD IN PATIENTS WITH CANCER: COHORT STUDY CASE

    PubMed Central

    Pranjic, Nurka; Bajraktarevic, Amila; Ramic, Enisa

    2016-01-01

    Introduction: embarrassed emotional experience may affect the ability to oncology patient effectively cope with cancer, symptoms and treatment. Distress extends a long period, from common, normal feelings of vulnerability, sadness and fears to problems of PTSD, depression, anxiety, panic, social isolation and the perception of spiritual crisis. The aim of the research is to determine the level of distress and PTSD in cancer patients. Patients and Methods: In a prospective, cohort study cases from 2011- 2014 were included patients with cancer who are treated under the supervision of his chosen family medicine doctor. Including a factor for the participation of patients in the study is that from the moment of diagnosis of malignant disease passed <12 months. The total sample was 174 of the planned 200 (response rate=87%). The subjects were divided into three groups. A key factor in the creation of the group was the time elapsed from the moment of acknowledgment and confirmation of the diagnosis: T1 <14 days, n=56 patients; T2>14 days-<6 months, n=79 patients; T3>6 months n=39 patients. To achieve the set goals of the research was used instruments of 3 questionnaires: Questionnaire on the clinical characteristics of patients with malignant disease, demographic and individual characteristics; questionnaire distress oncology patient–hospital scales of depression and anxiety, HADS scale (Hospital Anxiety and Depression Scale - HADS) and a rapid test for self-assessment of the symptoms of PTSD. Results: Age of patients was 54.63 ± 11:46 years, and the age of the respondents when they were diagnosed with cancer 54.34 ± 11.26 years. The prevalence of distress was a high 76% 82x higher than expected), and PTSD 55%. Predictors of burnout syndrome in cancer patients are all important determinants of malignant disease: the time elapsed since the diagnosis of the disease which determines the clinical status of malignant disease (β=0.280; P=0.001; 95% CI, 0742

  2. Toxicology Studies on Lewisite and Sulfur Mustard Agents: Modified Dominant Lethal Study of Sulfur Mustard in Rats Final Report

    SciTech Connect

    Sasser, L. B.; Cushing, J. A.; Kalkwarf, D. R.; Buschbom, R. L.

    1989-05-01

    Occupational health standards have not been established for sulfur mustard (HD) [bis{2-chloroethyl)-sulfide) ' a strong alkylating agent with known mutagenic properties. Little, however, is known about the mutagenic activity of HD in mammalian species and data regarding the dominant lethal effects of HD are ambiguous. The purpose of this study was to determine the dominant lethal effect in male and female rats orally exposed to HD. The study was conducted in two phases; a female dominant lethal phase and a male dominant lethal phase. Sprague-Dawley rats of each sex were administered 0.08, 0.20, or 0.50 mg/kg HD in sesame oil 5 days/week for 10 weeks. For the female phase, treated or untreated males were mated with treated females and their fetuses were evaluated at approximately 14 days after copulation. For the male dominant lethal phase, treated males cohabited with untreated femal (during 5 days of each week for 10 weeks) and females were sacrificed for fetal evaluation 14 days after the midweek of cohabitation during each of the 10 weeks. The appearance and behavior of the rats were unremarkable throughout the experiment and there were no treatment-related deaths. Growth rates were reduced in both female and male rats treated with 0.50 mg/kg HD. Indicators of reproductive performance did not demonstrate significant female dominant lethal effects, although significant male dominant lethal effects were observed at 2 and 3 week post-exposure. These effects included increases of early fetal resorptions and preimplantation losses and decreases of total live embryo implants. These effects were most consistently observed at a dose of 0.50 mg/kg, but frequently occurred at the lower doses. Although no treatment-related effects on male reproductive organ weights or sperm motility were found, a significant increase in the percentage of abnormal sperm was detected in males exposed to 0. 50 mg/kg HD. The timing of these effects is consistent with an effect during the

  3. Medical Castration Using the Investigational Oral GnRH Antagonist TAK-385 (Relugolix): Phase 1 Study in Healthy Males

    PubMed Central

    Shi, Hongliang; Faessel, Hélène M.; Saad, Fred

    2015-01-01

    Context: TAK-385 is a highly selective, oral, nonpeptide GnRH antagonist being investigated as a possible prostate cancer treatment. Objective: The objectives were to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics of TAK-385 on LH and testosterone. Design, Setting, and Participants: This was a three-part, randomized, double-blind, placebo-controlled, phase 1 dose-escalation study in 176 healthy male UK volunteers. Interventions: Part 1, single doses of TAK-385 (0 [placebo], 80, 120, 180, or 360 mg). Part 2, 14-day TAK-385 (0, 20, 40, 80, or 180 mg) daily. Part 3, 28-day TAK-385 (40 [with loading dose], 60, 80, or 160 mg) or placebo daily. Parts 2 and 3 included men aged 40–75 years. Main Outcome Measures: Main outcome measures included plasma concentrations of TAK-385, LH, and testosterone. Results: Oral TAK-385 was readily absorbed, and steady state was reached in ≤14 days. Food reduced TAK-385 systemic exposure by 47–52%. Mean serum testosterone levels declined ≤6 hours after TAK-385 administration. Loading doses up to 360 mg on day 1 or 360 mg on day 1 followed by 240 mg on day 2 reduced the time to achieve castrate testosterone levels from ≥7 to <3 days. TAK-385 doses ≥80 mg/d achieved sustained medical castration and trough TAK-385 concentrations >4 ng/mL. After discontinuation of TAK-385 on day 28, testosterone levels normalized in most subjects in ≤ 28 days. Common adverse events included bradycardia, headache, and hot flush (all grade ≤2). Conclusions: Oral TAK-385 (40–180 mg/d) was well tolerated and effectively lowered testosterone in healthy men. Planned phase 2 doses in men with hormone-sensitive prostate cancer are 80 and 120 mg/d. PMID:26502357

  4. STUDIES ON THE NATURE OF THE AGENT TRANSMITTING LEUCOSIS OF FOWLS

    PubMed Central

    Furth, J.

    1932-01-01

    The filterable agent transmitting leucosis resists drying, retaining its activity for at least 54 days. The conditions of successful desiccation have not been precisely ascertained. By the addition of glycerin the agent can be preserved for at least 104 days. It is not inactivated by freezing in liquid air. At 37.5°C. it loses its activity within 14 days, but retains some of its activity for at least 14 days when kept at 4°C. PMID:19870007

  5. Biofragmentable bowel anastomosis ring: comparative efficacy studies in dogs.

    PubMed

    Maney, J W; Katz, A R; Li, L K; Pace, W G; Hardy, T G

    1988-01-01

    Three studies were conducted in a total of 178 dogs to determine the efficacy of a biofragmentable bowel anastomosis ring (BAR) composed of polyglycolic acid and 12.5% barium sulfate. Wound strength and healing of BAR, suture, and staple colonic anastomoses were compared for intervals of up to 1 year. The effect of systemic steroid treatment and BAR size on anastomotic wound strength and healing was also studied. The BARs fragmented at a mean time of 15.06 days postoperatively and were passed in the feces without injury. Wound strength was determined by measurements of the pressure required to burst the anastomosed colonic segment and measurements of the tension required to break 10 mm wide longitudinal strips of the anastomosed segment. The studies demonstrated that wound strength had progressed to a point where continued mechanical support (with sutures or staples) was no longer required by 14 days in both nontreated and steroid-treated dogs. Gross healing evaluations at 21 days and beyond showed no differences due to anastomotic method. Microscopic evaluations suggested that residual granulation tissue was less at the sites of BAR asastomoses than at sites of suture or staple anastomoses at the 1-year interval, suggesting that healing may be better with BAR than with standard methods of colon anastomosis. PMID:3336869

  6. Toxicological studies of two compounds isolated from Loranthus globosus Roxb.

    PubMed

    Islam, Robiul; Alam, A H M Khurshid; Rahman, B M; Salam, K A; Hossain, Aslam; Baki, Abdullahil; Sadik, Golam

    2007-06-15

    The sub-acute toxicities of two compounds 3,4-dimethoxycinnamyl alcohol (1) and 3,4,5-trimethoxycinnamyl alcohol (2) isolated from the plant Loranthus globosus Roxb were studied on long Evan's rats. The studies included the gross general observation such as changes in body weight, haematological profiles [total count of Red Blood Cells (RBC) and White Blood Cells (WBC), differential count of WBC, platelet count and Haemoglobin (Hb)%], biochemical parameters of blood [Serum Glutamate Oxaloacetate Transaminase (SGOT), Serum Glutamate Pyruvate Transaminase (SGPT), Serum Alkaline Phosphatase (SALP), urea and creatinine) and histopathology of the liver, kidney, heart and lung of both control and experimental groups of rats. The changes in haematological and biochemical parameters were statistically not significant after the administration of compounds 1 and 2 in a dose of 300 microg/rat/day for consecutive 14 days. No abnormality was found in the histopathology of the liver, kidney, heart and lung in the experimental groups of rats following same dose when compared with control group. This preliminary study suggests that the isolated compounds may be used safely for clinical trial. PMID:19093449

  7. Effectiveness of the DreamSkin® garment on relieving symptoms of eczema/dermatitis using electrical and spectroscopic methods: A case study.

    PubMed

    Qassem, M; Kyriacou, P A

    2014-01-01

    Eczema is a common skin inflammatory disorder particularly among children. The treatment of which usually consists of the application of emollients and moisturisers to maintain skin moisture and to reduce the risk of inflammation, infection and exacerbative factors. Recently, DreamSkin® Health Limited has developed a unique polymer treatment for eczema. The polymer has been applied to medical grade silk clothing as a means of delivering the therapeutic benefits to the sufferers' skin. They claim that the polymer reduces the loss of moisture caused by evaporation from damaged skin; acts as a barrier against external irritants and helps to restore the skin's natural temperature management process. The aim of this study was to assess the products effectiveness at providing symptomatic relief for a volunteer with confirmed eczema and atopic dermatitis over a period of 14 days. Both skin capacitance and NIR spectra were collected during the course of the study, using the Corneometer® CM 825 and a spectrophotometer equipped with a customized reflectance probe for measurements in the Near Infrared region. The treated area showed visibly improved skin and overall results from both techniques showed a noticeable increase in skin water content after 14 days, peaking on the 7th day. However, slight differences were observed in the 7 magnitude of increase between the two instruments. Future work will focus on expanding this study to include more cases as well as performing statistical analysis to build upon our previous work in the area of skin hydration determinations using Near Infrared Spectroscopy. PMID:25570800

  8. Comparative study of 0.2% and 0.12% digluconate chlorhexidine mouth rinses on the level of dental staining and gingival indices

    PubMed Central

    Najafi, Mohammad Hassan; Taheri, Morteza; Mokhtari, Majid Reza; Forouzanfar, Ali; Farazi, Fateme; Mirzaee, Mona; Ebrahiminik, Zahra; Mehrara, Reza

    2012-01-01

    Background: Chlorhexidine (CHX) as a gold standard chemical agent appears to be the most effective antimicrobial agent for reduction of both plaque and gingivitis. The aim of this study was to compare the efficacy of two concentrations of digluconate chlorhexidine (CHX) solutions (0.12% and 0.20%) on gingival indices and the level of dental staining during 14 days. Materials and Methods: in this double-blind controlled clinical trial study 60 patients with moderate to severe gingivitis aged 17–56 years were randomly selected and divided to three groups: Group I (placebo) Group II (0.12% CHX), and Group III (0.2% CHX). Patients rinsed their mouthwashes twice a day after brushing. Before the examination and after 14 days plaque index, gingival index, bleeding index, and stain index were evaluated. The data were analyzed by “Mann–Whitney” test and P value was 0.05. Results: the results showed that plaque index and gingival index significantly reduced in Groups II and III in comparison with the placebo group (P < 0.0001). However, the two concentrations did not differ significantly from each other (P = 0.552). Same results were observed in term of gingival bleeding index with this different that 0.2% CHX was significantly more efficient than 0.12% CHX (P < 0.0001). CHX mouthrinse, both concentrations, significantly increased the dental staining level (intensity and area) in comparison with the placebo group. Remarkable difference also was seen between 2 CHX concentrations so that the 0.2% CHX caused much more staining on the teeth than 0.12% CHX. Conclusion: based on the results of this study we can conclude that the lower concentrations of CHX should be prescribed, decreasing side effects, since higher concentrations do not seem to be more effective in controlling dental plaque and gingivitis. PMID:23087736

  9. Myorelaxant Effect of Bee Venom Topical Skin Application in Patients with RDC/TMD Ia and RDC/TMD Ib: A Randomized, Double Blinded Study

    PubMed Central

    Baron, Stefan

    2014-01-01

    The aim of the study was the evaluation of myorelaxant action of bee venom (BV) ointment compared to placebo. Parallel group, randomized double blinded trial was performed. Experimental group patients were applying BV for 14 days, locally over masseter muscles, during 3-minute massage. Placebo group patients used vaseline for massage. Muscle tension was measured twice (TON1 and TON2) in rest muscle tonus (RMT) and maximal muscle contraction (MMC) on both sides, right and left, with Easy Train Myo EMG (Schwa-medico, Version 3.1). Reduction of muscle tonus was statistically relevant in BV group and irrelevant in placebo group. VAS scale reduction was statistically relevant in both groups: BV and placebo. Physiotherapy is an effective method for myofascial pain treatment, but 0,0005% BV ointment gets better relief in muscle tension reduction and analgesic effect. This trial is registered with Clinicaltrials.gov NCT02101632. PMID:25050337

  10. Development of a Feeder for Uninterrupted Centrifugation Studies

    NASA Technical Reports Server (NTRS)

    Mulenburg, Gerald M.; Vasques, Marilyn F.; Gundo, Daniel P.; Griffith, Jon B.; Wade, Charles E. (Technical Monitor)

    1994-01-01

    A specialized paste diet feeder was developed in support of a hypergravity (2G) centrifuge study. The centrifuge study was to be compared to a previously flown Russian Cosmos spaceflight so experimental parameters of the 14 day spaceflight had to be duplicated. In order to duplicate at hyper G an experiment that took place in weightlessness, all other conditions must be as identical as possible. Stopping the centrifuge to provide maintenance for the animals causes unacceptable changes in experimental research results. Thus the experimental protocol required the delivery of a designated amount of paste diet at regular intervals for a two week period without stopping the centrifuge. A centrifuge and a stationary control cage, each containing 10 laboratory rats, were fitted with feeders that were calibrated to provide 140 plus or minus 2g of paste diet every 6 hours. This paper describes development of the feeder design and results of its operation over the two week experiment. The design philosophy and details of the feeder system are provided with recommendations for future such devices.

  11. Studies on a suitable antibiotic therapy for treating swine brucellosis.

    PubMed

    Dieste-Pérez, L; Fraile, L; de Miguel, M J; Barberán, M; Blasco, J M; Muñoz, P M

    2015-08-01

    The aim of this work was developing effective treatments against Brucella suis biovar 2, responsible for swine brucellosis in Europe. MICs for antibiotics used classically in brucellosis and two new macrolides (tulathromycin and tildipirosin) were determined for 33 B. suis biovar 2 field and B. suis reference strains. MIC90 values ranged from 0.01 to 0.25 μg/mL. The best candidates, given alone or combined, were then evaluated in mice. Ten groups (n = 7) of BALB/c mice were inoculated (1 × 10(5) CFU/mouse) with a virulent B. suis biovar 2 field strain. All groups, excepting untreated control, were treated for 14 days with, respectively, doxycycline, dihydrostreptomycin, tulathromycin (one or two doses), or tildipirosin (one or two doses) given alone, and doxycycline combined with dihydrostreptomycin, tulathromycin, or tildipirosin. Combined tildipirosin treatment was the most effective, then selected for pig studies. Sixteen B. suis biovar 2 naturally infected sows were treated with oxytetracycline (20 mg/kg BW/daily) for 21 days. The half of these received also tildipirosin (4 mg/kg BW) in two doses with a 10-day interval. An extensive bacteriological study conducted ten days after ceasing treatments proved the efficacy of this combined oxytetracycline/tildipirosin treatment. PMID:25413993

  12. A comparative sealability study of different retrofilling materials.

    PubMed

    Ozata, F; Erdilek, N; Tezel, H

    1993-07-01

    The purpose of this study was to compare the sealing ability of high-copper amalgam, glass ionomer cement, and silver glass ionomer cement as retrofilling materials when used with and without varnish. Seventy extracted human single-rooted anterior teeth were instrumented and the root canals obturated with laterally condensed gutta-percha and sealer. The apical 3 mm of each root was resected and a 2 mm-deep apical Class I preparation cut. The roots were then randomly allocated to six groups of 10 teeth and retrofilled with one of the experiment materials. Group I comprised high-copper amalgam; group 2, high-copper amalgam with cavity varnish; group 3, glass ionomer cement without varnish; group 4, glass ionomer cement with varnish; group 5, silver glass ionomer cement without varnish; and group 6, silver glass ionomer cement with varnish. Two groups of five roots each were used as positive and negative controls. The root surfaces were coated with nail polish and specimens immersed in 2% methylene blue solution for 14 days. After vertical sectioning, dye penetration was examined under a stereomicroscope. The results of the study were analysed statistically. The sealing ability of the conventional glass ionomer cement with varnish was significantly better while dye penetration was higher in silver glass ionomer cement without varnish group than the other groups (P < 0.01). PMID:8225643

  13. First-in-Human Dose Study of the Novel Transforming Growth Factor-β Receptor I Kinase Inhibitor LY2157299 Monohydrate in Patients with Advanced Cancer and Glioma

    PubMed Central

    Rodon, Jordi; Carducci, Michael A.; Sepulveda-Sánchez, Juan M; Azaro, Analia; Calvo, Emiliano; Seoane, Joan; Braña, Irene; Sicart, Elisabet; Gueorguieva, Ivelina; Cleverly, Ann L.; Pillay, N. Sokalingum; Desaiah, Durisala; Estrem, Shawn T.; Paz-Ares, Luis; Holdhoff, Matthias; Blakeley, Jaishri; Lahn, Michael M.; Baselga, Jose

    2015-01-01

    Purpose TGFβ signaling plays a key role in tumor progression, including malignant glioma. Small-molecule inhibitors such as LY2157299 monohydrate (LY2157299) block TGFβ signaling and reduce tumor progression in preclinical models. To use LY2157299 in the treatment of malignancies, we investigated its properties in a first-in-human dose (FHD) study in patients with cancer. Experimental Design Sixty-five patients (58 with glioma) with measurable and progressive malignancies were enrolled. Oral LY2157299 was given as a split dose morning and evening on an intermittent schedule of 14 days on and 14 days off (28-day cycle). LY2157299 monotherapy was studied in dose escalation (part A) first and then evaluated in combination with standard doses of lomustine (part B). Safety was assessed using Common Terminology Criteria for Adverse Events version 3.0, echocardiography/Doppler imaging, serum troponin I, and brain natriuretic peptide (BNP) levels. Antitumor activity was assessed by RECIST and Macdonald criteria. Results In part A, 16.6% (5/30) and in part B, 7.7% (2/26) of evaluable patients with glioma had either a complete (CR) or a partial response (PR). In both parts, 15 patients with glioma had stable disease (SD), 5 of whom had SD ≥6 cycles of treatment. Therefore, clinical benefit (CR+PR+SD ≥6 cycles) was observed in 12 of 56 patients with glioma (21.4%). LY2157299 was safe, with no cardiac adverse events. Conclusions On the basis of the safety, pharmacokinetics, and antitumor activity in patients with glioma, the intermittent administration of LY2157299 at 300 mg/day is safe for future clinical investigation. PMID:25424852

  14. Neuroprotection by α2-Adrenergic Receptor Stimulation after Excitotoxic Retinal Injury: A Study of the Total Population of Retinal Ganglion Cells and Their Distribution in the Chicken Retina.

    PubMed

    Galindo-Romero, Caridad; Harun-Or-Rashid, Mohammad; Jiménez-López, Manuel; Vidal-Sanz, Manuel; Agudo-Barriuso, Marta; Hallböök, Finn

    2016-01-01

    We have studied the effect of α2-adrenergic receptor stimulation on the total excitotoxically injured chicken retinal ganglion cell population. N-methyl-D-aspartate (NMDA) was intraocularly injected at embryonic day 18 and Brn3a positive retinal ganglion cells (Brn3a+ RGCs) were counted in flat-mounted retinas using automated routines. The number and distribution of the Brn3a+ RGCs were analyzed in series of normal retinas from embryonic day 8 to post-hatch day 11 retinas and in retinas 7 or 14 days post NMDA lesion. The total number of Brn3a+ RGCs in the post-hatch retina was approximately 1.9x106 with a density of approximately 9.2x103 cells/mm2. The isodensity maps of normal retina showed that the density decreased with age as the retinal size increased. In contrast to previous studies, we did not find any specific region with increased RGC density, rather the Brn3a+ RGCs were homogeneously distributed over the central retina with decreasing density in the periphery and in the region of the pecten oculli. Injection of 5-10 μg NMDA caused 30-50% loss of Brn3a+ cells and the loss was more severe in the dorsal than in the ventral retina. Pretreatment with brimonidine reduced the loss of Brn3a+ cells both 7 and 14 days post lesion and the protective effect was higher in the dorsal than in the ventral retina. We conclude that α2-adrenergic receptor stimulation reduced the impact of the excitotoxic injury in chicken similarly to what has been shown in mammals. Furthermore, the data show that the RGCs are evenly distributed over in the retina, which challenges previous results that indicate the presence of specific high RGC-density regions of the chicken retina. PMID:27611432

  15. The novel 5-HT1A receptor agonist, NLX-112 reduces l-DOPA-induced abnormal involuntary movements in rat: A chronic administration study with microdialysis measurements.

    PubMed

    McCreary, Andrew C; Varney, Mark A; Newman-Tancredi, Adrian

    2016-06-01

    Although l-DOPA alleviates the motor symptoms of Parkinson's disease (PD), it elicits troublesome l-DOPA-induced dyskinesia (LID) in a majority of PD patients after prolonged treatment. This is likely due to conversion of l-DOPA to dopamine as a 'false neurotransmitter' from serotoninergic neurons. The highly selective and efficacious 5-HT1A receptor agonist, NLX-112 (befiradol or F13640) shows potent activity in a rat model of LID (suppression of Abnormal Involuntary Movements, AIMs) but its anti-AIMs effects have not previously been investigated following repeated administration. Acute administration of NLX-112 (0.04 and 0.16 mg/kg i.p.) reversed l-DOPA (6 mg/kg)-induced AIMs in hemiparkinsonian rats with established dyskinesia. The activity of NLX-112 was maintained following repeated daily i.p. administration over 14 days and was accompanied by pronounced decrease of striatal 5-HT extracellular levels, as measured by in vivo microdialysis, indicative of the inhibition of serotonergic activity. A concurrent blunting of l-DOPA-induced surge in dopamine levels on the lesioned side of the brain was observed upon NLX-112 administration and these neurochemical responses were also seen after 14 days of treatment. NLX-112 also suppressed the expression of AIMs in rats that were being primed for dyskinesia by repeated l-DOPA administration. However, when treatment of these rats with NLX-112 was stopped, l-DOPA then induced AIMs with scores that resembled those of control rats. The present study shows that the potent anti-AIMs activity of NLX-112 is maintained upon repeated administration and supports the ongoing clinical development of NLX-112 as a novel antidyskinetic agent for PD patients receiving l-DOPA treatment. PMID:26777281

  16. Region Specific Response of Intervertebral Disc Cells to Complex Dynamic Loading: An Organ Culture Study Using a Dynamic Torsion-Compression Bioreactor

    PubMed Central

    Chan, Samantha C. W.; Walser, Jochen; Käppeli, Patrick; Shamsollahi, Mohammad Javad; Ferguson, Stephen J.; Gantenbein-Ritter, Benjamin

    2013-01-01

    The spine is routinely subjected to repetitive complex loading consisting of axial compression, torsion, flexion and extension. Mechanical loading is one of the important causes of spinal diseases, including disc herniation and disc degeneration. It is known that static and dynamic compression can lead to progressive disc degeneration, but little is known about the mechanobiology of the disc subjected to combined dynamic compression and torsion. Therefore, the purpose of this study was to compare the mechanobiology of the intervertebral disc when subjected to combined dynamic compression and axial torsion or pure dynamic compression or axial torsion using organ culture. We applied four different loading modalities [1. control: no loading (NL), 2. cyclic compression (CC), 3. cyclic torsion (CT), and 4. combined cyclic compression and torsion (CCT)] on bovine caudal disc explants using our custom made dynamic loading bioreactor for disc organ culture. Loads were applied for 8 h/day and continued for 14 days, all at a physiological magnitude and frequency. Our results provided strong evidence that complex loading induced a stronger degree of disc degeneration compared to one degree of freedom loading. In the CCT group, less than 10% nucleus pulposus (NP) cells survived the 14 days of loading, while cell viabilities were maintained above 70% in the NP of all the other three groups and in the annulus fibrosus (AF) of all the groups. Gene expression analysis revealed a strong up-regulation in matrix genes and matrix remodeling genes in the AF of the CCT group. Cell apoptotic activity and glycosaminoglycan content were also quantified but there were no statistically significant differences found. Cell morphology in the NP of the CCT was changed, as shown by histological evaluation. Our results stress the importance of complex loading on the initiation and progression of disc degeneration. PMID:24013824

  17. A Phase 1 Study of 131I-CLR1404 in Patients with Relapsed or Refractory Advanced Solid Tumors: Dosimetry, Biodistribution, Pharmacokinetics, and Safety

    PubMed Central

    Grudzinski, Joseph J.; Titz, Benjamin; Kozak, Kevin; Clarke, William; Allen, Ernest; Trembath, LisaAnn; Stabin, Michael; Marshall, John; Cho, Steve Y.; Wong, Terence Z.; Mortimer, Joanne; Weichert, Jamey P.

    2014-01-01

    Introduction 131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK) and safety profiles of 131I-CLR1404. Methods Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of 131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15–35 minutes, 4–6, 18–24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on 127I-CLR1404 mass measurements. To evaluate renal clearance of 131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software. Results Single administrations of 370 MBq of 131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma 127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t) values were 72.2 ng/mL and 15753 ng•hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow. Conclusions Preliminary data suggest that 131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent. Trial Registration ClinicalTrials.gov NCT00925275 PMID:25402488

  18. The Mt. Diwata study on the Philippines 2000-treatment of mercury intoxicated inhabitants of a gold mining area with DMPS (2,3-dimercapto-1-propane-sulfonic acid, Dimaval).

    PubMed

    Böse-O'Reilly, S; Drasch, G; Beinhoff, C; Maydl, S; Vosko, M R; Roider, G; Dzaja, D

    2003-05-20

    Ninty-five inhabitants of the gold mining area of Mt. Diwata (on Mindanao, Philippines), who were diagnosed to be mercury (Hg) intoxicated, were orally treated with 2 x 200 mg of the chelating agent DMPS (Dimaval, Co. Heyl, Germany) for 14 days in the course of a UNIDO project focusing on mercury pollution abatement. Blood and urine samples before and after treatment, urine after the first application of DMPS and a hair sample were collected and analyzed for Hg. Before and after treatment extensive anamnestic data were collected, medical and neurological investigations and some neuro-psychological tests were performed. In spite of the short time of treatment most of the patients reported a marked improvement of the complaints which were stated by them before the therapy and which are characteristic for a chronic Hg intoxication, for example tremor, loss of memory, sleeplessness, metallic taste, etc. But even in some of the objective neurological parameters like hypo-mimia, Romberg test and tests for tremor/ataxia a statistical significant improvement could be found. Significant improvements could also be found in two neuro-psychological tests (pencil tapping and Frostig). In some cases an extreme high urinary Hg excretion was found under the chelating therapy with DMPS, and by this a distinct reduction of the Hg body burden. Nevertheless, in most cases Hg in blood and urine was not markedly decreased by the treatment. This shows that the duration of the treatment (14 days) was not sufficient for a permanent decrease in Hg. As DMPS excretes Hg mainly through the kidney, it can be concluded that in most cases even after 14 days of treatment there was an ongoing redistribution of Hg from other tissues to the kidney. In conclusion, this study proves that a chelating therapy with DMPS is highly effective even in the case of a mixed chronic and acute intoxication with an unknown combination of Hg vapor, inorganic Hg and organic Hg=methylmercury (MeHg), as characteristic

  19. Flooding and Emergency Room Visits for Gastrointestinal Illness in Massachusetts: A Case-Crossover Study

    PubMed Central

    Wade, Timothy J.; Lin, Cynthia J.; Jagai, Jyotsna S.; Hilborn, Elizabeth D.

    2014-01-01

    Introduction Floods and other severe weather events are anticipated to increase as a result of global climate change. Floods can lead to outbreaks of gastroenteritis and other infectious diseases due to disruption of sewage and water infrastructure and impacts on sanitation and hygiene. Floods have also been indirectly associated with outbreaks through population displacement and crowding. Methods We conducted a case-crossover study to investigate the association between flooding and emergency room visits for gastrointestinal illness (ER-GI) in Massachusetts for the years 2003 through 2007. We obtained ER-GI visits from the State of Massachusetts and records of floods from the National Oceanic and Atmospheric Association’s Storm Events Database. ER-GI visits were considered exposed if a flood occurred in the town of residence within three hazard periods of the visit: 0–4 days; 5–9 days; and 10–14 days. A time-stratified bi-directional design was used for control selection, matching on day of the week with two weeks lead or lag time from the ER-GI visit. Fixed effect logistic regression models were used to estimate the risk of ER-GI visits following the flood. Results and Conclusions A total of 270,457 ER-GI visits and 129 floods occurred in Massachusetts over the study period. Across all counties, flooding was associated with an increased risk for ER-GI in the 0–4 day period after flooding (Odds Ratio: 1.08; 95% Confidence Interval: 1.03–1.12); but not the 5–9 days (Odds Ratio: 0.995; 95% Confidence Interval: 0.955–1.04) or the 10–14 days after (Odds Ratio: 0.966, 95% Confidence Interval: 0.927–1.01). Similar results were observed for different definitions of ER-GI. The effect differed across counties, suggesting local differences in the risk and impact of flooding. Statewide, across the study period, an estimated 7% of ER-GI visits in the 0–4 days after a flood event were attributable to flooding. PMID:25329916

  20. Study on the potential toxicity of a thymoquinone-rich fraction nanoemulsion in Sprague Dawley rats.

    PubMed

    Tubesha, Zaki; Imam, Mustapha Umar; Mahmud, Rozi; Ismail, Maznah

    2013-01-01

    Toxicological studies constitute an essential part of the effort in developing an herbal medicine into a drug product. A newly developed thymoquinone-rich fraction nanoemulsion (TQRFNE) has been prepared using a high pressure homogenizer. The purpose of this study was to investigate the potential acute toxicity of this nanoemulsion in Sprague Dawley rats. The acute toxicity studies were conducted as per the OECD guidelines 425, allowing for the use of test dose limit of 20 mL TQRFNE (containing 44.5 mg TQ)/kg. TQRFNE and distilled water (DW) as a control were administered orally to both sexes of rats on Day 0 and observed for 14 days. All the animals appeared normal, and healthy throughout the study. There was no observed mortality or any signs of toxicity during the experimental period. The effects of the TQRFNE and DW groups on general behavior, body weight, food and water consumption, relative organ weight, hematology, histopathology, and clinical biochemistry were measured. All the parameters measured were unaffected as compared to the control (DW) group. The administration of 20 mL TQRFNE /kg was not toxic after an acute exposure. PMID:23803717

  1. Stress, Workload and Physiology Demand During Extravehicular Activity: A Pilot Study

    PubMed Central

    Rai, Balwant; Kaur, Jasdeep; Foing, Bernard H

    2012-01-01

    Background: Extravehicular activity (EVA), such as exercise performed under unique environmental conditions, is essential for supporting daily living in weightlessness and for further space exploration like long Mars mission. Aim: The study was planned stress, workload, and physiological demands of simulated Mars exploration. Materials and Methods: In this study, the six-person crew lived (24 hours) for 14 days during a short-term stay at the Mars Desert Research Station. The heart rates, salivary cortisol, workload, peak oxygen uptake or maximal aerobic capacity of the crew are measured before, during and after an EVA. Results: Data for heart rate showed the same trend as peak oxygen uptake or maximal aerobic capacity, with a maximal increase to 85% of peak. The rating of subscale showed a significant increase in EVA as compared to run. Salivary cortisol levels and heart rates were increased in both groups, although significant increased of cortisol levels and heart rates more in EVA as compared to hill running crew members. Conclusion: Further study is required on large scale taken into account of limitations of this study and including other physiological and psychological parameters in Mars analog environment. PMID:22754877

  2. In vitro time-kill curves study of three antituberculous combinations against Mycobacterium tuberculosis clinical isolates.

    PubMed

    López-Gavín, Alexandre; Tudó, Griselda; Rey-Jurado, Emma; Vergara, Andrea; Hurtado, Juan Carlos; Gonzalez-Martín, Julian

    2016-01-01

    The objective of this study was to examine the in vitro synergism of three-drug combinations against Mycobacterium tuberculosis (levofloxacin/linezolid/ethambutol, levofloxacin/amikacin/ethambutol and levofloxacin/linezolid/amikacin) using the time-kill curves method. In total, 8 multidrug-resistant and 12 drug-susceptible M. tuberculosis isolates were used. Minimum inhibitory concentrations (MICs) of the isolates for each drug were determined by the proportions method. Time-kill curves were studied for the three combinations proposed over 14 days using two different protocols. In protocol 1, 0.5× MIC for each drug was used. In protocol 2, 0.5× MIC for levofloxacin and linezolid and 0.25× MIC for amikacin and ethambutol were used. The MICs for all of the isolates studied were 0.5 mg/L for levofloxacin and linezolid and 2.5 mg/L for ethambutol and amikacin. All of the combinations displayed an additive activity compared with the most active individual drug. In conclusion, these results demonstrate that the three combinations tested were equally effective against M. tuberculosis isolates. The study of antituberculous combinations using in vitro methods is an excellent first step to predict their effect in clinical development phases as well as to test new regimens of the antituberculous drugs currently available. PMID:26691020

  3. Acute and repeated dose toxicity studies of different β-cyclodextrin-based nanosponge formulations.

    PubMed

    Shende, Pravin; Kulkarni, Yogesh A; Gaud, R S; Deshmukh, Kiran; Cavalli, Roberta; Trotta, Francesco; Caldera, Fabrizio

    2015-05-01

    Nanosponges (NS) show promising results in different fields such as medicine, agriculture, water purification, fire engineering and so on. The present study was designed to evaluate toxicity of different NS formulations (namely, S1-S6) synthesized with different cross-linking agents such as carbonyl diimidazole, pyromellitic dianhydride and hexamethylene diisocynate; and preparation methods in experimental animals. Acute and repeated dose toxicity studies of formulations were carried out as per OECD guidelines 423 and 407, respectively. For acute toxicity study, formulations were administered to female rats at doses of 300 and 2000 mg/kg orally. The general behaviour of the rats was continuously monitored for 1 h after dosing, periodically during the first 24 h and daily thereafter for a total of 14 days. On day 14, animals were fasted overnight, weighed, and sacrificed. After sacrification, animals were subjected to necropsy. For repeated dose toxicity study, rats of either sex were orally administered with formulations at the dose of 300 mg/kg per day for a period of 28 days. The maximally tolerated dose of all formulations was found to be 2000 mg/kg. Repeated administration of formulations for 28 days did not show any significant changes in haematological and biochemical parameters in experimental animals. These results indicate that the formulations are safe, when tested in experimental animals. PMID:25754724

  4. Production, composition and toxicology studies of Enzogenol® Pinus radiata bark extract.

    PubMed

    Frevel, Mathias A E; Pipingas, Andrew; Grigsby, Warren J; Frampton, Chris M; Gilchrist, Nigel L

    2012-12-01

    Enzogenol® pine bark extract is a dietary supplement and food ingredient produced by water extraction of Pinus radiata. We present production method, composition, and safety data from rat and dog toxicological and human clinical studies. The dry powder contains proanthocyanidins (>80%), taxifolin (1-2%), other flavonoids and phenolic acids (up to 8%), and carbohydrates (5-10%). Reverse mutation assays showed lack of mutagenic activity. Single and 14-day repeat dosing in rats and dogs had no influence on body weight, feed consumption, blood chemistry, and haematology at any dose level. There were no treatment related findings on gross and detailed necroscopy, organ weights, organ weight ratios and histology. The only adverse events were emesis and diarrhoea in dogs occurring mainly in un-fed condition and at the highest dose level in a total of 18% of applications. The MTD and NOAEL in the present rat and dog studies were 2500 and 750 mg/kg/day, respectively. Consumption of 480 mg/day for 6 months and 960 mg/day for 5 weeks in two human studies showed Enzogenol® had no adverse influence on liver and kidney function, haematology, and did not cause any adverse events. Our studies indicate lack of toxicity of Enzogenol® and support safe use as a food ingredient. PMID:22982471

  5. Antioxidant and Toxicity Studies of 50% Methanolic Extract of Orthosiphon stamineus Benth

    PubMed Central

    Lim, Chung Pin; Fung Ang, Lee; Por, Lip Yee; Wong, Siew Tung; Asmawi, Mohd. Zaini

    2013-01-01

    The present study evaluated the antioxidant activity and potential toxicity of 50% methanolic extract of Orthosiphon stamineus (Lamiaceae) leaves (MEOS) after acute and subchronic administration in rats. Superoxide radical scavenging, hydroxyl radical scavenging, and ferrous ion chelating methods were used to evaluate the antioxidant properties of the extract. In acute toxicity study, single dose of MEOS, 5000 mg/kg, was administered to rats by oral gavage, and the treated rats were monitored for 14 days. While in the subchronic toxicity study, MEOS was administered orally, at doses of 1250, 2500, and 5000 mg/kg/day for 28 days. From the results, MEOS showed good superoxide radical scavenging, hydroxyl radical scavenging, ferrous ion chelating, and antilipid peroxidation activities. There was no mortality detected or any signs of toxicity in acute and subchronic toxicity studies. Furthermore, there was no significant difference in bodyweight, relative organ weight, and haematological and biochemical parameters between both male and female treated rats in any doses tested. No abnormality of internal organs was observed between treatment and control groups. The oral lethal dose determined was more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of MEOS for both male and female rats is considered to be 5000 mg/kg per day. PMID:24490155

  6. Safety assessment of methanol extract of red dragon fruit (Hylocereus polyrhizus): acute and subchronic toxicity studies.

    PubMed

    Hor, Sook Yee; Ahmad, Mariam; Farsi, Elham; Yam, Mun Fei; Hashim, Mohd Akmal; Lim, Chung Pin; Sadikun, Amirin; Asmawi, Mohd Zaini

    2012-06-01

    Recently, the fruits of Hylocereus polyrhizus, known as red dragon fruit, have received much attention from growers worldwide. However, there is little toxicological information regarding the safety of repeated exposure to these fruits. The present study evaluated the potential toxicity of a methanol extract of H. polyrhizus fruit after acute and subchronic administration in rats. In the acute toxicity study, single doses of fruit extract (1250, 2500 and 5000 mg/kg) were administered to rats by oral gavage, and the rats were then monitored for 14 days. In the subchronic toxicity study, the fruit extract was administered orally to rats at doses of 1250, 2500 and 5000 mg/kg/day for 28 days. There was no mortality or signs of acute or subchronic toxicity. There was no significant difference in body weight, relative organ weight or hematological parameters in the subchronic toxicity study. Biochemical analysis showed some significant changes, including creatinine, globulin, total protein and urea levels. No abnormality of internal organs was observed between treatment and control groups. The lethal oral dose of the fruit extract is more than 5000 mg/kg and the no-observed-adverse-effect level (NOAEL) of the extract for both male and female rats is considered to be 5000 mg/kg per day for 28 days. PMID:22440551

  7. Distributed situation awareness in complex collaborative systems: A field study of bridge operations on platform supply vessels

    PubMed Central

    Sandhåland, Hilde; Oltedal, Helle A; Hystad, Sigurd W; Eid, Jarle

    2015-01-01

    This study provides empirical data about shipboard practices in bridge operations on board a selection of platform supply vessels (PSVs). Using the theoretical concept of distributed situation awareness, the study examines how situation awareness (SA)-related information is distributed and coordinated at the bridge. This study thus favours a systems approach to studying SA, viewing it not as a phenomenon that solely happens in each individual's mind but rather as something that happens between individuals and the tools that they use in a collaborative system. Thus, this study adds to our understanding of SA as a distributed phenomenon. Data were collected in four field studies that lasted between 8 and 14 days on PSVs that operate on the Norwegian continental shelf and UK continental shelf. The study revealed pronounced variations in shipboard practices regarding how the bridge team attended to operational planning, communication procedures, and distracting/interrupting factors during operations. These findings shed new light on how SA might decrease in bridge teams during platform supply operations. The findings from this study emphasize the need to assess and establish shipboard practices that support the bridge teams' SA needs in day-to-day operations. Practitioner points Provides insights into how shipboard practices that are relevant to planning, communication and the occurrence of distracting/interrupting factors are realized in bridge operations. Notes possible areas for improvement to enhance distributed SA in bridge operations. PMID:26028823

  8. G6PD Deficiency and Antimalarial Efficacy for Uncomplicated Malaria in Bangladesh: A Prospective Observational Study

    PubMed Central

    Ley, Benedikt; Alam, Mohammad Shafiul; Thriemer, Kamala; Hossain, Mohammad Sharif; Kibria, Mohammad Golam; Auburn, Sarah; Poirot, Eugenie; Price, Ric N.; Khan, Wasif Ali

    2016-01-01

    Background The Bangladeshi national treatment guidelines for uncomplicated malaria follow WHO recommendations but without G6PD testing prior to primaquine administration. A prospective observational study was conducted to assess the efficacy of the current antimalarial policy. Methods Patients with uncomplicated malaria, confirmed by microscopy, attending a health care facility in the Chittagong Hill Tracts, Bangladesh, were treated with artemether-lumefantrine (days 0–2) plus single dose primaquine (0.75mg/kg on day2) for P. falciparum infections, or with chloroquine (days 0–2) plus 14 days primaquine (3.5mg/kg total over 14 days) for P. vivax infections. Hb was measured on days 0, 2 and 9 in all patients and also on days 16 and 30 in patients with P. vivax infection. Participants were followed for 30 days. The study was registered with the clinical trials website (NCT02389374). Results Between September 2014 and February 2015 a total of 181 patients were enrolled (64% P. falciparum, 30% P. vivax and 6% mixed infections). Median parasite clearance times were 22.0 (Interquartile Range, IQR: 15.2–27.3) hours for P. falciparum, 20.0 (IQR: 9.5–22.7) hours for P. vivax and 16.6 (IQR: 10.0–46.0) hours for mixed infections. All participants were afebrile within 48 hours, two patients with P. falciparum infection remained parasitemic at 48 hours. No patient had recurrent parasitaemia within 30 days. Adjusted male median G6PD activity was 7.82U/gHb. One male participant (1/174) had severe G6PD deficiency (<10% activity), five participants (5/174) had mild G6PD deficiency (10–60% activity). The Hb nadir occurred on day 2 prior to primaquine treatment in P. falciparum and P. vivax infected patients; mean fractional fall in Hb was -8.8% (95%CI -6.7% to -11.0%) and -7.4% (95%CI: -4.5 to -10.4%) respectively. Conclusion The current antimalarial policy remains effective. The prevalence of G6PD deficiency was low. Main contribution to haemolysis in G6PD normal

  9. Toxicology and carcinogenesis studies of acrylamide (CASRN 79-06-1) in F344/N rats and B6C3F1 mice (feed and drinking water studies).

    PubMed

    2012-07-01

    Acrylamide, a water-soluble α,β-unsaturated amide, is a contaminant in baked and fried starchy foods, including french fries, potato chips, and bread, as a result of Maillard reactions involving asparagine and reducing sugars. Additional sources of acrylamide exposure include cigarettes, laboratory procedures involving polyacrylamide gels, and various occupations (e.g, monomer production and polymerization processes). Acrylamide is carcinogenic in experimental animals. To obtain data for developing quantitative risk assessments for dietary exposures to acrylamide, the Food and Drug Administration nominated acrylamide for an in-depth toxicological evaluation by the National Toxicology Program. As part of this evaluation, male and female B6C3F1/Nctr (C57BL/6N x C3H/HeN MTV-) mice and male and female F344/N Nctr rats were exposed to acrylamide (at least 99.4% pure) in drinking water for 2 years. 2-WEEK STUDY IN RATS: Groups of four male and four female F344/N rats were administered 0, 0.14, 0.35, 0.70, 1.41, 3.52, or 7.03 mM acrylamide in the drinking water (0, 10, 25, 50, 100, 250, or 500 ppm acrylamide) or 0.0, 7.4, 18.5, 37, 74, 185, or 370 mg acrylamide per kg diet for 14 days. One male rat administered 7.03 mM acrylamide in the drinking water died on day 14. Male and female rats receiving 7.03 mM acrylamide weighed 56% and 64% of controls, respectively. Male and female rats fed 370 mg acrylamide per kg diet weighed 74% and 83% of controls, respectively. Female rats receiving 3.52 mM acrylamide in drinking water and male rats fed 185 mg acrylamide per kg diet weighed 85% and 89% of controls, respectively. Rats receiving 7.03 mM acrylamide in drinking water or 370 mg acrylamide per kg diet exhibited hind-leg paralysis on day 14. Mild to moderate dilatation of the urinary bladder was observed in all rats given 370 mg acrylamide per kg diet, and in three of four male rats and all four female rats given 7.03 mM acrylamide in drinking water, and in one of four male

  10. A Prospective, Descriptive, Quality Improvement Study to Decrease Incontinence-Associated Dermatitis and Hospital-Acquired Pressure Ulcers.

    PubMed

    Hall, Kimberly D; Clark, Rebecca C

    2015-07-01

    Incontinence is a common problem among hospitalized patients and has been associated with multiple health complications, including incontinence-associated dermatitis (IAD) and hospital-acquired pressure ulcers (HAPUs). A prospective, descriptive study was conducted in 2 acute care neurology units to 1) assess the prevalence of incontinence and incidence of IAD and HAPUs among incontinent patients, and 2) evaluate the effect of caregiver education and use of a 1-step cleanser, moisturizer, barrier product on the development of IAD and HAPUs among patients with incontinence. During a period of 1 month, the incontinence status of admitted patients was recorded and skin was assessed for the presence/absence of IAD and HAPUs twice per day. After the 1-month data collection, all clinicians on the study units completed a facility-based online education program about IAD, HAPUs, and skin care followed by the implementation of a 1-step cleanser/barrier product for skin care of all patients with incontinence. Data collection procedures remained the same. Data were collected using a paper/pencil instrument and entered into a spreadsheet for analysis. Descriptive statistics were calculated and prevalence and incidence rates were compared between the pre-intervention and post-intervention phase using Fisher's exact analysis. During the first phase of the study, 17 of 40 admitted patients (42.5%) were incontinent. Of those, 5 (29.4%) developed IAD and all of these patients developed HAPUs (5 of 40 admitted, 29.4%) during an average length of stay of 7.3 (range: 2-14) days. In the intervention phase of the study, 25 of 46 (54.3%) patients were incontinent and none developed IAD or a HAPU during an average length of stay of 7.4 (range: 2-14) days. The average Braden scale score was 14.14 in the pre-intervention group of patients with incontinence and 12.74 in the intervention group. The prevalence of incontinence among patients admitted to acute care neurology units and the rate

  11. Randomized, Double-Blind, Phase II, Multicenter Study Evaluating the Safety/Tolerability and Efficacy of JNJ-Q2, a Novel Fluoroquinolone, Compared with Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infection ▿ †

    PubMed Central

    Covington, Paul; Davenport, J. Michael; Andrae, David; O'Riordan, William; Liverman, Lisa; McIntyre, Gail; Almenoff, June

    2011-01-01

    JNJ-Q2 is a fluoroquinolone with broad coverage including methicillin-resistant Staphylococcus aureus (MRSA). A double-blind, multicenter, phase II noninferiority study treated 161 patients for 7 to 14 days, testing the efficacy of JNJ-Q2 (250 mg, twice a day [BID]) versus linezolid (600 mg, BID) in patients with acute bacterial skin and skin structure infections (ABSSSI). The prespecified criterion for noninferiority was 15%. Primary intent-to-treat analysis was unable to declare noninferiority, as the risk difference lower bound of the 95% confidence interval between treatments was 19% at 36 to 84 h postrandomization for the composite end point of lesion assessment and temperature. Prespecified clinical cure rates 2 to 14 days after completion of therapy were similar (83.1% for JNJ-Q2 versus 82.1% for linezolid). Post hoc analyses revealed that JNJ-Q2 was statistically noninferior to linezolid (61.4% versus 57.7%, respectively; P = 0.024) based on the 2010 FDA guidance, which defines treatment success as lack of lesion spread and afebrile status within 48 to 72 h postrandomization. Despite evidence of systemic disease, <5% of patients presented with fever, suggesting fever is not a compelling surrogate measure of systemic disease resolution for this indication. Nausea and vomiting were the most common adverse events. Of the patients, 86% (104/121) had S. aureus isolated from the infection site; 63% of these were MRSA. The results suggest JNJ-Q2 shows promise as an effective treatment for ABSSSI, demonstrating (i) efficacy for early clinical response (i.e., lack of spread of lesions and absence of fever at 48 to 72 h), and (ii) cure rates for ABSSSI pathogens (especially MRSA) consistent with the historical literature. PMID:21947389

  12. In vivo comparative study of tissue reaction to bare and antimicrobial polymer coated transcutaneous implants.

    PubMed

    Calliess, Tilman; Bartsch, Ivonne; Haupt, Maike; Reebmann, Mattias; Schwarze, Michael; Stiesch, Meike; Pfaffenroth, Cornelia; Sluszniak, Magda; Dempwolf, Wibke; Menzel, Henning; Witte, Frank; Willbold, Elmar

    2016-04-01

    We coated transcutaneous implants made of titanium alloy Ti6Al4V with copolymer dimethyl (2-methacryloyloxy-ethyl) phosphonate and 4-vinylpyridine and investigated the tissue reaction with respect to its biocompatible and antimicrobial properties in vivo. We distinguished between clinically observable superficial inflammations and histologically detectable deep infections. The vinylpyridine moieties were transferred into cationic pyridinium groups by reaction with hexyl bromide. Thus polymers with both antimicrobial capacity and good biocompatibility were obtained. In a short-term study, we implanted specially designed bare or coated implants in hairless but immunocompetent mice and analyzed the tissue reaction histologically. No difference was found between bare and coated implants in the initial healing phase of up to 14days; however, after 21days the scar tissue formation was higher in the bare implant group. The degree of epithelial downgrowth was comparable in both groups at any time point. In a long-term study of up to 168days, we analyzed resistance to infection. In the bare implant group, 7 of the 12 implantation sites became infected deep whereas in the coated implant group only two deep infections were observed. The other implantation sites showed only superficial signs of inflammation. These results generally accord with previous in-vitro studies. PMID:26838901

  13. Disaccharidase activities in small intestine of rotavirus-infected suckling mice: a histochemical study.

    PubMed

    Collins, J; Candy, D C; Starkey, W G; Spencer, A J; Osborne, M P; Stephen, J

    1990-10-01

    A histochemical study of the time course of the appearance and location of lactase and alpha-glucosidase (used to detect sucrase and maltase) activities was carried out on control and rotavirus-infected mice from 7 to 14 days old. The overall pattern of enzyme activity was in agreement with previous quantitative studies on the activities of these enzymes. No evidence was obtained to support the idea that lactase deficiency was the result of repopulation of villi (denuded of lactase-producing villus cells) with immature lactase-negative cells. Low lactase activity was more likely to reflect profound changes in metabolically crippled cells, and recovery of lactase activity with recovery of normal metabolic functions. The location of enzyme activity to brush border regions rather than the cytoplasm of villus enterocytes enhances the significance of previous quantitative studies on these enzymes. The timing and duration of diminished lactase activities were such that they were unlikely to cause the induction or perpetuation of diarrhea in murine rotavirus diarrhea. The appearance in infected animals of alpha-glucosidase 3 days earlier than normal indicates that, in addition to reversible changes seen with lactase, developmental changes were accelerated that affected both crypt and villus cells. PMID:2123244

  14. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule

    PubMed Central

    Pickar, J. H.; Amadio, J. M.; Bernick, B. A.; Mirkin, S.

    2016-01-01

    Abstract Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem®, reference) in postmenopausal women (aged 40–65 years) at 10-μg and 25-μg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-μg study and 36 completed the 25-μg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and C max and earlier t max. No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-μg and 25-μg doses. Both doses of each product were safe and well-tolerated. PMID:26857443

  15. Amphiphilic poly-N-vynilpyrrolidone nanoparticles: Cytotoxicity and acute toxicity study.

    PubMed

    Kuskov, A N; Kulikov, P P; Shtilman, M I; Rakitskii, V N; Tsatsakis, A M

    2016-10-01

    The aim of the present study was to evaluate the cytotoxicity against MCF-7 cells and acute intraperitoneal toxicity of amphiphilic poly-N-vinylpyrrolidone nanoparticles to confirm possibility of their application for creation of novel drug delivery systems. The effect of cellular uptake of polymeric nanoparticles on human cancer cell line MCF-7 cells was investigated by MTT assay. MTT analysis showed that tested amphiphilic polymers were essentially non-toxic. In acute toxicity studies, LD50 and other toxicity indexes were evaluated, under which no deaths or treatment related complications were observed even in high concentration treatment for 14 days of experiment. For histological analysis, organs of the animals were weighed and examined. No animal died during the study and no significant changes have been observed regarding body weight, feed consumption, organ weight or histological data. Obtained results show that amphiphilic poly-N-vinylpyrrolidone nanoparticles possessed no toxicity against cells and in animals after intraperitoneal administration. Thus, amphiphilic PVP nanoparticles demonstrate high potential as carriers for novel high-effective drug delivery systems. PMID:27539747

  16. Pharmacokinetic studies of solubilized estradiol given vaginally in a novel softgel capsule.

    PubMed

    Pickar, J H; Amadio, J M; Bernick, B A; Mirkin, S

    2016-04-01

    Objective To evaluate the bioavailability and safety of a novel vaginal capsule containing solubilized bioidentical 17β-estradiol for vulvar and vaginal atrophy and compare its pharmacokinetics with that of an approved vaginal estradiol tablet in healthy postmenopausal women. Methods Two randomized, single-dose, two-way cross-over, relative bioavailability trials compared the pharmacokinetics of a solubilized vaginal estradiol softgel capsule (TX-004HR, test) with that of a vaginal estradiol tablet (Vagifem®, reference) in postmenopausal women (aged 40-65 years) at 10-μg and 25-μg doses. In each study, women were randomly assigned to receive a single dose of the test capsule or reference tablet, followed by a single dose of the alternate drug after a 14-day washout. Results Thirty-five women completed the 10-μg study and 36 completed the 25-μg study. Significantly lower systemic levels of estradiol, estrone, and estrone sulfate at both doses of the test product were observed compared with equivalent doses of the reference product, with lower AUC0-24 and Cmax and earlier tmax. No adverse events were reported in either trial. Conclusion TX-004HR, a novel estradiol vaginal softgel capsule, exhibited significantly lower systemic exposure than equivalent doses of an approved vaginal estradiol tablet at both 10-μg and 25-μg doses. Both doses of each product were safe and well-tolerated. PMID:26857443

  17. Toxicological studies of aqueous extract of Acacia nilotica root

    PubMed Central

    Adesokan, Abdulfatai Ayoade; Salawu, Oluwakanyinsola Adeola; Akanji, Musbau Adewunmi

    2015-01-01

    Acacia nilotica is a widely used plant in traditional medical practice in Northern Nigeria and many African countries. The aim of this study was to determine the toxicological effects of a single dose (acute) and of repeated doses (sub-acute) administration of aqueous extract of A. nilotica root in rodents, following our earlier study on antiplasmodial activity. In the acute toxicity test, three groups of Swiss albino mice were orally administered aqueous extract of A. nilotica (50, 300 and 2000 mg/kg body weight) and signs of toxicity were observed daily for 14 days. In the sub-acute toxicity study, four groups of 12 rats (6 male and 6 female) were used. Group 1 received 10 ml/kg b.w distilled water (control), while groups 2, 3 and 4 received 125, 250 and 500 mg/kg b.w of the extract, respectively, for 28 consecutive days by oral gavage. Signs of toxicity/mortality, food and water intake and body weight changes were observed. Biochemical parameters were analysed in both plasma and liver homogenate. In the acute and sub-acute toxicity studies, the extract did not cause mortality. A significant reduction in the activity of lactate dehydrogenase was observed at 250 and 500 mg/kg b.w, while alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase activities were significantly higher than control values at 500 mg/kg b.w. The aqueous extract of A. nilotica was found to be safe in single dose administration in mice but repeated administration of doses higher than 250 mg/kg b.w of the extract for 28 days in rats may cause hepatotoxicity. PMID:27486360

  18. Comparative study on the effect of Eurycoma longifolia and Smilax myosotiflora on male rats fertility

    NASA Astrophysics Data System (ADS)

    Mahmoud, Amal Salem Farag; Noor, Mahanem Mat

    2013-11-01

    The effects of Eurycoma longifolia Jack and Smilax myosotiflora were studied on sperm quality include sperm count, motility, viability and histology of the testis and pregnancy rate after mating with fertile proved females, as well as litter size on Sprague-Dawley (S-D) adult male rats. After dosing them with distilled water group A, group B 150 mg/kg body weight of aqueous extract of E. longifolia roots, group C 150 mg/kg body weight aqueous extract of S. myosotiflora leaf and group D 150 mg/kg body weight of E. longifolia combined with 150 mg/kg S. myosotiflora body weight daily for 14 days of stage (a) and 28 days for stage (b) of treatments. Results exhibited no significant variation (P>0.05) of stage (a),while results showed that E. longifolia Jack increase (P<0.05) the sperm count, motility, viability and histology of the testis and gender (male) of the litter size respectively of stage (b). This study provides evidence that E. longifolia Jack is a potent stimulator of fertility in male rat.

  19. Does famotidine enhance tumor infiltrating lymphocytes in breast cancer? Results of a randomized prospective pilot study.

    PubMed

    Parshad, Rajinder; Kapoor, Sorabh; Gupta, Siddhartha Datta; Kumar, Arvind; Chattopadhyaya, Tushar K

    2002-01-01

    Thirty patients with breast cancer were prospectively randomized into case and control groups receiving 40 mg famotidine preoperatively for 10-14 days and routine premedication, respectively. Surgical specimens were evaluated objectively for tumor infiltrating lymphocytes in the center and in the periphery of the tumor along with evaluation of metastatic lymph nodes for reactive changes. Ten famotidine-treated cases (67%) showed significant lymphocytic infiltration in the center compared to 4 controls (27%) (p = 0.03). Eleven cases (77%) had significant lymphocytic infiltration in the periphery (p = 0.03) compared to 5 controls (33%). Considering both sites, lymphocytic response was significant in 9 (60%) cases as opposed to only 3 (20%) controls (p = 0.03). This response did not correlate with the stage, grade of tumor or menopausal status of patients in either group. Seventy-eight percent (78%) of the cases showed significant reactive changes in the metastatic lymph nodes as compared to 22% in controls (p < 0.01). This study suggests that famotidine enhances tumor infiltrating lymphocytes in breast cancer and might have potential as an immunomodulator. A larger confirmatory study is suggested. PMID:12234028

  20. (1)H nuclear magnetic resonance-based metabolomics study of earthworm Perionyx excavatus in vermifiltration process.

    PubMed

    Wang, Lei; Huang, Xulei; Laserna, Anna Karen Carrasco; Li, Sam Fong Yau

    2016-10-01

    In this study, (1)H nuclear magnetic resonance (NMR)-based metabolomics approach was used to characterize the metabolic response of the earthworm Perionyx excavatus in continuous vermifiltration for two months under hydraulic loading rates of 1m(3)m(-2)d(-1) (VF1) and 1.5m(3)m(-2)d(-1) (VF1.5). Both VF1 and VF1.5 showed higher removal of chemical oxygen demand and total nitrogen than the biofilter without earthworms. Principal component analysis of the NMR spectra of earthworm metabolites showed significant separations between those not subjected to wastewater filtration (control) and VF1 or VF1.5. Temporal variations of earthworm biomass, and the identified metabolites that are significantly different between control, VF1 and VF1.5 revealed that worms underwent increasing metabolic activity within 20days in VF1 and 14days in VF1.5, then decreasing metabolic activity. The use of NMR-based metabolomics in monitoring earthworm metabolism was demonstrated to be a novel approach in studying engineered vermifiltration systems. PMID:27469092

  1. Acute Toxicity Study of Zerumbone-Loaded Nanostructured Lipid Carrier on BALB/c Mice Model

    PubMed Central

    Rahman, Heshu Sulaiman; Rasedee, Abdullah; Othman, Hemn Hassan; Chartrand, Max Stanley; Namvar, Farideh; Abdul Samad, Nozlena; Andas, Reena Joys; Ng, Kuan Beng; How, Chee Wun

    2014-01-01

    Zerumbone- (ZER-) loaded nanostructure lipid carrier (NLC) (ZER-NLC) prepared for its antileukemia effect in vitro was evaluated for its toxicological effects by observing changes in the liver, kidney, spleen, lung, heart, and brain tissues, serum biochemical parameters, total haemogram, and bone marrow stem cells. The acute toxicity study for ZER-NLC was conducted by orally treating BALB/c mice with a single dose with either water, olive oil, ZER, NLC, or ZER-NLC for 14 days. The animals were observed for clinical and behavioral abnormalities, toxicological symptoms, feed consumption, and gross appearance. The liver, kidney, heart, lung, spleen, and brain tissues were assessed histologically. Total haemogram was counted by hemocytometry and microhematocrit reader. Bone marrow examination in terms of cellular morphology was done by Wright staining with bone marrow smear. Furthermore, serum biochemical parameters were determined spectrophotometrically. Grossly all treated mice, their investigated tissues, serum biochemical parameters, total haemogram, and bone marrow were normal. At oral doses of 100 and 200 mg/kg ZER-NLC there was no sign of toxicity or mortality in BALB/c mice. This study suggests that the 50% lethal dose (LD50) of ZER-NLC is higher than 200 mg/kg, thus, safe by oral administration. PMID:25276798

  2. Genotoxicity Studies of Titanium Dioxide Nanoparticles (TiO2NPs) in the Brain of Mice

    PubMed Central

    Mohamed, Hanan R. H.

    2016-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are excessively used and represent one of the top five most commonly used nanoparticles worldwide. Recently, various studies referred to their toxic potential on various organs using different treatment route. Male Swiss Webster mice were orally administrated TiO2NPs (500 mg/kg b.w.) daily for five consecutive days and then animals were sacrificed at 24 h, 7 days, or 14 days after the last treatment. The present results report that exposure to TiO2NPs produces mild to moderate changes in the cytoarchitecture of brain tissue in a time dependent manner. Moreover, Comet assay revealed the apoptotic DNA fragmentation, while PCR-SSCP pattern and direct sequencing showed point mutation of Presenilin 1 gene at exon 5, gene linked to inherited forms of the Alzheimer's disease. Therefore, from these findings, the present study concluded that TiO2NPs is genotoxic and mutagenic to brain tissue which in turn might lead to Alzheimer's disease incidence. PMID:27034902

  3. A Time Study of Physicians’ Work in a German University Eye Hospital to Estimate Unit Costs

    PubMed Central

    Wolff, Jan; McCrone, Paul; Patel, Anita; Auber, Gerd; Reinhard, Thomas

    2015-01-01

    Background Technical efficiency of hospital services is debated since performance has been heterogeneous. Staff time represents the main resource in patient care and its inappropriate allocation has been identified as a key factor of inefficiency. The aim of this study was to analyse the utilisation of physicians’ work time stratified by staff groups, tasks and places of work. A further aim was to use these data to estimate resource use per unit of output. Methods A self-reporting work-sampling study was carried during 14-days at a University Eye Hospital. Staff costs of physicians per unit of output were calculated at the wards, the operating rooms and the outpatient unit. Results Forty per cent of total work time was spent in contact with the patient. Thirty per cent was spent with documentation tasks. Time spent with documentation tasks declined monotonically with increasing seniority of staff. Unit costs were 56 € per patient day at the wards, 77 € and 20 € per intervention at the operating rooms for inpatients and outpatients, respectively, and 33 € per contact at the outpatient unit. Substantial differences in resources directly dedicated to the patient were found between these locations. Conclusion The presented data provide unprecedented units costs in inpatient Ophthalmology. Future research should focus on analysing factors that influence differences in time allocation, such as types of patients, organisation of care processes and composition of staff. PMID:25803022

  4. [Clinical study of the efficacy of albendazole treatment in human hydatidosis].

    PubMed

    Rădulescu, S; Angelescu, N; Horvat, T; Lazăr, L; Creţu, C; Popa, L; Filiu, P; Ene, V; Burcoş, T; Ifrim, S; Popa, G

    1997-01-01

    A follow-up study of Albendazol effectiveness therapy in human hydatid diseases was carry out using WHO methodology. Albendazole was given at a dose of 10 mg/Kg body/day in cycles of 28 days separated by 14 days without treatment. The efficacy of chemotherapy was evaluated by clinical improvement and changes in the cyst's morphology (detachment and collapse of the cyst membrane and increased density of the cyst fluid). We performed this study in 134 patients with hydatidosis: 17 patients with pre and post surgery treatment, 50 patients with post surgery treatment and 67 patients with chemotherapy only. Albendazole was effective in the hydatid disease; the patients with complex chemotherapy treatment did not report any secondary hydatidosis during the follow-up period (max. 2 years); the patients with exclusive chemotherapy reported 79% successful response, only 21% of them remained with unchanged cyst's size, but with modified internal structure. The therapeutic response depends of the cyst's size and its visceral site. PMID:9462951

  5. In vivo tumor growth inhibition and biodistribution studies of locked nucleic acid (LNA) antisense oligonucleotides

    PubMed Central

    Fluiter, Kees; ten Asbroek, Anneloor L. M. A.; de Wissel, Marit B.; Jakobs, Marja E.; Wissenbach, Margit; Olsson, Håkan; Olsen, Otto; Oerum, Henrik; Baas, Frank

    2003-01-01

    Locked nucleic acids (LNA) are novel high-affinity DNA analogs that can be used as genotype-specific drugs. The LNA oligonucleotides (LNA PO ODNs) are very stable in vitro and in vivo without the need for a phosphorothiolated backbone. In this study we tested the biological fate and the efficacy in tumor growth inhibition of antisense oligonucleotides directed against the gene of the large subunit of RNA polymerase II (POLR2A) that are completely synthesized as LNA containing diester backbones. These full LNA oligonucleotides strongly reduce POLR2A protein levels. Full LNA PO ODNs appeared to be very stable compounds when injected into the circulation of mice. Full LNA PO ODNs were continuously administered for 14 days to tumor-bearing nude mice. Tumor growth was inhibited sequence specifically at dosages from 1 mg/kg/day. LNA PO ODNs appeared to be non-toxic at dosages <5 mg/kg/day. Biodistribution studies showed the kidneys to have the highest uptake of LNA PO ODNs and urinary secretion as the major route of clearance. This report shows that LNA PO ODNs are potent genotype-specific drugs that can inhibit tumor growth in vivo. PMID:12560491

  6. LED phototherapy on midpalatal suture after rapid maxilla expansion: a Raman spectroscopic study

    NASA Astrophysics Data System (ADS)

    Rosa, Cristiane B.; Habib, Fernando Antonio L.; de Araújo, Telma M.; dos Santos, Jean N.; Cangussu, Maria Cristina T.; Barbosa, Artur Felipe S.; de Castro, Isabele Cardoso V.; Soares, Luiz Guilherme P.; Pinheiro, Antonio L. B.

    2015-03-01

    A quick bone formation after maxillary expansion would reduce treatment timeand the biomodulating effects of LED light could contribute for it. The aim of this study was to analyze the effect of LED phototherapy on the acceleration of bone formation at the midpalatal suture after maxilla expansion. Thirty rats divided into 6 groups were used on the study at 2 time points - 7 days: Control; Expansion; and Expansion + LED; and 14 days: Expansion; Expansion + LED in the first week; Expansion and LED in the first and second weeks. LED irradiation occurred at every 48 h during 2 weeks. Expansion was accomplished using a spatula and maintained with a triple helicoid of 0.020" stainless steel orthodontic wire. A LED light (λ850 ± 10nm, 150mW ± 10mW, spot of 0.5cm2, t=120 sec, SAEF of 18J/cm2) was applied in one point in the midpalatal suture immediately behind the upper incisors. Near infrared Raman spectroscopic analysis of the suture region was carried and data submitted to statistical analyzes (p≤0.05). Raman spectrum analysis demonstrated that irradiation increased hydroxyapatite in the midpalatal suture after expansion. The results of this indicate that LED irradiation; have a positive biomodulation contributing to the acceleration of bone formation in the midpalatal suture after expansion procedure.

  7. Gingival response in orthodontic patients: Comparative study between self-ligating and conventional brackets.

    PubMed

    Folco, Alejandra A; Benítez-Rogé, Sandra C; Iglesias, Marina; Calabrese, Diana; Pelizardi, Cristina; Rosa, Alcira; Brusca, Marisa I; Hecht, Pedro; Mateu, María E

    2014-01-01

    Orthodontic brackets contribute to the accumulation of bacterial plaque on tooth surfaces because they hinder oral hygiene. In contrast to conventional brackets, self-ligating brackets do not require additional parts to support the arches, thus improving dental hygiene. The aim of this study was to compare the gingival response in orthodontic patients wearing self-ligating or conventional brackets. A sample of 22 patients aged 16 to 30 years was divided into two groups: Group A, treated with selfligating brackets (Damon system) and Group B, treated with conventional brackets (Roth technique). The following were assessed during the treatment: Plaque Index (PI), Gingival Index (GI) and Probing Depth (PD), and sub-gingival samples were taken from teeth 14/24 for microbiological observation. No statistically significant difference was found between Groups A and B; p>0.05 (sign-ranked) or between PI, GI and PD at the different times (Friedman's Analysis of Variance), even though the indices were found to increase at 14 days, particularly for self-ligating brackets. The quantity and quality of microorganisms present were compatible with health on days 0, 28 and 56. As from day 14 there is a predominance of microbiota compatible with gingivitis in both groups. In the samples studied, orthodontic treatment increases bacterial plaque and inflammatory gingival response, but gingival-periodontal health can be maintained with adequate basic therapy. Self-ligating and conventional brackets produced similar gingival response. PMID:25560690

  8. Bioequivalence study of two oral tablet formulations containing tenofovir disoproxil fumarate in healthy volunteers.

    PubMed

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Tenofovir disoproxil fumarate (TDF, CAS 147127-20-6) is a nucleotide reverse transcriptase inhibitor which is indicated in combination with other antiretroviral agents for the management of HIV-1 infection. The objective of this study was to compare the rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 300 mg of TDF and the innovator product. A randomized, single-center, open-label, single-dose, two-way crossover bioequivalence study in 40 healthy adult subjects was conducted. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 48 h and plasma levels of tenofovir (TFV) were determined by a validated HPLC assay. Rate and extent of absorption were similar between products. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence between the two formulations using the equivalence interval of 80 and 125%. In healthy subjects, the point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 0.99 (0.92-1.02), 0.99 (0.95-1.03) and 0.93 (0.85-1.02), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21355446

  9. Study of influence on harvesting point in Brazilian Tommy Atkins mangoes submitted to gamma radiation

    NASA Astrophysics Data System (ADS)

    Sabato, S. F.; Cruz, J. N.; Rela, P. R.; Broisler, P. O.

    2009-07-01

    Brazil is a great producer of tropical fruits including mangoes. Among several purposes gamma radiation can be applied as phytosanitary treatment. This is well studied in scientific papers and more recently demonstrated through commercial advances like bilateral protocols established between India and USA. The whole experiment evolved two parts where each of them used fruits from different maturity stages (stages 2 and 3). This experiment was carried out with around 300 fruits in each part of the study. The main objective was to get the experience close to commercial conditions. The irradiation was realized in Multipurpose Cobalt-60 source belonging to IPEN-CNEN/SP (developed in house by own technology). The absorbed doses were 0.2, 0.5 and 0.75 kGy. After irradiation all fruits were kept at 12 °C in acclimatized chamber during 14 days. After this period the fruits were brought to environmental conditions (25 °C) for around 14 more days of duration. These conditions were established to simulate the exportation conditions from Brazil to distant countries. Physical-chemical analysis (pH, titrable acidity, total soluble solids (°Brix) and texture) as well as visual observation (mass loss, rotting, internal and skin color) were evaluated. The results from this experiment could demonstrate that the characteristics of the mangoes are more dependent on time and temperature storage rather than irradiation.

  10. Phytochemical Screening and Acute Oral Toxicity Study of Java Tea Leaf Extracts

    PubMed Central

    Safinar Ismail, Intan; Azam, Amalina Ahmad; Abas, Faridah; Shaari, Khozirah; Sulaiman, Mohd Roslan

    2015-01-01

    The term Java tea refers to the decoction of Orthosiphon stamineus (OS) Benth (Lamiaceae) leaves, which are widely consumed by the people in Europe and South East Asian countries. The OS leaves are known for their use in traditional medicinal systems as a prophylactic and curative agent for urinary stone, diabetes, and hypertension and also as a diuretic agent. The present study was aimed at evaluating its possible toxicity. Herein, the major phytochemical constituents of microwave dried OS leaf, which is the common drying process for tea sachets in the market, were also identified. The acute oral toxicity test of aqueous, 50% aqueous ethanolic, and ethanolic extracts of OS was performed at a dose of 5000 mg/Kg body weight of Sprague-Dawley rats. During the 14-day study, the animals were observed for any mortality, behavioral, motor-neuronal abnormalities, body weight, and feed-water consumption pattern. The hematological and serum biochemical parameters to assess the kidney and liver functions were carried out, along with the histological analysis of these organs. It was found that all microwave dried OS leaf extracts did not cause any toxic effects or mortality at the administered dose. No abnormality was noticed in all selected parameters in rats of both sexes as compared with their respective control groups. Thus, the possible oral lethal dose for microwave dried Java tea leaves is more than 5000 mg/Kg body weight. PMID:26819955

  11. An open-label study of naftifine hydrochloride 1% gel in the treatment of tinea versicolor.

    PubMed

    Gold, Michael H; Bridges, Tancy; Avakian, Edward; Plaum, Stefan; Pappert, Eric J; Fleischer, Alan B; Hardas, Bhushan

    2011-01-01

    Tinea versicolor (TV) is a superficial cutaneous fungal infection characterized by cutaneous pigment changes, pruritus, scaling, and erythema. This open-label, single-center pilot study evaluated the efficacy and safety of naftifine 1% gel applied twice daily for 2 weeks in 10 men and women (median age 38 years) with TV. Baseline mycology status was determined by potassium hydroxide (KOH) and microscopy and clinical symptom severity (CSS) scored by the investigator using a 0 to 9 scale (0=absent, 9=worst). Patients applied naftifine HCI 1% gel to the affected area twice daily for 14 days. They returned for follow-up efficacy and safety assessments at the end of treatment (week 2), 2 weeks after treatment (week 4), and 6 weeks after treatment (week 8). All patients had a positive mycology at baseline; one was KOH negative at week 2, two were negative at week 4, and five (50%) were negative at week 8. Mean investigator total CSS score decreased from a baseline value of 4.7 to 3.2 at week 2 (32% improvement), 2.6 at week 4 (45% improvement), and 2.7 at week 8 (43% improvement). The patients rated their symptoms to be improved at all follow-up visits. There were no treatment-related adverse events during the study. These results suggest that naftifine 1% gel is a safe and efficacious topical treatment for TV. PMID:22165042

  12. Epidemiology of Clostridium difficile infection: results of a hospital-based study in Krakow, Poland.

    PubMed

    Czepiel, J; Kędzierska, J; Biesiada, G; Birczyńska, M; Perucki, W; Nowak, P; Garlicki, A

    2015-11-01

    Over the past two decades Clostridium difficile infection (CDI) has appeared as a major public health threat. We performed a retrospective study based on the records of patients hospitalized for CDI at the University Hospital in Krakow, Poland, between 2008 and 2014. In the study period, CDI occurred in 1009 individuals. There were 790 (78%) individuals who developed infection only once, whereas 219 (22%) developed infection more than once. The percentage of deaths within 14 days of CDI confirmation was 2·4%, with a mean age of 74·2 ± 15·9 years. Crude mortality was 12·9% in medical wards, 5·6% for surgical wards and 27·7% in the ICU setting. The time span between diagnosis and death was 5·1 days on average. Between 2008 and 2012 a 6·5-fold increase of CDI frequency with a posterior stabilization and even reduction in 2013 and 2014 was observed. According to the data analysed, 2/3 patients in our population developed CDI during their hospitalization even though they were admitted for different reasons. Medical wards pose a significantly higher risk of CDI than the surgical ones. Age is a risk factor for CDI recurrence. In the case of patients who died, death occurred shortly after diagnosis. The first CDI episode poses much higher risk of mortality than the consecutive ones. PMID:25858553

  13. Mirtazapine in amphetamine detoxification: a placebo-controlled pilot study.

    PubMed

    Kongsakon, Ronnachai; Papadopoulos, Konstantinos I; Saguansiritham, Rapeepun

    2005-09-01

    The present study aimed to assess the safety and efficacy of mirtazapine in amphetamine detoxification in a 14-day randomized, placebo-controlled pilot trial in a Thai population. Subjects retained at a Specialized Probation Center, Department of Probation, Ministry of Justice, Thailand (n=20), who met DSM-IV criteria for amphetamine dependence and the inclusion criteria of the study, were randomized for either mirtazapine treatment or placebo. Efficacy was assessed by the Amphetamine Withdrawal Questionnaire (AWQ) for amphetamine withdrawal symptoms and the Montgomery-Asberg Depression rating scale (MADRS) for depression. Mirtazapine safety was assessed by interview during each follow-up period on days 3 and 14 after treatment. Nine subjects were randomized to the mirtazapine group and 11 to the placebo group. Among the initial 20 subjects, 16 (seven in the mirtazapine and nine in the placebo group) completed the study. There were significant improvements in the total AWQ score changes in the mirtazapine group versus placebo both at days 3 (P<0.005) and 14 (P<0.030). Significant improvements in favour of mirtazapine were also seen in the hyperarousal and the anxiety subscale score changes at days 3 (P<0.029) and 14 (P<0.018), respectively. No significant differences were seen (P>0.05) in the MADRS scores changes within or between the groups. Mild adverse events, such as headache, sedation, nausea and vomiting, were reported. In conclusion, despite its small sample size, this randomized, placebo-controlled pilot trial lends support to the hypothesis that mirtazapine may be an option in the meager armamentarium of amphetamine detoxification treatment. PMID:16096515

  14. Study design of the International Stroke Trial (IST), baseline data, and outcome in 984 randomised patients in the pilot study.

    PubMed Central

    1996-01-01

    BACKGROUND AND PURPOSE: To test the design and feasibility of a very large randomised controlled trial assessing the efficacy and safety of antithrombotic therapy started within 48 hours of symptom onset in patients with suspected acute ischaemic stroke. DESIGN: Randomised controlled multicentre open study, with a 3 x 2 factorial design, allocating patients to: medium dose subcutaneous heparin (12,500 units twice per day), versus low dose subcutaneous heparin (5000 units twice per day) versus no heparin; and aspirin (300 mg daily) versus no aspirin. Treatment was given for two weeks or until discharge from hospital if sooner. RESULTS: 984 patients were randomised. CT was performed in 924 (94%) (before randomisation in 622/984 (63%). Within 14 days: 97 patients had died (10%), 30 (3.0%) had a fatal or non-fatal recurrent ischaemic stroke, nine (0.9%) had fatal or non-fatal recurrent stroke due to intracranial haemorrhage, and eight (0.8%) had a fatal or non-fatal pulmonary embolus. At six months, vital status was known for 975 patients (99%), of whom 210 (22%) were dead, 373 (38%) were alive but dependent, and 225 (23%) were independent but not fully recovered. CONCLUSIONS: The trial procedures proved practicable and a wide variety of patients were recruited. Sample size calculation based on the event rates confirmed that reliable evidence on the balance of risk and benefit of early antithrombotic therapy might require a study with more than 20,000 patients. Recruitment rates in the pilot study indicated that if about 200 hospitals participated, recruitment could be completed by 1997. PMID:8774398

  15. Pre-clinical and Clinical Safety Studies of CMX-2043: A Cytoprotective Lipoic Acid Analogue for Ischaemia–Reperfusion Injury

    PubMed Central

    Kates, Steven A; Lader, Alan S; Casale, Ralph; Beeuwkes, Reinier

    2014-01-01

    CMX-2043 is an α-lipoic acid analogue targeted to reduction of cellular injury and organ damage due to ischaemia–reperfusion injury (IRI). It has been shown to be effective in a rat model of cardiac IRI. The studies here reported evaluate its safety and pharmacokinetic profile in preparation for human clinical studies in procedures associated with IRI. Safety and tolerability were tested in standard pre-clinical in vitro and animal models and in a Phase 1 human clinical trial. CMX-2043 did not bind to a wide range of receptors and specific targets at approximately 4 μg/mL (10 μM). It was not mutagenic by Ames assay, did not produce chromosome aberrations in Chinese hamster ovary (CHO) cells, and was negative for clastogenic potential. Toxicological studies in rats including both single and 14-day repeat intravenous doses and in dogs (single intravenous dose) with a 2-week recovery period were conducted. The NOAEL in rats and dogs was 30 and >10 mg/kg, respectively. No serious adverse events were reported in a placebo-controlled, sequential dose escalation Phase 1 clinical trial. The low toxicity in the pre-clinical studies and the absence of adverse events in the Phase 1 trial have supported investigation of CMX-2043 in a human efficacy trial. PMID:24751172

  16. Socioeconomic status and duration and pattern of sickness absence. A 1-year follow-up study of 2331 hospital employees

    PubMed Central

    2010-01-01

    Background Sickness absence increases with lower socioeconomic status. However, it is not well known how this relation depends on specific aspects of sickness absence or the degree to which socioeconomic differences in sickness absence may be explained by other factors. The purpose of the study was to examine differences in sickness absence among occupational groups in a large general hospital; how they depend on combinations of frequency and duration of sickness absence spells; and if they could be explained by self-reported general health, personal factors and work factors. Methods The design is a 1-year prospective cohort study of 2331 hospital employees. Baseline information include job title, work unit, perceived general health, work factors and personal factors recorded from hospital administrative files or by questionnaire (response rate 84%). Sickness absence during follow-up was divided into short (1-3 days), medium (4-14 days) and long (>14 days) spells, and into no absence, "normal" absence (1-3 absences of certain durations) and "abnormal" absence (any other absence than "normal"). Socioeconomic status was assessed by job titles grouped in six occupational groups by level of education (from doctors to cleaners/porters). Effects of occupational group on sickness absence were adjusted for significant effects of age, gender, general health, personal factors and work factors. We used Poisson or logistic regression analysis to estimate the effects of model covariates (rate ratios (RR) or odds ratios (OR)) and their 95% confidence intervals (CI). Results With a few exceptions sickness absence increased with decreasing socioeconomic status. However, the social gradient was quite different for different types of sickness absence. The gradient was strong for medium spells and "abnormal" absence, and weak for all spells, short spells, long spells and "normal" absence. For cleaners compared to doctors the adjusted risk estimates increased 4.2 (95% CI 2.8-6.2) and

  17. A Pilot Chemical and Physical Stability Study of Extemporaneously Compounded Levetiracetam Intravenous Solution.

    PubMed

    Raphael, Chenzira D; Zhao, Fang; Hughes, Susan E; Juba, Katherine M

    2015-01-01

    Levetiracetam is a commonly used antiepileptic medication for tumor-related epilepsy. However, the 100 mL intravenous (IV) infusion volume can be burdensome to imminently dying hospice patients. A reduced infusion volume would improve patient tolerability. The purpose of this study was to evaluate the stability of 1000 mg/25 mL (40 mg/mL) levetiracetam IV solution in sodium chloride 0.9%. We prepared levetiracetam 40 mg/mL IV solution and added it to polyvinyl chloride (PVC) bags, polyolefin bags, and polypropylene syringes. Triplicate samples of each product were stored at refrigeration (2-8°C) and analyzed on days 0, 1, 4, 7, and 14. Samples were subjected to visual inspection, pH measurement, and stability-indicating high-performance liquid chromatography (HPLC) analysis. Over the 2-week storage period, there was no significant change in visual appearance or pH for any of the stability samples. The HPLC results confirmed that all stability samples retained 94.2-101.3% of initial drug concentration and no degradation products or leachable material from the packaging materials were observed. We conclude that levetiracetam 1000 mg/25 mL IV solution in sodium chloride 0.9% is physically and chemically stable for up to 14 days under refrigeration in polypropylene syringes, PVC bags, and polyolefin bags. PMID:26654410

  18. Evaluation of biomarkers following autologous osteochondral transplantation in the equine stifle joint - An experimental study.

    PubMed

    Tuska, Pál; Tóth, Balázs; Vásárhelyi, Gábor; Hangody, László; Papp, Miklós; Bodó, Gábor

    2016-06-01

    The purpose of this study was to evaluate changes in biomarker and synovial parameters following autologous osteochondral transplantation (AOT) in the equine stifle joint, to test the hypothesis whether synovial parameters would show significant differences at selected time points following the surgery (at days 3, 14, 60 and 180) compared to baseline level (at day 0). Surgical intervention was performed in both stifles of nine horses (n = 18). The joints were randomly assigned to operated and sham-operated groups. Grafts 8.5 mm in diameter were harvested from the femoropatellar (FP) joint under arthroscopic control and the medial femorotibial (MFT) joints had AOT using mosaicplasty (MP) instrumentation, while the sham FP and sham MFT joints underwent arthroscopy and miniarthrotomy without transplantation, respectively. Synovial fluid (SF) parameters were evaluated at days 4, 14, 60 and 180. Data were analysed by two-way repeated- measures analysis of variance (ANOVA), and P < 0.05 was considered significant. During the first 10-14 days after surgery, lameness of degree 2-3/5 [American Association of Equine Practitioners (AAEP) scores] was present, which disappeared after 60 days. Joints with transplantation showed significant increases in synovial white blood cell count (WBC), total protein (TP), substance P, C1,2C and CS846 epitope concentration at day 3 compared to baseline and shamoperated joints (P < 0.05). These parameters returned to the baseline values by two months after surgery and remained within normal levels at 6 months postoperatively. PMID:27342088

  19. Complicated grief after traumatic loss: a 14-month follow up study.

    PubMed

    Kersting, Anette; Kroker, K; Steinhard, J; Lüdorff, K; Wesselmann, U; Ohrmann, P; Arolt, V; Suslow, T

    2007-12-01

    The traumatic loss of an unborn child after TOP due to fetal malformation and/or severe chromosomal disorders in late pregnancy is a major life-event and a potential source of serious psychological problems for those women. To obtain information on the course of grief following a traumatic loss, 62 women who had undergone TOP between the 15th and 32nd gestational week were investigated in a longitudinal study design and compared with 65 women after spontaneous delivery of a full-term healthy child. Grief, posttraumatic stress, depression, anxiety and psychiatric disorders were evaluated 14 days, 6 months and 14 months after the event, implementing validated self-report and clinician rated instruments. Compared to women after spontaneous delivery, women after induced TOP were significantly more stressed regarding all psychological outcomes at all three measuring points. Especially, 14 months after TOP 13.7% of the women fulfilled all criteria of a complicated grief diagnoses following Horowitz et al. (1997, Am J Psychiat 154:7904-7910). 16.7% were diagnosed as having a manifest psychiatric disorder according to DSM-IV. All in all, 25% of these women were critically affected by the traumatic loss. TOP for fetal anomaly is to be seen as a major life event, which causes complicated grief reactions and psychiatric disorders for a substantial number of women. PMID:17629729

  20. Evaluation of the effect of oral omeprazole on canine cerebrospinal fluid production: A pilot study.

    PubMed

    Girod, M; Allerton, F; Gommeren, K; Tutunaru, A C; de Marchin, J; Van Soens, I; Ramery, E; Peeters, D

    2016-03-01

    Administration of omeprazole by ventriculo-cisternal perfusion or intravenously has been shown to decrease cerebrospinal fluid (CSF) production in dogs and rabbits. Oral omeprazole has consequently been recommended to reduce CSF production in dogs with conditions in which clinical signs may be attributable to an accumulation of CSF in the central nervous system (e.g. hydrocephalus, syringomyelia). The albumin quotient (QAlb), the ratio between CSF and serum albumin concentration, has been proposed as a reliable means to evaluate CSF production; decreasing CSF production should cause an increase in QAlb. The aims of this study were to assess the effect of oral administration of omeprazole on QAlb in dogs and to compare two methods to assess CSF albumin concentration. Fifteen healthy Beagle dogs received omeprazole (1.2 mg/kg/day) orally for 14 days; CSF and blood were obtained before and after treatment. CSF albumin concentrations were evaluated by nephelometry and high-resolution protein electrophoresis. Regardless of the method used for measuring albumin, QAlb did not change significantly following oral omeprazole administration, suggesting that CSF production in healthy dogs may not be affected by chronic oral therapy with omeprazole. PMID:26852945

  1. Studies of Hard and Soft Tissue Elemental Compositions in Mice and Rats Subjected to Simulated Microgravity

    NASA Astrophysics Data System (ADS)

    Mehta, Rahul; Lane, Ryan A.; Fitch, Hannah M.; Ali, Nawab; Soulsby, Michael; Chowdhury, Parimal

    2009-03-01

    Microgravity has profound effects on skeletal as well as other body systems. To investigate the effect of microgravity, we have used a NASA validated Hind-limb suspension (HLS) animal model of simulated weightlessness. Groups of mice and rats were subjected to hind limb suspension between 1 and 14 days while the control groups were maintained without suspension for the same duration. To study the effect of diet, some groups of animals were fed on a special diet with defined composition. At term, the animals were sacrificed and the tibia, femur, and skull bones were collected. In addition, soft tissues from pancreas and muscles were also collected. All of the bones and tissues samples were analyzed for elemental analysis using Energy Dispersive Spectroscopy (EDS) equipped on a Scanning Electron Microscope (SEM). In the EDS, 10-20 keV electrons bombarded the samples and a Si (Li) detector measured K-, L- and M-shell x-rays. Independently, X-Ray Fluorescence (XRF) provided the data for comparison and normalization. Flame software, with Fuzzy Logic, was used to form elemental ratios. Elemental analysis of bone samples indicated a variation in the compositional ratios of calcium, potassium, oxygen and carbon in the leg bones and skulls of the HLS versus control specimens. These variations showed dependence on sample position in the bone.

  2. In vivo studies of low level laser (light) therapy for traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Xuan, Weijun; Wu, Qiuhe; Huang, Ying-Ying; Ando, Takahiro; Huang, Liyi; Hamblin, Michael R.

    2012-03-01

    Low-level laser (or light) therapy (LLLT) is attracting growing interest to treat both stroke and traumatic brain injury (TBI). The fact that near-infrared light can penetrate into the brain allows non-invasive treatment to be carried out with a low likelihood of treatment-related adverse events. It is proposed that red and NIR light is absorbed by chromophores in the mitochondria of cells leading to changes in gene transcription and upregulation of proteins involved in cell survival, antioxidant production, collagen synthesis, reduction of chronic inflammation and cell migration and proliferation. We developed a mouse model of controlled cortical impact (CCI) TBI and examined the effect of 0, 1, 3, and 14 daily 810-nm CW laser treatments in the CCI model as measured by neurological severity score and wire grip and motion test. 1 laser Tx gave a significant improvement while 3 laser Tx was even better. Surprisingly 14 laser Tx was no better than no treatment. Histological studies at necropsy suggested that the neurodegeneration was reduced at 14 days and that the cortical lesion was repaired by BrdU+ve neural progenitor (stem) cells at 28 days. Transcranial laser therapy is a promising treatment for acute (and chronic TBI) and the lack of side-effects and paucity of alternative treatments encourages early clinical trials.

  3. A prospective cohort study of the use of domiciliary intravenous antibiotics in bronchiectasis

    PubMed Central

    Bedi, Pallavi; Sidhu, Manjit K; Donaldson, Lucienne S; Chalmers, James D; Smith, Maeve P; Turnbull, Kim; Pentland, Joanna L; Scott, Jenny; Hill, Adam T

    2014-01-01

    Background: We introduced domiciliary intravenous (IV) antibiotic therapy in patients with bronchiectasis to promote patient-centred domiciliary treatment instead of hospital inpatient treatment. Aim: To assess the efficacy and safety of domiciliary IV antibiotic therapy in patients with non-cystic fibrosis bronchiectasis. Methods: In this prospective study conducted over 5 years, we assessed patients’ eligibility for receiving domiciliary treatment. All patients received 14 days of IV antibiotic therapy and were monitored at baseline/day 7/day 14. We assessed the treatment outcome, morbidity, mortality and 30-day readmission rates. Results: A total of 116 patients received 196 courses of IV antibiotics. Eighty courses were delivered as inpatient treatment, 32 as early supported discharge (ESD) and 84 as domiciliary therapy. There was significant clinical and quality of life improvement in all groups, with resolution of infection in 76% in the inpatient group, 80% in the ESD group and 80% in the domiciliary group. Morbidity was recorded in 13.8% in the inpatient group, 9.4% in the ESD group and 14.2% in the domiciliary IV group. No mortality was recorded in either group. Thirty-day readmission rates were 13.8% in the inpatient group, 12.5% in the ESD group and 14.2% in the domiciliary group. Total bed days saved was 1443. Conclusion: Domiciliary IV antibiotic therapy in bronchiectasis is clinically effective and was safe in our cohort of patients. PMID:25340361

  4. Decreased human circadian pacemaker influence after 100 days in space: a case study

    NASA Technical Reports Server (NTRS)

    Monk, T. H.; Kennedy, K. S.; Rose, L. R.; Linenger, J. M.

    2001-01-01

    OBJECTIVE: The objectives of this study were (1) to assess the circadian rhythms and sleep of a healthy, 42-year-old male astronaut experiencing microgravity (weightlessness) for nearly 5 months while living aboard Space Station Mir as it orbited Earth and (2) to determine the effects of prolonged space flight on the endogenous circadian pacemaker, as indicated by oral temperature and subjective alertness rhythms, and their ramifications for sleep, alertness, and performance. METHODS: For three 12- to 14-day blocks of time (spread throughout the mission), oral temperatures were taken and subjective alertness was self-rated five times per day. Sleep diaries and performance tests were also completed daily during each block. RESULTS: Examination of the subject's circadian alertness and oral temperature rhythms suggested that the endogenous circadian pacemaker seemed to function quite well up to 90 days in space. Thereafter (on days 110-122), the influence of the endogenous circadian pacemaker on oral temperature and subjective alertness circadian rhythms was considerably weakened, with consequent disruptions in sleep. CONCLUSIONS: Space missions lasting more than 3 months might result in diminished circadian pacemaker influence in astronauts, leading to eventual sleep problems.

  5. Identification and survival studies of Mycobacterium tuberculosis within Laboratory-Fermented bovine milk

    PubMed Central

    2014-01-01

    Background Mycobacterium tuberculosis and Mycobacterium bovis are the classic agents causing tuberculosis (TB) in humans and animals respectively. Transmission of tuberculous bacteria to humans usually occurs by inhalation of aerosols containing droplets of tubercle bacilli or via consumption of contaminated foods and drinks, primarily milk. The practice of milk pooling, including from cows with TB of the udder, further exacerbates the situation by rendering the whole milk supply infective. The simultaneous presence of indigenous lactic acid bacteria (LAB) in Mycobacterium-contaminated milk is believed to confer protective effect when the milk is adequately fermented. This study assessed the effect of LAB on the viability of mycobacteria in inherently contaminated pool of raw milk during fermentation as a function of time. Findings Growth was obtained in the pooled raw milk culture, and identified to be M. tuberculosis. This M. tuberculosis growth was undetectable in the milk culture by day 7 as assessed by plating serial dilutions of the milk culture for up to 14 days. Conclusions Some LAB species appear to show inhibitory effect on tubercle bacilli. If proven by more rigorous, controlled experimental results regarding such effect, selected LAB (with proven safety and efficacy) may have potential applications as anti-mycobacterial agents. PMID:24666844

  6. Wound healing studies of skin incisions in animal models: laser soldering versus other bonding methods

    NASA Astrophysics Data System (ADS)

    Simhon, David; Vasilyev, Tamar; Brosh, Tamar; Nevo, Zvi; Tennenbaum, Tamar; Kariv, Naam; Katzir, Abraham

    2003-06-01

    In the past, we have successfully used laser soldering for bonding cuts in the skin of medium and large size animal models. In this work, we have used the same method for bonding cuts on the backs of rabbits and mature pigs model. Cuts were created in dorsally depilated skins of rabbits and mature pigs. 47% bovine serum albumin (BSA) solder was applied onto the approximated edges of each cut, using a special approximation device. An infrared fiberoptic CO2 laser system was used to heat a spot on the cut, under good temperature control, to 65°C for 10 seconds. Other glued or sutured cuts, served as controls. Immediate tensile strength measurements were done on bonded incisions in rabbit skins. We found that laser soldered incisions exhibited similar strength to one bonded by cayanoacrylate glue. No dehiscence of wound edges was found in both treatments. The laser soldering procedure was 25% faster then suturing. A 14-day follow up of the bonded pig skin incisions was carried out, using punch biopsies. We found better aesthetic appearance of the soldered incisions. We observed better and faster wound repair in the laser-soldered scars, using histological and molecular staining. The temperature controlled laser soldering offers immediate strength similar to that of cyanoacrylate glues and better aesthetic and wound healing properties, in comparison to suturing techniques. We have clearly demonstrated the potential of this novel technique, which will pave thw way for clinical studies.

  7. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    NASA Technical Reports Server (NTRS)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  8. Antimicrobial effect of chlorhexidine digluconate in dentin: In vitro and in situ study

    PubMed Central

    Borges, Fátima Maria Cavalcante; de Melo, Mary Anne Sampaio; Lima, Juliana Paiva Marques; Zanin, Iriana Carla Junqueria; Rodrigues, Lidiany Karla Azevedo

    2012-01-01

    Aim: The aim of this study was to evaluate a very short-term in vitro and in situ effect of 2% chlorhexidine-digluconate-based (CHX) cavity cleanser on the disinfection of dentin demineralized by cariogenic bacteria. Materials and Methods: Human dentin slabs were randomly allocated and used in 2 distinct phases, in vitro and in situ, for obtaining demineralized dentin. In vitro, the slabs (n=15) were immersed for 5 days in BHI broth inoculated with Streptococcus mutans CTT 3440. In situ, a double-blind design was conducted in one phase of 14 days, during which 20 volunteers wore palatal devices containing two human dental dentin slabs. On 5th day in vitro and 14th day in situ, the slabs were allocated to the two groups: Control group (5 μl of 0.9% NaCl solution) and CHX group (5 μl of 2% chlorhexidine digluconate solution, Cavity Cleanser™ BISCO, Schaumburg, IL, EUA), for 5 minutes. The microbiological analyses were performed immediately before and after the treatments. Results: The log reductions means found for CHX treatment on tested micro organisms were higher when compared to Control group either in vitro or in situ conditions. Conclusions: Our results showed that CHX was effective in reducing the cultivable microbiota in contaminated dentin. Furthermore, although the use of chlorhexidine-digluconate-based cavity disinfectant did not completely eliminate the viable microorganisms, it served as a suitable agent to disinfect tooth preparations. PMID:22368330

  9. A morphological study of the effects of ozone on rat lung. I. Short-term exposure.

    PubMed

    Hiroshima, K; Kohno, T; Owada, H; Hayashi, Y

    1987-12-01

    In order to determine the effects of ozone on lungs and the course of cell renewal after damage, young male rats were exposed to 3 ppm of ozone for 4 hr. They were killed at 1, 6, 12, and 18 hr and 1, 2, 3, 4, 7, and 14 days after exposure. One hour before the killing, dividing cells were labeled with tritiated thymidine. Type 1 cells of centriacinar location and bronchiolar cells were severely damaged after exposure. Labeling indices of type 2 cells and bronchiolar nonciliated cells increased 1 day after exposure. Hyperplasia of type 2 cells and bronchiolar nonciliated cells was observed 2 and 3 days after exposure. Ciligenesis of bronchiolar ciliated cells occurred 4 days after exposure. Our study shows that injured type 1 cells are repaired by proliferation of type 2 cells and that injured bronchiolar ciliated and Clara cells are repaired by proliferation of bronchiolar nonciliated cells. These undifferentiated cells are probably progenitors of ciliated cells and Clara cells, and some nonciliated cells are in a transitional form between nonciliated and type 2 cells. PMID:3678465

  10. Study of thermal effect on breast tumor metabolism and growth using metabonomics.

    PubMed

    Dai, Guangchen; Jia, Wei; Hu, Xiaofang; Xu, Lisa X

    2013-01-01

    In this study, the biological effects of long-term mild hyperthermia treatment on tumor metabolism and growth were investigated using 4T1 murine mammary carcinoma, a common animal model of metastatic breast cancer. Periodic thermal treatment (12 hours per day) was applied to tumors and carried out for 3 days, 7 days, 14 days, and 21 days, respectively. The metabolites of tumor tissues were analyzed by gas chromatography-mass spectrometry. The results showed that the growth rate of thermally treated tumors was inversely related to the abundance of long chain fatty acids and acyl glycerols identified in tumor tissues. In the first two weeks, the growth of thermally treated tumors was significantly inhibited, while there was an obvious accumulation of long chain fatty acids and acyl glycerols in tumor tissues. In the third week, the thermally treated tumors adapted to the thermal environment and started to regrow, while the abundance of long chain fatty acids and acyl glycerols decreased in the tumor tissues. These observations suggested that the blockade of long chain fatty acid synthesis during mild hyperthermia treatment of tumors could improve the long-term treatment effect by limiting the supply of substance and energy for tumor re-growth. PMID:24110083

  11. Effects of ethylene dibromide on hydra oligactis: parent and offspring toxicity study

    SciTech Connect

    Wilson, B.A.; Adams, J.A.

    1988-04-01

    Ethylene Dibromide (EDB) has become increasingly prevalent in the environment due to its uses as soil, fruit, and grain fumigants, lead scavengers in petrol, and industrial solvent. Because of its increasing environmental prevalence and its proposed toxic effects of EDB on Hydras, parents (P1) which have been pre-exposed to an established sublethal concentration for 14 days. The effect of nonexposed offspring (F1/P2) taken from pre-exposed parents (P1) versus their untreated offspring (F2) will also be evaluated. This mortality study revealed that the LC50 of both parents and F1's shifted from 50 mg/L, to 106.25 mg/L and 118.75 mg/L respectively, which suggest that exposed Hydras possibly become more tolerant to EDB. In the F2 generation, after 48 and 72 hrs 10% mortality was observed in the 200 mg/L group, 30% at 250 mg/L and 20% at 300 mg/L which indicated that the resistance to EDB toxicity is inheritable. There is also a strong dose-response correlation between EDB concentration and mortality.

  12. FT-Raman spectroscopy study of organic matrix degradation in nanofilled resin composite.

    PubMed

    Soares, Luís Eduardo Silva; Nahórny, Sídnei; Martin, Airton Abrahão

    2013-04-01

    This in vitro study evaluated the effect of light curing unit (LCU) type, mouthwashes, and soft drink on chemical degradation of a nanofilled resin composite. Samples (80) were divided into eight groups: halogen LCU, HS--saliva (control); HPT--Pepsi Twist®; HLC--Listerine®; HCP--Colgate Plax®; LED LCU, LS--saliva (control); LPT--Pepsi Twist®; LLC--Listerine®; LCP--Colgate Plax®. The degree of conversion analysis and the measure of the peak area at 2,930 cm-1 (organic matrix) of resin composite were done by Fourier-transform Raman spectroscopy (baseline, after 7 and 14 days). The data were subjected to multifactor analysis of variance (ANOVA) at a 95% confidence followed by Tukey's HSD post-hoc test. The DC ranged from 58.0% (Halogen) to 59.3% (LED) without significance. Differences in the peak area between LCUs were found after 7 days of storage in S and PT. A marked increase in the peak intensity of HLC and LLC groups was found. The soft-start light-activation may influence the chemical degradation of organic matrix in resin composite. Ethanol contained in Listerine® Cool Mint mouthwash had the most significant degradation effect. Raman spectroscopy is shown to be a useful tool to investigate resin composite degradation. PMID:23388411

  13. Carotid endarterectomy under regional analgesia:a retrospective study (1988-1999).

    PubMed

    Singh, S M; Rajmohan, T; Juneja, R; Mehta, Y; Trehan, N

    2001-01-01

    The procedure of carotid endarterectomy is more or less standardized. Controversies persist on many technical issues, one of which is general versus regional anaesthesia. We retrospectively evaluated the influence of regional analgesia on perioperative complications, the hospital stay and the perioperative mortality after carotid endarterectomy in 53 patients. All the patients in the study received deep cervical block regional anaesthesia (Winne's technique) for carotid endarterectomy. Indications for surgery included transient ischaemic haemodynamically significant stenosis. Shunt was used in 7 cases (13.2%). General anaesthesia was supplemented in 2 patients (3.8%). There was no perioperative mortality. Permanent non-fatal neurologic deficit occurred in 1 patient (1.9%) and temporary neurologic Deficit occurred in 1 patient (1.9%). The mean ICU stay was 1.85 (+/-0.82) days and the hospital stay was 5.2 (+/-1.14) days. On the basis of our data we believe that under regional anaesthesia carotid endarterectomy can be performed with acceptable complications and that regional anaesthetic technique is safe and well tolerated by the patients. PMID:17851155

  14. Acute and Sub-Acute Toxicity Studies of Plumeria alba Linn. (Apocynaceae) Hydroalcoholic Extract in Rat

    PubMed Central

    Tessou, K. Z.; Lawson-Evi, P.; Metowogo, K.; Diallo, A.; Eklu-Gadegkeku, K.; Aklikokou, K.; Gbeassor, M.

    2013-01-01

    Plumeria alba Linn (Apocynaceae) is used in Togolese traditional medicine to treat diabetes mellitus and wounds. The present investigation was carried out to evaluate the toxicity of hydroalcoholic extract of Plumeria alba roots in Sprague Dawley rats. The acute toxicity test was conducted by administering orally dose of 5 g/Kg. General behavior and mortality were examined for up to 14 days. The sub-acute toxicity test was performed by daily gavage at 250, 500 and 1000 mg/Kg for 28 days. Body weight and blood glucose were measured weekly. Hematological and biochemical parameters, relative organ weight were determined at the end of the 28 days administration. In acute study, no adverse effect of the extract was observed at 5.0 g/Kg. Sub-acute oral administration of the extract at the dose up to 1000 mg/Kg did not induce death or significant changes in body weight, relative weight of vital organs, hematological parameters and was not associated with liver and kidney toxicity. PMID:24711763

  15. [Study on standard of safe application of thiamethoxam on GAP of Lonicera japonica].

    PubMed

    Liu, Ya-nan; Li, Yong; Dong, Jie; Zhang, Jin-liang; Wang, Pin-shu; Ding, Wan-long

    2015-09-01

    The paper is aimed to establish a method of residue analysis for thiamethoxam and to study its degradation dynamic and final residue and its standard of safe application of thiamethoxam on Lonicera japonica. Samples extracted with methanol by ultrasonication were purified with dichloromethane by liquid-liquid extraction and SPE column and analysed by HPLC-UV. The results showed that average rate was 84.91%-94.44% and RSD 1.74%-4.96% with addition of thiamethoxam in respectively diverse concentration, which meets inspection requirement of pesticide residue. Two kinds of dosages of thiamethoxam were treated- varying from recommended dosage (90 g x hm(-2)) to high dosage (135 g x hm(-2)), Results of two years test showed that thiamethoxam was degraded more than 90% seven days after application and the half - life period of thiamethoxam was 1.54-1.66 d. The digestion rate of thiamethoxam was fast in the L. japonica. The recommended MRL of thiamethoxam in the L. japonica is 0.1 mg x kg(-1), the dosage of 25% thiamethoxam WDG from 90-135 g x hm(-2) is sprayed less than three times a year on L. japonica and 14 days is proposed for the safety interval of the last pesticide application's and harvest's date. PMID:26983196

  16. Collaborative work on evaluation of ovarian toxicity. 6) Two- or four-week repeated-dose studies and fertility study of cisplatin in female rats.

    PubMed

    Nozaki, Yusuke; Furubo, Eiko; Matsuno, Takayuki; Fukui, Rie; Kizawa, Kazuo; Kozaki, Tsukasa; Sanzen, Takahiro

    2009-01-01

    The main aim of the present study is to determine the optimal administration period of cisplatin with regards to its toxic effects on ovarian morphology in the repeated-dose toxicity study. Cisplatin was administered to female SD rats intraperitoneally once daily at dose levels of 0.25, 0.5, 1.0 and 2.0 mg/kg for 2 weeks, or at dose levels of 0.125, 0.25 and 0.5 mg/kg for 4 weeks in the repeated-dose toxicity study. In the female fertility study, 0.25, 0.5 and 1.0 mg/kg of cisplatin were administered in the same manner from 14 days prior to mating to Day 7 of gestation. In the repeated-dose toxicity study, a decrease in large follicle, an increase in atresia of medium and large follicles, and/or a decrease in currently formed corpus luteum were observed in animals receiving 1.0 and 2.0 mg/kg for 2 weeks, and decreases in small and/or large follicles and an increase in atresia of large follicle were observed in animals receiving 0.25 and 0.5 mg/kg for 4 weeks on the histopathological examination of the ovaries. In the female fertility study, the copulation and fertility indices in the animals receiving 1.0 mg/kg tended to be lower than those in the control animals. In conclusion, histopathological changes in the ovary that were attributable to cisplatin dosing were detected by detailed observation of the ovary in the 2-week study; and therefore, a 2-week administration period is sufficient to evaluate the ovarian toxicity of cisplatin. PMID:19265292

  17. Micro-PIXE study of Ag in digestive glands of a nano-Ag fed arthropod ( Porcellio scaber, Isopoda, Crustacea)

    NASA Astrophysics Data System (ADS)

    Tkalec, Živa Pipan; Drobne, Damjana; Vogel-Mikuš, Katarina; Pongrac, Paula; Regvar, Marjana; Štrus, Jasna; Pelicon, Primož; Vavpetič, Primož; Grlj, Nataša; Remškar, Maja

    2011-10-01

    Micro-proton induced X-ray emission (micro-PIXE) method was applied to study the micro-localization of silver (Ag) in digestive glands of a terrestrial arthropod (Porcellio scaber) after feeding on silver nanoparticles (nano-Ag) dosed food. The aim of our work was to assess whether feeding on nano-Ag results in the assimilation of silver (Ag) in digestive gland cells. To study micro-localization and elemental distribution of Ag, the animals were fed on food dosed with nanoparticles for 14 days under controlled laboratory conditions. At the end of the feeding exposure, the animals were dissected and digestive glands prepared for micro-PIXE analyses and TEM investigation. The results obtained by micro-PIXE documented high amounts of Ag inside S-cells of the digestive gland epithelium; however, TEM investigation did not show particle aggregates inside digestive gland cells. Also no adverse effect on feeding behavior was recorded what is a measure of toxic effects. We explain the presence of Ag inside the cells as a result of the assimilation of dissoluted Ag ions from ingested nano-Ag particles. Assimilation of excessive amounts of ingested metal ions in S-cells is a well known metal detoxification mechanism in isopods. We discuss the advantages of using micro-PIXE for the micro-localization of elements in biological tissue in studies of interactions between nanoparticles and biological systems.

  18. Application of microencapsulation for toxicology studies. I. Principles and stabilization of trichloroethylene in gelatin-sorbitol microcapsules.

    PubMed

    Melnick, R L; Jameson, C W; Goehl, T J; Kuhn, G O

    1987-05-01

    Microencapsulation is an innovative, alternative means of incorporating volatile, reactive, and/or unpalatable chemicals into animal feed for toxicologic studies. For such usage, the materials in the microcapsule shell must not adversely affect the laboratory animals, and the encapsulation process must not alter the chemical under study. Trichloroethylene (TCE), a volatile chemical identified in drinking water, was encapsulated in gelatin-sorbitol microcapsules. The concentration of TCE ranged from 40 to 43% (w/w) and most particles (approximately 85%) were between 300 and 420 micron in diameter. Under optimum storage conditions, loss of TCE from the microcapsules was less than 1% per month. Less than 2% of the TCE was lost from microcapsules held in uncovered petri dishes at ambient temperature and humidity for 14 days. Microencapsulated TCE was mixed with NIH-07 rodent feed at a level of 50 mg microcapsules/g feed (equivalent to 20.6 mg TCE/g feed) and stored at room temperature for 7 days in an open container or for 21 days in a sealed container. There was no detectable loss of TCE from the feed blends stored under these conditions. Thus, the stability of TCE in gelatin-sorbitol microcapsules is adequate for dosed-feed toxicity studies of this chemical. PMID:3609532

  19. Salivary antioxidants of male athletes after aerobic exercise and garlic supplementation on: A randomized, double blind, placebo-controlled study

    PubMed Central

    Damirchi, Arsalan; Saati Zareei, Alireza; Sariri, Reyhaneh

    2015-01-01

    Purpose Production of reactive oxygen species and reactive nitrogen species is a natural biological event in metabolism. However, the presence of antioxidants can highly reduce the negative effect of free radicals. Thus, the efficiency of antioxidant system in the physiology of exercise is very important. Design Considering the known antioxidant capacity of garlic, the purpose of this study was to evaluate the effect on combining 14 days aerobic exercise till exhaustion with garlic extract supplementation on the antioxidant capacity of saliva. Methods Sixteen young men volunteered to participate in this randomized, double blind, placebo-controlled study and were randomly placed into two groups, placebo (Group I) and garlic extract (Group II). The participants performed exhaustive aerobic exercise on a treadmill before and after supplementation. Their unstimulated salivary samples were collected before, immediately after, and 1 h after the activity. The antioxidant activity in terms of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) was then measured in the collected samples using their specific substrates. Results A significant increase in salivary antioxidant activity of SOD, POD, and CAT was observed in saliva of the supplement group compared to the placebo group (P ≤ 0.05). Conclusion The findings from this study suggest that increased activity of antioxidant enzymes could possibly decrease exercise-induced oxidative damage in male athletes. PMID:26605139

  20. Comparative analysis between Chamomilla recutita and corticosteroids on wound healing. An in vitro and in vivo study.

    PubMed

    Martins, Manoela Domingues; Marques, Márcia Martins; Bussadori, Sandra Kalil; Martins, Marco Antonio Trevizani; Pavesi, Vanessa Christina Santos; Mesquita-Ferrari, Raquel Agnelli; Fernandes, Kristianne Porta Santos

    2009-02-01

    The comparison of chamomile and corticosteroids for treating ulcers was done in vitro and in vivo. The experimental groups were: control; chamomile recutita; triamcinolone acetonide and clobetasol propionate. For the in vitro study the cell viability of fibroblasts cultured for 24 h in media conditioned by the substances was obtained by the MTT reduction analysis. For the in vivo study, 125 male rats were submitted to experimental ulcers treated or not (control) by the substances tested. At 1, 3, 5, 7 and 14 days later 5 animals of each group were sacrificed. The lesions were analyzed by means of clinical observation and histological wound-healing grading. Data were compared by ANOVA (p study, we concluded that chamomile in comparison to corticosteroids promotes faster wound healing process. PMID:18803230

  1. Comparative study between two animal models of extrapyramidal movement disorders: prevention and reversion by pecan nut shell aqueous extract.

    PubMed

    Trevizol, Fabiola; Benvegnú, Dalila M; Barcelos, Raquel C S; Pase, Camila S; Segat, Hecson J; Dias, Verônica Tironi; Dolci, Geisa S; Boufleur, Nardeli; Reckziegel, Patrícia; Bürger, Marilise E

    2011-08-01

    Acute reserpine and subchronic haloperidol are animal models of extrapyramidal disorders often used to study parkinsonism, akinesia and tardive dyskinesia. In humans, these usually irreversible and disabling extrapyramidal disorders are developed by typical antipsychotic treatment, whose pathophysiology has been related to oxidative damages development. So far, there is no treatment to prevent these problems of the psychiatric clinic, and therefore further studies are needed. Here we used the animal models of extrapyramidal disorders cited above, which were performed in two distinct experiments: orofacial dyskinesia (OD)/catalepsy induced by acute reserpine and subchronic haloperidol after (experiment 1) and before (experiment 2) oral treatment with pecan shell aqueous extract (AE), a natural and promissory antioxidant. When administered previously (exp.1), the AE prevented OD and catalepsy induced by both reserpine and haloperidol. When reserpine and haloperidol were administered before the extract (exp.2), the animals developed OD and catalepsy all the same. However, the orofacial parameter (but not catalepsy) in both animal models was reversed after 7 and 14 days of AE treatment. These results indicate that, acute reserpine and subchronic haloperidol administrations induced similar motor disorders, although through different mechanisms, and therefore are important animal models to study the physiopathology of extrapyramidal disorders. Comparatively, the pecan shell AE was able to both prevent and reverse OD but only to prevent catalepsy. These results reinforce the role of oxidative stress and validate the two animal models used here. Our findings also favor the idea of prevention of extrapyramidal disorders, rather than their reversal. PMID:21356248

  2. Effects of Different Surface Treatment Methods and MDP Monomer on Resin Cementation of Zirconia Ceramics an In Vitro Study

    PubMed Central

    Tanış, Merve Çakırbay; Akçaboy, Cihan

    2015-01-01

    Introduction: Resin cements are generally preferred for cementation of zirconia ceramics. Resin bonding of zirconia ceramics cannot be done with the same methods of traditional ceramics because zirconia is a silica-free material. In recent years, many methods have been reported in the literature to provide the resin bonding of zirconia ceramics. The purpose of this in vitro study is to evaluate effects of different surface treatments and 10-metacryloxydecyl dihydrogen phosphate (MDP) monomer on shear bond strength between zirconia and resin cement. Methods: 120 zirconia specimens were treated as follows: Group I: sandblasting, group II: sandblasting + tribochemical silica coating + silane, group III: sandblasting + Nd:YAG (neodymium: yttrium-aluminum-garnet) laser. One specimen from each group was evaluated under scanning electron microscope (SEM). Specimens in each group were bonded either with conventional resin cement Variolink II or with a MDP containing resin cement Panavia F2.0. Subgroups of bonded specimens were stored in distilled water (37°C) for 24 hours or 14 days. Following water storage shear bond strength test was performed at a crosshead speed of 1 mm/min in a universal test machine. Then statistical analyses were performed. Results: Highest shear bond strength values were observed in group II. No significant difference between group I and III was found when Panavia F2.0 resin cement was used. When Variolink II resin cement was used group III showed significantly higher bond strength than group I. In group I, Panavia F2.0 resin cement showed statistically higher shear bond strength than Variolink II resin cement. In group II no significant difference was found between resin cements. No significant difference was found between specimens stored in 37°C distilled water for 24 hours and 14 days. In group I surface irregularities with sharp edges and grooves were observed. In group II less roughened surface was observed with silica particles. In group

  3. Phase I and II studies of the combination of recombinant human interferon-gamma and 5-fluorouracil in patients with advanced colorectal carcinoma.

    PubMed

    Ajani, J A; Rios, A A; Ende, K; Abbruzzese, J L; Edwards, C; Faintuch, J S; Saks, S; Gutterman, J U; Levin, B

    1989-04-01

    Based on the in vitro and in vivo data suggesting synergistic cytolysis by the combination of 5-fluorouracil and interferon-gamma against a variety of malignant cell lines including a human colon carcinoma cell line (HT-29), we initiated studies in patients with advanced colon or rectal carcinoma. Forty-six patients received 5-fluorouracil as an intravenous injection on days 1-5 and recombinant human interferon-gamma as an intramuscular injection on days 1-14, followed by a rest period of 14 days; courses were repeated every 28 days. In the phase I study, cohorts of two patients received a stepwise dose level increase to achieve the maximum tolerated dose (MTD), at which a total of six patients were studied. The dose levels constituting the MTD were as follows: 5-fluorouracil (500 g/m2/day) and recombinant gamma-interferon (0.5 mg/m2/day). Four patients achieved a partial response in the phase I study. In the phase II study, 30 patients received therapy at the MTD. Among 29 evaluable patients in the phase II study, two patients achieved a partial response. Common toxicities included malaise, fever, anorexia, nausea and vomiting, and diarrhea. Transient severe myelosuppression was common but did not result in significant morbidity. Our data suggest that the combination of 5-fluorouracil and recombinant gamma-interferon did not have the same antitumor effect in patients as it had in the preclinical experiments. PMID:2499663

  4. Lung Resection Using Transumbilical Incision: An Animal Survival Study

    PubMed Central

    Yin, Shun-Ying; Yen-Chu; Wu, Yi-Cheng; Liu, Chien-Ying; Hsieh, Ming-Ju; Yuan, Hsu-Chia; Ko, Po-Jen

    2015-01-01

    Introduction: Transumbilical single-port surgery is a potentially less invasive approach to many types of abdominal surgeries and offers better cosmetic outcomes than conventional 3-port laparoscopic surgery. It avoids the complication of intercostal neuralgia and may reduce the risk of pulmonary complications after video-assisted thoracic surgery. This study evaluated the feasibility of transumbilical lung wedge resection. Methods: Lung resection was performed in 11 beagle dogs weighing 5.9 to 8.5 kg. A 3-cm umbilical incision and one diaphragmatic incision were made, and an endoscopic stapler was used. The diaphragmatic incisions were repaired under video guidance using a V-Loc knotless suturing device (Covidien, Mansfield, Massachusetts). Animals were monitored daily for signs of postoperative infection. White blood cell count, C-reactive protein level, and IL-6 level were measured in all animals. Animals were euthanized 14 days after surgery and underwent necropsy evaluation. Results: Accurate lung resection was achieved in 10 of 11 animals during a median operative time of 98 minutes (range 60–165). In 1 animal, transumbilical lung resection was not possible and was converted to thoracotomy. All animals survived without major postoperative complications. At necropsy, evidence of uneventful healing of the stapled resection margin and diaphragmatic wound were found. There was no evidence of vital organ injury or intrathoracic infection. Conclusion: A transumbilical approach to thoracic cavity exploration and stapled lung resection is technically feasible. Primary suturing of the diaphragmatic incision is a simple and effective means of diaphragmatic wound closure. This may be an alternative to video-assisted thoracic surgery for the management of simple thoracic disease. PMID:25848173

  5. Anaesthesia for awake craniotomy: A retrospective study of 54 cases

    PubMed Central

    Sokhal, Navdeep; Rath, Girija Prasad; Chaturvedi, Arvind; Dash, Hari Hara; Bithal, Parmod Kumar; Chandra, P Sarat

    2015-01-01

    Background and Aims: The anaesthetic challenge of awake craniotomy is to maintain adequate sedation, analgesia, respiratory and haemodynamic stability in an awake patient who should be able to co-operate during intraoperative neurological assessment. The current literature, sharing the experience on awake craniotomy, in Indian context, is minimal. Hence, we carried out a retrospective study with the aim to review and analyse the anaesthetic management and perioperative complications in patients undergoing awake craniotomy, at our centre. Methods: Medical records of 54 patients who underwent awake craniotomy for intracranial lesions over a period of 10 years were reviewed, retrospectively. Data regarding anaesthetic management, intraoperative complications and post-operative course were recorded. Results: Propofol (81.5%) and dexmedetomidine (18.5%) were the main agents used for providing conscious sedation to facilitate awake craniotomy. Hypertension (16.7%) was the most commonly encountered complication during intraoperative period, followed by seizures (9.3%), desaturation (7.4%), tight brain (7.4%), and shivering (5.6%). The procedure had to be converted to general anaesthesia in one of patients owing to refractory brain bulge. The incidence of respiratory and haemodynamic complications were comparable in the both groups (P > 0.05). There was less incidence of intraoperative seizures in patients who received propofol (P = 0.03). In post-operative period, 20% of patients developed new motor deficit. Mean intensive care unit stay was 2.8 ± 1.9 day (1–14 days) and mean hospital stay was 7.0 ± 5.0 day (3–30 days). Conclusions: ‘Conscious sedation’ was the technique of choice for awake craniotomy, at our institute. Fentanyl, propofol, and dexmedetomidine were the main agents used for this purpose. Patients receiving propofol had less incidence of intraoperative seizure. Appropriate selection of patients, understanding the procedure of surgery, and judicious

  6. Human habitation field study of the Habitat Demonstration Unit (HDU)

    NASA Astrophysics Data System (ADS)

    Litaker, Harry L.; Archer, Ronald D.; Szabo, Richard; Twyford, Evan S.; Conlee, Carl S.; Howard, Robert L.

    2013-10-01

    Landing and supporting a permanent outpost on a planetary surface represents humankind's capability to expand its own horizons and challenge current technology. With this in mind, habitability of these structures becomes more essential given the longer durations of the missions. The purpose of this evaluation was to obtain preliminary human-in-the-loop performance data on the Habitat Demonstration Unit (HDU) in a Pressurized Excursion Module (PEM) configuration during a 14-day simulated lunar exploration field trial and to apply this knowledge to further enhance the habitat's capabilities for forward designs. Human factors engineers at the NASA/Johnson Space Center's Habitability and Human Factors Branch recorded approximately 96 h of crew task performance with four work stations. Human factors measures used during this study included the NASA Task Load Index (TLX) and customized post questionnaires. Overall the volume for the PEM was considered acceptable by the crew; however; the habitat's individual work station volume was constrained when setting up the vehicle for operation, medical operations, and suit maintenance while general maintenance, logistical resupply, and geo science was considered acceptable. Crew workload for each station indicated resupply as being the lowest rated, with medical operations, general maintenance, and geo science tasks as being light, while suit maintenance was considered moderate and general vehicle setup being rated the highest. Stowage was an issue around the habitat with the Space Exploration Vehicle (SEV) resupply stowage located in the center of the habitat as interfering with some work station volumes and activities. Ergonomics of the geo science station was considered a major issue, especially with the overhead touch screens.

  7. Length of hospital stay after hip fracture and risk of early mortality after discharge in New York state: retrospective cohort study

    PubMed Central

    Nikkel, Lucas E; Kates, Stephen L; Schreck, Michael; Maceroli, Michael; Mahmood, Bilal

    2015-01-01

    Study question Can the length of hospital stay for hip fracture affect a patient’s risk of death 30 days after discharge? Methods In a retrospective cohort study, population based registry data from the New York Statewide Planning and Research Cooperative System (SPARCS) were used to investigate 188 208 patients admitted to hospital for hip fracture in New York state from 2000 to 2011. Patients were aged 50 years and older, and received surgical or non-surgical treatment. The main outcome measure was the mortality rate at 30 days after hospital discharge. Study answer and limitations Hospital stays of 11-14 days for hip fracture were associated with a 32% increased odds of death 30 days after discharge, compared with stays lasting one to five days (odds ratio 1.32 (95% confidence interval 1.19 to 1.47)). These odds increased to 103% for stays longer than 14 days (2.03 (1.84 to 2.24)). Other risk factors associated with early mortality included discharge to a hospice facility, older age, metastatic disease, and non-surgical management. The 30 day mortality rate after discharge was 4.5% for surgically treated patients and 10.7% for non-surgically treated patients. These findings might not be generalizable to populations in other US states or in other countries. The administrative claims data used could have been incomplete or include inaccurate coding of diagnoses and comorbid conditions. The database also did not include patient socioeconomic status, which could affect access to care to a greater extent in New York state than in European countries. Specific cause of death was not available because few autopsies are performed in this population. What this study adds By contrast with recent findings in Sweden, decreased length of hospital stay for hip fracture was associated with reduced rates of early mortality in a US cohort in New York state. This could reflect critical system differences in the treatment of hip fractures between Europe and the USA. Funding

  8. Assessment of carcinogenic risk from personal exposure to benzo(a)pyrene in the Total Human Environmental Exposure Study (THEES)

    SciTech Connect

    Butler, J.P.; Post, G.B.; Lioy, P.J.; Waldman, J.M.; Greenberg, A. )

    1993-07-01

    The Total Human Environmental Exposure Study (THEES) was an investigation of multimedia exposure to the ubiquitous environmental carcinogen, benzo(a)pyrene (BaP). The three-phase study was conducted in Phillipsburg, New Jersey and involved the participation of 14-15 individuals (8-10 homes) during each 14-day monitoring period. Microenvironmental sampling of air, food, water and soil indicated that environmental exposure to BaP was primarily through air and food. Exposure and risk estimates were, therefore, based on the results of personal monitoring of breathing zone air and prepared food samples. Based on a comparison of the range and magnitude of inhalation and dietary BaP exposures, food ingestion was clearly the predominant exposure to pathway. The relative contributions of other potential sources of community exposure to BaP (e.g., soil and drinking water ingestion) were also assessed. The excess cancer risk estimates for food ingestion were consistently greater than those for personal air, reflecting both the predominantly higher BaP exposures through the diet and the higher carcinogenic potency value for oral exposure. Overall, the total lifetime risk from personal exposure to BaP for nonsmokers in the community was estimated at 10(-5). In identifying risk reduction options, it is important to account for the observation that personal activities, lifestyle, and diet strongly influenced individual exposures to BaP.

  9. A comparative study of the influence of three pure titanium plates with different micro- and nanotopographic surfaces on preosteoblast behaviors.

    PubMed

    Zuo, Jun; Huang, Xunzhi; Zhong, Xiaoxia; Zhu, Bangshang; Sun, Qiang; Jin, Chengyu; Quan, Hongzhi; Tang, Zhangui; Chen, Wantao

    2013-11-01

    There is a great demand for dental implants with the ability to accelerate periimplant bone regeneration. Modification of surface micro- and nanotopographies has been revealed to affect bone cell metabolism. In this study, we utilized dielectric barrier discharge (DBD) technology to modify commercially pure titanium (Ti-tr) surfaces and then investigated the cytocompability of DBD-modified Ti surface when compared with machined (Ti-m) and polished (Ti-p) Ti surfaces. These three kinds of Ti plates exhibited different surface energies and topographies at the micro- and nanoscale levels. The DBD-treated pure Ti surface significantly enhances cell adhesion, spread, and proliferation of MC3T3-E1 preosteoblast cells compared with the Ti-p and Ti-m surfaces, suggesting that Ti-tr has better cytocompatibility compared with the other two surfaces. Preosteoblast cells on Ti-m surface exhibited higher alkaline phosphatase activity than cells on Ti-tr and Ti-p surfaces 14 days after seeding. No significant difference in alkaline phosphatase activity was observed between cells grown on Ti-tr and Ti-p surfaces. Our study demonstrated that DBD modification significantly enhanced cell adhesion, spread, and proliferation of preosteoblasts with no negative effects on cell differentiation. Microtopography and nanotopography of the surfaces of different materials and chemical/energetic properties have a synergistic effect on cell attachment, proliferation, and differentiation. PMID:23625827

  10. An experimental study for syndiotactic polyvinyl alcohol spheres as an embolic agent: can it maintain spherical shape in vivo?

    PubMed

    Chun, Ho Jong; Lee, Hae Giu; Lyoo, Won Seok; Lee, Ji Youl; Kim, Jina

    2014-01-01

    Syndiotactic polyvinyl alcohol (PVA) had been developed to overcome the drawbacks of atactic PVA spheres that deform easily, which can lead to non-target embolization. This study was performed to evaluate the in vivo stability of spherical shape of the syndiotactic PVA spheres. Selective arteriography and transarterial embolization (TAE) were performed in the main renal arteries of eight New Zealand white rabbits using syndiotactic PVA sphere that consisted of syndiotactic PVA skin and a copolymer core of vinyl acetate/vinyl pivalate. The size of the syndiotactic PVA spheres used for the TAE was 212-355 μm. The rabbits were sacrificed 12-14 days after TAE. Gross and microscopic examinations of each kidney were performed. The microscopic examination showed infarction of all embolized kidneys. Syndiotactic PVA spheres were seen uniformly within the arterial lumen and appeared as round ring-like structures without any deformity. The syndiotactic PVA spheres exclusively occupied the arterial lumen. As a conclusion, syndiotactic PVA spheres maintained their spherical shape without significant deformation in this in vivo short-term experimental study. Further investigation is necessary for evaluation of detailed effects of physical stability in tumor embolization. PMID:24948458

  11. A Randomized, Double-blind, Placebo-Controlled Study of Efficacy of Oral Acyclovir in the Treatment of Pityriasis Rosea

    PubMed Central

    2014-01-01

    Background: Pityriasis rosea is an acute self-limiting skin disorder of unknown aetiology. Recently human herpes virus 6 and 7 has been hypothesized to be the cause of pityriasis rosea. Objective: To determine the efficacy of acyclovir, an anti-viral drug, in the treatment of pityriasis rosea. Materials and Methods: A randomized, double-blind, placebo-controlled study of efficacy of oral acyclovir in the treatment of pityriasis rosea was conducted on 73 patients. Thirty eight randomly selected patients were started on oral acyclovir. Thirty-five patients were prescribed placebo. The patients as well as the chief investigator were unaware of the therapeutic group to which patients belonged (acyclovir or placebo). Patients in both the groups were evaluated clinically after 7 and 14 days following the first visit and the data were analysed. Results: Follow up data of 60 patients was available and these were included in the statistical analysis. 53.33% and 86.66% of the patients belonging to the acyclovir group showed complete resolution on the 7th day and 14th day respectively following the first visit compared to 10% and 33.33% of patients from the placebo group. The findings were statistically significant. Conclusion: The study showed that high dose acyclovir is effective in the treatment of pityriasis rosea. PMID:24995231

  12. In vitro studies on the influence of surface modification of Ni-Ti alloy on human bone cells.

    PubMed

    Chrzanowski, Wojciech; Neel, Ensanya A Abou; Armitage, David A; Zhao, Xin; Knowles, Jonathan C; Salih, Vehid

    2010-06-15

    The in vitro cell behavior on Nitinol after different surface treatments was investigated. As references samples, commercially pure titanium (cpTi) and bioactive titanium were used. The surface treatments influenced the topography, surface energy, crystallographic structure, ion release, chemistry, and ability to form apatite layer from simulated body fluids. Regardless of the surface treatment, the bioactivity study showed that the kinetics of apatite film formation was similar for all tested samples. No clear indication of the surface characteristics influence on the ability for calcium-phosphate precipitation was evident. Cell activity studies showed that ground nickel titanium, spark oxidized and thermally oxidized (at 400 degrees C and below) had higher cellular activity and caused increased alkaline phosphatase (ALP) and osteocalcin (OC) expression which was comparable to control tissue culture plastic and titanium reference samples. Regardless of surface modifications, preimmersion of the samples in media for 72 h resulted in cell proliferation at the same level for all samples. Therefore, it can be concluded that preconditioning of samples alters surface properties and modulates the cell response regardless of the initial surface treatment and its properties. Moreover, a detrimental effect on cell response was observed after 7 and 14 days in culture for alkali treated samples. This was attributed to a high surface nickel concentration and a high nickel ion release rate from these surfaces. PMID:20024896

  13. Effectiveness of probiotic, chlorhexidine and fluoride mouthwash against Streptococcus mutans – Randomized, single-blind, in vivo study

    PubMed Central

    Jothika, Mohan; Vanajassun, P. Pranav; Someshwar, Battu

    2015-01-01

    Aim: To determine the short-term efficiency of probiotic, chlorhexidine, and fluoride mouthwashes on plaque Streptococcus mutans level at four periodic intervals. Materials and Methods: This was a single-blind, randomized control study in which each subject was tested with only one mouthwash regimen. Fifty-two healthy qualified adult patients were selected randomly for the study and were divided into the following groups: group 1- 10 ml of distilled water, group 2- 10 ml of 0.2% chlorhexidine mouthwash, group 3- 10 ml of 500 ppm F/400 ml sodium fluoride mouthwash, and group 4- 10 ml of probiotic mouthwash. Plaque samples were collected from the buccal surface of premolars and molars in the maxillary quadrant. Sampling procedure was carried out by a single examiner after 7 days, 14 days, and 30 days, respectively, after the use of the mouthwash. All the samples were subjected to microbiological analysis and statistically analyzed with one-way analysis of variance (ANOVA) and post-hoc test. Results: One-way ANOVA comparison among groups 2, 3, and 4 showed no statistical significance, whereas group 1 showed statistically significant difference when compared with groups 2, 3, and 4 at 7th, 14th, and 30th day. Conclusion: Chlorhexidine, sodium fluoride, and probiotic mouthwashes reduce plaque S. mutans levels. Probiotic mouthwash is effective and equivalent to chlorhexidine and sodium fluoride mouthwashes. Thus, probiotic mouthwash can also be considered as an effective oral hygiene regimen. PMID:25984467

  14. Does work stress make you shorter? An ambulatory field study of daily work stressors, job control, and spinal shrinkage.

    PubMed

    Igic, Ivana; Ryser, Samuel; Elfering, Achim

    2013-10-01

    Body height decreases throughout the day due to fluid loss from the intervertebral disk. This study investigated whether spinal shrinkage was greater during workdays compared with nonwork days, whether daily work stressors were positively related to spinal shrinkage, and whether job control was negatively related to spinal shrinkage. In a consecutive 2-week ambulatory field study, including 39 office employees and 512 days of observation, spinal shrinkage was measured by a stadiometer, and calculated as body height in the morning minus body height in the evening. Physical activity was monitored throughout the 14 days by accelerometry. Daily work stressors, daily job control, biomechanical workload, and recreational activities after work were measured with daily surveys. Multilevel regression analyses showed that spinal disks shrank more during workdays than during nonwork days. After adjustment for sex, age, body weight, smoking status, biomechanical work strain, and time spent on physical and low-effort activities during the day, lower levels of daily job control significantly predicted increased spinal shrinkage. Findings add to knowledge on how work redesign that increases job control may possibly contribute to preserving intervertebral disk function and preventing occupational back pain. PMID:24099165

  15. Histopathological and expression profiling studies of early tumor responses to near-infrared PDT treatment in SCID mice

    NASA Astrophysics Data System (ADS)

    Starkey, Jean R.; Rebane, Aleksander; Drobizhev, Mikhail A.; Meng, Fanqin; Gong, Aijun; Elliott, Aleisha; McInnerney, Kate; Pascucci, Elizabeth; Spangler, Charles W.

    2008-02-01

    A novel class of porphyrin-based near-infrared photodynamic therapy (PDT) sensitizers is studied. We achieve regressions of human small cell lung cancer (NCI-H69), non-small cell lung cancer (A 459) and breast cancer (MDAMB- 231) xenografts in SCID mice at significant tissue depth by irradiation with an amplified femtosecond pulsed laser at 800 nm wavelength. Significant tumor regressions were observed during the first 10-14 days post treatment. Tumor histopathology was consistent with known PDT effects, while no significant changes were noted in irradiated normal tissues. In vivo imaging studies using intravenous injections of fluorescent dextran demonstrated an early loss of tumor blood flow. RNA was isolated from NCI-H69 PDT treated SCID mouse xenografts and paired untreated xenografts at 4 hours post laser irradiation. Similarly RNA was isolated from PDT treated and untreated Lewis lung carcinomas growing in C57/Bl6 mice. Expression profiling was carried out using Affymetrix TM human and mouse GeneChips®. Cluster analysis of microarray expression profiling results demonstrated reproducible increases in transcripts associated with apoptosis, stress, oxygen transport and gene regulation in the PDT treated NCI-H69 samples. In addition, PDT treated Lewis lung carcinomas showed reproducible increases in transcripts associated with immune response and lipid biosynthesis. PDT treated C57/Bl6 mice developed cytotoxic T cell activity towards this tumor, while untreated tumor bearing mice failed to do so.

  16. Sonoelastography in the evaluation of capsule formation after breast augmentation – preliminary results from a follow-up study

    PubMed Central

    Paczkowska, Katarzyna; Kubasik, Mikołaj; Opala, Tomasz

    2015-01-01

    Introduction There are many indications for breast augmentation, including reconstruction after mastectomy, correction of congenital disorders and cosmetic procedures. The most frequent local complication of this surgery is capsule formation due to fibrosis. The aim of the study was to assess the usefulness of sonoelastography in the evaluation of capsule formation around silicone implants. Material and methods The study group included 13 patients aged 20 to 41, who underwent breast augmentation with silicone implants. Their 26 breasts were examined before surgery, 7 and 14 days and a minimum of 8.5 months after surgery. The breast stiffness was assessed with tonometry and shear wave elastography to evaluate elasticity of the breast tissue and capsule formation after surgery. Results We assessed the correlation between capsular elasticity measured at successive visits and the Baker scale. There were no significant relationships between any pairs of variables (p > 0.05). We also analyzed the correlation between the time of the follow-up and changes in the tissue elasticity of every region – no significant relationship was found. The greatest decrease in pericapsular elasticity was established in lower and inner quadrants. Moreover, there was a significant difference between the elasticity of the tissue before and 1 week after surgery (p < 0.05) and no significant changes in the elasticity before surgery and at the end of the follow-up. Conclusions Sonoelastography is precise in evaluation of capsule formation after breast augmentation. It may show changes that cannot be assessed using palpation. PMID:27478461

  17. A comparative study of the side effects between pseudoephedrine in Loratadine plus Pseudoephedrine Sulfate Repetabs Tables and loratadine + pseudoephedrine tablet in treatment of allergic rhinitis in Thai patients.

    PubMed

    Supiyaphun, Pakpoom; Chochaipanichnon, Ladda; Kerekhanjanarong, Virachai; Saengpanich, Supinda

    2002-06-01

    The objective of the study was to evaluate the adverse reactions of Loratadine plus Pseudoephedrine Sulfate Repetabs Tables (LTD+PSE Repetabs) (Loratadine 5 mg + Pseudoephedrine 120 mg) twice daily with that of loratadine (5 mg) twice daily and pseudoephedrine (60 mg) quarter daily in the treatment of patients with allergic rhinitis. The study was designed as an investigator-blind, parallel group study. In this study, 56 patients were equally separated into 2 groups and treated for 14 days with either LTD+PSE Repetabs or loratadine + pseudoephedrine tablet. Both groups were comparable in age, gender, weight; baseline systolic blood pressure, diastolic blood pressure and pulse rate. The change of systolic blood pressure, diastolic blood pressure, and pulse rate did not reach clinical significance throughout the study period. There was no significant difference in occurrences of insomnia, palpitation, mouth dryness and anxiety. However, the incidence of patients with tremor at day 14 in the loratadine + pseudoephedrine tablet group was significantly higher than the LTD+PSE Repetabs group (39% vs 10.7%, p-value = 0.03). Furthermore, one patient in the loratadine + pseudoephedrine tablet group had to discontinue medication at day 7 due to insomnia. In conclusion, LTD+PSE Repetabs is well tolerated and has fewer adverse effects when compared to the loratadine + pseudoephedrine tablet. PMID:12322847

  18. A Novel Murine Model of Established Staphylococcal Bone Infection in the Presence of a Fracture Fixation Plate to Study Therapies Utilizing Antibiotic-laden Spacers after Revision Surgery

    PubMed Central

    Inzana, Jason A.; Schwarz, Edward M.; Kates, Stephen L.; Awad, Hani A.

    2014-01-01

    Mice are the small animal model of choice in biomedical research due to the low cost and availability of genetically engineered lines. However, the devices utilized in current mouse models of implant-associated bone infection have been limited to intramedullary or trans-cortical pins, which are not amenable to treatments involving extensive debridement of a full-thickness bone loss and placement of a segmental antibiotic spacer. To overcome these limitations, we developed a clinically faithful model that utilizes a locking fracture fixation plate to enable debridement of an infected segmental bone defect (full-thickness osteotomy) during a revision surgery, and investigated the therapeutic effects of placing an antibiotic-laden spacer in the segmental bone defect. To first determine the ideal time point for revision following infection, a 0.7 mm osteotomy in the femoral mid-shaft was stabilized with a radiolucent PEEK fixation plate. The defect was inoculated with bioluminescent Staphylococcus aureus, and the infection was monitored over 14 days by bioluminescent imaging (BLI). Osteolysis and reactive bone formation were assessed by X-ray and micro-computed tomography (micro-CT). The active bacterial infection peaked by 5 days post-inoculation, however the stability of the implant fixation became compromised by 10–14 days post-inoculation due to osteolysis around the screws. Thus, day 7 was defined as the ideal time point to perform the revision surgery. During the revision surgery, the infected tissue was debrided and the osteotomy was widened to 3 mm to place a poly-methyl methacrylate spacer, with or without vancomycin. Half of the groups also received systemic vancomycin for the remaining 21 days of the study. The viable bacteria remaining at the end of the study were measured using colony forming unit assays. Volumetric bone changes (osteolysis and reactive bone formation) were directly measured using micro-CT image analysis. Mice that were treated with

  19. Studies on the bioequivalence of second generation cephalosporins: cefaclor capsules and suspension.

    PubMed

    Koytchev, Rossen; Ozalp, Yildiz; Erenmemisoglu, Aydin; Tyutyulkova, Nadejda; Gatchev, Emil; Alpan, Recep Serdar

    2004-09-01

    The aim of the present studies, performed in two different groups of volunteers, was to prove the bioequivalence of 500 mg cefaclor (CAS 70356-03-5) test and reference capsules (Losefar 500 mg Capsules as test and an originator product as reference; study 1) and cefaclor 250 mg/5 mL test and reference suspensions (Losefar 250 mg/5 mL Granules oral suspension as test and an originator product as reference; study 2). Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 8 h post dosing, and concentrations of cefaclor were determined by HPLC method. In the first study, the 90% confidence intervals for intra-individual ratios of AUC0-t and Cmax of cefaclor were 0.99-1.08 for AUC0-t and 0.82-1.06 for Cmax, and thus within the acceptance ranges for bioequivalence trials. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of cefaclor administered as suspensions were 1.10-1.19 and 1.02-1.21, respectively. These values were also within the acceptance range. Concerning the secondary parameter tmax the 90% confidence interval for the intra-individual differences for cefaclor were between -0.13 - 0.13 in the first and between 0.00 - 0.13 in the second study, respectively. In the light of the results of the studies reported here it can be concluded that cefaclor test formulations, i.e. capsules and suspension are bioequivalent to the respective reference formulations. PMID:15497664

  20. Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study.

    PubMed

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2016-01-01

    Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional "value." In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters C max, t max, and area under the curve (AUC) were determined in plasma within the interval of 0-12 h. When comparing the ratio estimates of AUC and C max for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism. PMID:27092303

  1. Pilot Study on Folate Bioavailability from a Camembert Cheese Reveals Contradictory Findings to Recent Results from a Human Short-term Study

    PubMed Central

    Mönch, Sabine; Netzel, Michael; Netzel, Gabriele; Ott, Undine; Frank, Thomas; Rychlik, Michael

    2016-01-01

    Different dietary sources of folate have differing bioavailabilities, which may affect their nutritional “value.” In order to examine if these differences also occur within the same food products, a short-term human pilot study was undertaken as a follow-up study to a previously published human trial to evaluate the relative native folate bioavailabilities from low-fat Camembert cheese compared to pteroylmonoglutamic acid as the reference dose. Two healthy human subjects received the test foods in a randomized cross-over design separated by a 14-day equilibrium phase. Folate body pools were saturated with a pteroylmonoglutamic acid supplement before the first testing and between the testings. Folates in test foods and blood plasma were analyzed by stable isotope dilution assays. The biokinetic parameters Cmax, tmax, and area under the curve (AUC) were determined in plasma within the interval of 0–12 h. When comparing the ratio estimates of AUC and Cmax for the different Camembert cheeses, a higher bioavailability was found for the low-fat Camembert assessed in the present study (≥64%) compared to a different brand in our previous investigation (8.8%). It is suggested that these differences may arise from the different folate distribution in the soft dough and firm rind as well as differing individual folate vitamer proportions. The results clearly underline the importance of the food matrix, even within the same type of food product, in terms of folate bioavailability. Moreover, our findings add to the increasing number of studies questioning the general assumption of 50% bioavailability as the rationale behind the definition of folate equivalents. However, more research is needed to better understand the interactions between individual folate vitamers and other food components and the potential impact on folate bioavailability and metabolism. PMID:27092303

  2. Toxicology and carcinogenesis studies of amosite asbestos (CAS No. 12172-73-5) in F344/N rats (feed studies). Technical report series

    SciTech Connect

    McConnell, E.E.

    1990-11-01

    Carcinogenesis studies of amosite asbestos alone or in combination with the intestinal carcinogen 1,2-dimethylhydrazine dihydrochloride (DMH) were conducted in male and female F344/N rats. Amosite asbestos was administered at a concentration of 1% in pelleted diet for the entire lifetime of the rats, starting with the dams of the study animals. The DMH was administered by gavage at a dose of 7.5 mg/kg for males and 15 mg/kg for females every 14 days, starting at 8 weeks of age, for a total of five doses. The administration of DMH did not affect body weight gain either in amosite-exposed or nonexposed animals. Significant increases in the incidences of C-cell carcinomas of the thyroid gland (untreated control, 11/117; amosite, 50/246, P<0.05; amosite preweaning gavage, 14/100) and of leukemia (38/117; 106/249, P<0.05; 49/100, P<0.01) in male rats were observed in amosite-exposed groups. However, the biologic significance of the C-cell carcinomas in relation to amosite asbestos exposure is discounted because of a lack of significance when C-cell adenomas and carcinomas were combined and because the positive effect was not observed in the amosite preweaning gavage group. DMH caused a high incidence (62%-74%) of intestinal neoplasia in amosite-exposed and nonexposed groups. Neither an enchanced carcinogenic nor a protective effect was demonstrated by exposure to amosite asbestos. Under the conditions of these feed studies, amosite asbestos was not overtly toxic, did not affect survival, and was not carcinogenic when ingested at a concentration of 1% in the diet by male or female F344/N rats. The cocarcinogenic studies using DMH were considered inadequate because of the high incidence of DMH-induced intestinal neoplasia in both the amosite asbestos-exposed and nonexposed groups.

  3. Prenatal and developmental toxicity study of meclizine and caffeine combination in female albino Wistar rats.

    PubMed

    Sandeep, M; Alvin, Jose M

    2014-12-01

    Meclizine and caffeine combination is used for the treatment of morning sickness. Both compounds are teratogenic and caffeine is known to possess anti-fertility activity also. The present study was undertaken to evaluate the reproductive toxic effect of meclizine and caffeine combination. Three doses were taken for the study; low dose (LD; meclizine 3.7 mg/kg and caffeine 3 mg/kg) was selected from commercially available formulation, middle dose (MD; meclizine 37 mg/kg and caffeine 30 mg/kg) and high dose (HD; meclizine 370 mg/kg and caffeine 300 mg/kg). The mixture was administered 1-7 days and 8-14 days for fertility and embryotoxic studies respectively. Laparotomy was done on 10t day of gestation period. Number of implants and corpora lutea were counted, pre and post-implantation losses were determined. In embryo toxicity study fetuses were evaluated for external, skeletal and visceral examination. High dose was removed from both fertility and embryotoxicity studies due to its severe toxicity to the dam. Significant anti-fertility activity was observed at middle dose. Embryotoxicity study showed significant reduction in fetal body weight, body length and body mass index, dam body weight gain on gestation day 14. Absolute kidney weight in MD and absolute and relative spleen weight in both LD and MD were significantly reduced. There was no increase in external or internal congenital anomalies at both LD and MD. The, results suggest that prescription of meclizine and caffeine for morning sickness in early pregnancy should be reviewed carefully. PMID:25651609

  4. No protection by oral terbutaline against exercise-induced asthma in children: a dose-response study.

    PubMed

    Fuglsang, G; Hertz, B; Holm, E B

    1993-04-01

    We wanted to assess the protective effects on exercise-induced asthma as well as the clinical efficacy and safety of increasing doses of a new sustained-release formulation of terbutaline sulphate, in 17 asthmatic children aged 6-12 yrs (mean 9 yrs). Placebo, 2, 4 and 6 mg terbutaline were given b.i.d. for 14 days, in a randomized, double-blind, cross-over design. At the end of each two week period, an exercise test was performed and plasma terbutaline was measured. Compared with placebo, no significant effect was seen on asthma symptoms monitored at home, or on exercise-induced asthma. The percentage falls in FEV1 after the exercise test were 36, 35, 27 and 28%, after placebo, 4, 8 and 12 mg terbutaline.day-1, respectively. There was no correlation between plasma terbutaline and dose of terbutaline. A small but statistically significant dose-related increase in morning and evening peak expiratory flow (PEF) recordings occurred, but the incidence of side-effects also increased with the dose given. There was a trend towards more side-effects when the high doses were used, and two patients withdrew from the study because of side-effects at this dose. It is concluded that continuous treatment, even with high doses of oral terbutaline, does not offer clinically useful protection against exercise-induced asthma. PMID:8491302

  5. In vitro study of the neuropathic potential of the organophosphorus compounds fenamiphos and profenofos: Comparison with mipafox and paraoxon.

    PubMed

    Emerick, Guilherme L; Fernandes, Laís S; de Paula, Eloísa Silva; Barbosa, Fernando; dos Santos, Neife Aparecida Guinaim; dos Santos, Antonio Cardozo

    2015-08-01

    Organophosphorus-induced delayed neuropathy (OPIDN) is a central-peripheral distal axonopathy that develops 8-14 days after poisoning by a neuropathic organophosphorus compound (OP). Several OPs that caused OPIDN were withdrawn from the agricultural market due to induction of serious delayed effects. Therefore, the development of in vitro screenings able to differentiate neuropathic from non-neuropathic OPs is of crucial importance. Thus, the aim of this study was to evaluate the differences in the neurotoxic effects of mipafox (neuropathic OP) and paraoxon (non-neuropathic OP) in SH-SY5Y human neuroblastoma cells, using the inhibition and aging of neuropathy target esterase (NTE), inhibition of acetylcholinesterase (AChE), activation of calpain, neurite outgrowth, cytotoxicity and intracellular calcium as indicators. Additionally, the potential of fenamiphos and profenofos to cause acute and/or delayed effects was also evaluated. Mipafox had the lowest IC50 and induced the highest percentage of aging of NTE among the OPs evaluated. Only mipafox was able to cause calpain activation after 24 h of incubation. Concentrations of mipafox and fenamiphos which inhibited at least 70% of NTE were also able to reduce neurite outgrowth. Cytotoxicity was higher in non-neuropathic than in neuropathic OPs while the intracellular calcium levels were higher in neuropathic than in non-neuropathic OPs. In conclusion, the SH-SY5Y cellular model was selective to differentiate neuropathic from non-neuropathic OPs; fenamiphos, but not profenofos presented results compatible with the induction of OPIDN. PMID:25910916

  6. Alternative biological-treatment processes for remediation of creosote- and PCP-contaminated materials: Bench-scale treatability studies

    SciTech Connect

    Mueller, J.G.; Lantz, S.E.; Blattman, B.O.; Middaugh, D.P.; Chapman, P.J.

    1991-03-01

    Bench-scale biotreatability studies were performed to determine the most effective of two bioremediation application strategies to ameliorate creosote- and pentachlorophenol (PCP)-contaminated soils present at the American Creosote Works Superfund site, Pensacola, Florida: solid-phase bioremediation or slurry-phase bioremediation. When indigenous microorganisms were employed as biocatalysts, solid-phase bioremediation was slow and ineffective (8-12 weeks required to biodegrade >50% of resident organics). Biodegradation was limited to lower-molecular-weight constituents rather than the more hazardous, higher-molecular-weight (HMW) compounds; PCP and HMW polycyclic aromatic hydrocarbons (PAHs) containing 4 or more fused rings resisted biological attach. Moreover, supplementation with aqueous solution of inorganic nutrients had little effect on the overall effectiveness of the treatment strategy. Alternatively, slurry-phase bioremediation was much more effective: >50% of targeted organics were biodegraded in 14 days. Again, however, more persistent contaminants, such as PCP and HMW PAHs, were not extensively degraded when subjected to the action of indigenous microorganisms.

  7. A retrospective study of deep sternal wound infections: clinical and microbiological characteristics, treatment, and risk factors for complications.

    PubMed

    Chan, Monica; Yusuf, Erlangga; Giulieri, Stefano; Perrottet, Nancy; Von Segesser, Ludwig; Borens, Olivier; Trampuz, Andrej

    2016-03-01

    Deep sternal wound infection (DSWI) is a feared complication following cardiac surgery. This study describes clinical, microbiological, and treatment outcomes of DSWI and determines risk factors for complications. Of 55 patients with DSWI, 66% were male and mean age was 68.2years. Initial sternotomy was for coronary artery bypass graft in 49% of patients. Sternal debridement at mean 25.4±18.3days showed monomicrobial (94%), mainly Gram-positive infection. Secondary sternal wound infection (SSWI) occurred in 31% of patients, was mostly polymicrobial (71%), and was predominantly due to Gram-negative bacilli. Risk factors for SSWI were at least 1 revision surgery (odds ratio [OR] 4.8 [95% confidence interval {CI} 1.0-22.4], P=0.047), sternal closure by muscle flap (OR 4.6 [1.3-16.8], P=0.02), delayed sternal closure (mean 27 versus 14days, P=0.03), and use of vacuum-assisted closure device (100% versus 58%, P=0.008). Hospital stay was significantly longer in patients with SSWI (69days versus 48days, P=0.04). PMID:26707065

  8. Prospective Study of Plasmodium vivax Malaria Recurrence after Radical Treatment with a Chloroquine-Primaquine Standard Regimen in Turbo, Colombia.

    PubMed

    Zuluaga-Idárraga, Lina; Blair, Silvia; Akinyi Okoth, Sheila; Udhayakumar, Venkatachalam; Marcet, Paula L; Escalante, Ananias A; Alexander, Neal; Rojas, Carlos

    2016-08-01

    Plasmodium vivax recurrences help maintain malaria transmission. They are caused by recrudescence, reinfection, or relapse, which are not easily differentiated. A longitudinal observational study took place in Turbo municipality, Colombia. Participants with uncomplicated P. vivax infection received supervised treatment concomitantly with 25 mg/kg chloroquine and 0.25 mg/kg/day primaquine for 14 days. Incidence of recurrence was assessed over 180 days. Samples were genotyped, and origins of recurrences were established. A total of 134 participants were enrolled between February 2012 and July 2013, and 87 were followed for 180 days, during which 29 recurrences were detected. The cumulative incidence of first recurrence was 24.1% (21/87) (95% confidence interval [CI], 14.6 to 33.7%), and 86% (18/21) of these events occurred between days 51 and 110. High genetic diversity of P. vivax strains was found, and 12.5% (16/128) of the infections were polyclonal. Among detected recurrences, 93.1% (27/29) of strains were genotyped as genetically identical to the strain from the previous infection episode, and 65.5% (19/29) of infections were classified as relapses. Our results indicate that there is a high incidence of P. vivax malaria recurrence after treatment in Turbo municipality, Colombia, and that a large majority of these episodes are likely relapses from the previous infection. We attribute this to the primaquine regimen currently used in Colombia, which may be insufficient to eliminate hypnozoites. PMID:27185794

  9. A Ground Observation Based Climatology and Forecasting of Winter Fog: Study over Ghaziabad, National Capital Region, India

    NASA Astrophysics Data System (ADS)

    Srivastava, S. K., Sr.; Sharma, D. A.; Sachdeva, K.

    2015-12-01

    Long term ground observations (1971-2010) have been analyzed over Ghaziabad city, National Capital Region to understand the characteristics of fog phenomenon and its relevance during winter months. We observed mean maximum fog occurrence during December (~23 days) followed by January (~21 days), November (~20 days), February (~14 days) and October (~11 days) respectively. A remarkable increase has been noticed in fog occurrence during October-to-February in last four decades. During 1971-80 to 2001-2010 the mean frequency of fog occurrence had increased by 205.5% in October month and 50.2% in November month. Similarly, mean frequency of fog occurrence increased by 51%, 97% and 119% during December, January and February respectively over the same period. We observed statistically significant increasing trend in fog occurrence from October-to-February during the study period at 95% confidence level. The magnitude of trend is 0.50, 0.47, 0.30, 0.39 and 0.37 for October, November, December, January and February, respectively. The magnitude of trend is highest in October but the occurrence frequency is highest in December. The forecast values obtained from ARIMA model indicates that the number of fog days is going to increase further during October-to-February in the forthcoming years. The data combined with knowledge of meteorology and topography suggested significant conclusions about increase in the fog events in the near future.

  10. Under-recognized pertussis in adults from Asian countries: a cross-sectional seroprevalence study in Malaysia, Taiwan and Thailand.

    PubMed

    Koh, M T; Liu, C-S; Chiu, C-H; Boonsawat, W; Watanaveeradej, V; Abdullah, N; Zhang, Xh; Devadiga, R; Chen, J

    2016-04-01

    Surveillance data on the burden of pertussis in Asian adults are limited. This cross-sectional study evaluated the prevalence of serologically confirmed pertussis in adults with prolonged cough in Malaysia, Taiwan and Thailand. Adults (⩾19 years) with cough lasting for ⩾14 days without other known underlying cause were enrolled from outpatient clinics of seven public and/or private hospitals. Single blood samples for anti-pertussis toxin antibodies (anti-PT IgG) were analysed and economic impact and health-related quality of life (EQ-5D) questionnaires assessed. Sixteen (5·13%) of the 312 chronically coughing adults had serological evidence of pertussis infection within the previous 12 months (anti-PT IgG titre ⩾62·5 IU/ml). Three of them were teachers. Longer duration of cough, paroxysms (75% seroconfirmed, 48% non-seroconfirmed) and breathlessness/chest pain (63% seroconfirmed, 36% non-seroconfirmed) were associated with pertussis (P < 0·04). Of the seroconfirmed patients, the median total direct medical cost per pertussis episode in public hospitals (including physician consultations and/or emergency room visits) was US$13 in Malaysia, US$83 in Taiwan (n = 1) and US$26 in Thailand. The overall median EQ-5D index score of cases was 0·72 (range 0·42-1·00). Pertussis should be considered in the aetiology of adults with a prolonged or paroxysmal cough, and vaccination programmes considered. PMID:26468043

  11. Prevention and Treatment of Lower Limb Deep Vein Thrombosis after Radiofrequency Catheter Ablation: Results of a Prospective active controlled Study

    PubMed Central

    Li, Lan; Zhang, Bao-jian; Zhang, Bao-ku; Ma, Jun; Liu, Xu-zheng; Jiang, Shu-bin

    2016-01-01

    We conducted a prospective, single-center, active controlled study from July 2013 to January 2015, in Chinese patients with rapid ventricular arrhythmia who had received radiofrequency catheter ablation (RFCA) treatment to determine formation of lower extremity deep vein thrombosis (LDVT) post RFCA procedure, and evaluated the effect of rivaroxaban on LDVT. Patients with asymptomatic pulmonary thromboembolism who had not received any other anticoagulant and had received no more than 36 hours of treatment with unfractionated heparin were included. Post RFCA procedure, patients received either rivaroxaban (10 mg/d for 14 days beginning 2–3 hours post-operation; n = 86) or aspirin (100 mg/d for 3 months beginning 2–3 hours post-operation; n = 90). The primary outcome was a composite of LDVT occurrence, change in diameter of femoral veins, and safety outcomes that were analyzed based on major or minor bleeding events. In addition, blood flow velocity was determined. No complete occlusive thrombus or bleeding events were reported with either of the group. The lower incidence rate of non-occluded thrombus in rivaroxaban (5.8%) compared to the aspirin group (16.7%) indicates rivaroxaban may be administered post-RFCA to prevent and treat femoral venous thrombosis in a secure and effective way with a faster inset of action than standard aspirin therapy. PMID:27329582

  12. Comparative Study on Vegetative and Reproductive Development between Weedy Rice Morphotypes and Commercial Rice Varieties in Perak, Malaysia

    PubMed Central

    Ahmed, Quazi Nasim; Hussain, PMD Zainudin; Othman, Ahmad Sofiman

    2012-01-01

    This study was conducted to examine the variabilities in the chronology of vegetative and reproductive development of weedy rice (Oryza spp.) in comparison with commercial varieties. Data at different growth stages of 14 weedy rice morphotypes and 4 commercial rice varieties were recorded and analysed. Plant height of all weedy rice morphotypes were observed to be significantly higher compared to the commercial varieties at every growth stages; increase in height was between 10–37 cm for weedy rice morphotype, for every 2 weeks. Initial tillering ability at 14 days after planting (DAP) was higher in weedy morphotypes, however all the commercial rice varieties produced significantly higher number of tillers throughout the rest of the vegetative phases. Correlation between plant height and tiller number detected that taller plants produce fewer tillers than shorter plants. Higher leaf area index (LAI) of all weedy morphotypes except PWR01 at early growth stages indicated the vigorous growth of the morphotypes. Weedy rice morphotypes showed a wide range of anthesis and maturity duration. Accessions from the same weedy rice morphotypes were more heterogeneous in the flowering, anthesis and maturity period than the commercial varieties. These traits enables identification of weedy rice morphotypes at their different growth stages in the field. PMID:24575230

  13. Effects of Etlingera elatior extracts on lead acetate-induced testicular damage: A morphological and biochemical study

    PubMed Central

    HAW, KHOR YEN; CHAKRAVARTHI, SRIKUMAR; HALEAGRAHARA, NAGARAJA; RAO, MALLIKARJUNA

    2012-01-01

    Lead causes damage to the whole body by inducing oxidative stress. This includes the testis, in which spermatogenesis is affected. Etlingera elatior, a consumable plant that is being extensively studied for its high anti-oxidant properties, was tested against the effect of lead acetate in experimental rats. Rats were divided into groups consisting of a control, lead acetate only, Etlingera elatior treatment only, concurrent treatment of lead acetate and Etlingera elatior, post-treatment of lead acetate followed by Etlingera elatior and preventive group of Etlingera elatior followed by lead acetate. The substances were administered for 14 days and the effects were measured by protein carbonyl content (PCC), superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity in the testis, as well as the testosterone level in the serum. Histological changes in the testis were also observed. Results showed that Etlingera elatior induced a significant reduction in the testis PCC activity, while at the same time it significantly increased the activities of SOD and GPx in the testis, and the testosterone level in the serum. Etlingera elatior also improved the histology of the testis when compared to the lead acetate-treated group. On the whole, Etlingera elatior is effective against oxidative damage caused by lead acetate in the testis. PMID:22969852

  14. Studies on the regulatory effect of Peony-Glycyrrhiza Decoction on prolactin hyperactivity and underlying mechanism in hyperprolactinemia rat model.

    PubMed

    Wang, Di; Wang, Wei; Zhou, Yulin; Wang, Juan; Jia, Dongxu; Wong, Hei Kiu; Zhang, Zhang-Jin

    2015-10-01

    Clinical trials have demonstrated the beneficial effects of Peony-Glycyrrhiza Decoction (PGD) in alleviating antipsychotic-induced hyperprolactinemia (hyperPRL) in schizophrenic patients. In previous experiment, PGD suppressed prolactin (PRL) level in MMQ cells, involving modulating the expression of D2 receptor (DRD2) and dopamine transporter (DAT). In the present study, hyperPRL female rat model induced by dopamine blocker metoclopramide (MCP) was applied to further confirm the anti-hyperpPRL activity of PGD and underlying mechanism. In MCP-induced hyperPRL rats, the elevated serum PRL level was significantly suppressed by either PGD (2.5-10 g/kg) or bromocriptine (BMT) (0.6 mg/kg) administration for 14 days. However, in MCP-induced rats, only PGD restored the under-expressed serum progesterone (P) to control level. Both PGD and BMT administration restore the under-expression of DRD2, DAT and TH resulted from MCP in pituitary gland and hypothalamus. Compared to untreated group, hyperPRL animals had a marked reduction on DRD2 and DAT expression in the arcuate nucleus. PGD (10 g/kg) and BMT (0.6 mg/kg) treatment significant reversed the expression of DRD2 and DAT. Collectively, the anti-hyperPRL activity of PGD associates with the modulation of dopaminergic neuronal system and the restoration of serum progesterone level. Our finding supports PGD as an effective agent against hyperPRL. PMID:26297122

  15. Effects of a caspase and a calpain inhibitor on resting energy expenditures in normal and hypermetabolic rats: a pilot study.

    PubMed

    Vana, P G; LaPorte, H M; Kennedy, R H; Gamelli, R L; Majetschak, M

    2016-07-18

    Several diseases induce hypermetabolism, which is characterized by increases in resting energy expenditures (REE) and whole body protein loss. Exaggerated protein degradation is thought to be the driving force underlying this response. The effects of caspase and calpain inhibitors on REE in physiological and hypermetabolic conditions, however, are unknown. Thus, we studied whether MDL28170 (calpain inhibitor) or z-VAD-fmk (caspase inhibitor) affect REE under physiological conditions and during hypermetabolism post-burn. Rats were treated five times weekly and observed for 6 weeks. Treatment was started 2 h (early) or 48 h (late) after burn. In normal rats, MDL28170 transiently increased REE to 130 % of normal during week 2-4. z-VAD-fmk reduced REE by 20-25 % throughout the observation period. Within 14 days after burns, REE increased to 130+/-5 %. Whereas MDL28170/early treatment did not affect REE, MDL28170/late transiently increased REE to 180+/-10 % of normal by week 4 post-burn. In contrast, with z-VAD-fmk/early REE remained between 90-110 % of normal post-burn. z-VAD-fmk/late did not affect burn-induced increases in REE. These data suggest that caspase cascades contribute to the development of hypermetabolism and that burn-induced hypermetabolism can be pharmacologically modulated. Our data point towards caspase cascades as possible therapeutic targets to attenuate hypermetabolism after burns, and possibly in other catabolic disease processes. PMID:27070748

  16. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design.

    PubMed Central

    Dodd, D E; Frank, F R; Fowler, E H; Troup, C M; Milton, R M

    1987-01-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration (ranging from 25-3506 ppm). MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC50 tests with 14-day postexposure follow-up were conducted, and the LC50 (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented. PMID:3622426

  17. The influence of diet and dimethylhydrazine on the large intestine of vervet monkeys: scanning and transmission electron microscope studies.

    PubMed Central

    Jaskiewicz, K.; Kritchevsky, D.; Venter, F. S.; van Wyk, W. E.

    1987-01-01

    The study was designed to identify diet and carcinogen-dependent ultrastructural changes in the epithelium of macroscopically normal colonic mucosa in primates. Seventy adult female vervet monkeys were divided into seven equal treatment groups. Four received a Western high-fat low fibre diet (WD), two a prudent low-fat higher fibre diet (PD) and one a control low-fat high fibre diet (CD). Three groups (2 WD, 1 PD) received dimethylhydrazine intramuscularly at 14 day intervals. After 18 months, monkeys of two groups on the WD were transferred to the PD (WD----PD) and 30 months later all were killed. Mucosae of caecum, colon transversum and rectum were examined by scanning and transmission electron microscopy and showed close similarity to that of humans. Rectal mucosae showed increased surface goblet cell secretory activity, mucin production and microvillar changes related to WD and WD----PD. The enhancing effect of a carcinogen on ultrastructural changes such as cellular pleomorphism, cytoplasmic interbridging, nuclear and nucleolar irregularities and appearance of argentaffin cells in the free surface epithelium were noted predominantly in high-fat treated animals. Such changes observed in the upper part of crypt, orifice and free surface epithelium can be characteristic for precancerous change and could be utilised practically in the detection of precursor lesions of the colon. Images Fig. 9 Fig. 10 Figs. 11 & 12 Fig. 1 Fig. 2 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Figs. 13 & 14 PMID:3620336

  18. Toxicological evaluation of advanced glycation end product Nε-(carboxymethyl)lysine: Acute and subacute oral toxicity studies.

    PubMed

    Liu, Xin; Zheng, Liangqing; Zhang, Rong; Liu, Gang; Xiao, Shensheng; Qiao, Xiaoting; Wu, Yongning; Gong, Zhiyong

    2016-06-01

    Nε-(carboxymethyl)lysine (CML) as a novel potential noxious compound in various food products has aroused extensive concern in recent years. This study aimed to investigate the oral acute and subacute toxicity of CML in mice as per OECD 420 and 407 guidelines. Acute administration of 2000 and 5000 mg/kg CML did not induce any mortality within 14 days, nevertheless some toxicological symptoms and histopathological changes were observed. The estimated LD50 of CML was >5000 mg/kg. In subacute toxicity test, CML was dosed at 200, 500 and 1000 mg/kg in both genders for 28 days. The body weights reduced which was accompanied with the decrease of food consumptions. Hematology parameters viz. RBC, HGB and MCH showed minor alteration but these were still within normal range. Biochemical analysis of hepatic and renal function markers showed significant elevating in AST, ALT, Cr and BUN etc. Histopathological alterations were observed in lung, liver, kidney and spleen. Subacute toxicity of CML involved oxidative stress caused by reducing antioxidant enzyme (SOD and GSH-Px) activities, and significantly increasing lipid peroxide (MDA) level. In conclusion, CML was unlikely to present an acute hazard, but repeated administration could produce deleterious effects on mice especially inducing liver and kidney damage through oxidative stress. PMID:26921796

  19. Biological effects of short-term, high-concentration exposure to methyl isocyanate. I. Study objectives and inhalation exposure design

    SciTech Connect

    Dodd, D.E.; Frank, F.R.; Fowler, E.H.; Troup, C.M.; Milton, R.M.

    1987-06-01

    Early reports from India indicated that humans were dying within minutes to a few hours from exposure to methyl isocyanate (MIC). Attempts to explain the cause(s) of these rapid mortalities is where Union Carbide Corporation concentrated its post-Bhopal toxicologic investigations. The MIC studies involving rats and guinea pigs focused primarily on the consequences of acute pulmonary damage. All MIC inhalation exposures were acute, of short duration (mainly 15 min), and high in concentration. MIC vapors were statically generated in a double chamber exposure design. Precautionary measures taken during exposures are discussed. Guinea pigs were more susceptible than rats to MIC exposure-related early mortality. A greater than one order of magnitude difference was observed between an MIC concentration that caused no early mortality in rats (3506 ppm) and an MIC concentration that caused partial (6%) early mortality in guinea pigs (225 ppm) for exposures of 10 to 15 min duration. For both species, the most noteworthy clinical signs during exposure were lacrimation, blepharospasm, and mouth breathing. Fifteen minute LC/sub 50/ tests with 14-day postexposure follow-up were conducted, and the LC/sub 50/ (95% confidence limit) values were 171 (114-256) ppm for rats and 112 (61-204) ppm for guinea pigs. Target exposure concentrations for the toxicologic investigations of MIC-induced early mortality were established. A short summary of pertinent results of Union Carbide Corporation's post-Bhopal toxicologic investigations is presented.

  20. Evaluation of Mallotus oppositifolius Methanol Leaf Extract on the Glycaemia and Lipid Peroxidation in Alloxan-Induced Diabetic Rats: A Preliminary Study

    PubMed Central

    Nwaehujor, C. O.; Ezeigbo, I. I.; Nwinyi, F. C.

    2013-01-01

    Objective. Mallotus oppositifolius (Geiseler) Müll. Arg. (Euphorbiaceae) is folklorically used to “treat” diabetic conditions in some parts of Nigeria therefore the study, to investigate the extract of the leaves for activities on hyperglycaemia, lipid peroxidation, and increased cholesterol levels in vivo in alloxan diabetic rats as well as its potential antioxidant activity in vitro. Methods. Albino rats (240–280 g) were given an injection of 120 mg/kg body weight, i.p. of alloxan monohydrate. After 8 days, diabetic animals with elevated fasting blood glucose levels (>9 mmol/L) were considered and selected for the study. Results. Oral treatment with the extract administered every 12 h by gavage at doses of 100, 200, and 400 mg/kg of the extract to the test rats, for 14 days, resulted in a significant dose-dependent decrease in blood glucose levels from 12.82 ± 1.02 mmol/dL to 4.92 ± 2.01 mmol/dL at the highest dose of 400 mg/kg compared to the control drug and glibenclamide as well as attendant significant decline in diabetic rats employed in the study. Conclusion. The extract also showed in vitro concentration-dependent antioxidant activity following the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) and ferric reducing assays. Findings further suggest the presence of active antidiabetic and antioxidant principles in M. oppositifolius leaves. PMID:24224091

  1. Biofilm forming capacity of Enterococcus faecalis on Gutta-percha points treated with four disinfectants using confocal scanning laser microscope: An in vitro study

    PubMed Central

    Ravi Chandra, Polavarapu Venkata; Kumar, Vemisetty Hari; Reddy, Surakanti Jayaprada; Kiran, Dandolu Ram; Krishna, Muppala Nagendra; Kumar, Golla Vinay

    2015-01-01

    Background: The aim of this study was to evaluate and compare the in vitro biofilm forming capacity of Enterococcus faecalis on Gutta-percha points disinfected with four disinfectants. Materials and Methods: A total of 50 Gutta-percha points used in this study were divided into four test groups based on disinfectant (5.25% sodium hypochlorite, 2% chlorhexidine gluconate, 20% neem, 13% benzalkonium chloride [BAK]), and one control group. The Gutta-percha points were initially treated with corresponding disinfectants followed by anaerobic incubation in Brain Heart Infusion broth suspended with human serum and E. faecalis strain for 14 days. After incubation, these Gutta-percha points were stained with Acridine Orange (Sigma – Aldrich Co., St. Louis, MO, USA) and 0.5 mm thick cross section samples were prepared. The biofilm thickness of E. faecalis was analyzed quantitatively using a confocal scanning laser microscope. Results statistically analyzed using analysis of variance. P < 0.05 was considered to be significant. Results: Confocal scanning laser microscope showed reduced amount of E. faecalis biofilm on Gutta-percha points treated with BAK and sodium hypochlorite. Post-hoc (least square differences) test revealed that there is no statistically significant difference between BAK and sodium hypochlorite groups (P > 0.05). Conclusion: This study illustrates that the Gutta-percha points disinfected with sodium hypochlorite and BAK showed minimal biofilm growth on its surface. PMID:26288622

  2. A comparative study of the effects of topical application of Aloe vera, thyroid hormone and silver sulfadiazine on skin wounds in Wistar rats

    PubMed Central

    Norouzian, Mohsen; Zarein-Dolab, Saeed; Dadpay, Masoomeh; Gazor, Roohollah

    2012-01-01

    Many research studies report the healing effects of Aloe Vera, thyroid hormone cream and silver sulfadiazine. However, the effects of these therapeutic agents are not well understood and have not been compared in one study. This study aimed at investigating the effects of topical application of an Aloe vera gel, a thyroid hormone cream and a silver sulfadiazine cream on the healing of skin wounds surgically induced in Wistar rats for determining the treatment of choice. In a randomized controlled trial, twelve male rats, aged 120 days and with a mean weight of 250 to 300 g, were divided randomly into 5 groups based on drug treatments: Aloe vera gel (AV), thyroid hormone cream (TC), silver sulfadiazine 1% (S), vehicle (V) and control. To evaluate the efficacy of each treatment technique, a biomechanical approach was used to assess tensile stress after 14 days of treatment. Tensile stress was significantly improved in the Aloe vera gel group as compared with the other four groups (P≤0.05). While the other treatment options resulted in better healing than the control group, this difference was not significant. We conclude that Aloe vera topical application accelerated the healing process more than thyroid hormone, silver sulfadiazine and vehicle in surgically induced incisions in rats. PMID:22474470

  3. Erosive potential of commonly used beverages, medicated syrup, and their effects on dental enamel with and without restoration: An in vitro study

    PubMed Central

    Trivedi, Krishna; Bhaskar, Vijay; Ganesh, Mahadevan; Venkataraghavan, Karthik; Choudhary, Prashant; Shah, Shalin; Krishnan, Ramesh

    2015-01-01

    Aim: This study evaluates erosive potential of commonly used beverages, medicated syrup, and their effects on dental enamel with and without restoration in vitro. Materials and Methods: Test medias used in this study included carbonated beverage, noncarbonated beverage, high-energy sports drink medicated cough syrup, distilled water as the control. A total of 110 previously extracted human premolar teeth were selected for the study. Teeth were randomly divided into two groups. Test specimens were randomly distributed to five beverages groups and comprised 12 specimens per group. Surface roughness (profilometer) readings were performed at baseline and again, following immersion for 14 days (24 h/day). Microleakage was evaluated. The results obtained were analyzed for statistical significance using SPSS-PC package using the multiple factor ANOVA at a significance level of P < 0.05. Paired t-test, Friedman test ranks, and Wilcoxon signed ranks test. Results: For surface roughness high-energy sports drink and noncarbonated beverage showed the highly significant difference with P values of 0.000 and 0.000, respectively compared to other test media. For microleakage high-energy sports drink had significant difference in comparison to noncarbonated beverage (P = 0.002), medicated syrup (P = 0.000), and distilled water (P = 0.000). Conclusion: High-energy sports drink showed highest surface roughness value and microleakage score among all test media and thus greater erosive potential to enamel while medicated syrup showed least surface roughness value and microleakage among all test media. PMID:26538901

  4. FOURTEEN-DAY TOXICITY STUDY OF 1,3,5-TRINITROBENZENE IN FISCHER 344 RATS

    EPA Science Inventory

    Toxic effects of 1,3,5-trinitrobenzene (TNB) in male and female rats were evaluated by feeding powdered certified laboratory chow diet supplemented with varied concentrations of TNB (0,50,200,400,800 and 1200 mg kg-1 diet) for 14 days. Food intake by female rats in 400,800 and 12...

  5. Fate of anthracene in an artificial stream: a case study

    SciTech Connect

    Landrum, P.F.; Bartell, S.M.; Giesy, J.P.; Leversee, G.J.; Bowling, J.W.; Haddock, J.; LaGory, K.; Gerould, S.; Bruno, M.

    1984-04-01

    The fate of anthracene, a representative polycyclic aromatic hydrocarbon, was followed in a large outdoor stream microcosm. The major nonadvective route for the removal of anthracene was photolytic degradation to anthraquinone (half-life 43 min). The anthraquinone also photolyzed rapidly in this shallow stream system. Excluding the plastic channel liner, the sediment acts as the major sink for anthracene, absorbing 0.2% of the 14-day input dose. The periphyton community was the second most important sink, absorbing 0.04% of the input dose. All other compartments were of significantly less importance on a mass basis. Anthracene (11 micrograms liter-1) caused photo-induced 100% mortality of the bluegill sunfish in 9 hr in the upstream reach. Fish at the downstream station survived for approximately 26 hr and all died within 1 hr of each other. Other organisms, clams and dragonfly larvae, started to die off toward the end of the 14-day input period.

  6. Glucocorticoid effect on repair processes in vascular connective tissue. Morphological examination and biochemical studies on collagen RNA and DNA in rabbit aorta.

    PubMed

    Manthorpe, R; Garbarsch, C; Lorenzen, I

    1975-10-01

    Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced. Prednisone caused a decrease in 0.45 M NaCl soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to non-dialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone. It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue. A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular

  7. Immunohistochemical Approach to Study Cylindrospermopsin Distribution in Tilapia (Oreochromis niloticus) under Different Exposure Conditions

    PubMed Central

    Guzmán-Guillén, Remedios; Gutiérrez-Praena, Daniel; Risalde, María de los Ángeles; Moyano, Rosario; Prieto, Ana Isabel; Pichardo, Silvia; Jos, Ángeles; Vasconcelos, Vitor; Cameán, Ana María

    2014-01-01

    Cylindrospermopsin (CYN) is a cytotoxic cyanotoxin produced by several species of freshwater cyanobacteria (i.e., Aphanizomenon ovalisporum). CYN is a tricyclic alkaloid combined with a guanidine moiety. It is well known that CYN inhibits both protein and glutathione synthesis, and also induces genotoxicity and the alteration of different oxidative stress biomarkers. Although the liver and kidney appear to be the main target organs for this toxin based on previous studies, CYN also affects other organs. In the present study, we studied the distribution of CYN in fish (Oreochromis niloticus) under two different exposure scenarios using immunohistochemical (IHC) techniques. In the first method, fish were exposed acutely by intraperitoneal injection or by gavage to 200 µg pure CYN/Kg body weight (bw), and euthanized after 24 h or five days of exposure. In the second method, fish were exposed by immersion to lyophilized A. ovalisporum CYN-producing cells using two concentration levels (10 or 100 µg/L) for two different exposure times (7 or 14 days). The IHC was carried out in liver, kidney, intestine, and gills of fish. Results demonstrated a similar pattern of CYN distribution in both experimental methods. The organ that presented the most immunopositive results was the liver, followed by the kidney, intestine, and gills. Moreover, the immunolabeling signal intensified with increasing time in both assays, confirming the delayed toxicity of CYN, and also with the increment of the dose, as it is shown in the sub-chronic assay. Thus, IHC is shown to be a valuable technique to study CYN distribution in these organisms. PMID:24406981

  8. Acute oral toxicity studies of Swietenia macrophylla seeds in Sprague Dawley rats

    PubMed Central

    Balijepalli, Madhu Katyayani; Suppaiah, Velan; Chin, An-me; Buru, Ayuba Sunday; Sagineedu, Sreenivasa Rao; Pichika, Mallikarjuna Rao

    2015-01-01

    Background: Swietenia macrophylla King. (Meliaceae) seeds (SMS); commonly known as sky fruit and locally known in Malaysia as Tunjuk Langit; have been used in traditional Malay medicine for the treatment of diabetes and hypertension. The people eat only a tiny amount of raw seed, weighing not more than 5 mg. Aim: To evaluate the safety of Swietenia macrophylla seeds (SMS) at a single-dose oral administration of 2 g/kg body weight (bw) in sprague dawley (SD) rats. Materials and Methods: Eight-week old male and female SD rats were administered a single-oral dose of 2g/kg bw. The rats’ general behavior, and toxic signs were observed throughout the 14-day study period. The food and water intake by rats and their body weight were monitored during the study period. At the end of the study period, the relative weights of the organs (lung, liver, spleen, heart, kidney, testis, stomach); the hematological and biochemical parameters were measured; the architecture and histology of the organs (liver, kidney and lungs) were observed. Results: Oral administration of SMS to rats did not affect, either food or water intake; relative organ weight of vital organs; the hematological and biochemical parameters; did not show significant changes in the architecture and histology of vital organs. Overall, there were neither signs of toxicity nor deaths recorded during the study period. Conclusion: The rat dose of 2 g/kg bw is equivalent to the human dose of 325 mg/kg bw, which is well below the usual amount consumed by people, did not show any signs of toxicity in rats. PMID:25598633

  9. Feasibility Study: Home Telemonitoring for Patients With Lung Cancer in a Mountainous Rural Area

    PubMed Central

    Petitte, Trisha M.; Narsavage, Georgia L.; Chen, Yea-Jyh; Coole, Charles; Forth, Tara; Frick, Kevin D.

    2015-01-01

    Purpose/Objectives To explore the feasibility of rural home telemonitoring for patients with lung cancer. Design Exploratory, descriptive, observational. Setting Patient homes within a 75-mile radius of the study hospital in West Virginia. Sample 10 patients hospitalized with lung cancer as a primary or secondary-related diagnosis. Methods Data included referral and demographics, chart reviews, and clinical data collected using a HomMed telemonitor. Five patients received usual care after discharge; five had telemonitors set up at home for 14 days with daily phone calls for nurse coaching; mid- and end-study data were collected by phone and in homes through two months. Main Research Variables Enrollment and retention characteristics, physiologic (e.g., temperature, pulse, blood pressure, weight, O2 saturation) and 10 symptom datapoints, patient and family telemonitor satisfaction. Findings Of 45 referred patients, only 10 consented; 1 of 5 usual care and 3 of 5 monitored patients completed the entire study. Telemonitored data transmission was feasible in rural areas with high satisfaction; symptom data and physiologic data were inconsistent but characteristic of lung cancer. Conclusions Challenges included environment, culture, technology, and overall enrollment and retention. Physiologic and symptom changes were important data for nurse coaching on risks, symptom management, and clinician contact. Implications for Nursing Enrollment and retention in cancer research warrants additional study. Daily monitoring is feasible and important in risk assessment, but length of time to monitor signs and symptoms, which changed rapidly, is unclear. Symptom changes were useful as proxy indicators for physiologic changes, so risk outcomes may be assessable by phone for patient self-management coaching by nurses. PMID:24578075

  10. Ultrasound-Guided Pulsed Radiofrequency for Carpal Tunnel Syndrome: A Single-Blinded Randomized Controlled Study

    PubMed Central

    2015-01-01

    Objective We assessed the therapeutic efficiency of ultrasound-guided pulsed radiofrequency (PRF) treatment of the median nerve in patients with carpal tunnel syndrome (CTS). Methods We conducted a prospective, randomized, controlled, single-blinded study. Forty-four patients with CTS were randomized into intervention or control groups. Patients in the intervention group were treated with PRF and night splint, and the control group was prescribed night splint alone. Primary outcome was the onset time of significant pain relief assessed using the visual analog scale (VAS), and secondary outcomes included evaluation of the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) results, cross-sectional area (CSA) of the median nerve, sensory nerve conduction velocity (SNCV) of the median nerve, and finger pinch strength. All outcome measurements were performed at 1, 4, 8, and 12 weeks after treatment. Results Thirty-six patients completed the study. The onset time of pain relief in the intervention group was significantly shorter (median onset time of 2 days vs. 14 days; hazard ratio = 7.37; 95% CI, 3.04–17.87) compared to the control group (p < 0.001). Significant improvement in VAS and BCTQ scores (p < 0.05) was detected in the intervention group at all follow-up periods compared to the controls (except for the severity subscale of BCTQ at week 1). Ultrasound-guided PRF treatment resulted in a lower VAS score and stronger finger pinch compared to the control group over the entire study. Conclusions Our study shows that ultrasound-guided PRF serves as a better approach for pain relief in patients with CTS. Trial Registration ClinicalTrials.gov NCT02217293 PMID:26067628

  11. Acute oral toxicity and biodistribution study of zinc-aluminium-levodopa nanocomposite

    NASA Astrophysics Data System (ADS)

    Kura, Aminu Umar; Saifullah, Bullo; Cheah, Pike-See; Hussein, Mohd Zobir; Azmi, Norazrina; Fakurazi, Sharida

    2015-03-01

    Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study ( P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration.

  12. The effect of fluoride toothpaste on root dentine demineralization progression: a pilot study.

    PubMed

    Botelho, Juliana Nunes; Del Bel Cury, Altair Antoninha; Silva, Wander Jose da; Tenuta, Livia Maria Andalo; Cury, Jaime Aparecido

    2014-01-01

    The anticaries effect of fluoride (F) toothpaste containing 1100 µg F/g in reducing enamel demineralization is well established, but its effect on dentine has not been extensively studied. Furthermore, it has been shown that toothpaste containing a high F concentration is necessary to remineralize root dentine lesions, suggesting that a 1100 µg F/g concentration might not be high enough to reduce root dentine demineralization, particularly when dentine is subjected to a high cariogenic challenge. Thus, the aim of this pilot study was to evaluate in situ the effect of F toothpaste, at a concentration of 1100 µg F/g, on dentine demineralization. In a crossover and double-blind study, conducted in two phases of 14 days, six volunteers wore a palatal appliance containing four slabs of bovine root dentine whose surface hardness (SH) was previously determined and to which a 10% sucrose solution was applied extra-orally 8×/day. Volunteers used a non-F toothpaste (negative control) or F toothpaste (1100 µg F/g, NaF/SiO2) three times a day. On the 10th and 14th days of each phase, two slabs were collected and SH was determined again. Dentine demineralization was assessed as percentage of SH loss (%SHL). The effect of toothpaste was significant, showing lower %SHL for the F toothpaste group (42.0 ± 9.7) compared to the non-F group (62.0 ± 6.4; p < 0.0001), but the effect of time was not significant (p > 0.05). This pilot study suggests that F toothpaste at 1100 µg F/g is able to decrease dentine caries even under a high cariogenic challenge of biofilm accumulation and sugar exposure. PMID:24554099

  13. Oral Toxicity Study and Skin Sensitization Test of a Cricket.

    PubMed

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-04-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  14. Oral Toxicity Study and Skin Sensitization Test of a Cricket

    PubMed Central

    Ryu, Hyeon Yeol; Lee, Somin; Ahn, Kyu Sup; Kim, Hye Jin; Lee, Sang Sik; Ko, Hyuk Ju; Lee, Jin Kyu; Cho, Myung-Haing; Ahn, Mi Young; Kim, Eun Mi; Lim, Jeong Ho; Song, Kyung Seuk

    2016-01-01

    Crickets have been attracting considerable interest in the field of nutrition and toxicology due to the global exhaustion of food resulting from a growing population. The cricket is normally eaten in several countries after roasting, similar to the grasshopper; however, safety evaluation data on cricket powder is limited. Here, we performed general toxicity studies of cricket powder including a single, 2-week repeated dose range evaluation test, a 13-week repeated oral dose toxicity test in Sprague-Dawley rats, a single oral dose toxicity test in Beagle dogs, and a skin sensitization test in guinea pigs following the Organization for Economic Cooperation and Development test guidelines 406 and 408 in addition to Good Laboratory Practice. To investigate the NOAEL and target organs of cricket powder, Sprague-Dawley rats were allocated to 4 groups: vehicle control, 1,250 mg/kg, 2,500 mg/kg, 5,000 mg/kg dose test groups and cricket powder was administered over 13 weeks after single dose and dose range finding studies in rats based on the results of the single oral administration toxicity study in rats and Beagle dogs. The results of the study showed that the NOAEL of cricket powder was over 5,000 mg/kg for both sexes of rats without adverse effects in a 13-week repeated oral toxicity study and there was no skin hypersensitivity reaction. Therefore, our results reveal that crickets can be widely used as a new substitute food or nutrient resource. PMID:27123167

  15. Study of Subchronic Toxicity of Relatox on Sexually Immature Animals.

    PubMed

    Churin, A A; Fomina, T I; Ermolaeva, L A; Vetoshkina, T V; Dubskaya, T Yu; Lamzina, T Yu; Fedorova, E P; Neupokoeva, O V; Nikiforova, A N

    2015-11-01

    Intramuscular injections of Relatox in therapeutic and toxic doses to young outbred laboratory rats for 14 days caused no changes in the peripheral blood and bone marrow parameters, serum biochemical parameters, and morphology of the major viscera. In the toxic dose, the drug caused local irritation (inflammation, atrophy, and sclerosis in muscle tissue). Regeneration processes started in muscle tissue 7 days after Relatox withdrawal. PMID:26593416

  16. A multicenter phase II study of sepantronium bromide (YM155) plus rituximab in patients with relapsed aggressive B-cell Non-Hodgkin lymphoma.

    PubMed

    Papadopoulos, Kyriakos P; Lopez-Jimenez, Javier; Smith, Scott E; Steinberg, Joyce; Keating, Anne; Sasse, Carolyn; Jie, Fei; Thyss, Antoine

    2016-08-01

    This phase II study evaluated YM155, a novel small-molecule survivin suppressant, in combination with rituximab in patients with relapsed aggressive B-cell non-Hodgkin lymphoma (NHL) who failed or were not candidates for autologous stem cell transplant (ASCT). During 14-day cycles, 41 patients received YM155 (5mg/m(2)/d) by continuous intravenous (IV) infusion for 168 hours (day 1-7), and rituximab (375mg/m(2)) IV on days 1 and 8 during cycles 1-4 and repeated for 4 cycles every 10 cycles. Forty patients (97.6%) had prior rituximab and 15 patients (36.6%) prior ASCT. Most frequent grade 3-4 adverse events were neutropenia (19.5%) and thrombocytopenia (12.2%). In the per-protocol set (n = 34), objective response rate was 50% and median progression-free survival 17.9 months. Median overall survival was not reached at study termination (median follow-up, 23 months). YM155 in combination with rituximab was tolerable with encouraging antitumor activity and durable responses in relapsed aggressive B-cell NHL patients. PMID:26857688

  17. Histopathological studies of acute and chronic effects of Calliandra portoricensis leaf extract on the stomach and pancreas of adult Swiss albino mice

    PubMed Central

    Ofusori, David A; Adejuwon, Adebomi O

    2011-01-01

    Objective To evaluate the consequence of oral administration of Calliandra portoricensis (C. portoricensis) leaf extract on the stomach and pancreas in Swiss albino mice. Methods Three groups of mice (B, C and D) were treated with 4 mg/kg of C. portoricensis extract. Group A was the control and received an equivalent volume of distilled water. Group B received C. portoricensis leaf extract for 7 days, Group C received C. portoricensis leaf extract for 14 days, and Group D received C. portoricensis leaf extract for 28 days. At different stages in the study, the mice were sacrificed and the stomach and pancreas were excised and fixed in 10% formol saline for histological analysis. Results The result showed a normal microstructural outline in groups B and C as compared with the control. However, animals in group D showed disorganization of the mucosa and discontinuation of epithelial lining of the stomach while the islets of Langerans in the pancreas were at various degree of degeneration as compared with the control mice. Conclusions The present finding suggests that chronic administration (28 days as seen in this study) of C. portoricensis leaf extract may inhibit the proper function of the stomach and pancreas. PMID:23569755

  18. How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study

    PubMed Central

    Léger, Julie; Tandé, Didier; Plouzeau, Chloé; Valentin, Anne Sophie; Jolivet-Gougeon, Anne; Lemarié, Carole; Kempf, Marie; Héry-Arnaud, Geneviève; Bret, Laurent; Juvin, Marie Emmanuelle; Giraudeau, Bruno; Burucoa, Christophe

    2015-01-01

    Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI. PMID:26637380

  19. A randomized study of the effects of food on the pharmacokinetics of once-daily extended-release hydromorphone in healthy volunteers.

    PubMed

    Moore, Kenneth Todd; St-Fleur, Dominique; Marricco, Nadia Cardillo; Ariyawansa, Jay; Pagé, Véronique; Natarajan, Jayalakshmi; Morelli, Gaetano; Richarz, Ute

    2011-11-01

    This randomized, open-label, crossover study investigated the influence of food on the pharmacokinetics of extended-release hydromorphone in 30 healthy volunteers. Participants received extended-release hydromorphone 16 mg in the fasted state and immediately after a high-fat breakfast. In addition, the pharmacokinetics of a 16-mg dose of extended-release hydromorphone and a 16-mg daily dose (4 mg qid) of immediate-release hydromorphone in the fasted state were compared. Treatments were separated by washout periods of 7 to 14 days. Naltrexone was given throughout each treatment period to block the opioid effects of hydromorphone. The 90% confidence intervals (CIs) of the ratios of geometric means for maximum plasma concentrations (C(max)) and area under the plasma concentration-time curve (AUC) for extended-release hydromorphone in the fed and fasted states were within the bioequivalence criteria range of 80% to 125%. In the fasted state, the 90% CIs of the ratios of AUC geometric means for extended-release hydromorphone and immediate-release hydromorphone were also within the bioequivalence range. Both hydromorphone treatments were well tolerated. This study shows that the bioavailability of extended-release hydromorphone is not affected by food and that the bioavailability of extended-release hydromorphone under fasting conditions is comparable with that of the immediate-release formulation when administered at the same total daily dose. PMID:21098692

  20. Study of changes in phosphate, calcium and fluoride ions in plaque and saliva after the administration of a fluoride mouth rinse.

    PubMed

    Poureslami, H R; Torkzadeh, M; Sefadini, M R

    2007-01-01

    In this study, the effects of 0.2% sodium fluoride mouthwash solution on calcium, phosphate and fluoride ion contents of saliva and microbial plaque was assessed. Fourteen volunteer students (7-12 years of age) of a boarding educational centre in Kerman City (Iran) were selected and under defined conditions, their saliva and plaque samples were collected. The concentrations of fluoride, calcium and phosphate ions of the samples were determined, and after 14 days, under the same conditions, the students were asked to rinse their mouth with 0.2% sodium fluoride mouthwash solution. The second set of saliva and plaque samples were collected and the concentrations of the ions were determined. Data was analyzed using paired t-test and the results were presented as tables. P < 0.05 was considered as statistically significant. After using 0.2% sodium fluoride mouthwash solution, a significant increase was observed in the F 2 ion concentration both plaque ( P P < 0.000) of all the studied subjects, while the concentration of phosphate decreased in both saliva and plaque; however, this decrease was significant only in plaque ( P < 0.01). The calcium ion concentration decreased in both plaque and saliva; however, in none of them, the decrease was significant ( P> 0.09 and P> 0.2, respectively). PMID:17951927

  1. Increase of 20-HETE synthase after brain ischemia in rats revealed by PET study with 11C-labeled 20-HETE synthase-specific inhibitor

    PubMed Central

    Kawasaki, Toshiyuki; Marumo, Toshiyuki; Shirakami, Keiko; Mori, Tomoko; Doi, Hisashi; Suzuki, Masaaki; Watanabe, Yasuyoshi; Chaki, Shigeyuki; Nakazato, Atsuro; Ago, Yukio; Hashimoto, Hitoshi; Matsuda, Toshio; Baba, Akemichi; Onoe, Hirotaka

    2012-01-01

    20-Hydroxyeicosatetraenoic acid (20-HETE), an arachidonic acid metabolite known to be produced after cerebral ischemia, has been implicated in ischemic and reperfusion injury by mediating vasoconstriction. To develop a positron emission tomography (PET) probe for 20-HETE synthase imaging, which might be useful for monitoring vasoconstrictive processes in patients with brain ischemia, we synthesized a 11C-labeled specific 20-HETE synthase inhibitor, N′(4-dimethylaminohexyloxy)phenyl imidazole ([11C]TROA). Autoradiographic study showed that [11C]TROA has high-specific binding in the kidney and liver consistent with the previously reported distribution of 20-HETE synthase. Using transient middle cerebral artery occlusion in rats, PET study showed significant increases in the binding of [11C]TROA in the ipsilateral hemisphere of rat brains after 7 and 10 days, which was blocked by co-injection of excess amounts of TROA (10 mg/kg). The increased [11C]TROA binding on the ipsilateral side returned to basal levels within 14 days. In addition, quantitative real-time PCR revealed that increased expression of 20-HETE synthase was only shown on the ipsilateral side on day 7. These results indicate that [11C]TROA might be a useful PET probe for imaging of 20-HETE synthase in patients with cerebral ischemia. PMID:22669478

  2. Evaluation of a peripherally selective antiandrogen (Casodex) as a tool for studying the relationship between testosterone and spermatogenesis in the rat.

    PubMed

    Chandolia, R K; Weinbauer, G F; Behre, H M; Nieschlag, E

    1991-03-01

    The endocrine profile and the effects on spermatogenesis of the new antiandrogen, Casodex [2RS)-4-cyano-3-(4-fluorophenylsulphonyl)-2-anilide, CAS) were evaluated in the adult rat. In the first experiment rats were administered CAS at daily doses of 10, 20 and 40 mg/kg for 14 days. For comparison groups receiving flutamide (FL, 10 mg/kg) and ethane dimethane sulphonate (EDS) were included. Unlike FL, administration of CAS (10 and 20 mg/kg) did not significantly raise serum concentrations of gonadotropic hormones and testosterone. With 40 mg/kg CAS gonadotropin secretion, but not testosterone levels, were elevated on day 15. Administration of CAS lowered the weight of the seminal vesicles and coagulating glands comparable to the administration of the Leydig cell toxin EDS. In contrast to FL a significant loss of germ cells in stage VII of spermatogenesis was observed with CAS. In a second experiment the ability of FL and CAS to block testicular androgen action was compared in rats with reduced testicular androgen production induced by a gonadotropin-releasing hormone antagonist. Both antiandrogens markedly enhanced spermatogenic involution as revealed by quantitative flow cytometric analysis of germ cell numbers. The study demonstrates that (a) CAS is a peripherally selective antiandrogen and (b) CAS might provide a feasible approach to study androgen dependence of spermatogenesis in the presence of normal FSH levels. PMID:1848993

  3. How Many Samples and How Many Culture Media To Diagnose a Prosthetic Joint Infection: a Clinical and Microbiological Prospective Multicenter Study.

    PubMed

    Bémer, Pascale; Léger, Julie; Tandé, Didier; Plouzeau, Chloé; Valentin, Anne Sophie; Jolivet-Gougeon, Anne; Lemarié, Carole; Kempf, Marie; Héry-Arnaud, Geneviève; Bret, Laurent; Juvin, Marie Emmanuelle; Giraudeau, Bruno; Corvec, Stéphane; Burucoa, Christophe

    2016-02-01

    Although numerous perioperative samples and culture media are required to diagnose prosthetic joint infection (PJI), their exact number and types have not yet been definitely determined with a high level of proof. We conducted a prospective multicenter study to determine the minimal number of samples and culture media required for accurate diagnosis of PJI. Over a 2-year period, consecutive patients with clinical signs suggesting PJI were included, with five perioperative samples per patient. The bacteriological and PJI diagnosis criteria were assessed using a random selection of two, three, or four samples and compared with those obtained using the recommended five samples (references guidelines). The results obtained with two or three culture media were then compared with those obtained with five culture media for both criteria. The times-to-positivity of the different culture media were calculated. PJI was confirmed in 215/264 suspected cases, with a bacteriological criterion in 192 (89%). The PJI was monomicrobial (85%) or polymicrobial (15%). Percentages of agreement of 98.1% and 99.7%, respectively, for the bacteriological criterion and confirmed PJI diagnosis were obtained when four perioperative samples were considered. The highest percentages of agreement were obtained with the association of three culture media, a blood culture bottle, a chocolate agar plate, and Schaedler broth, incubated for 5, 7, and 14 days, respectively. This new procedure leads to significant cost saving. Our prospective multicenter study showed that four samples seeded on three culture media are sufficient for diagnosing PJI. PMID:26637380

  4. Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1)

    PubMed Central

    Schwartz, G K; LoRusso, P M; Dickson, M A; Randolph, S S; Shaik, M N; Wilner, K D; Courtney, R; O'Dwyer, P J

    2011-01-01

    Background: This phase I, open-label, first-in-human study determined dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of PD 0332991, an oral cyclin-dependent kinase 4/6 inhibitor with potent anti-proliferative activity in vitro/vivo. Methods: A total of 33 patients with retinoblastoma protein-positive advanced solid tumours or non-Hodgkin's lymphoma refractory to standard therapy or for which no therapy was available received PD 0332991 once daily (QD) for 14 days followed by 7 days off treatment (21-day cycles; Schedule 2/1). Results: Six patients had DLTs (18% four receiving 200 mg QD; two receiving 225 mg QD); the MTD was 200 mg QD. Treatment-related, non-haematological adverse events occurred in 29 patients (88%) during cycle 1 and 27 patients (82%) thereafter. Adverse events were generally mild–moderate. Of 31 evaluable patients, one with testicular cancer achieved a partial response; nine had stable disease (⩾10 cycles in three cases). PD 0332991 was slowly absorbed (mean Tmax 4.2 h) and eliminated (mean half-life 26.7 h). Volume of distribution was large (mean 3241 l) with dose-proportional exposure. Using a maximum effective concentration model, neutropenia was proportional to exposure. Conclusion: PD 0332991 was generally well tolerated, with DLTs related mainly to myelosuppression. The MTD, 200 mg QD, is recommended for phase II study. PMID:21610706

  5. Comparative study of emerging micropollutants removal by aerobic activated sludge of large laboratory-scale membrane bioreactors and sequencing batch reactors under low-temperature conditions.

    PubMed

    Kruglova, Antonina; Kråkström, Matilda; Riska, Mats; Mikola, Anna; Rantanen, Pirjo; Vahala, Riku; Kronberg, Leif

    2016-08-01

    Four emerging micropollutants ibuprofen, diclofenac, estrone (E1) and 17α-ethinylestradiol (EE2) were studied in large laboratory-scale wastewater treatment plants (WWTPs) with high nitrifying activity. Activated sludge (AS) with sludge retention times (SRTs) of 12days and 14days in sequencing batch reactors (SBRs) and 30days, 60days and 90days in membrane bioreactors (MBRs) were examined at 8°C and 12°C. Concentrations of pharmaceuticals and their main metabolites were analysed in liquid phase and solid phase of AS by liquid chromatography-tandem mass spectrometry (LC-MS/MS). A remarkable amount of contaminants were detected in solids of AS, meaning the accumulation of micropollutants in bacterial cells. The biodegradation rate constants (Kbiol) were affected by SRT and temperature. MBR with a 90-day SRT showed the best results of removal. Conventional SBR process was inefficient at 8°C showing Kbiol values lower than 0.5lgSS(-1)d(-1) for studied micropollutants. PMID:27128192

  6. Toxicologic evaluation of tungsten: 28-day inhalation study of tungsten blue oxide in rats.

    PubMed

    Rajendran, Narayanan; Hu, Shu-Chieh; Sullivan, Dennis; Muzzio, Miguel; Detrisac, Carol J; Venezia, Carmen

    2012-12-01

    The toxicity and toxicokinetics of tungsten blue oxide (TBO) were examined. TBO is an intermediate in the production of tungsten powder, and has shown the potential to cause cellular damage in in vitro studies. However, in vivo evidence seems to indicate a lack of adverse effects. The present study was undertaken to address the dearth of longer-term inhalation toxicity studies of tungsten oxides by investigating the biological responses induced by TBO when administered via nose-only inhalation to rats at levels of 0.08, 0.325, and 0.65 mg TBO/L of air for 6 h/day for 28 consecutive days, followed by a 14-day recovery period. Inhaled TBO was absorbed systemically and blood levels of tungsten increased as inhaled concentration increased. Among the tissues analyzed for tungsten levels, lung, femur and kidney showed increased levels, with lung at least an order of magnitude greater than kidney or femur. By exposure day 14, tungsten concentration in tissues had reached steady-state. Increased lung weight was noted for both terminal and recovery animals and was attributed to deposition of TBO in the lungs, inducing a macrophage influx. Microscopic evaluation of tissues revealed a dose-related increase in alveolar pigmented macrophages, alveolar foreign material and individual alveolar foamy macrophages in lung. After a recovery period there was a slight reduction in the incidence and severity of histopathological findings. Based on the absence of other adverse effects, the increased lung weights and the microscopic findings were interpreted as nonadverse response to exposure and were not considered a specific reaction to TBO. PMID:23216159

  7. Hypoglycemic and anti-hyperglycemic study of Gynura procumbens leaf extracts

    PubMed Central

    Algariri, Khalid; Meng, Kuong Y; Atangwho, Item J; Asmawi, Mohd Z; Sadikun, Amirin; Murugaiyah, Vikneswaran; Ismail, Norhyati

    2013-01-01

    Objective To study the antidiabetic activity of Gynura procumbens (G. procumbens) used in the traditional management of diabetes in Southern Asia. Methods G. procumbens leaves were extracted sequentially with graded percentage of ethanol in water (95%, 75%, 50%, 25% and 0%), and the extracts were tested for antidiabetic activity using acute (7 h), subcutaneous glucose tolerance test and sub-chronic (14 d) test in non-diabetic and streptozotocin-induced diabetic rats. The extracts were further subjected to phytochemical studies. Results In acute dose (1 g/kg), the extracts significantly lowered fasting blood glucose (FBG) in streptozotocin-induced diabetic rats (P<0.05). However, the FBG-lowering effect of the 25% extract compared to the other extracts, was rapid (47% after 2 h) and the highest: 53%, 53% and 60% in the 3rd, 5th, and 7th h, respectively (P<0.05), comparable only to the effect of metformin. Furthermore, the extracts suppressed peak FBG in subcutaneous glucose tolerance test, but only the 0% and 25% extracts, and metformin sustained the decrease until the 90th min (P<0.05). Moreover, in the 14 days study, the 25% extract exerted the highest FBG-lowering effect, namely 49.38% and 65.43% on days 7 and 14, respectively (P<0.05), similar to the effect of metformin (46.26% and 65.42%). Total flavanoid and phenolic contents in the extracts were found to decrease with increase in polarity of extraction solvents. The composition of reference compounds (chlorogenic acid, rutin, astragalin and kaempferol-3-O-rutinoside) followed a similar trend. Conclusions G. procumbens contains antidiabetic principles, most extracted in 25% ethanol. Interaction among active components appears to determine the antidiabetic efficacy, achieved likely by a metformin-like mechanism. PMID:23646298

  8. The validity and acceptability of a text-based monitoring system for pediatric asthma studies.

    PubMed

    Gahleitner, Florian; Legg, Julian; Holland, Emma; Pearson, Sarah; Roberts, Graham

    2016-01-01

    A meaningful analysis in research requires robust, valid data. Paper diaries allow the collection of data from individuals over time but are notorious for poor compliance and validity. SMS-technology is a novel method for data collection in medical research. Time-tagged SMS are transferred directly to an electronic file. We used SMS to collect symptoms and peak flow rate (PEFR) meter readings from 32 children with asthma. Parents responded first to five SMS daily for 7 days during an asymptomatic period and then for 14 days during a cold. Compliance with use of PEFR meter and SMS system were assessed. Digital PEFR meters enabled data download at the end of the study to confirm validity of transmitted data. Parents of 24 participants provided feedback about this data collection tool. Mean (±SD) "SMS-diary and PEFR-meter compliance" were 96% (±8) and 84% (±21) during baseline and 91% (±12) and 82% (±20) during cold respectively. Correctly reported PEFR values were found in 65.5% of all cases, in 8.3% PEFR values sent were "self-invented" and 2.4% of values were missing. All of the 22 parents completing the baseline questionnaire were happy to use SMS for this study. Of the 20 parents completing the follow up questionnaire, 95% (19/20) found the system user-friendly, 55% (11/20) would be more likely to participate in studies if they were using SMS data collection and 25% (5/20) were "sometimes unhappy" about receiving messages. This real-time capture of data is well accepted and could avoid some of the pitfalls of backfilled paper diaries. PMID:25847724

  9. The kinetics of the oxidation of pyrite by ferric ions and dissolved oxygen: An electrochemical study

    SciTech Connect

    Holmes, P.R.; Crundwell, F.K.

    2000-01-01

    The dissolution of pyrite is important in the geochemical cycling of iron and sulphur, in the formation of acid mine drainage, and in the extraction of metals by bacterial leaching. Many researchers have studied the kinetics of dissolution, and the rate of dissolution has often been found to be half-order in ferric ions or oxygen. Previous work has not adequately explained the kinetics of dissolution of pyrite. The dissolution of pyrite is an oxidation-reduction reaction. The kinetics of the oxidation and reduction half-reactions was studied independently using electrochemical techniques of voltammetry. The kinetics of the overall reaction was studied by the electrochemical technique of potentiometry, which consisted of measuring the mixed potential of a sample of corroding pyrite in solutions of different compositions. The kinetics of the half reactions are related to the kinetics of the overall dissolution reaction by the condition that there is no accumulation of charge. This principle is used to derive expressions for the mixed potential and the rate of dissolution, which successfully describe the mixed potential measurements and the kinetics of dissolution reported in the literature. It is shown that the observations of half-order kinetics and that the oxygen in the sulphate product arises from water are both a direct consequence of the electrochemical mechanism. Thus it is concluded that the electrochemical reaction steps occurring at the mineral-solution interface control the rate of dissolution. Raman spectroscopy was used to analyze reaction products formed on the pyrite surface. The results indicated that small amounts of polysulphides form on the surface of the pyrite. However, it was also found that the mixed (corrosion) potential does not change over a 14-day leaching period. This indicates that even though polysulphide material is present on the surface, it does not influence the rate of the reactions occurring at the surface. Measurement of the

  10. Studies on Porcine Circovirus Type 2 Vaccination of 5-Day-Old Piglets ▿

    PubMed Central

    O'Neill, K. C.; Shen, H. G.; Lin, K.; Hemann, M.; Beach, N. M.; Meng, X. J.; Halbur, P. G.; Opriessnig, T.

    2011-01-01

    Porcine circovirus type 2 (PCV2) vaccines have become widely used since they became available in 2006. It is not uncommon for producers to use PCV2 vaccines in pigs younger than what is approved by manufacturers. The objective of this study was to determine the efficacy of a chimeric and a subunit PCV2 vaccine administered at 5 or 21 days of age. Forty-eight PCV2-naïve piglets were randomly divided into six groups of eight pigs each. Vaccination was done at day 5 or day 21, followed by triple challenge with PCV2, porcine parvovirus (PPV), and porcine reproductive and respiratory syndrome virus (PRRSV) at day 49. Vaccinated pigs seroconverted to PCV2 approximately 14 days postvaccination and had a detectable neutralizing antibody response by 21 days postvaccination regardless of age at vaccination. At day 49, the pigs vaccinated with the chimeric vaccine had significantly higher levels of neutralizing antibodies than the pigs vaccinated with the subunit vaccine. After challenge, vaccinated pigs had significantly decreased levels of PCV2 viremia and a decreased prevalence and severity of microscopic lesions compared to the positive-control group, which had severe lymphoid lesions associated with abundant PCV2 antigen, compatible with PCV-associated disease. The results of this study indicate that, under the conditions of this study, vaccination of PCV2-naïve pigs at day 5 or day 21 resulted in development of a detectable humoral immune response and provided reduction or complete protection against PCV2 viremia and PCV2-associated lesions after triple challenge with PCV2, PPV, and PRRSV. PMID:21940407

  11. Impact of oseltamivir use on the reduction of complications in patients with influenza: a prospective study.

    PubMed

    Vardakas, Konstantinos Z; Theocharis, George; Tansarli, Giannoula S; Rafailidis, Petros; Falagas, Matthew E

    2016-09-01

    To evaluate the factors associated with oseltamivir prescription and to study the effectiveness of oseltamivir in reducing influenza-related complications. A prospective cohort study using the SOS Doctors (a network of physicians who perform house-call visits in Attica, Greece). Patients with confirmed or clinically suspected influenza were followed up to 14 days during the 2011-2012 influenza period. 410 patients with confirmed or suspected influenza were included. Healthy adults were mainly enrolled, with a median age of 44 years. Influenza diagnosis was mainly based on clinical criteria (65.8 % of patients). Oseltamivir was prescribed for 45.4 % of them. In a multivariate analysis, prescription of oseltamivir was associated with the attending physician (p < 0.001), positive influenza test (p < 0.001) and diabetes (p = 0.027). Data on complications were available for 351 patients, and 50 (15.8 %) of them reported at least one. Seven patients required hospitalization. Types of complications (pneumonia, bronchitis, etc.) were not significantly different between patients receiving and those not receiving oseltamivir. In the multivariate analysis, higher oseltamivir prescription rate was associated with fewer complications (p < 0.001). Bearing in mind the limitations of a non-randomized study, in a real-life setting, oseltamivir prescription and the rate of complications in patients with influenza were associated with the attending physician, underlying diseases and diagnostic tests. Overall, when the frequency of oseltamivir prescription increased, the influenza-related complications decreased. PMID:27368992

  12. Decreased organ failure in patients with severe SIRS and septic shock treated with the platelet-activating factor antagonist TCV-309: a prospective, multicenter, double-blind, randomized phase II trial. TCV-309 Septic Shock Study Group.

    PubMed

    Poeze, M; Froon, A H; Ramsay, G; Buurman, W A; Greve, J W

    2000-10-01

    Sepsis and organ failure remain the main cause of death on the ICU. Sepsis is characterized by a severe inflammatory response, in which platelet-activating factor (PAF) is considered to play an important role. This study investigated whether treatment with the PAF-antagonist TCV-309 reduces morbidity and mortality in patients with septic shock. The study was conducted as a double-blind, randomized, placebo controlled multicenter study. The included patients had to fulfill the SIRS criteria with a clinical suspicion of infection, an admission APACHE II score greater than 15, and shock, defined as a mean arterial pressure <70 mmHg and/or a decrease > or =40 mmHg despite adequate fluid resuscitation. Patients received 1.0 mg/kg TCV-309 or placebo, twice daily, intravenously during 14 days. The prospectively set goals were MOF score, recovery from shock, mortality, and assessment of the safety of the medication. A total of 98 patients were included of which 97 were analyzed on an intention-to-treat basis. The overall survival at day 56 of TCV-309 treated patients was similar compared to placebo treated patients (51.0% vs. 41.7%, P = 0.47). In contrast, the mean percentage of failed organs per patient present after 14 days in the TCV-309 treated patients was significantly lower compared to the placebo treated patients (11.9% vs. 25.1%, P = 0.04), leading to a reduced need for vasopressors, dialysis, and ventilatory support. Furthermore, the mean APACHE-II score during treatment with TCV-309 was significantly lower and the number of patients recovered from shock after day 14 was significantly higher in the TCV-309 treated patient group (2/32 vs. 9/29, P = 0.01). The number of adverse events was not significantly different between the TCV-309 and placebo treated patients. TCV-309 did not change overall mortality of septic shock, however a substantial reduction in organ dysfunction and morbidity, frequently associated with septic shock was achieved, without significant

  13. Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections

    PubMed Central

    Ramesh, Mayakonda Krishnamurthy; Cesnauskas, Gintaras; Novikovs, Nikolajs; Stefanova, Penka; Sutcliffe, Joyce A.; Walpole, Susannah M.

    2014-01-01

    Eravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogens in vitro, including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.) PMID:24342651

  14. Toxicity of colloidal silica nanoparticles administered orally for 90 days in rats

    PubMed Central

    Kim, Yu-Ri; Lee, Seung-Young; Lee, Eun Jeong; Park, Sung Ha; Seong, Nak-won; Seo, Heung-Sik; Shin, Sung-Sup; Kim, Seon-Ju; Meang, Eun-Ho; Park, Myeong-Kyu; Kim, Min-Seok; Kim, Cheol-Su; Kim, Soo-Ki; Son, Sang Wook; Seo, Young Rok; Kang, Boo Hyon; Han, Beom Seok; An, Seong Soo A; Lee, Beom-Jun; Kim, Meyoung-Kon

    2014-01-01

    This study was undertaken to investigate the potential toxicity and establish the no observed adverse effect level (NOAEL) and target organ(s) of negatively charged colloidal silica particles of different sizes, ie, SiO2EN20(−) (20 nm) or SiO2EN100(−) 2(100 nm), administered by gavage in Sprague-Dawley rats. After verification of the physicochemical properties of the SiO2 particles to be tested, a preliminary dose range-finding study and 90-day repeated dose study were conducted according to the Organisation for Economic Cooperation and Development test guideline. Based on the results of the 14-day dose range-finding study, a high dose was determined to be 2,000 mg/kg, and middle and low doses were set at 1,000 and 500 mg/kg, respectively. In the 90-day toxicity study, there were no animal deaths in relation to administration of SiO2 particles of either size. In addition, no treatment-related clinical changes or histopathological findings were observed in any of the experimental groups. Moreover, no difference in toxic effects from chronic exposure to SiO2EN20(−)(20 nm) or SiO2EN100(−) (100 nm) was observed. The results of this study indicate that the NOAEL for SiO2EN20(−) and SiO2 EN100(−) would most likely be 2,000 mg/kg, and no target organ was identified in rats of either sex. PMID:25565827

  15. Chronic escalating cocaine exposure, abstinence/withdrawal, and chronic re-exposure: effects on striatal dopamine and opioid systems in C57BL/6J mice.

    PubMed

    Zhang, Yong; Schlussman, Stefan D; Rabkin, Jacqui; Butelman, Eduardo R; Ho, Ann; Kreek, Mary Jeanne

    2013-04-01

    Cocaine addiction is a chronic relapsing disease with periods of chronic escalating self-exposure, separated by periods of abstinence/withdrawal of varying duration. Few studies compare such cycles in preclinical models. This study models an "addiction-like cycle" in mice to determine neurochemical/molecular alterations that underlie the chronic, relapsing nature of this disease. Groups of male C57BL/6J mice received acute cocaine exposure (14-day saline/14-day withdrawal/13-day saline + 1-day cocaine), chronic cocaine exposure (14 day cocaine) or chronic re-exposure (14-day cocaine/14-day withdrawal/14-day cocaine). Escalating-dose binge cocaine (15-30 mg/kg/injection × 3/day, i.p. at hourly intervals) or saline (14-day saline) was administered, modeling initial exposure. In "re-exposure" groups, after a 14-day injection-free period (modeling abstinence/withdrawal), mice that had received cocaine were re-injected with 14-day escalating-dose binge cocaine, whereas controls received saline. Microdialysis was conducted on the 14th day of exposure or re-exposure to determine striatal dopamine content. Messenger RNA levels of preprodynorphin (Pdyn), dopamine D1 (Drd1) and D2 (Drd2) in the caudate putamen were determined by real-time PCR. Basal striatal dopamine levels were lower in mice after 14-day escalating exposure or re-exposure than in those in the acute cocaine group and controls. Pdyn mRNA levels were higher in the cocaine groups than in controls. Long-term adaptation was observed across the stages of this addiction-like cycle, in that the effects of cocaine on dopamine levels were increased after re-exposure compared to exposure. Changes in striatal dopaminergic responses across chronic escalating cocaine exposure and re-exposure are a central feature of the neurobiology of relapsing addictive states. PMID:23164614

  16. Multicenter Phase II Study of Sequential Radioembolization-Sorafenib Therapy for Inoperable Hepatocellular Carcinoma

    PubMed Central

    Chow, Pierce K. H.; Poon, Donald Y. H.; Khin, Maung-Win; Singh, Harjit; Han, Ho-Seong; Goh, Anthony S. W.; Choo, Su-Pin; Lai, Hee-Kit; Lo, Richard H. G.; Tay, Kiang-Hiong; Lim, Teong-Guan; Gandhi, Mihir; Tan, Say-Beng; Soo, Khee-Chee

    2014-01-01

    Background The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies. Methods Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS). Results Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ≥1 toxicity; 15 (52%) grade ≥3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively. Conclusions This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib. Trial Registration ClinicalTrials.gov NCT00712790. PMID:24614178

  17. Lutein bioavailability from lutein ester-fortified fermented milk: in vivo and in vitro study.

    PubMed

    Granado-Lorencio, Fernando; Herrero-Barbudo, Carmer; Olmedilla-Alonso, Begoña; Blanco-Navarro, Inmaculada; Pérez-Sacristán, Belén

    2010-02-01

    We assessed the bioavailability of lutein from lutein-fortified fermented milk using in vivo and in vitro approaches. Twenty-four volunteers were randomized to take lutein-fortified fermented milk at two levels of fortification. Single-dose bioavailability study (2x100 ml, ca. 8 or 16 mg of lutein) was performed using a three-point approach (baseline, 3.5 and 6.5 h). Multiple-dose study consisted of consuming one serving/day (ca. 4 or 8 mg/100 ml) for 14 days. Blood samples for biochemical, hematological and lutein analysis were drawn at baseline, Day 7 and Day 14. In vitro bioaccessibility was assessed by a static gastrointestinal digestion model. Lutein content, in vitro ester hydrolysis and micellarization, and lutein concentrations achieved in serum were analyzed by HPLC. In vivo, post-prandial response was higher using the high content fermented milk, but the percentage of absorption was not different according to the dose consumed. Net increments at Day 7 and Day 14 were significantly higher on consuming the high-dose milk as well. In vitro, lutein ester hydrolysis was incomplete regardless of the amount initially present. Free lutein released was higher using the high-dose fermented milk, but the percentage of hydrolysis was similar at both levels of fortification. In the micellar phase, the percentage of free and total lutein was not different according to the dose. Our results support the suitability of the fermented milk as a carrier of lutein esters and an in vivo dose-dependent effect upon regular consumption and suggest the usefulness of in vitro models to provide relevant information to predict in vivo responses. PMID:19201183

  18. A Study on Health Seeking Behaviors of Patients of Post-Kala-Azar Dermal Leishmaniasis

    PubMed Central

    Basher, Ariful; Nath, Proggananda; Nabi, Shah Golam; Selim, Shahjada; Rahman, Md Fashiur; Sutradhar, Satya Ranjan; Faiz, Abul; Bhuiyan, Matiur Rahman; Ahmed, Be-Nazir; Rahman, Ridwanur

    2015-01-01

    Post-Kala-Azar Dermal Leishmaniasis (PKDL) remains a major public health threat in Bangladesh. A cross-sectional study was carried out in Surya Kanta Kala azar Research Centre (SKKRC), Mymensingh, from January 2012 to July 2013 to evaluate the health seeking behaviour and the length of delay of PKDL management. The consecutive 200 diagnosed PKDL cases that got treatment in SKKRC hospital were subjected to evaluation. Most (98%) of the patients were not aware and had no knowledge about PKDL, though 87.5% had a history of history of Kala-azar treatment. Many patients reported first to village doctor (15.5%), the pharmacy shop (10%), or traditional health provider (7.5%) upon recognition of symptom. The time between the initial symptom recognition and first medical consultation (patient delay) ranged from 10 days to 4745 days (13 years) with a median of 373 days (mean: 696; IQR: 138 to 900 days). The time between first medical consultations to definite treatment (system delay) ranged from 0 days to 1971 days (5.4 years), with a median delay of 14 days (mean: 46.48; IQR: 7 to 44 days) that was reported in this study. Age, education, occupation, and residential status had significant association with patient delay (P < 0.05). Educational status, occupation, number of treatment providers, and first health care provider had a significant association with system delay (P < 0.05). Success in PKDL diagnosis and treatment requires specific behavior from patients and health care providers which facilitate those practices. PMID:26788500

  19. Rapid Response Team activation in New Zealand hospitals-a multicentre prospective observational study.

    PubMed

    Psirides, A J; Hill, J; Jones, D

    2016-05-01

    We aimed to describe the epidemiology of Rapid Response Team (RRT) activation in New Zealand public hospitals. We undertook a prospective multicentre observational study of RRT activations in 11 hospitals for consecutive 14-day periods during October-December 2014. A standardised case report form was used to collect data on patient demographics, RRT activation criteria and timing, vital signs on RRT arrival, team composition and intervention, treatment limitation and patient outcome at day 30. Three hundred and thirteen patients received 351 RRT calls during the study period. Patients were admitted under a medical specialty in 177 (56.5%) instances. Median duration from hospital admission to first RRT call was two days. Eighty-six percent of RRT calls were to inpatient wards. A total of 43.4% of RRT calls occurred between 0800 and 1700 hours (38% of the day) and 75.5% of RRT calls were activated by ward nurses. A median of three staff attended each call. Common triggers for RRT activation were increased Early Warning Score (56.2%) and staff concern (25.7%). During the RRT call, 2.8% of patients died; 19.8% died by day 30. New 'Not For Resuscitation' orders were written in 22.5% of RRT calls. By day 30, 56.2% of patients had been discharged home alive. In conclusion, RRTs in New Zealand are multidisciplinary, mostly nurse-activated and predominantly respond to deteriorating medical (rather than surgical) patients. Most patients remain on the ward. The RRT frequently implements treatment limitations. Given almost one in five patients die within 30 days, over half of whom die within 72 hours of RRT review, surviving the RRT call may provide false reassurance that the patient will subsequently do well. PMID:27246940

  20. A multistate tuberculosis pharmacometric model: a framework for studying anti-tubercular drug effects in vitro

    PubMed Central

    Clewe, Oskar; Aulin, Linda; Hu, Yanmin; Coates, Anthony R. M.; Simonsson, Ulrika S. H.

    2016-01-01

    Objectives Mycobacterium tuberculosis can exist in different states in vitro, which can be denoted as fast multiplying, slow multiplying and non-multiplying. Characterizing the natural growth of M. tuberculosis could provide a framework for accurate characterization of drug effects on the different bacterial states. Methods The natural growth data of M. tuberculosis H37Rv used in this study consisted of viability defined as cfu versus time based on data from an in vitro hypoxia system. External validation of the natural growth model was conducted using data representing the rate of incorporation of radiolabelled methionine into proteins by the bacteria. Rifampicin time–kill curves from log-phase (0.25–16 mg/L) and stationary-phase (0.5–64 mg/L) cultures were used to assess the model's ability to describe drug effects by evaluating different linear and non-linear exposure–response relationships. Results The final pharmacometric model consisted of a three-compartment differential equation system representing fast-, slow- and non-multiplying bacteria. Model predictions correlated well with the external data (R2 = 0.98). The rifampicin effects on log-phase and stationary-phase cultures were separately and simultaneously described by including the drug effect on the different bacterial states. The predicted reduction in log10 cfu after 14 days and at 0.5 mg/L was 2.2 and 0.8 in the log-phase and stationary-phase systems, respectively. Conclusions The model provides predictions of the change in bacterial numbers for the different bacterial states with and without drug effect and could thus be used as a framework for studying anti-tubercular drug effects in vitro. PMID:26702921

  1. The study on the mechanical characteristics of articular cartilage in simulated microgravity

    NASA Astrophysics Data System (ADS)

    Niu, Hai-Jun; Wang, Qing; Wang, Yue-Xiang; Li, Ang; Sun, Lian-Wen; Yan, Yan; Fan, Fan; Li, De-Yu; Fan, Yu-Bo

    2012-10-01

    The microgravity environment of a long-term space flight may induce acute changes in an astronaut's musculo-skeletal systems. This study explores the effects of simulated microgravity on the mechanical characteristics of articular cartilage. Six rats underwent tail suspension for 14 days and six additional rats were kept under normal earth gravity as controls. Swelling strains were measured using high-frequency ultrasound in all cartilage samples subject to osmotic loading. Site-specific swelling strain data were used in a triphasic theoretical model of cartilage swelling to determine the uniaxial modulus of the cartilage solid matrix. No severe surface irregularities were found in the cartilage samples obtained from the control or tail-suspended groups. For the tail-suspended group, the thickness of the cartilage at a specified site, as determined by ultrasound echo, showed a minor decrease. The uniaxial modulus of articular cartilage at the specified site decreased significantly, from (6.31 ± 3.37)MPa to (5.05 ± 2.98)MPa ( p < 0.05). The histology-stained image of a cartilage sample also showed a reduced number of chondrocytes and decreased degree of matrix staining. These results demonstrated that the 14 d simulated microgravity induced significant effects on the mechanical characteristics of articular cartilage. This study is the first attempt to explore the effects of simulated microgravity on the mechanical characteristics of articular cartilage using an osmotic loading method and a triphasic model. The conclusions may provide reference information for manned space flights and a better understanding of the effects of microgravity on the skeletal system.

  2. Analysis of human alveolar osteoblast behavior on a nano-hydroxyapatite substrate: an in vitro study

    PubMed Central

    2014-01-01

    Background Nano-hydroxyapatite (nHA) is a potential ideal biomaterial for bone regeneration. However, studies have yet to characterize the behavior of human osteoblasts derived from alveolar bone on nHA. Thus, the aim of the present study was to evaluate the influence of nHA on the adhesion, proliferation and differentiation of these alveolar bone-derived cells. Methods Primary human alveolar osteoblasts were collected from the alveolar ridge of a male periodontal patient during osseous resective surgery and grown on culture plates coated with either polylysine or polylysine with nano-hydroxyapatite (POL/nHA) composite. The cells were grown and observed for 14 days, and then assessed for potential modifications to osteoblasts homeostasis as evaluated by quantitative reverse transcriptase-polymerase chain reaction (real time RT-PCR), scanning electron microscopy and atomic force microscopy. Results Real time PCR revealed a significant increase in the expression of the selected markers of osteoblast differentiation (bone morphogenetic protein (BMP)-2,-5,-7, ALP, COLL-1A2, OC, ON) in cells grown on the POL/nHA substrate. In addition, as compared with the POL surface, cells grown on the POL/nHA substrate demonstrated better osteoconductive properties, as demonstrated by the increase in adhesion and spreading, likely as a result of the increased surface roughness of the composite. Conclusions The increased expression of BMPs and osteoinductive biomarkers suggest that nano-hydroxyapatite may stimulate the proliferation and differentiation of local alveolar osteoblasts and thus encourage bone regeneration at sites of alveolar bone regeneration. PMID:24650194

  3. Feasibility and Outcome of Proximal Catheter Ileostomy – A Pilot Study

    PubMed Central

    Ansari, Maulana M.; Ahmad, Shakeel; Hasan, Syed H.; Haleem, Shahla

    2011-01-01

    Background/Aim: Loop ileostomy has high complication rates and causes much patient inconvenience. This study was carried out to evaluate the feasibility and outcome of a proximal catheter ileostomy in place of loop ileostomy in patients treated by intestinal repair and/or resection-anastomosis.Design: Prospective study.Setting: J. N. Medical College Hospital, Aligarh Muslim University, Aligarh, India. Patients and Methods: From November 2006 to November 2009, in all patients treated surgically by primary repair and/or resection-anastomosis of small and/or large bowel, we constructed a catheter ileostomy when a defunctioning proximal protective loop ileostomy was considered advisable. Catheter ileostomy was constructed in the fashion of catheter jejunostomy, with postoperative saline irrigation. Results: Catheter ileostomy was performed in 20 patients in the 3-year period. The mean age of the subjects was 28.6 years and the male: female ratio was 1.86:1. Four patients died of septicemia and multiple organ failure unrelated to catheter ileostomy in the immediate postoperative period. Catheter ileostomy started functioning within 48 hours of the operation, and twice-daily irrigation was found sufficient in 81.25% of the surviving patients. Only one patient developed peritubal leak with mild skin excoriation that cleared within 5 days. Another patient with Koch's abdomen underwent conversion to loop colostomy on re-exploration for postoperative adhesive obstruction. There was no instance of intestinal leak. Ileostomy wounds closed spontaneously within 7–14 days of catheter removal, and none required formal closure. Hospital stay ranged from 12–35 days (mean: 23 days). Conclusions: Catheter ileostomy is effective in protecting intestinal anastomosis/repair; there is minimal morbidity and no catheter-related leak/mortality, and we recommend the procedure. PMID:21727735

  4. The Benefit of a Mechanical Needle Stimulation Pad in Patients with Chronic Neck and Lower Back Pain: Two Randomized Controlled Pilot Studies

    PubMed Central

    Hohmann, Claudia; Ullrich, Isabella; Lauche, Romy; Choi, Kyung-Eun; Lüdtke, Rainer; Rolke, Roman; Cramer, Holger; Saha, Felix Joyonto; Rampp, Thomas; Michalsen, Andreas; Langhorst, Jost; Dobos, Gustav; Musial, Frauke

    2012-01-01

    Objectives. The objective was to investigate whether a treatment with a needle stimulation pad (NSP) changes perceived pain and/or sensory thresholds in patients with chronic neck (NP) and lower back pain (BP). Methods. 40 patients with chronic NP and 42 patients with chronic BP were equally randomized to either treatment or waiting list control group. The treatment group self-administered a NSP over a period of 14 days. Pain ratings were recorded on numerical rating scales (NRSs). Mechanical detection thresholds (MDTs) and pressure pain thresholds (PPTs) were determined at the site of maximal pain and in the adjacent region, vibration detection thresholds (VDT) were measured at close spinal processes. The Northwick Park Neck Pain Questionnaire (NPQ) and the Oswestry Disability Index (ODI) were utilized for the NP and BP study, respectively. Results. NRS ratings were significantly reduced for the treatment groups compared to the control groups (NP: P = .021 and BP: P < .001), accompanied by a significant increase of PPT at pain maximum (NP: P = .032 and BP: P = .013). There was no effect on VDT and MDT. The NPQ showed also a significant improvement, but not the ODI. Conclusions. The mechanical NSP seems to be an effective treatment method for chronic NP and BP. PMID:22997531

  5. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    PubMed

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P < 0.001). Both drugs caused a significant rise in number of platelets on the 7th and the 14th day of treatment. Compared to IVIG, except a significant drop in hemoglobin concentration (P < 0.001), anti-D had lower rate of side effects including fever (P < 0.05), allergy (P < 0.01), and headache (P < 0.001). Our results showed that anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. PMID:26991138

  6. Can a bleaching toothpaste containing Blue Covarine demonstrate the same bleaching as conventional techniques? An in vitro, randomized and blinded study

    PubMed Central

    DANTAS, Andréa Abi Rached; BORTOLATTO, Janaina Freitas; RONCOLATO, Ávery; MERCHAN, Hugo; FLOROS, Michael Christopher; KUGA, Milton Carlos; de OLIVEIRA, Osmir Batista

    2015-01-01

    ABSTRACT Objective The purpose of this in vitro study was to compare the efficacy of a bleaching toothpaste containing Blue Covarine vs. conventional tooth bleaching techniques using peroxides (both in-office and at-home). Material and Methods Samples were randomly distributed into five experimental groups (n=15): C - Control; BC – Bleaching toothpaste containing Blue Covarine; WBC – Bleaching toothpaste without Blue Covarine; HP35 - In-office bleaching using 35% hydrogen peroxide; and CP10 – At-home bleaching with 10% carbamide peroxide. The dental bleaching efficacy was determined by the color difference (ΔE), luminosity (ΔL), green-red axis (Δa), and blue-yellow axis (Δb). The CIELab coordinates were recorded with reflectance spectroscopy at different times: T0 - baseline, T1 – immediately after bleaching, T2 - 7 days, T3 - 14 days, and T4 - 21 days after the end of treatments. Data were analyzed by a repeated measures mixed ANOVA and post hoc Bonferroni test, with a significance level of 5%. Results No significant differences were found between the treatment groups C, BC, and WBC. The groups HP35 and CP10 showed significantly higher whitening efficacy than groups C, BC, and WBC. Conclusions There were no significant differences in the whitening efficacy between a Blue Covarine containing toothpaste, a standard whitening toothpaste, and a control. Neither of the whitening toothpastes tested were as effective as in-office or at-home bleaching treatments. PMID:26814462

  7. Effect of platelet-activating factor receptor antagonist, etizolam, on resolution of chronic subdural hematoma--a prospective study to investigate use as conservative therapy.

    PubMed

    Hirashima, Yutaka; Kurimoto, Masanori; Nagai, Shoichi; Hori, Emiko; Origasa, Hideki; Endo, Shunro

    2005-12-01

    Inflammatory reaction is very important for formation of the neomembrane of chronic subdural hematoma (CSDH). The present study evaluated medical treatment with the platelet-activating factor receptor antagonist, etizolam, for the resolution of CSDH, and the factors indicating surgery or conservative therapy. Alternate patients were assigned to the etizolam group or control group without medical treatment. Patients in the etizolam group received 3.0 mg etizolam per day for 14 days. A total of 53 patients were followed up for at least 6 months. Univariate analysis of differences in demographic characteristics, clinical findings, and initial computed tomography (CT) findings, and multiple logistic regression analysis of the relationship between etizolam treatment and requirement for surgery using age, sex, low density of hematoma on CT, and paresis as confounders were performed. Etizolam treatment (adjusted odds ratio [OR] 0.156, 95% confidence interval [CI] 0.024-0.999, p = 0.049) was negatively correlated with requirement for surgery. Low density of hematoma (adjusted OR 0.125, 95% CI 0.019-0.846, p = 0.033) was found to be an independent negative predictor, and paresis as an initial symptom (adjusted OR 6.35, 95% CI 1.04-38.7, p = 0.045) was an independent positive predictor of requirement for surgery. Etizolam administration can promote the resolution of CSDH, especially at the stage of hygroma appearing as low density on CT. Surgery is recommended if the patient presents with paresis. PMID:16377949

  8. A comparative study of antiplaque and antigingivitis effects of herbal mouthrinse containing tea tree oil, clove, and basil with commercially available essential oil mouthrinse

    PubMed Central

    Kothiwale, Shaila V.; Patwardhan, Vivek; Gandhi, Megha; Sohoni, Rahul; Kumar, Ajay

    2014-01-01

    Background: The relatively safe nature and cost-effectiveness of herbal extracts have led to a resurgent interest in their utility as therapeutic agents. Therefore, this prospective, double-blind, randomly controlled clinical trial was designed to compare the antiplaque and antigingivitis effects of newly formulated mouthrinse containing tea tree oil (TTO), clove, and basil with those of commercially available essential oil (EO) mouthrinse. Materials and Methods: Forty patients were selected for a 21-day study period and randomly divided into two groups. The test group patients were given newly formulated herbal mouthrinse and the control group patients were given commercially available EO mouthrinse. The Plaque Index (PI), Gingival Index (GI), and Papillary Marginal Attachment (PMA) Index were recorded at baseline, 14 days, and 21 days. The microbial colony forming units (CFU) were assessed at baseline and 21 days. Results: Test group patients using herbal mouthrinse showed significant improvement in GI (0.16), PI (0.57), and PMA (0.02) scores. These improvements were comparable to those achieved with commercially available EO mouthrinse. However, the aerobic and anaerobic CFU of microbiota were reduced with the herbal mouthrinse (P = 0.0000). Conclusion: The newly formulated herbal mouthrinse and commercially available mouthrinse were beneficial clinically as antiplaque and antigingivitis agents. Newly formulated mouthrinses showed significant reduction in microbial CFU at 21 days. So, our findings support the regular use of herbal mouthrinse as an antiplaque, antigingivitis, and antimicrobial rinse for better efficacy. PMID:25024544

  9. The Effect of an Eextremely Low Frequency Magnetic Field on Larvae Production in the Parasite-Host System: Fasciola hepatica-Galba truncatula: a Preliminary Study.

    PubMed

    Kołodziejczyk, Lidia; Podraza, Wojciech; Gonet, Bolesław; Dzika, Ewa; Kosik-Bogacka, Danuta I

    2016-01-01

    The aim of this study was to determine the effect of an extremely low-frequency magnetic field (ELFMF) on the production of liver fluke larvae in a parasite-host system: Fasciola hepatica--Galba truncatula. Both F. hepatica eggs and F. hepatica-infected snails were exposed to an ELFMF (50 Hz, 2.0 mT) for 14 days and 36 days, respectively. F. hepatica-infected snails were divided into 4 groups, 10 specimens each. The snails of groups I and II were infected with F. hepatica larvae--miracidia obtained from control cultures, while the snails of groups III and IV were infected with miracidia reared from eggs that had been incubated in an ELFMF. After infection, the snails of groups II and IV were placed in an ELFMF, while those of groups I (control) and III were housed outside the ELFMF. At 36 days post-infection (dpi) there were no statistically significant differences between the number of F. hepatica larvae--cercariae and metacercariae, obtained from G. truncatula snails in the control group (group I) and the snail groups exposed to ELFMF (groups II, III and IV). However, a statistically significant difference between the average number of F. hepatica larvae in snail groups III and IV may indicate that the duration of exposure to ELFMF, i.e. embryogenesis period vs. the entire larval development, played a role in the production of F. hepatica larvae, and resulted in a reduction of their number. PMID:27172713

  10. COMPARATIVE STUDY OF THE EFFECTS OF LOW-LEVEL LASER AND LOW-INTENSITY ULTRASOUND ASSOCIATED WITH BIOSILICATE® ON THE PROCESS OF BONE REPAIR IN THE RAT TIBIA

    PubMed Central

    Oliveira, Poliani de; Fernandes, Kelly Rosseti; Sperandio, Evandro Fornias; Pastor, Fabio Alexandre Casarin; Nonaka, Keico Okino; Parizotto, Nivaldo Antonio; Renno, Ana Claudia Muniz

    2015-01-01

    Objective: Verify the effects of the association between Biosilicate® and ultrasound and, Biosilicate® and laser in bone consolidation process of rats, through the biomechanical and histological analysis. Methods: Forthy male rats were used. The animals were randomized into four groups (n=10): control group fracture no treated (CGF); group treated with Biosilicate® (BG); group treated with Biosilicate® and laser (BLG); group treated with Biosilicate® and ultrasound (BUG). Results: The biomechanical analysis showed no significant difference among any groups after 14 days post-surgery. In the morphometric analysis, the control group showed moderate presence of new formed bone tissue inside the defects areas and the Biosilicate® group showed similar results. Despite those facts, the biomaterial osteogenic potential was demonstrated by the great amount of cells and bone tissue around the particles. Curiously, the Biosilicate® plus laser or ultrasound groups showed lower amounts of bone tissue deposition when compared with control fracture and Biosilicate® groups. Conclusion: The data from this study can conclude that Biosilicate® was able to accelerate and optimized the bone consolidation, through the modulation of the inflammatory process and the stimulation of new bone formation. However, when resources were associated, there are no positive results. PMID:27027088

  11. [Preliminary study on effect of Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces on intestinal flora of mice].

    PubMed

    Yang, Ze-rui; Zeng, Gui-mei; Peng, Li-hua; Zhang, Miao-miao; Cheng, Jin-le; Zhan, Ruo-ting

    2015-08-01

    This study aims to analyze and compare the effect of cell wall-broken decoction pieces, conventional decoction pieces and conventional powder of Rhodiolae Crenulatae Radix et Rhizoma on the intestinal flora of normal mice. The conventional bacterial culture and PCR-DGGE (polymerase chain reaction-denaturing gradient gel electrophoresis) were adopted for the mice after the oral administration for 14 days. According to the bacterial culture results, the 1/8 dose cell wall-broken decoction pieces group showed fewer Enterococcus and Escherichia coli bacillus but more Lactobacillus and Bifidobacterium than the conventional decoction pieces group and the traditional powder group (P <0.05). Meanwhile, on the basis of the PCR-DGGE results, the 1/8 dose cell wall-broken decoction pieces group revealed the highest Shannon-Wiener index (H) and species richness (S) among the seven groups, with extremely significant differences compared with the normal group (P <0.01), significant differences compared with the conventional decoction pieces group and the conventional powder group (P <0.05) and a high intra-group similarity. In conclusion, the long-term intake of 1/8 dose Rhodiolae Crenulatae Radix et Rhizoma cell wall-broken decoction pieces showed a certain effect in regulating intestinal tract by promoting the growth of Lactobacillus and Bifidobacterium. Furthermore, the intestinal flora community will become more stable. PMID:26677710

  12. Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion.

    PubMed Central

    De Wit, S; Hermans, P; Sommereijns, B; O'Doherty, E; Westenborghs, R; van de Velde, V; Cauwenbergh, G F; Clumeck, N

    1992-01-01

    The pharmacokinetics of oral administration of R 82913, or tetrahydroimidazol [4,5,1-jk]-benzodiazepin-2(1H)-one or -thione (TIBO), was compared with those of intravenous administration in five AIDS patients. TIBO was administered as a single daily 1-h infusion of 100 mg for 29 days and orally as a single daily dose for 14 days with three consecutive regimens of 100, 200, and 100 mg with probenecid (1 g) daily. Each cycle was followed by a wash-out period. Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid. Trough levels obtained with oral administration systematically remained far below the 90% inhibitory concentration of TIBO against human immunodeficiency virus type 1 (HIV-1). Tolerance of TIBO was excellent. No clinical efficacy could be demonstrated. p24 antigenemia decreased significantly in one patient under intravenous therapy. TIBO derivatives are promising anti-HIV-1 agents in vitro, but improvement of oral bioavailability is needed before implementation of long-term efficacy and tolerability studies. Moreover, rapid emergence of resistance, which has been recently documented, constitutes a major problem with most nonnucleoside reverse transcriptase inhibitors. PMID:1482134

  13. A pilot study of the DBT coach: an interactive mobile phone application for individuals with borderline personality disorder and substance use disorder.

    PubMed

    Rizvi, Shireen L; Dimeff, Linda A; Skutch, Julie; Carroll, David; Linehan, Marsha M

    2011-12-01

    Dialectical behavior therapy (DBT) has received strong empirical support and is practiced widely as a treatment for borderline personality disorder (BPD) and BPD with comorbid substance use disorders (BPD-SUD). Therapeutic success in DBT requires that individuals generalize newly acquired skills to their natural environment. However, there have been only a limited number of options available to achieve this end. The primary goal of this research was to develop and test the feasibility of the DBT Coach, a software application for a smartphone, designed specifically to enhance generalization of a specific DBT skill (opposite action) among individuals with BPD-SUD. We conducted a quasiexperimental study in which 22 individuals who were enrolled in DBT treatment programs received a smartphone with the DBT Coach for 10 to 14 days and were instructed to use it as needed. Participants used the DBT Coach an average of nearly 15 times and gave high ratings of helpfulness and usability. Results indicate that both emotion intensity and urges to use substances significantly decreased within each coaching session. Furthermore, over the trial period, participants reported a decrease in depression and general distress. Mobile technology offering in vivo skills coaching may be a useful tool for reducing urges to use substances and engage in other maladaptive behavior by directly teaching and coaching in alternative, adaptive coping behavior. PMID:22035988

  14. Bioconcentration of Ag, Cd, Co, Mn and Zn in the Mangrove Oyster (Crassostrea gasar) and Preliminary Human Health Risk Assessment: A Radiotracer Study.

    PubMed

    Kuranchie-Mensah, Harriet; Teyssié, Jean-Louis; Oberhänsli, François; Tumnoi, Yutthana; Pouil, Simon; Warnau, Michel; Metian, Marc

    2016-09-01

    Bioaccumulation kinetics of five dissolved metals were determined in the mangrove oyster Crassostrea gasar, using corresponding radiotracers ((54)Mn, (57)Co, (65)Zn, (109)Cd and (110m)Ag). Additionally, their bioaccessibility to human consumers was estimated. Results indicated that over a 14-day exposure (54)Mn and (57)Co were linearly concentrated in oysters whereas (109)Cd, (65)Zn and (110m)Ag were starting to saturate (steady-state not reached). Whole-body concentration factors at 14 days (CF14d in toto) ranged from 187 ± 65 to 629 ± 179 with the lowest bioconcentration capacity for Co and the highest for Ag. Depuration kinetics were best described by a double-exponential model with associated biological half-lives ranging from 26 days (Ag) to almost 8 months (Zn and Cd). Bioaccessible fraction of the studied elements was estimated using in vitro digestions, which suggested that oysters consumed seasoned with lemon enhanced the accessibility of Cd, Mn and Zn to human consumers, but not Ag and Co. PMID:27194421

  15. Evaluation of potential health effects of 10 kHz magnetic fields: A short-term mouse toxicology study

    SciTech Connect

    Robertson, I.G.C.; Wilson, W.R.; Dawson, B.V.; Zwi, L.J.; Green, A.W.; Boys, J.T.

    1996-05-01

    A high-frequency inductive power distribution (HID) technology has been developed that generates sinusoidal magnetic fields at a frequency of 10 kHz. In typical industrial applications, field intensities in the order of 0.2 mT can be expected between the current-carrying coils. Because the possible health effects of 10 kHz sinusoidal magnetic fields of this type had never been investigated, a broad evaluation of possible effects on animal health was made in a preliminary 14 day acute study and in a 90 day subchromic study using male and female B6C3F1 mice. Exposures were at 0.08, 0.28, and 1.0 mT vs a background exposure of 3.7 {micro}T and were essentially continuous. These studies failed to demonstrate any health effects that can be clearly related to the magnetic field exposure. No changes in animal behavior or indications of morbidity were detected during the initial exposure to the fields. There were no significant differences in body weight between exposed and unexposed (control) mice at any time int h study, and the clinical chemistry and hematology parameters were essentially unchanged. Although minor differences in some clinical chemistry and hematology parameters were seen between control and exposure groups, the lack of exposure dependence, the lack of consistency between sexes, and the lack of correspondence with the results of the two studies all suggest that these were chance associations. Even if the changes were real, the magnitude of the changes was very small and does not indicate serious biological effects. Finally, all organs were macroscopically and microscopically normal except for isolated, generally mild, histological lesions and lesions that were ascribed to fighting among males. There was no obvious association with field intensity.

  16. TOXICOLOGY OF ORGANIC DRINKING WATER CONTAMINANTS: TRICHLOROMETHANE, BROMODICHLOROMETHANE, DIBROMOCHLOROMETHANE AND TRIBROMOMETHANE

    EPA Science Inventory

    This study evaluated the subchronic toxicity of selected halomethanes which are drinking water contaminants. The compounds studied were trichloromethane, bromodichloromethane, dibromochloromethane and tribromomethane. Subchronic 14-day gavage studies were performed with the use o...

  17. Rationale and design of a clinical trial of a low-molecular-weight heparin in preventing clinically important venous thromboembolism in medical patients: the prospective evaluation of dalteparin efficacy for prevention of venous thromboembolism in immobilized patients trial (the PREVENT study).

    PubMed

    Vaitkus, Paul T; Leizorovicz, A; Goldhaber, S Z

    2002-01-01

    The utility of low-molecular-weight heparin (LMWH) in the prophylaxis of venous thromboembolic disease has been examined using the surrogate endpoint of venographically identified thrombi. The largest portion of these thrombi were asymptomatic calf-vein thrombi. The clinical relevance of this observation is a matter of debate. The present study is designed to evaluate the impact of an LMWH on clinically important endpoints. The current study is a randomized, prospective, double-blinded, multicenter, multinational, controlled clinical trial comparing dalteparin with placebo in moderately high-risk hospitalized medical patients. A total of 3300 patients will be randomized to receive either 5,000 IU per day of dalteparin or placebo for 14 days. Patients will undergo appropriate evaluation for any symptomatic episodes and all patients will undergo a bilateral compression ultrasound (CUS) on day 21 to search for asymptomatic proximal thrombi. The primary endpoint is the combination of objectively confirmed symptomatic deep vein thrombi (DVT), fatal or non-fatal pulmonary emboli, all proximal DVT, and sudden death. This study will be the first study to examine clinically important endpoints in evaluating the effect of a LMWH in hospitalized medical patients. This study also is the first study to use CUS rather than venography in concordance with contemporary medical practice. This trial is thus designed to address this important question in a clinically relevant manner. PMID:12710842

  18. A Three Year Clinicopathological Study of Cases of Rupture Uterus

    PubMed Central

    Rathod, Setu; Swain, Sujata

    2015-01-01

    Introduction Rupture uterus is a life threatening obstetric complication with serious maternal and fetal side-effects. We report a 3 year (2010-2013) retrospective clinical study of pregnancy with rupture uterus cases attending a tertiary care hospital. Aim The aim of the study was to evaluate the incidence of rupture uterus, incidence as per age, parity, clinical presentations, risk factors, complications and management. Materials and Methods Retrospective data of 74 cases of rupture uterus in SCB Medical college, Cuttack was collected from case records of 26,547 deliveries during a 3 year span (2010-2013). Parameters like cause of rupture, type, site of rupture and outcome were recorded. The collected data was analysed by SPSS software v19. Results Out of 26,547 deliveries during the three year period, there were 74 cases of rupture uterus with an incidence of rupture 1 in 359 (0.28%). The mean age of rupture uterus was 27.4 years. 95.8% were multigravida and majority were referred cases from low socioeconomic status. Only 40.5% had the required minimum of four antenatal visits as recommended by WHO (World Health Organisation). A total of 48.6% of cases with rupture uterus had history of previous Caesarean section. Prolonged labour was present in 75.6% of the cases. Only 12.2% of the cases had history of oxytocin use whereas 9.5% had undergone an operative vaginal delivery. Obstructed labour was the cause in 24.3% of cases, 85.1% had complete rupture. Majority had a rupture in the anterior wall (69%) and 81.1% had rupture in lower segment of uterus. Only 17.6% had broad ligament haematoma, 10.8% colporrhexis and 6.8% had associated bladder injury. Repair was possible in only 39.2% of cases, whereas majority landed up in hysterectomy. Internal iliac ligation was done in 2.7% of cases. Perinatal mortality was 90.5% whereas maternal death was seen in 13.5% cases. One patient developed VVF (vesicovaginal fistula). Duration of hospital stay was upto 14 days in 81

  19. Actigraphy-defined Measures of Sleep and Movement Across the Menstrual Cycle In Midlife Menstruating Women: SWAN Sleep Study

    PubMed Central

    Zheng, Huiyong; Harlow, Siobán D; Kravitz, Howard M; Bromberger, Joyce; Buysse, Daniel J; Matthews, Karen A; Gold, Ellen B; Owens, Jane F; Hall, Martica

    2014-01-01

    Objective To evaluate patterns in actigraphy-defined sleep measures across the menstrual cycle, testing the hypothesis that sleep would be more disrupted in the premenstrual period, i.e. in the 14 days prior to menses. Methods A community-based, longitudinal study of wrist actigraphy-derived sleep measures was conducted with 163 women (58 African-American, 78 White, and 27 Chinese) of late reproductive age (mean=51.5, SD=2.0 years) from the Study of Women's Health Across the Nation (SWAN) Sleep Study. Daily measures of sleep [sleep efficiency (%) and total sleep time (minutes)] and movement during sleep [mean activity score (counts)] were characterized using wrist actigraphy across a menstrual cycle or 35 days, whichever was shorter. Data were standardized to 28 days to account for the variation of unequal cycle lengths and divided into four weekly segments for analyses. Results Sleep efficiency percentage declined gradually across the menstrual cycle, but the decline became pronounced in fourth week, the premenstrual period. Compared with third week, sleep efficiency declined by 5% (p<0.0001) and mean total sleep time was 25 minutes less (p=0.0002) in fourth week. No significant mean differences were found when comparing the means of second week versus third week. The association of weekly segments with sleep efficiency or minutes of total sleep time was modified by sociodemographic and lifestyle factors, including body mass index (BMI), race, study site, financial strain, marital status, and smoking. Conclusions Sleep varied systematically across the menstrual cycle in women of late reproductive age, including a gradual decline in sleep efficiency across all weeks, with a more marked change premenstrually during the last week of the menstrual cycle. These sleep changes may be modifiable by altering lifestyle factors. PMID:24845393

  20. Effect of chlorhexidine varnish on gingival growth in orthodontic patients: a randomized prospective split-mouth study

    PubMed Central

    Pretti, Henrique; Barbosa, Gabriella Lopes de Rezende; Lages, Elizabeth Maria Bastos; Gala-García, Alfonso; de Magalhães, Claudia Silami; Moreira, Allyson Nogueira

    2015-01-01

    Introduction: Fixed orthodontic appliances patients suffer limitations on the effective control of biofilm by mechanical methods, bringing the need of a coadjutant in the control of inflammation and oral health improvement. Objective: The aim of this prospective split-mouth blind study was to analyze the effect of a 40% chlorhexidine (CHX) varnish on gingival growth of patients with orthodontic fixed appliances. Methods: Healthy teenage patients with fixed orthodontic appliances and increased gingival volume were recruited (n = 30). Each individual was his own control, having in the maxilla one control side and one treatment side. An application of varnishes occurred on the vestibular area of the upper premolars and first molar crowns, on the control side (placebo varnish) and on the experimental side (EC40(r) Biodentic CHX varnish). The varnishes and sides were randomly chosen and its identification and group was kept by a third party observer and it was not revealed to the researchers and participants until the end of study. In order to establish a baseline registration, digital photographs were taken by a trained photographer before varnish application at baseline (T0), as well as 14 days (T14) and 56 days (T56) after the application. The gingival volume was calculated indirectly using the vestibular areas (mm2) of the upper second premolars' clinical crowns by RapidSketch(r) software, at all study times. The data were analyzed using ANOVA and the Turkey-Krammer test. Results: It was observed, in the final sample of 30 individuals, that at T0, the control and treatment groups were similar. At T14 and T56, a progressive reduction of the clinical crown area was seen in the control group, and an increase in the average area was detected in the experimental group (p < 0,05). Conclusions: The use of 40% CHX varnish decreases the gingival overgrowth in patients undergoing orthodontic treatment. Further studies are necessary to set the action time and frequency of

  1. Effects of Acid Treatment on Dental Zirconia: An In Vitro Study

    PubMed Central

    Xie, Haifeng; Shen, Shuping; Qian, Mengke; Zhang, Feimin; Chen, Chen; Tay, Franklin R.

    2015-01-01

    The aim of this study was to evaluate the effects of hydrofluoric (HF) acid, acetic acid, and citric acid treatments on the physical properties and structure of yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) at ambient temperature. In total, 110 bar-shaped zirconia specimens were randomly assigned to 11 groups. The specimens in the control group (C) received no surface treatment, while those in the Cage group were hydrothermally aged at 134°C and 0.2 MPa for 20 h. Ten specimens each were immersed at ambient temperature in 5% and 40% HF acid for 2 h (40HF0), 1 day (5HF1, 40HF1), and 5 days (5HF5, 40HF5), while 10 each were immersed at ambient temperature in 10% acetic acid and 20% citric acid for 7 (AC7, CI7) and 14 days (AC14, CI14). X-ray diffraction (XRD) was used to quantitatively estimate the monoclinic phase. Furthermore, flexural strength, surface roughness, and surface Vickers hardness were measured after treatment. Scanning electron microscopy (SEM) was used to characterize the surface morphology. The Cage group specimens exhibited an increased monoclinic phase and flexural strength. Furthermore, 40% HF acid immersion decreased the flexural strength and surface hardness and deteriorated the surface finish, while 5% HF acid immersion only decreased the surface hardness. All the HF acid-immersed specimens showed an etched surface texture on SEM observations, while the other groups did not. These findings suggest that the treatment of Y-TZP with 40% HF acid at ambient temperature causes potential damage, while treatment with 5% HF acid, acetic acid, and citric acid is safe. PMID:26301413

  2. Safety of pertussis vaccination in pregnant women in UK: observational study

    PubMed Central

    King, Bridget; Bryan, Phil

    2014-01-01

    Objective To examine the safety of pertussis vaccination in pregnancy. Design Observational cohort study. Setting The UK Clinical Practice Research Datalink. Participants 20 074 pregnant women with a median age of 30 who received the pertussis vaccine and a matched historical unvaccinated control group. Main outcome measure Adverse events identified from clinical diagnoses during pregnancy, with additional data from the matched child record identified through mother-child linkage. The primary event of interest was stillbirth (intrauterine death after 24 weeks’ gestation). Results There was no evidence of an increased risk of stillbirth in the 14 days immediately after vaccination (incidence rate ratio 0.69, 95% confidence interval 0.23 to 1.62) or later in pregnancy (0.85, 0.44 to 1.61) compared with historical national rates. Compared with a matched historical cohort of unvaccinated pregnant women, there was no evidence that vaccination accelerated the time to delivery (hazard ratio 1.00, 0.97 to 1.02). Furthermore, there was no evidence of an increased risk of stillbirth, maternal or neonatal death, pre-eclampsia or eclampsia, haemorrhage, fetal distress, uterine rupture, placenta or vasa praevia, caesarean delivery, low birth weight, or neonatal renal failure, all serious events that can occur naturally in pregnancy. Conclusion In women given pertussis vaccination in the third trimester, there is no evidence of an increased risk of any of an extensive predefined list of adverse events related to pregnancy. In particular, there was no evidence of an increased risk of stillbirth. Given the recent increases in the rate of pertussis infection and morbidity and mortality in neonates, these early data provide initial evidence for evaluating the safety of the vaccine in pregnancy for health professionals and the public and can help to inform vaccination policy making. PMID:25015137

  3. Whooping cough in school age children with persistent cough: prospective cohort study in primary care

    PubMed Central

    Harnden, Anthony; Grant, Cameron; Harrison, Timothy; Perera, Rafael; Brueggemann, Angela B; Mayon-White, Richard; Mant, David

    2006-01-01

    Objective To estimate the proportion of school age children with a persistent cough who have evidence of a recent Bordetella pertussis infection. Design Prospective cohort study (October 2001 to March 2005). Setting General practices in Oxfordshire, England. Participants 172 children aged 5-16 years who presented to their general practitioner with a cough lasting 14 days or more who consented to have a blood test. Main outcome measures Serological evidence of a recent Bordetella pertussis infection; symptoms at presentation; duration and severity of cough; sleep disturbance (parents and child). Results 64 (37.2%, 95% confidence interval 30.0% to 44.4%) children had serological evidence of a recent Bordetella pertussis infection; 55 (85.9%) of these children had been fully immunised. At presentation, children with whooping cough were more likely than others to have whooping (odds ratio 2.85, 95% confidence interval 1.39 to 5.82), vomiting (4.35, 2.04 to 9.25), and sputum production (2.39, 1.14 to 5.02). Children with whooping cough were also more likely to still be coughing two months after the start of their illness (85% v 48%; P = 0.001), continue to have more than five coughing episodes a day (P = 0.049), and cause sleep disturbance for their parents (P = 0.003). Conclusions For school age children presenting to primary care with a cough lasting two weeks or more, a diagnosis of whooping cough should be considered even if the child has been immunised. Making a secure diagnosis of whooping cough may prevent inappropriate investigations and treatment. PMID:16829538

  4. The German version of the Generalized Pathological Internet Use Scale 2: a validation study.

    PubMed

    Barke, Antonia; Nyenhuis, Nele; Kröner-Herwig, Birgit

    2014-07-01

    The Generalized Pathological Internet Use Scale (GPIUS2) assesses cognitive behavioral aspects of problematic Internet use. To date, the 15-item scale has only been available in English, and the aim of this study was to translate and validate a German version. An online sample (ON, n=1,041, age 24.2±7.2 years, 46.7% men) completed an Internet version of the translated GPIUS2, and a student sample (OF, n=841, age 23.5±3.0 years, 46.8% men) filled in a pencil and paper version. A third sample of 108 students (21.5±2.0 years, 25.7% men) completed the questionnaire twice to determine the 14-day retest reliability. Participants also answered questions regarding their Internet use habits (OF, ON) and depression, loneliness, and social anxiety (ON). The internal consistencies were α=0.91 (ON) and α=0.86 (OF). Item-whole correlations ranged from r=0.53 to r=0.69 (ON) and from r=0.39 to r=0.63 (OF). The 2 week retest reliability was rtt=0.85. Confirmatory factor analyses found a satisfactory fit for the factorial model proposed by Caplan for the original version. The GPIUS2 score correlated moderately with time spent on the Internet for private purposes in a typical week (ON: r=0.40; OF: r=0.36). Loneliness, depression, and social anxiety explained 46% of the variance in GPIUS2 scores. The German version of the GPIUS2 has good psychometric properties in a pencil and paper version as well as in a web-based format, and the observations regarding loneliness, depression, and social anxiety support the underlying model. PMID:24742070

  5. Genetic and Functional Studies of the Intervertebral Disc: A Novel Murine Intervertebral Disc Model

    PubMed Central

    Pelle, Dominic W.; Peacock, Jacqueline D.; Schmidt, Courtney L.; Kampfschulte, Kevin; Scholten, Donald J.; Russo, Scott S.; Easton, Kenneth J.; Steensma, Matthew R.

    2014-01-01

    Intervertebral disc (IVD) homeostasis is mediated through a combination of micro-environmental and biomechanical factors, all of which are subject to genetic influences. The aim of this study is to develop and characterize a genetically tractable, ex vivo organ culture model that can be used to further elucidate mechanisms of intervertebral disc disease. Specifically, we demonstrate that IVD disc explants (1) maintain their native phenotype in prolonged culture, (2) are responsive to exogenous stimuli, and (3) that relevant homeostatic regulatory mechanisms can be modulated through ex-vivo genetic recombination. We present a novel technique for isolation of murine IVD explants with demonstration of explant viability (CMFDA/propidium iodide staining), disc anatomy (H&E), maintenance of extracellular matrix (ECM) (Alcian Blue staining), and native expression profile (qRT-PCR) as well as ex vivo genetic recombination (mT/mG reporter mice; AdCre) following 14 days of culture in DMEM media containing 10% fetal bovine serum, 1% L-glutamine, and 1% penicillin/streptomycin. IVD explants maintained their micro-anatomic integrity, ECM proteoglycan content, viability, and gene expression profile consistent with a homeostatic drive in culture. Treatment of genetically engineered explants with cre-expressing adenovirus efficaciously induced ex vivo genetic recombination in a variety of genetically engineered mouse models. Exogenous administration of IL-1ß and TGF-ß3 resulted in predicted catabolic and anabolic responses, respectively. Genetic recombination of TGFBR1fl/fl explants resulted in constitutively active TGF-ß signaling that matched that of exogenously administered TGF-ß3. Our results illustrate the utility of the murine intervertebral disc explant to investigate mechanisms of intervertebral disc degeneration. PMID:25474689

  6. Brain-Machine-Interface in Chronic Stroke Rehabilitation: A Controlled Study

    PubMed Central

    Ramos-Murguialday, Ander; Broetz, Doris; Rea, Massimiliano; Läer, Leonhard; Yilmaz, Özge; Brasil, Fabricio L; Liberati, Giulia; Curado, Marco R; Garcia-Cossio, Eliana; Vyziotis, Alexandros; Cho, Woosang; Agostini, Manuel; Soares, Ernesto; Soekadar, Surjo; Caria, Andrea; Cohen, Leonardo G; Birbaumer, Niels

    2013-01-01

    Objective Chronic stroke patients with severe hand weakness, respond poorly to rehabilitation efforts. Here, we evaluated efficacy of daily brain-machine-interface training to increase the hypothesized beneficial effects of physiotherapy alone in patients with severe paresis in a double blind sham-controlled design proof of concept study. Methods 32 chronic stroke patients with severe hand weakness, were randomly assigned to two matched groups and participated in 17.8 ± 1.4 days of training rewarding desynchronization of ipsilesional oscillatory sensorimotor rhythms (SMR) with contingent online movements of hand and arm orthoses (experimental group , n=16). In the control group (sham group, n=16) movements of the orthoses occurred randomly. Both groups received identical behavioral physiotherapy immediately following BMI training or the control intervention. Upper limb motor function scores, electromyography from arm and hand muscles, placebo-expectancy effects and functional magnetic resonance imaging (MRI) blood oxygenation level dependent activity were assessed before and after intervention. Results A significant group × time interaction in upper limb Fugl-Meyer motor (cFMA) scores was found. cFMA scores improved more in the experimental than in the control group, presenting a significant improvement of cFMA scores (3.41±0.563 points difference, p=0.018) reflecting a clinically meaningful change from no activity to some in paretic muscles. cFMA improvements in the experimental group correlated with changes in functional MRI laterality index and with paretic hand electromyography activity. Placebo-expectancy scores were comparable for both groups. Interpretation The addition of BMI training to behaviorally oriented physiotherapy can be used to induce functional improvements in motor function in chronic stroke patients without residual finger movements and may open a new door in stroke neurorehabilitation. PMID:23494615

  7. Baseline Trajectories of Drinking Moderate Acamprosate and Naltrexone Effects in the COMBINE study

    PubMed Central

    Gueorguieva, Ralitza; Wu, Ran; Donovan, Dennis; Rounsaville, Bruce J; Couper, David; Krystal, John H.; O’Malley, Stephanie S

    2010-01-01

    Background The COMBINE Study evaluated the effects of acamprosate, naltrexone and the Combined Behavioral Intervention (CBI). In secondary analyses, our goals were to identify trajectories of any drinking prior to randomization, to characterize subjects in these trajectories, and to assess whether pre-randomization trajectories predict drinking outcomes and moderate treatment response. Methods We analyzed daily indicators of any drinking in 90 days prior to randomization using a trajectory-based approach. General linear models and generalized logistic regression assessed main and interactive effects of pre-randomization drinking trajectories and treatment on summary drinking measures during active treatment. Results We identified five trajectories of any drinking prior to randomization: “T1: frequent drinkers”, “T2: very frequent drinkers”, “T3: nearly daily drinkers”, “T4: consistent daily drinkers” and “T5: daily drinkers stopping early”. During treatment, “T3: nearly daily drinkers” and “T4: consistent daily drinkers” had significantly worse drinking outcomes than “T1: frequent drinkers” while “T5: daily drinkers stopping early” had comparable drinking outcomes to “T1: frequent drinkers”. Acamprosate significantly increased the chance of abstinence from heavy drinking for the “T2: very frequent drinking” trajectory but decreased the chance of abstinence from heavy drinking for “T5: daily drinkers stopping early”. Naltrexone differentially improved rates of continuous abstinence for very frequent drinkers. Conclusions Acamprosate benefited very frequent drinkers and contrary to expectations was associated with poorer response compared to placebo for consistent daily drinkers who had longer durations of pretreatment abstinence (e.g., ≥ 14 days). Baseline drinking trajectories also moderated naltrexone effects. These findings may help clinicians identify patients for whom acamprosate and naltrexone may be most

  8. Toxicological studies for some agricultural waste extracts on mosquito larvae and experimental animals

    PubMed Central

    El-Maghraby, Somia; Nawwar, Galal A; Bakr, Reda FA; Helmy, Nadia; Kamel, Omnia MHM

    2012-01-01

    Objective To evaluate some agricultural waste extracts as insecticide and their effects on enzyme activities in liver and kidney of male mice. Methods The insecticidal activity of five tested compounds (one crude extract and 4 waste compounds) was bioassay against the 3rd instars of the Culex pipiens (Cx. pipiens) larvae in the laboratory. The LC50 values of eucalyptol, apricot kernel, Rice bran, corn, black liquor and white liquor are 91.45, 1 166.1, 1 203.3, 21 449.65, 4 025.78 and 6 343.18 ppm, respectively. Selection of the compounds for the subsequent studies was not only dependent on LC50 values but also on the persistence of these wastes products on large scale. Results White and black liquor did not produce any gross effect at 200 mg/Kg body weight. No apparent toxic symptoms were observed in tested animals during the whole period of the experiment which run out for 14 days. No statistically significance was observed in the enzyme cholinesterase activity, the activities of liver enzymes and kidney function in treated mice with black and white liquors. While, no and slight inhibition was observed after the 2 weeks of treatment period with deltamethrin and fenitrothion reached to about 24% in plasma cholinesterase enzyme activity. Significantly increase in the activities of liver enzymes and kidney function in treated mice with deltamethrin and fenitrothion. Conclusions Black liquor can be used efficiently to control Cx. pipiens larvae under laboratory condition. Environmental problem caused by rice straw can be solved by converting the waste material to beneficial natural selective insecticide. PMID:23569971

  9. A randomized, double-masked, parallel-group, comparative study to evaluate the clinical efficacy and safety of 1% azithromycin–0.1% dexamethasone combination compared to 1% azithromycin alone, 0.1% dexamethasone alone, and vehicle in the treatment of subjects with blepharitis

    PubMed Central

    Hosseini, Kamran; Lindstrom, Richard L; Foulks, Gary; Nichols, Kelly K

    2016-01-01

    Purpose To evaluate the clinical efficacy and safety of a 1% azithromycin–0.1% dexamethasone combination in DuraSite (“combination”) compared to 0.1% dexamethasone in DuraSite, 1% azithromycin in DuraSite, and vehicle in the treatment of subjects with blepharitis. Materials and methods This was a Phase III, double-masked, vehicle-controlled, four-arm study in which 907 subjects with blepharitis were randomized to combination (n=305), 0.1% dexamethasone (n=298), 1% azithromycin (n=155), or vehicle (n=149). Ten study visits were scheduled: screening visit, days 1 and 4 (dosing phase) and 15, and months 1–6 (follow-up phase). On day 1, subjects applied one drop of the study drug to the eyelid of the inflamed eye(s) twice daily, and continued with twice-daily dosing for 14 days. After completing 14 days of dosing, subjects were followed for 6 months for efficacy and safety. Results A total of 57 subjects (6.3%) had complete clinical resolution at day 15: 25 (8.2%), 17 (5.7%), 8 (5.2%), and 7 (4.7%) subjects in the combination-, 0.1% dexamethasone-, 1% azithromycin-, and vehicle-treatment groups, respectively. The combination was superior to 1% azithromycin and vehicle alone, but not to 0.1% dexamethasone alone. Mean composite (total) clinical sign and symptom scores improved in all four treatment groups during the post-treatment evaluation phase for the intent-to-treat population, but outcomes were superior when a drop containing 0.1% dexamethasone was utilized. Clinical response was noted as early as day 4, and persisted as long as 6 months. Most adverse events were considered mild in severity and not related to the study drug. Conclusion A higher percentage of subjects in the combination group achieved complete clinical resolution of the signs and symptoms of blepharitis at day 15 than with 1% azithromycin and vehicle, but outcomes were similar to treatment with 0.1% dexamethasone alone. The combination was well tolerated. PMID:27570444

  10. Investigation of Poultry Waste for Anaerobic Digestion: A Case Study

    NASA Astrophysics Data System (ADS)

    Salam, Christopher R.

    Anaerobic Digestion (AD) is a biological conversion technology which is being used to produce bioenergy all over the world. This energy is created from biological feedstocks, and can often use waste products from various food and agricultural processors. Biogas from AD can be used as a fuel for heating or for co-generation of electricity and heat and is a renewable substitute to using fossil fuels. Nutrient recycling and waste reduction are additional benefits, creating a final product that can be used as a fertilizer in addition to energy benefits. This project was conducted to investigate the viability of three turkey production wastes as AD feedstock: two turkey litters and a material separated from the turkey processing wastewater using dissolved air flotation (DAF) process. The DAF waste contained greases, oils and other non-commodity portions of the turkey. Using a variety of different process methods, types of bacteria, loading rates and food-to-microorganism ratios, optimal loading rates for the digestion of these three materials were obtained. In addition, the co-digestion of these materials revealed additional energy benefits. In this study, batch digestion tests were carried out to treat these three feedstocks, using mesophilic and thermophilic bacteria, using loading rates of 3 and 6 gVS/L They were tested separately and also as a mixture for co-digestion. The batch reactor used in this study had total and working volumes of 1130 mL and 500 mL, respectively. The initial organic loading was set to be 3 gVS/L, and the food to microorganism ratio was either 0.6 or 1.0 for different treatments based on the characteristics of each material. Only thermophilic (50 +/- 2ºC) temperatures were tested for the litter and DAF wastes in continuous digestion, but mesophilic and thermophilic batch digestion experiments were conducted. The optimum digestion time for all experiments was 14 days. The biogas yields of top litter, mixed litter, and DAF waste under

  11. Toxicology and Carcinogenesis Studies of 4,4'-Diamino-2,2'-Stilbenedisulfonic Acid Disodium Salt (CAS No. 7336-20-1) in F344 Rats and B6C3F1 Mice (Feed Studies).

    PubMed

    1992-08-01

    4,4'-Diamino-2,2'-stilbenedisulfonic acid, disodium salt, is used in the synthesis of dyes and optical brighteners or fluorescent whitening agents. Toxicology and carcinogenesis studies were conducted by administering the chemical (approximately 14% water, 6% sodium chloride, 4% impurities, and 76% 4,4'-diamino-2,2'-stilbenedisulfonic acid) in feed to groups of F344/N rats and B6C3F1 mice of each sex for 14 days, 13 weeks, and 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium and Chinese hamster ovary cells. 14-Day Studies: Groups of five rats and five mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 14 days. All rats and mice survived to the end of the studies. The mean body weight gain of male rats receiving 50,000 or 100,000 ppm and of female rats and male and female mice receiving 100,000 ppm was significantly lower than those of the respective controls. Clinical findings included diarrhea in the rats and mice receiving 100,000 ppm. There were no chemical-related changes in absolute or relative organ weights in rats or mice. There were no gross or microscopic lesions related to chemical administration in rats or mice. 13-Week Studies: Groups of 10 rats and 10 mice of each sex were given 0, 6,250, 12,500, 25,000, 50,000, or 100,000 ppm 4,4'-diamino-2,2'-stilbenedisulfonic acid, disodium salt, in feed for 13 weeks. One female rat, six male mice, and one female mouse in the 100,000 ppm dose groups died during the studies. Mean body weight gain was significantly decreased in male rats and female mice receiving 50,000 or 100,000 ppm, in male mice receiving 25,000, 50,000, or 100,000 ppm, and in female rats receiving 100,000 ppm. Clinical findings in rats that received 50,000 or 100,000 ppm and in mice that received 100,000 ppm included diarrhea, emaciation, and hyperemia of the perineum. There were no biologically significant changes in

  12. Early Anti-Pseudomonal Acquisition in Young Patients with Cystic Fibrosis: Rationale and Design of the EPIC Clinical Trial and Observational Study

    PubMed Central

    Treggiari, Miriam M; Rosenfeld, Margaret; Mayer-Hamblett, Nicole; Retsch-Bogart, George; Gibson, Ronald L.; Williams, Judy; Emerson, Julia; Kronmal, Richard A; Ramsey, Bonnie W

    2009-01-01

    Background The primary cause of morbidity and mortality in patients with cystic fibrosis (CF) is progressive obstructive pulmonary disease due to chronic endobronchial infection, particularly with Pseudomonas aeruginosa (Pa). Risk factors for and clinical impact of early Pa infection in young CF patients are less well understood. Purpose The present studies are designed to evaluate risk factors and outcomes associated with early Pa acquisition, and the benefits and harms of four anti-pseudomonal treatment regimens in young CF patients initiated after the first Pa positive respiratory culture. Methods The Early Pseudomonas Infection Control (EPIC) program consists of two studies, a randomized multicenter trial in CF patients ages 1–12 years at first isolation of Pa from a respiratory culture, and a longitudinal cohort study enrolling Pa-negative patients. Using a factorial design, trial participants are assigned for 18 months to either anti-pseudomonal treatment on a scheduled quarterly basis (cycled therapy) or based on recovery of Pa from quarterly respiratory cultures (culture-based therapy). The study drugs include inhaled tobramycin (300 mg BID) for 28 days, combined with either oral ciprofloxacin (15–20 mg/kg BID) or oral placebo for 14 days. The primary endpoints of the trial are the time to pulmonary exacerbation requiring IV antibiotics or hospitalization for respiratory symptoms, and the proportion of patients with new Pa-positive respiratory cultures during the study. The broad goals of the observational study are to describe the risk factors and outcomes associated with early acquisition of Pa. 306 patients were randomized in the clinical trial and 1,787 were enrolled in the cohort study. Conclusions These companion studies will provide valuable epidemiological and microbiological information on early CF lung disease and Pa acquisition, and safety and clinical efficacy data on anti-pseudomonal treatment strategies for early Pa infections in the

  13. Latent class analysis identifies three subtypes of aggressive end-of-life care: a population-based study in Taiwan.

    PubMed

    Chen, Mei-Ling; Chen, Yun-Yi; Tang, Siew Tzuh

    2013-10-01

    The aggressiveness of end-of-life (EOL) cancer care has often been analysed by the occurrence of several indicators, separately or aggregately. Whether aggressive EOL cancer care has different subtypes is unknown. This study sought to identify distinct subtypes of aggressive EOL care based on usage patterns of aggressive EOL-care indicators and to explore demographic, disease and treatment factors associated with the identified subtypes. This retrospective study linked data from 2001 to 2006 from three Taiwanese databases: National Registration of Death Database, Cancer Registration System and National Health Insurance claims database. Adult cancer patients (N=203,642) who died in 2001-2006 were selected. For these cancer patients' last month of life, we analysed eight indicators of aggressive EOL care: receiving chemotherapy, >1 emergency room visit, >1 hospitalisation, hospitalisation for >14 days, intensive care unit admission, received cardiopulmonary resuscitation, received intubation and received mechanical ventilation. Subtypes of aggressive EOL care were identified by latent class analysis. Among the study population, only 22.3% were treated by medical oncologists. Based on their profiles of EOL care, deceased cancer patients were classified into three subgroups: 'not aggressive' (45%), 'intent to sustain life' (33%) and 'symptom crisis' group (22%). Patients assigned to the 'intent to sustain life' group were less likely to have metastatic disease and to receive hospice care in the last year of life, but more likely to be cared for by non-medical oncologists, to die within 2 months after diagnosis and to die in hospital. EOL cancer care may be improved by understanding factors related to different subtypes of aggressive EOL care. PMID:23756054

  14. Follow-up of phase I trial of adalimumab and rosiglitazone in FSGS: III. Report of the FONT study group

    PubMed Central

    2010-01-01

    Background Patients with resistant primary focal segmental glomerulosclerosis (FSGS) are at high risk of progression to chronic kidney disease stage V. Antifibrotic agents may slow or halt this process. We present outcomes of follow-up after a Phase I trial of adalimumab and rosiglitazone, antifibrotic drugs tested in the Novel Therapies in Resistant FSGS (FONT) study. Methods 21 patients -- 12 males and 9 females, age 16.0 ± 7.5 yr, and estimated GFR (GFRe) 121 ± 56 mL/min/1.73 m2 -- received adalimumab (n = 10), 24 mg/m2 every 14 days or rosiglitazone (n = 11), 3 mg/m2 per day for 16 weeks. The change in GFRe per month prior to entry and after completion of the Phase I trial was compared. Results 19 patients completed the 16-week FONT treatment phase. The observation period pre-FONT was 18.3 ± 10.2 months and 16.1 ± 5.7 months after the study. A similar percentage of patients, 71% and 56%, in the rosiglitazone and adalimumab cohorts, respectively, had stabilization in GFRe, defined as a reduced negative slope of the line plotting GFRe versus time without requiring renal replacement therapy after completion of the FONT treatment period (P = 0.63). Conclusion Nearly 50% of patients with resistant FSGS who receive novel antifibrotic agents may have a legacy effect with delayed deterioration in kidney function after completion of therapy. Based on this proof-of-concept preliminary study, we recommend long-term follow-up of patients enrolled in clinical trials to ascertain a more comprehensive assessment of the efficacy of experimental treatments. PMID:20113498

  15. Medical Research and Evaluation Facility (MREF) and studies supporting the Medical Chemical Defense Program on Task 89-01: Screening of candidate pretreatment and therapeutic compounds in in vivo models. Final report Jul 89-Sep 91

    SciTech Connect

    Olson, C.T.; Kiser, R.C.; Dill, G.S.

    1992-02-01

    This task was a continuation of Task 86-29 initiated for Contract D. It provided in vivo screens for evaluating the efficacy of candidate pretreatment and treatment compounds submitted by the Drug Assessment Division of U.S. Army Medical Research of Chemical Defense against soman, tabun, and/or cyanide. A total of 578 compounds were received for testing and their maximum solubility in-vehicles comparable with in vivo testing in mice was determined. Range-finding and median lethal dose determinations following IM and/or oral administrations were conducted for 436 compounds submitted for nerve agent screening and range finding and median lethal dose determinations following IP administration were conducted for up to 142 compounds submitted for cyanide screening. Of 332 compounds evaluated, 154 passed the GD treatment efficacy evaluation, and 90 of 156 compounds submitted passed the GA treatment efficacy evaluation. For pretreatment studies against a GD challenge, 224 of 379 compounds submitted passed the IM efficacy evaluation and 96 of 143 compounds submitted passed the oral efficacy evaluation. Only 12 of 133 compounds evaluated as cyanide pretreatment compounds passed the efficacy evaluations. The mission of Task 89-01 was combined under Task 91-20 for the duration of Contract DAMD17-89-C-9050.

  16. Experiment K-7-28: Lung Morphology Study

    NASA Technical Reports Server (NTRS)

    West, J. B.; Elliott, A. R.; Mathieu-Costello, O.; Kaplansky, A. S.

    1994-01-01

    There are no previous studies investigating the effect of microgravity exposure during spaceflight on lung tissue. We examined the ultrastructure of the left lungs of 5 Czechoslovakian Wistar rats flown on the 13 day, 19+ hr. Cosmos 2044 mission, and compared them to 5 vivarium and 5 synchronous controls at 1-g conditions, and 5 rats exposed to 14 days of tail-suspension. Within 10 minutes of sacrifice by decapitation, the lungs were removed and immersed in 3% glutaraldehyde in 0.1M phosphate buffer (total osmolarity of the fixative: 560 mOsm; pH = 7.4). The tissue stored at 5 C was transported to our laboratory where it was processed for light and electron microscopy. No significant perivascular cuffing caused by interstitial edema was present in the tissue samples. Some of the flight, tail-suspended, and synchronous control rats showed alveolar edema, while vivarium controls did not. The pulmonary capillaries appeared to be more congested in the flight animals than in the other groups. This could be related to the increased hematocrit due to the microgravity exposure. In all 5 flight, 4 tail-suspended, and 3 synchronous rats, red blood cells (RBC) were present in the alveolar spaces. The RBC were either suspended free in the alveoli or observed lining the alveolar wall. The frequency of RBC lining the alveolar walls appeared greater in the dorsal (gravity non-dependent) than in ventral (gravity dependent) regions of the lung in these three animal groups. In 3 of the vivarium controls, a few RBC were found in the alveolar spaces. Intra-capillary fluid-filled vesicles were observed in the flight, tail-suspended and synchronous animals, but not in the vivarium controls. The formation of intra-capillary fluid-filled vesicles has been previously associated with pulmonary hypertension induced by high altitude exposure and mitral stenosis. In conclusion, pulmonary hemorrhage and alveolar edema of unknown origin occurred to a greater extent in the flight, tail

  17. NTP Toxicology and Carcinogenesis Studies of 1-Chloro-2-propanol (Technical Grade) (CAS NO. 127-00-4) in F344/N Rats and B6C3F1 Mice (Drinking Water Studies.

    PubMed

    1998-09-01

    1-Chloro-2-propanol and its positional isomer, 2-chloro-1-propanol, are used as chemical intermediates for the manufacture of propylene oxide, a starting material for production of polyurethane polyols and propylene glycol. The National Cancer Institute nominated 1-chloro-2-propanol for study because of potential for human exposure due to its residues in various foods that are fumigated with ethylene oxide or propylene oxide. Male and female F344/N rats and B6C3F1 mice were exposed to technical grade 1-chloro-2-propanol (75% to 76%% 1-chloro-2-propanol; 24% to 25%% 2-chloro-1-propanol) in drinking water for 14 days, 14 weeks, or 2 years. Genetic toxicology studies were conducted in Salmonella typhimurium, cultured Chinese hamster ovary cells, Drosophila melanogaster, and mouse peripheral blood erythrocytes. Continuous breeding studies were conducted in Sprague-Dawley rats. 14-DAY STUDY IN RATS: Groups of 10 male and 10 female F344/N rats were administered 1-chloro-2-propanol in drinking water at concentrations of 0, 100, 330, 1,000, 3,300, or 10,000 ppm for 14 days. Two 10,000 ppm females died before the end of the study. The final mean body weights and body weight gains of 3,300 and 10,000 ppm rats were significantly less than those of the controls; rats in the 10,000 ppm groups lost weight. Water consumption by the 3,300 and 10,000 ppm groups was significantly less than that by the controls throughout the study. The thymus weights of 10,000 ppm rats were significantly less than those of the controls. Exposure to 1-chloro-2-propanol caused cytoplasmic alteration and degeneration of the acinar cells and fatty change in the pancreas, atrophy of the bone marrow, and atrophy and hematopoiesis of the spleen in males and females. 14-DAY STUDY IN MICE: Groups of 10 male and 10 female B6C3F1 mice were administered 1-chloro-2-propanol in drinking water at concentrations of 0, 100, 330, 1,000, 3,300, or 10,000 ppm for 14 days. One male mouse in the 10,000 ppm group died

  18. An open-label, phase 2, single centre, randomized, crossover design bioequivalence study of AndroForte 5 testosterone cream and Testogel 1% testosterone gel in hypogonadal men: study LP101.

    PubMed

    Wittert, G A; Harrison, R W; Buckley, M J; Wlodarczyk, J

    2016-01-01

    We compared a novel 5% testosterone (T) cream (AndroForte 5, Lawley Pharmaceuticals, Australia) with a 1% T gel (Testogel, Besins Healthcare, Australia). Using an open-label crossover design, subjects were randomized to one of two treatment sequences using either the T gel or T cream first in a 1 : 1 ratio. Each treatment period was 30 days with a 7-14 days washout period between them. On Days 1 and 30 of each treatment period blood was sampled at -15, -5 min, 0, 2, 4, 5, 6, 7, 8, 9, 10, 12 and 16 h post study drug administration. Sixteen men with established androgen deficiency aged between 29 and 73 years, who had undertaken a washout from prior testosterone therapy participated in the study. One subject failed to complete both arms and another was excluded post-completion because of a major protocol violation. Bioequivalence was established based on key pharmacokinetic (PK) variables: AUC, C(avg), C(max), T(max), % fluctuation (with and without baseline correction) for the two formulations of testosterone on Day 1 and Day 30. The ratio and 90% CI of AUC 0.99 (0.86-1.14), C(max) 1.02 (0.84-1.24) and C(avg) 0.99 (0.86-1.14) for T cream/T gel were within the predetermined bio-equivalence criteria of 80% to 125% at Day 30. There were no statistically significant differences between secondary biochemical markers: serum dihydrotestosterone (DHT), oestradiol (E2), sex hormone-binding globulin (SHBG), luteinizing hormone (LH) and (FSH). The two testosterone formulations were shown to be bioequivalent. PMID:26754331

  19. Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer.

    PubMed

    Chaftari, Anne-Marie; Hachem, Ray; Jordan, Mary; Garoge, Kumait; Al Hamal, Zainab; El Zakhem, Aline; Viola, George M; Granwehr, Bruno; Mulanovich, Victor; Gagel, Andrew; Reitzel, Ruth; Yousif, Ammar; Jiang, Ying; Raad, Issam

    2016-01-01

    Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.). PMID

  20. Case-Control Study of Telavancin as an Alternative Treatment for Gram-Positive Bloodstream Infections in Patients with Cancer

    PubMed Central

    Hachem, Ray; Jordan, Mary; Garoge, Kumait; Al Hamal, Zainab; El Zakhem, Aline; Viola, George M.; Granwehr, Bruno; Mulanovich, Victor; Gagel, Andrew; Reitzel, Ruth; Yousif, Ammar; Jiang, Ying; Raad, Issam

    2015-01-01

    Gram-positive bacterial infections are an important cause of morbidity and death among cancer patients, despite current therapy. In this case-control study, we evaluated the clinical outcomes and safety of telavancin in cancer patients with uncomplicated Gram-positive bloodstream infections (BSIs). Between March 2011 and May 2013, we enrolled cancer patients with uncomplicated Gram-positive BSIs to receive intravenous telavancin therapy for at least 14 days for Staphylococcus aureus and 7 days for other Gram-positive cocci. Patients with baseline creatinine clearance (CLCR) values of >50 ml/min received 10 mg/kg/day of telavancin, and those with CLCR values between 30 and 49 ml/min received 7.5 mg/kg/day. Patients were compared with a retrospective cohort of 39 historical patients with Gram-positive BSIs, matched for underlying malignancy, infecting organism, and neutropenia status, who had been treated with vancomycin. A total of 78 patients were analyzed, with 39 in each group. The most common pathogen causing BSIs was S. aureus (51%), followed by alpha-hemolytic streptococci (23%), Enterococcus spp. (15%), coagulase-negative staphylococci (8%), and beta-hemolytic streptococci (3%). Sixty-two percent of patients had hematological malignancies, and 38% had solid tumors; 51% of the patients were neutropenic. The overall response rate determined by clinical outcome and microbiological eradication at 72 h following the initiation of therapy, in the absence of relapse, deep-seated infections, and/or infection-related death, was better with telavancin than with vancomycin (86% versus 61%; P = 0.013). Rates of drug-related adverse events were similar in the two groups (telavancin, 31%; vancomycin, 23%; P = 0.79), with similar rates of renal adverse events. Telavancin may provide a useful alternative to standard vancomycin therapy for Gram-positive BSIs in cancer patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01321879.) PMID

  1. Evaluation of nitrogen dioxide photolysis rates in an urban area using data from the 1997 Southern California Ozone Study

    NASA Astrophysics Data System (ADS)

    Vuilleumier, Laurent; Bamer, Jeffrey T.; Harley, Robert A.; Brown, Nancy J.

    The photolysis of nitrogen dioxide and formaldehyde are two of the most influential reactions in the formation of photochemical air pollution, and their rates are computed using actinic flux determined from a radiative transfer model. In this study, we compare predicted and measured nitrogen dioxide photolysis rate coefficients ( jNO 2). We used the Tropospheric Ultraviolet-Visible (TUV) radiation transfer model to predict jNO 2 values corresponding to measurements performed in Riverside, California as part of the 1997 Southern California Ozone Study (SCOS'97). Spectrally resolved irradiance measured at the same site allowed us to determine atmospheric optical properties, such as aerosol optical depth and total ozone column, that are needed as inputs for the radiative transfer model. Matching measurements of aerosol optical depth, ozone column, and jNO 2 were obtained for 14 days during SCOS'97. By using collocated measurements of the light extinction caused by aerosols and ozone over the full height of the atmosphere as model input, it was possible to predict sudden changes in jNO 2 resulting from atmospheric variability. While the diurnal profile of the rate coefficient was readily reproduced, jNO 2 model predicted values were found to be consistently higher than measured values. The bias between measured and predicted values was 17-36%, depending on the assumed single scattering albedo. By statistical analysis, we restricted the most likely values of the single scattering albedo to a range that produced bias on the order of 20-25%. It is likely that measurement error is responsible for a significant part of the bias. The aerosol single scattering albedo was found to be a major source of uncertainty in radiative transfer model predictions. Our best estimate indicates its average value at UV-wavelengths for the period of interest is between 0.77 and 0.85.

  2. A 90-day study of subchronic oral toxicity of 20 nm, negatively charged zinc oxide nanoparticles in Sprague Dawley rats

    PubMed Central

    Park, Hark-Soo; Shin, Sung-Sup; Meang, Eun Ho; Hong, Jeong-sup; Park, Jong-Il; Kim, Su-Hyon; Koh, Sang-Bum; Lee, Seung-Young; Jang, Dong-Hyouk; Lee, Jong-Yun; Sun, Yle-Shik; Kang, Jin Seok; Kim, Yu-Ri; Kim, Meyoung-Kon; Jeong, Jayoung; Lee, Jong-Kwon; Son, Woo-Chan; Park, Jae-Hak

    2014-01-01

    Purpose The widespread use of nanoparticles (NPs) in industrial and biomedical applications has prompted growing concern regarding their potential toxicity and impact on human health. This study therefore investigated the subchronic, systemic oral toxicity and no-observed-adverse-effect level (NOAEL) of 20 nm, negatively charged zinc oxide (ZnOSM20(−)) NPs in Sprague Dawley rats for 90 days. Methods The high-dose NP level was set at 500 mg/kg of bodyweight, and the mid- and low-dose levels were set at 250 and 125 mg/kg, respectively. The rats were observed during a 14-day recovery period after the last NP administration for the persistence or reduction of any adverse effects. Toxicokinetic and distribution studies were also conducted to determine the systemic distribution of the NPs. Results No rats died during the test period. However, ZnOSM20(−) NPs (500 mg/kg) induced changes in the levels of anemia-related factors, prompted acinar cell apoptosis and ductular hyperplasia, stimulated periductular lymphoid cell infiltration and excessive salivation, and increased the numbers of regenerative acinar cells in the pancreas. In addition, stomach lesions were seen at 125, 250, and 500 mg/kg, and retinal atrophy was observed at 250 and 500 mg/kg. The Zn concentration was dose-dependently increased in the liver, kidney, intestines, and plasma, but not in other organs investigated. Conclusion A ZnOSM20(−) NP NOAEL could not be established from the current results, but the lowest-observed-adverse-effect level was 125 mg/kg. Furthermore, the NPs were associated with a number of undesirable systemic actions. Thus, their use in humans must be approached with caution. PMID:25565828

  3. Kiwifruit-derived supplements increase stool frequency in healthy adults: a randomized, double-blind, placebo-controlled study.

    PubMed

    Ansell, Juliet; Butts, Christine A; Paturi, Gunaranjan; Eady, Sarah L; Wallace, Alison J; Hedderley, Duncan; Gearry, Richard B

    2015-05-01

    The worldwide growth in the incidence of gastrointestinal disorders has created an immediate need to identify safe and effective interventions. In this randomized, double-blind, placebo-controlled study, we examined the effects of Actazin and Gold, kiwifruit-derived nutritional ingredients, on stool frequency, stool form, and gastrointestinal comfort in healthy and functionally constipated (Rome III criteria for C3 functional constipation) individuals. Using a crossover design, all participants consumed all 4 dietary interventions (Placebo, Actazin low dose [Actazin-L] [600 mg/day], Actazin high dose [Actazin-H] [2400 mg/day], and Gold [2400 mg/day]). Each intervention was taken for 28 days followed by a 14-day washout period between interventions. Participants recorded their daily bowel movements and well-being parameters in daily questionnaires. In the healthy cohort (n = 19), the Actazin-H (P = .014) and Gold (P = .009) interventions significantly increased the mean daily bowel movements compared with the washout. No significant differences were observed in stool form as determined by use of the Bristol stool scale. In a subgroup analysis of responders in the healthy cohort, Actazin-L (P = .005), Actazin-H (P < .001), and Gold (P = .001) consumption significantly increased the number of daily bowel movements by greater than 1 bowel movement per week. In the functionally constipated cohort (n = 9), there were no significant differences between interventions for bowel movements and the Bristol stool scale values or in the subsequent subgroup analysis of responders. This study demonstrated that Actazin and Gold produced clinically meaningful increases in bowel movements in healthy individuals. PMID:25931419

  4. Steady-state pharmacokinetics of extended-release hydromorphone (OROS hydromorphone): a randomized study in healthy volunteers.

    PubMed

    Moore, Kenneth Todd; St-Fleur, Dominique; Marricco, Nadia Cardillo; Ariyawansa, Jay; Pagé, Véronique; Natarajan, Jayalakshmi; Morelli, Gaetano; Richarz, Ute

    2010-01-01

    The steady-state pharmacokinetics of an extended-release formulation of hydromorphone, OROS hydromorphone, was investigated in a randomized, open-label, crossover study in healthy volunteers. Participants were randomly assigned to receive 16 mg of OROS hydromorphone once daily and 4 mg of immediate-release hydromorphone four times daily for five consecutive days. The two treatments were separated by a washout period of 7-14 days. Naltrexone was given throughout both treatment periods to block the opioid effects of hydromorphone. Steady-state hydromorphone concentrations were statistically analyzed using Helmert contrasts to determine when steady state was reached. A total of 30 participants were enrolled, of whom 29 completed both treatment periods. The two treatments produced comparable steady-state plasma drug concentrations, but peak-to-trough fluctuations were smaller with OROS hydromorphone (61 percent vs 172 percent) in comparison with immediate release hydromorphone. Overall systemic exposure to hydromorphone was similar between the two formulations. The ratio of the geometric means between the two formulations for the area under the concentration-time curves at steady state was 105.2 percent with a 90% confidence interval (CI) of 99.8-110.8 (geometric mean: 102.7 percent; 90% CI: 97.6-108.2 after correcting for measured drug content), which was within the bioequivalence range (80-125 percent). The analysis of Helmert contrasts showed that steady state conditions were attained by day 4. Both treatments were well tolerated. This study shows that OROS hydromorphone maintains steady-state plasma drug concentrations within the same range as immediate-release hydromorphone at the same total daily dose, with less fluctuation. PMID:21046932

  5. Basic toxicology and metabolism studies of 1,5-anhydro-D-fructose using bacteria, cultured mammalian cells, and rodents.

    PubMed

    Yu, Shukun; Mei, Jie; Ahrén, Bo

    2004-10-01

    1,5-Anhydro-D-fructose (AF) is a monosaccharide occurring in edible morels, red seaweeds and certain mammalian tissues. It can be formed directly from starch and glycogen in vivo by alpha-1,4-glucan lyase (EC 4.2.2.13). In this study, the toxicity, absorption and metabolism of AF using bacteria, mammalian cells, rat and mouse models were examined. In Ames test, AF showed no genotoxicity using five strains of the bacterium Salmonella typhimurium TA 98, 100, 102, 1535 and 1537. AF caused no mammalian gene mutation as tested with mouse lymphoma L5178Y cells. AF did not cause toxic symptoms in rats when it was administered as a single oral dose of 5 g/kg and observed over a 14-day period. Furthermore, at necropsy, no signs of abnormality were detected. Daily intraperitoneal (ip) administration of 2 g/kg AF to mice did not induce adverse effects throughout a 28-day period. Radioactive tracing experiments using 14C-labeled AF indicated that AF was efficiently absorbed since the major portion of radioactive material was recovered in urine. Further work using unlabeled AF indicated that the cyclic polyol 1,5-anhydro-D-sorbitol (AS) increased dramatically in both blood and urine upon AF administration at 1 g/kg ip, suggesting the existence of an efficient reduction mechanism from AF to AS, which was then excreted in urine. In conclusion, these studies indicate that AF had low or no toxicity and showed no mutagenicity. PMID:15354319

  6. Study on cerebroprotective actions of Clerodendron glandulosumleaves extract against long term bilateral common carotid artery occlusion in rats.

    PubMed

    Surapaneni, Saritha; Prakash, T; Ansari, MdAsif; Manjunath, Pm; Kotresha, D; Goli, Divakar

    2016-05-01

    Stroke is a major cause of death and disability worldwide. The resulting burden on the society continues to grow, with increase in the incidence of stroke. Oxidative stress has been involved in the pathogenesis of several neurological diseases including acute stroke.Focal and global cerebral ischemia represents diseases that are common in the human population.In recent years much attention is being paid towards the exploration of herbal preparation, antioxidant agents and combination therapies including COX-2 inhibitors in experimental model of stroke.Possible effect of a hydroalcoholic leaf extract of Clerodendron glandulosumColeb (C. glandulosum)on oxidant-antioxidant status in ischemia-hypoperfusion injury in the rat forebrain has been investigated.Healthy adult male Wistar albino rats were divided into five groups (n=8). Group I was served as Sham control (normal saline 1ml/kg, orally), group II was served hypoperfusion control (normal saline 1ml/kg, orally), group III, group IV were served as hydroalcoholic extract treated (200 and 400mg/kg, orally) and group V was treated with Quercetin (10mg/kg, orally) for 14days to assess preventive and curative effects of C. glandulosum. Flavonoid and phenolic compounds exhibit a broad spectrum of biological activity, including antioxidant. C. glandulosum extract (200 and 400mg/kg, p.o) was administered orally, once daily for a period of 2 weeks after the occlusion of BCCA. After 14th days rats were subjected to behavioral studies. After behavioral studies animals were sacrificed and brain was removed and homogenized. Estimation of Lipid peroxidation (LPO) Myeloperoxidase (MPO), estimation of protein levels and the activities of Superoxide dismutase (SOD), Catalase (CAT), were performed. Infarct size and histopathological changes were observed in treated groups. PMID:27133043

  7. Assessment of the effects of laser or LED photobiomodulation on hypothyroid rats of cutaneous wound healing: A morphometric study.

    NASA Astrophysics Data System (ADS)

    De Castro, Isabele Cardoso Vieira; Paraguassú, Gardênia Matos; dod Reis Júnior, João Alves; Xavier, Flávia Caló Aquino; Rodriguez, Tânia Tavares; Ramalho, Maria José Pedreira; Pinheiro, Antônio L. B.; Ramalho, Luciana Maria Pedreira

    2012-09-01

    Hypothyroid has been associated to a disruption of the body's metabolism, including the healing process. Laser and LED have been shown to be effective on improving healing in many situations, but their benefit in the improvement of healing on hypothyroidism remains unknown. The aim of this study was to assess, morphometrically, the influence of Laser (λ660nm, 24 J/cm2, 40mW, CW, spot output= 4mm2;) and LED (λ630nm ± 20, 24 J/cm2, 150mW, CW, spot output= 0.5 cm2) on the wound healing of rats with Hypothyroid. Under general anesthesia, a standard surgical wound (1cm2) was created on the dorsum of 72 male Wistar rats divided into 6 groups of 12 animals each: G1: Euthyroid; G2: Euthyroid + Laser; G3: Euthyroid + LED; G4: Hypothyroid; G5: Hypothyroid + Laser and G6: Hypothyroid + LED. Hypothyroidism was induced in rats with propylthiouracil (0.05g/100mL) administered orally for 4 weeks and maintained until the end of the experiment. Rats were irradiated after surgery each 48h then killed after 7 and 14 days. Statistical analysis was performed using ANOVA and Tukey's test. Hypothyroid rats with phototherapy laser or LED showed significant less wound contraction than euthyroid's rats at the 7th day (p<0.05). At the 14th day, the longitudinal measurement was significantly higher in euthyroids (control and irradiated with laser) when compared to the hypothyroid group (p <0.05). This study has shown that hypothyroidism delays wound healing and Laser and LED photobiomodulation using 24 J/cm2 per session improved cutaneous wound healing in hypothyroid rats.

  8. Incidence of Venous Thromboembolism in Patients Undergoing Major Hip Surgeries at a Single Institution: A Prospective Study

    PubMed Central

    Yamanaka, Yasuhiro; Ito, Hiroshi

    2016-01-01

    Background: Venous thoromboembolism (VTE) is one of the most significant complications after hip surgeries. Many studies have been reported about the incidence of VTE after THA, but a small number of reports were found concerning Periacetabular osteotomy, Revision THA and Surgery for hip fracture postoperatively. Furthermore, there exists no comparative study of the incidence of VTE among major hip surgeries at a single institution. We reported the incidence of VTE among hip surgeries performed at a single institution. Methods: A total of 820 Hip surgeries were performed at same institution. The procedures included 420 hips that underwent primary total hip arthroplasties (THA), 91 revision or removal of total hip arthroplasties (Revision THA), 144 periacetabular osteotomy (PAO) and 165 surgery for hip fracture (SHF) between 2006 and 2012. VTE was detected by Multidetector computed tomography (MDCT) that scanned 768 cases and by ultrasound that scanned 52cases postoperative 10-14 days. Results: The overall incidence of VTE was 12.2% (100 of 820). The incidence of VTE after THA was 13.1% (55 of 420), Revision THA was 13.2% (12 of 91), PAO was 2.1% (3 of 144) and SHF was 18.1% (30 of 165). The incidence of VTE was significantly higher in SHF than in PAO. Conclusion: This data indicates that the incidence of VTE after PAO is significantly lower than SHF and relatively lower than THA and Revision THA. A younger age and non-invasion of the bone marrow of the femur may have affected the result. Prophylaxis therapy was effective especially on SHF. PMID:27499823

  9. Tolerability of Nasal Delivery of Humidified and Warmed Air at Different Temperatures: A Randomised Double-Blind Pilot Study

    PubMed Central

    Bibby, Susan; Reddy, Sumeet; Cripps, Terrianne; McKinstry, Steve; Weatherall, Mark; Beasley, Richard; Pilcher, Janine

    2016-01-01

    Objectives. Delivery of warmed, humidified air via nasal high flow therapy could potentially reduce replication of temperature-sensitive viruses in the upper respiratory tract. This study investigates whether nasal high flow therapy is well tolerated by healthy adults at 37°C and 41°C. Methods. In this randomised, double-blind, controlled crossover pilot trial, nasal high flow therapy was used to deliver humidified air at 35 L/min, at either 37°C or 41°C, for three one-hour sessions of use over one day. The alternative was delivered at least 14 days later. Ten healthy, nonsmoking adults were asked, via questionnaire after each day's use, whether they would use nasal high flow therapy while being unwell with a cold or flu if it was demonstrated to improve symptoms. Results. All participants completed both interventions. Eighty percent responded “yes” to future use of nasal high flow therapy, for both 37°C and 41°C. There was no significant change from baseline in saccharin times following either intervention or in the following morning. Conclusions. Delivering humidified air via nasal high flow therapy at both 37°C and 41°C is well tolerated by healthy adults. This supports investigation into the potential use of nasal high flow therapy as treatment in viral upper respiratory tract infections. Trial Registration. This trial is registered with ACTRN12614000183684 (tolerability study of nasal delivery of humidified & warmed air). PMID:27127650

  10. Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

    PubMed Central

    Traversa, Giuseppe; Spila-Alegiani, Stefania; Bianchi, Clara; Ciofi degli Atti, Marta; Frova, Luisa; Massari, Marco; Raschetti, Roberto; Salmaso, Stefania; Scalia Tomba, Gianpaolo

    2011-01-01

    Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age. PMID:21298113

  11. The effect of kynurenic acid on the synthesis of selected cytokines by murine splenocytes - in vitro and ex vivo studies.

    PubMed

    Małaczewska, Joanna; Siwicki, Andrzej K; Wójcik, Roman M; Turski, Waldemar A; Kaczorek, Edyta

    2016-01-01

    Kynurenic acid (KYNA), a secondary product of the kynurenine pathway of tryptophan degradation, known mainly as an endogenous neuroprotectant, shows also immunotropic properties. Some quantities of KYNA are present in food and are effectively absorbed in the gastrointestinal tract. Since the spleen is an important target of dietary immunomodulators, the aim of the study was to determine the effect of exogenous KYNA on murine splenocytes. Splenocytes isolated from adult BALB/c mice were used in the study. Firstly, the effect of increasing KYNA concentrations (0-5 mM) on the viability, and proliferative and cytokine response (interleukin 1β [IL-1β], IL-6, IL-10, tumor necrosis factor α [TNF-α]) of murine splenocytes under in vitro conditions was determined. Then, proliferative and cytokine responses were determined in cells derived from animals receiving kynurenic acid in drinking water at concentrations of 2.5, 25, or 250 mg/l for 7-14 days. Cytokine levels were measured using commercial immunoassay (ELISA) kits, and cell viability and proliferation was determined with MTT reduction assay. Exogenous KYNA was characterised by a low level of cytotoxicity towards murine splenocytes, and was well tolerated by the animals receiving it in drinking water. As expected, it exhibited anti-inflammatory action towards the activated splenocytes, under both in vitro and ex vivo conditions. Surprisingly, however, KYNA itself influenced the activity of resting, non-stimulated cells, exerting an immunostimulant effect in vitro, and an immunosuppressive effect under ex vivo conditions. The obtained results indicate not only anti-inflammatory, but also more complex, immunomodulating properties of KYNA, which require more detailed investigation. PMID:27095921

  12. Bioequivalence study of two oral tablet formulations containing saquinavir mesylate boosted with ritonavir in healthy male subjects.

    PubMed

    Yerino, Gustavo A; Halabe, Emilia K; Zini, Elvira; Feleder, Ethel C

    2011-01-01

    Saquinavir (SAQ) mesylate (CAS 149845-06-7) is a potent inhibitor of the HIV-1 protease indicated in combination with other antiretrovirals for the management of HIV-1 infection. The objective of this study was to compare rate and extent of absorption and to assess the bioequivalence between a new pharmaceutical equivalent tablet formulation containing 500 mg of SAQ mesylate and the innovator film coated tablet formulation. A randomized, single-center, open-label, two-treatment, two-sequence, three-period, replicated crossover bioequivalence study in 40 healthy male subjects was conducted. All subjects received 100 mg ritonavir (CAS 155213-67-5) twice daily for a run-in period of 3 days before treatment. Dosing was separated by a wash-out period of 14 days. Blood samples were collected over 72 h and plasma levels of SAQ were determined by a validated HPLC/UV assay. The 90% confidence interval (CI) of the ratio of the geometric means for log-transformed C(max), AUC(last) and AUC(inf) values were used to assess bioequivalence using the equivalence interval of 80-125%. Point estimate and 90% CI of the ratios of C(max), AUC(last) and AUC(inf) values were 94.9 (80.9-111.3), 97.4 (82.4-115.4) and 97.4 (82.5-115.0), respectively. Both treatments exhibited similar tolerability and safety. It was concluded that the new pharmaceutical product was bioequivalent to the innovator. PMID:21950153

  13. Hepatoprotective activity of Thunbergia laurifolia Linn extract in rats treated with ethanol: in vitro and in vivo studies.

    PubMed

    Pramyothin, Pornpen; Chirdchupunsare, Hemvala; Rungsipipat, Anudep; Chaichantipyuth, Chaiyo

    2005-12-01

    Primary cultures of rat hepatocyte and rats were used as the in vitro and in vivo models to evaluate the hepatoprotective activity of aqueous extract from Thunbergia laurifolia (TLE). Ethanol was selected as hepatotoxin. Silymarin (SL) was the reference hepatoprotective agent. In the in vitro study, MTT reduction assay and release of transaminases (ALT and AST) were the criteria for cell viability. Primary cultures of rat hepatocyte (24 h culturing) were treated with ethanol (96 microl/ml) and various concentrations of TLE (2.5, 5.0, 7.5 and 10.0 mg/ml) or SL (1, 2 and 3 mg/ml) for 2 h. Ethanol decreased MTT (%) nearly by half. Both TLE and SL increased MTT reduction and brought MTT (%) back to normal. Ethanol induced release of ALT and AST was also reduced by TLE (2.5 and 5.0 mg/ml) and SL (1 mg/ml). In the in vivo study, serum transaminases, serum triglyceride (STg) together with hepatic triglyceride (HTg) and histopathological examination were the criteria for evidences of liver injury. Ethanol (4 g/(kg day), po for 14 days) caused the increase in ALT, AST, HTg and centrilobular hydropic degeneration of hepatocytes. TLE at 25 mg/(kg day), po, or SL at 5 mg/(kg day), po, for 7 days after ethanol enhanced liver cell recovery by bringing HTg, ALT and/or AST back to normal. These results suggest that TLE and SL possess the hepatoprotective activity against ethanol induced liver injury in both primary cultures of rat hepatocyte and rats. PMID:16085378

  14. Comparative safety of interleukin-1 blockade with anakinra in patients with ST-segment elevation acute myocardial infarction (from the VCU-ART and VCU-ART2 pilot studies).

    PubMed

    Abbate, Antonio; Kontos, Michael Christopher; Abouzaki, Nayef Antar; Melchior, Ryan David; Thomas, Christopher; Van Tassell, Benjamin Wallace; Oddi, Claudia; Carbone, Salvatore; Trankle, Cory Ross; Roberts, Charlotte Susan; Mueller, George Herman; Gambill, Michael Lucas; Christopher, Sanah; Markley, Roshanak; Vetrovec, George Wayne; Dinarello, Charles Anthony; Biondi-Zoccai, Giuseppe

    2015-02-01

    Two pilot studies of interleukin-1 (IL-1) blockade in ST-segment elevation myocardial infarction (STEMI) showed blunted acute inflammatory response and overall favorable outcomes at 3 months follow-up. We hereby present a patient-level pooled analysis with extended follow-up of 40 patients with clinically stable STEMI randomized to anakinra, a recombinant IL-1 receptor antagonist, 100 mg/day for 14 days or placebo in a double-blinded fashion. End points included death, cardiac death, recurrent acute myocardial infarction (AMI), stroke, unstable angina, and symptomatic heart failure. Median follow-up was 28 (interquartile range 3 to 38) months. Sixteen patients (40%) had a total of 22 adverse cardiovascular events: 1 cardiac death, 4 recurrent AMI, 5 episodes of unstable angina pectoris requiring hospitalization and/or urgent revascularization, and 11 new diagnoses of heart failure. Treatment with anakinra was associated with a hazard ratio of 1.08 (95% confidence interval 0.31 to 3.74, p = 0.90) for the combined end point of death, recurrent AMI, unstable angina pectoris, or stroke and a hazard ratio of 0.16 (95% confidence interval 0.03 to 0.76, p = 0.008) for death or heart failure. In conclusion, IL-1 blockade with anakinra for 2 weeks appears, therefore, to have a neutral effect on recurrent ischemic events, whereas it may prevent new-onset heart failure long term after STEMI. PMID:25482680

  15. A comparative study of red and blue light-emitting diodes and low-level laser in regeneration of the transected sciatic nerve after an end to end neurorrhaphy in rabbits.

    PubMed

    Takhtfooladi, Mohammad Ashrafzadeh; Sharifi, Davood

    2015-12-01

    This study aimed at evaluating the effects of red and blue light-emitting diodes (LED) and low-level laser (LLL) on the regeneration of the transected sciatic nerve after an end-to-end neurorrhaphy in rabbits. Forty healthy mature male New Zealand rabbits were randomly assigned into four experimental groups: control, LLL (680 nm), red LED (650 nm), and blue LED (450 nm). All animals underwent the right sciatic nerve neurotmesis injury under general anesthesia and end-to-end anastomosis. The phototherapy was initiated on the first postoperative day and lasted for 14 consecutive days at the same time of the day. On the 30th day post-surgery, the animals whose sciatic nerves were harvested for histopathological analysis were euthanized. The nerves were analyzed and quantified the following findings: Schwann cells, large myelinic axons, and neurons. In the LLL group, as compared to other groups, an increase in the number of all analyzed aspects was observed with significance level (P < 0.05). This finding suggests that postoperative LLL irradiation was able to accelerate and potentialize the peripheral nerve regeneration process in rabbits within 14 days of irradiation. PMID:26415928

  16. Endocrine-mediated effects of two benzene related compounds, 1-chloro-4-(chloromethyl)benzene and 1,3-diethyl benzene, based on subacute oral toxicity studies using rats.

    PubMed

    Yamasaki, Kanji; Ishii, Satoko; Kikuno, Tsukasa; Minobe, Yasushi

    2012-08-01

    The purpose of this study was to investigate the endocrine-mediated effects of the benzene-related compounds with reference to Organization for Economic Co-operation and Development (OECD) Test Guideline No. 407. Rats were orally gavaged with 0, 10, 50, and 250 mg/kg/day of 1-chloro-4-(chloromethyl)benzene, and 0, 25, 150, and 1000 mg/kg/day of 1,3-diethyl benzene for at least 28 days, beginning at 8 weeks of age. Thyroid dysfunction was observed in rats given the 1,3-diethyl benzene. Serum T4 values increased in all groups of male rats and in the 1000 mg/kg group of female rats, and TSH values also increased in the 1000 mg/kg groups of both sexes after 28 days' administration. Decreased T3 values were observed in the 1000 mg/kg group of female rats after 28 days' administration, and hormone values increased in the 1000 mg/kg groups of both sexes after the 14-day recovery period. In addition, thyroid weight increased in the 1000 mg/kg groups and thyroid follicular cell hyperplasia was detected in one male rat from the 1000 mg/kg group after 28 days' administration. Endocrine-mediated effects, including thyroid dysfunction were not observed in any groups of rats treated with 1-chloro-4-(chloromethyl)benzene. Our results indicated that endocrine-mediated effects such as thyroid dysfunction were associated with some benzene-related compounds. PMID:22643015

  17. Analysis of human exposure to benzo(a)pyrene via inhalation and food ingestion in the Total Human Environmental Exposure Study (THEES)

    SciTech Connect

    Waldman, J.M.; Lioy, P.J.; Greenberg, A.; Butler, J.P. )

    1991-04-01

    The Total Human Environmental Exposure Study (THEES) focuses on benzo(a)pyrene (BaP) as an example of a combustion-generated polycyclic aromatic hydrocarbon (PAH) compound. Primary pathways for environmental exposures to BaP are inhalation and ingestion. This program of field studies was conducted in Phillipsburg, New Jersey, a small, industrial city in the Delaware River valley. The study protocols included direct monitoring of BaP exposures via inhalation and ingestion pathways during three separate periods, each lasting 14 days. BaP concentrations in air were sampled at outdoor and in-home locations, with personal air sampling added during the latter two phases. Cooked food samples from each household were acquired, using a constant portion second plate' of each meal prepared at home. Ambient levels were 4-10 times higher during the cold months compared with the late summer study period. Space heating and regional aerosol were major contributors to community levels of BaP in the air during the wintertime. Penetration of outdoor air, cooking activities, combustion appliances, and cigarette smoke were important sources of indoor air exposures. Cooking activities, besides releasing BaP-enriched particles indoors, produced food imbued with BaP and added substantially to exposure via the ingestion route. Among the study subjects, the range and magnitude of dietary exposures (2 to 500 ng/d) were much greater than for inhalation (10 to 50 ng/d). Nevertheless, there were ample individual cases where inhalation of BaP was the predominant exposure route. Indoor air BaP levels were closely correlated with ambient levels in most of the homes. For some individuals, measured personal air BaP exposures were adequately predicted by time-weighting of microenvironmental (i.e., outdoor and in-home) concentrations.

  18. Safety, Acceptability, and Feasibility of Early Infant Male Circumcision Conducted by Nurse-Midwives Using the AccuCirc Device: Results of a Field Study in Zimbabwe

    PubMed Central

    Mavhu, Webster; Larke, Natasha; Hatzold, Karin; Ncube, Getrude; Weiss, Helen A; Mangenah, Collin; Chonzi, Prosper; Mugurungi, Owen; Mufuka, Juliet; Samkange, Christopher A; Gwinji, Gerald; Cowan, Frances M; Ticklay, Ismail

    2016-01-01

    ABSTRACT Background: For prevention of HIV, early infant male circumcision (EIMC) needs to be scaled up in countries with high HIV prevalence. Routine EIMC will maintain the HIV prevention gains anticipated from current adult male circumcision initiatives. We present here the results of a field study of EIMC conducted in Zimbabwe. Methods: The study was observational and based on the World Health Organization (WHO) framework for clinical evaluation of male circumcision devices. We recruited parents of newborn male infants between August 2013 and July 2014 from 2 clinics. Nurse-midwives used the AccuCirc device to circumcise eligible infants. We followed participants for 14 days after EIMC. Outcome measures were EIMC safety, acceptability, and feasibility. Results: We enrolled 500 male infants in the field study (uptake 11%). The infants were circumcised between 6 and 60 days postpartum. The procedure took a median of 17 minutes (interquartile range of 5 to 18 minutes). Mothers’ knowledge of male circumcision was extensive. Of the 498 mothers who completed the study questionnaire, 91% knew that male circumcision decreases the risk of HIV acquisition, and 83% correctly stated that this prevention is partial. Asked about their community’s perception of EIMC, 40% felt that EIMC will likely be viewed positively in their community; 13% said negatively; and 47% said the perception could be both ways. We observed 7 moderate or severe adverse events (1.4%; 95% confidence interval, 0.4% to 2.4%). All resolved without lasting effects. Nearly all mothers (99%) reported great satisfaction with the outcome, would recommend EIMC to other parents, and would circumcise their next sons. Conclusion: This first field study in sub-Saharan Africa of the AccuCirc device for EIMC demonstrated that EIMC conducted by nurse-midwives with this device is safe, feasible, and acceptable to parents. PMID:27413083

  19. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats.

    PubMed

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan; Lee, Hye-Yeong; Kang, Jong-Koo

    2015-12-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  20. Acute and 28-Day Subacute Toxicity Studies of Hexane Extracts of the Roots of Lithospermum erythrorhizon in Sprague-Dawley Rats

    PubMed Central

    Han, Chung-Tack; Kim, Myoung-Jun; Moon, Seol-Hee; Jeon, Yu-Rim; Hwang, Jae-Sik; Nam, Chunja; Park, Chong-Woo; Lee, Sun-Ho; Na, Jae-Bum; Park, Chan-Sung; Park, Hee-Won; Lee, Jung-Min; Jang, Ho-Song; Park, Sun-Hee; Han, Kyoung-Goo; Choi, Young Whan

    2015-01-01

    Lithospermum erythrorhizon has long been used as a traditional oriental medicine. In this study, the acute and 28-day subacute oral dose toxicity studies of hexane extracts of the roots of L. erythrorhizon (LEH) were performed in Sprague-Dawley rats. In the acute toxicity study, LEH was administered once orally to 5 male and 5 female rats at dose levels of 500, 1,000, and 2,000 mg/kg. Mortality, clinical signs, and body weight changes were monitored for 14 days. Salivation, soft stool, soiled perineal region, compound-colored stool, chromaturia and a decrease in body weight were observed in the extract-treated groups, and no deaths occurred during the study. Therefore, the approximate lethal dose (ALD) of LEH in male and female rats was higher than 2,000 mg/kg. In the subacute toxicity study, LEH was administered orally to male and female rats for 28 days at dose levels of 25, 100, and 400 mg/kg/day. There was no LEH-related toxic effect in the body weight, food consumption, ophthalmology, hematology, clinical chemistry and organ weights. Compound-colored (black) stool, chromaturia and increased protein, ketone bodies, bilirubin and occult blood in urine were observed in the male and female rats treated with the test substance. In addition, the necropsy revealed dark red discoloration of the kidneys, and the histopathological examination showed presence of red brown pigment or increased hyaline droplets in the renal tubules of the renal cortex. However, there were no test substance-related toxic effects in the hematology and clinical chemistry, and no morphological changes were observed in the histopathological examination of the kidneys. Therefore, it was determined that there was no significant toxicity because the changes observed were caused by the intrinsic color of the test substance. These results suggest that the no-observed-adverse-effect Level (NOAEL) of LEH is greater than 400 mg/kg/day in both sexes. PMID:26877842

  1. 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

  2. [The effect of a different level of crude protein in the feed of chickens from 1 to 14 days after hatching on the development of body weight, the biochemical parameters of the liver and breast muscle and the serum level of total protein and albumin].

    PubMed

    Forner, C; Kolb, E; Taubert, U

    1991-02-01

    The effect of a concentration of crude protein of 170 or of 227 g/kg in the ration of chicken from the 1st to the 14th day after hatching on biochemical values of the liver, the M. pectoralis superficialis and the serum was analysed. The significance of developmental investigations in domestic animals under normal and pathological conditions is discussed. PMID:2025215

  3. A phase I study of danusertib (PHA-739358) in adult patients with accelerated or blastic phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia resistant or intolerant to imatinib and/or other second generation c-ABL therapy

    PubMed Central

    Borthakur, Gautam; Dombret, Herve; Schafhausen, Philippe; Brummendorf, Tim Henrik; Boissel, Nicolas; Jabbour, Elias; Mariani, Mariangela; Capolongo, Laura; Carpinelli, Patrizia; Davite, Cristina; Kantarjian, Hagop; Cortes, Jorge E.

    2015-01-01

    Danusertib is a pan-aurora kinase inhibitor with potent activity against Abl kinase including the gatekeeper T315I mutant. A phase 1 dose escalation study of danusertib was conducted in patients with accelerated or blastic phase chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Two dosing schedules were studied: schedule A, in which danusertib was given by 3-hour intravenous infusion daily for 7 consecutive days (days 1–7) in a 14-day cycle, and schedule B, in which the danusertib was given by 3-hour intravenous infusion daily for 14 consecutive days (days 1–14) in a 21-day cycle. A total of 37 patients were treated, 29 with schedule A and eight with schedule B. The recommended phase 2 dose for schedule A was 180 mg/m2. Enrollment to schedule B was stopped early because of logistical problems with the frequency of infusions. Febrile neutropenia and mucositis were dose-limiting toxicities in schedule A. Four patients with T315I ABL kinase mutation, all treated with schedule A, responded. Danusertib has an acceptable toxicity profile and is active in patients with Bcr-Abl-associated advanced hematologic malignancies. This study was registered with the European Clinical Trails Data Base (EudraCT number 2007-004070-18). PMID:25887498

  4. First study on efficacy and tolerability of a new alkylphosphocholine molecule (oleylphosphocholine-OlPC) in the treatment of canine leishmaniosis due to Leishmania infantum.

    PubMed

    Hernández, Leticia; Gálvez, Rosa; Montoya, Ana; Checa, Rocio; Bello, Alba; Bosschaerts, Tom; Jansen, Herwig; Rupérez, Cristina; Fortin, Anny; Miró, Guadalupe

    2014-01-01

    The alkylphosphocholine oleylphosphocholine (OlPC) represents a potential new therapy for the treatment of canine leishmaniosis caused by Leishmania infantum. The aim of the present study was to evaluate the efficacy and safety of OlPC in a small cohort of dogs naturally infected with L. infantum and defined as clinically sick (LeishVet stages II and III). A total of eight dogs were included in the study and were treated orally with 4 mg/kg OlPC for 14 days. Dogs were assessed at the clinical and parasitological level at four time points during a total follow-up period of 90 days (before treatment and at 15, 30, and 90 days post-treatment onset). Ln-PCR, real-time quantitative PCR, antibody testing (IFAT), and culture of bone marrow aspirates were evaluated at the four time points. OlPC treatment induced a rapid and satisfactory clinical recovery in terms of clinical score reduction and weight gain, and treatment efficacy was found to be associated with a decrease in bone marrow parasitic load. Serological titers measured by IFAT were stable in any of the treated dogs at any time point after treatment. OlPC was well tolerated and no severe adverse events were noted in any of the treated dogs; even some dogs showed slight intestinal disorders. This proof-of-principle study is the first to show that short oral treatment with OlPC improves clinical signs of canine L. infantum leishmaniosis, highlighting the need to perform additional studies to optimize the dosing regimen and to assess long-term treatment efficacy of this drug. PMID:24192865

  5. A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis.

    PubMed

    Trachtman, Howard; Fervenza, Fernando C; Gipson, Debbie S; Heering, Peter; Jayne, David R W; Peters, Harm; Rota, Stefano; Remuzzi, Giuseppe; Rump, L Christian; Sellin, Lorenz K; Heaton, Jeremy P W; Streisand, James B; Hard, Marjie L; Ledbetter, Steven R; Vincenti, Flavio

    2011-06-01

    Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25  ml/min per 1.73  m(2), and a urine protein to creatinine ratio over 1.8  mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4  mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73  m(2)). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2  mg/mg with all three Black patients having a mean decline of 3.6  mg/mg. The half-life of fresolimumab was ∼14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary. PMID:21368745

  6. A phase 1, single-dose study of fresolimumab, an anti-TGF-β antibody, in treatment-resistant primary focal segmental glomerulosclerosis

    PubMed Central

    Trachtman, Howard; Fervenza, Fernando C; Gipson, Debbie S; Heering, Peter; Jayne, David R W; Peters, Harm; Rota, Stefano; Remuzzi, Giuseppe; Rump, L Christian; Sellin, Lorenz K; Heaton, Jeremy P W; Streisand, James B; Hard, Marjie L; Ledbetter, Steven R; Vincenti, Flavio

    2011-01-01

    Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-β (TGF-β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m2, and a urine protein to creatinine ratio over 1.8 mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4 mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73 m2). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2 mg/mg with all three Black patients having a mean decline of 3.6 mg/mg. The half-life of fresolimumab was ∼14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary. PMID:21368745

  7. An Open-Label Randomized Crossover Trial of Lyophilized Black Raspberries on Postprandial Inflammation in Older Overweight Males: A Pilot Study.

    PubMed

    Sardo, Christine L; Kitzmiller, Joseph P; Apseloff, Glen; Harris, Robin B; Roe, Denise J; Stoner, Gary D; Jacobs, Elizabeth T

    2016-01-01

    This study was a 14-day, outpatient, open-label randomized crossover trial of lyophilized black raspberries (BRBs) in older overweight or obese males to determine whether BRB consumption affects postprandial inflammation associated with consumption of a high-fat high-calorie (HFHC) meal. Ten study participants consumed 45 g/d of lyophilized BRBs for 4 days, followed by a HFHC breakfast plus BRBs on day 6 or consumed the HFHC breakfast on day 6 without previous consumption of BRBs and then crossed over to the other treatment after a 2-day washout period. Blood samples were obtained before and 1, 2, 4, 8, and 12 hours after consumption of the HFHC breakfast. The primary study outcomes were changes in area under the concentration-time curve (AUC) for interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α). The secondary outcomes were safety and tolerability of lyophilized BRB powder. The chronology and values of measured serum concentrations for IL-6, TNF-α, and CRP were consistent with those described previously by other investigators. The AUC of serum IL-6 was lowered significantly (P = 0.03, n = 10) with BRB consumption (34.3 ± 7.6 pg·mL⁻¹·h⁻¹ compared with 42.4 ± 17.9 pg·mL⁻¹·h⁻¹ for consumption of the HFHC meal alone). However, no significant differences (change in AUC) were calculated for serum CRP and TNF-α. The findings of this pilot study suggest that consumption of lyophilized BRBs may attenuate postprandial inflammation in overweight or obese males consuming a HFHC meal. Further investigation of BRBs is warranted to better elucidate their inflammomodulatory potential. PMID:23982695

  8. [Biochemical, physicochemical and functional characterization of turbot (Scophthalmus maximus). Study of the changes occurring during the 4 degrees C storage].

    PubMed

    Abugoch, Lilian; Tapia, Cristian; Aravena, María Elena; López, Luis; Ramírez, Alberto; Oyarzo, Manuel

    2011-06-01

    The turbot (Scophthalmus maximus) is a kind of flatfish that is well adapted to intensive farm culture. After the harvest it is necessary to know the physicochemical, biochemical and technological properties and if during the refrigerated storage, changes of these properties are developed. The main objective of the study was the assessment of the proximal composition, the biochemical, physicochemical and functional properties, and how they are influenced during the 16 days storage at 4 degrees C. Parameters such as centesimal composition, PAGE-SDS, and protein thermal stability through a DSC were carried out. pH, total volatile base-nitrogen (TVB-N) dripping, texture, holding water capacity (WHC), emulsification (EC) and gelification (GC) were also determined. Results for the proximal composition were: humidity 76.3%; fat content 2.71%; proteins 19.6%; and ashes 1.3%. Two different thermal transitions at 47.5 degrees C (myosin) and 76.9 degrees C (actin) were observed. The PAGE-SDS showed profiles corresponding to myofibrilars and sarcoplasmatic proteins, which presented no changes during the storage. pH experimented an increase from 5.9 to 6.6; TVB-N showed a variation from 20.0 to 39.5 mg TVB-N/100 g of muscle at the day 16. The WHC started with a 10.5% and ended in 58.1%; no GC was observed. The increase of the EC and WHC during the storage was due to conformational changes of proteins. The compression force presented a fluctuation between 111.2 and 106.0 N and the shear strain decreased during the storage from 148.6 to 95.2 N. The dripping showed a variation between 1.7% and 2.5%. According to the results of the storage during 16 days at 4 degrees C, the NBV-T content determined a shelf life of 14 days. PMID:22308947

  9. A Phase I Study of EKB-569 in Combination with Capecitabine in Patients with Advanced Colorectal Cancer

    PubMed Central

    Laheru, Dan; Croghan, Gary; Bukowski, Ronald; Rudek, Michelle; Messersmith, Wells; Erlichman, Charles; Pelley, Robert; Jimeno, Antonio; Donehower, Ross; Boni, Joseph; Abbas, Richat; Martins, Patricia; Zacharchuk, Charles; Hidalgo, Manuel

    2011-01-01

    Purpose To determine the maximum tolerated dose (MTD), characterize the principal toxicities, and assess the pharmacokinetics of EKB-569, an oral selective irreversible inhibitor of the epidermal growth factor receptor tyrosine kinase, in combination with capecitabine in patients with advanced colorectal cancer. Experimental Design Patients were treated with EKB-569 daily for 21days and capecitabine twice daily for14 days of a 21-day cycle. The dose levels of EKB-569 (mg/day) and capecitabine (mg/m2 twice daily) assessed were 25/750, 50/750, 50/1,000 and 75/1,000. An expanded cohort was enrolled at the MTD to better study toxicity and efficacy. Samples of plasma were collected to characterize the pharmacokinetics of the agents. Treatment efficacy was assessed every other cycle. Results A total of 37 patients, the majority of whom had prior chemotherapy, received a total of 163 cycles of treatment. Twenty patients were treated at the MTD, 50 mg EKB-569, daily and 1,000 mg/m2 capecitabine twice daily. Dose-limiting toxicities were diarrhea and rash. No patients had complete or partial responses but 48% had stable disease. The conversion of capecitabine to 5-fluorouracil was higher for the combination of EKB-569 and capecitabine (321 ± 151 ng*h/mL) than for capecitabine alone (176 ± 62 ng*hours/mL; P = 0.0037). Conclusion In advanced colorectal cancer, 50 mg EKB-569 daily can be safely combined with 1,000 mg/m2 capecitabine twice a day. A statistically significant increase in plasma levels of 5-fluorouracil for the combination of EKB-569 and capecitabine may be due to the single-dose versus multiple-dose exposure difference, variability in exposure or a potential drug interaction. PMID:18765554

  10. An experimental study on the effects of nutrient enrichment on organic carbon storage in western Pacific oligotrophic gyre

    NASA Astrophysics Data System (ADS)

    Liu, J.; Jiao, N.; Tang, K.

    2014-02-01

    Carbon sequestration in the ocean is of great concern with respect to the mitigation of global warming. How to hold the fixed organic carbon in the presence of tremendous heterotrophic microorganisms in marine environments is the central issue. We have previously hypothesized that excessive nutrients would ultimately decrease the storage of organic carbon in marine environments. To test it out, a series of in situ nutrient enrichment incubation experiments were conducted at a site (17.59° N, 127.00° E) within the Western Pacific oligotrophic gyre. Five treatments were employed: glucose or algal exudation organic material (EOM) and nitrate and phosphate were added alone or in combination to approximate final concentrations of 10 μmol C kg-1, 1 μmol N kg-1 and 0.11 μmol P kg-1 respectively. The results showed that the dissolved organic carbon (DOC) consumption rates and bacterial community specific growth rates were enhanced by inorganic nutrients enrichment treatments during the initial 48 h incubation. At the end of 14 days incubation, about 1/3 (average 3.29 μmol C kg-1) more organic carbon was respired from the glucose enriched incubation with addition of inorganic nutrients compared to that without addition of inorganic nutrients. In the case no essential nutrients were available, even glucose could not be efficiently used by bacteria and thus remained in the environment. These results suggest that repletion of inorganic nutrients has negative impacts on carbon preservation, presumably due to elevated nutrient-stimulated bacterial metabolism and respiration, which is meaningful for potential coastal water management and worth for further studies.

  11. Factors for Assessing the Effectiveness of Early Rehabilitation after Minimally Invasive Total Knee Arthroplasty: A Prospective Cohort Study

    PubMed Central

    Amano, Tetsuya; Tamari, Kotaro; Tanaka, Shigeharu; Uchida, Shigehiro; Ito, Hideyuki; Morikawa, Shinya; Kawamura, Kenji

    2016-01-01

    The effectiveness of current rehabilitation programs is supported by high-level evidence from the results of randomized controlled trials, but an increasing number of patients are not discharged from the hospital because of the schedule of the critical path (CP). The present study aimed to determine which factors can be used to assess the effectiveness of early rehabilitation. We enrolled 123 patients with medial knee osteoarthritis (OA) who had undergone unilateral minimally invasive total knee arthroplasty for the first time. The following factors were assessed preoperatively: the maximum isometric muscle strength of the knee extensors and flexors, maximum knee and hip joint angle, pain, 5-m maximum walking speed, sex, age, body mass index, exercise habits, Kellgren-Lawrence grade, femorotibial angle, failure side (bilateral or unilateral knee OA), and functional independence measure. We re-evaluated physical function (i.e., muscle strength, joint angle, and pain) and motor function (5-m maximum walking speed) 14 days postoperatively. Changes in physical function, motor function (5-m maximum walking speed), and number of days to independent walking were used as explanatory variables. The postoperative duration of hospitalization (in days) was used as the dependent variable in multivariate analyses. These analyses were adjusted for sex, age, body mass index, exercise habits, Kellgren-Lawrence grade, femorotibial angle, failure side, and functional independence measure. The duration of hospitalization was significantly affected by the number of days to independent walking (p < 0.001, β = 0.507) and a change in the 5-m maximum walking speed (p = 0.016, β = -0.262). Multiple regression analysis showed that the radiographic knee grade (p = 0.029, β = 0.239) was a significant confounding factor. Independent walking and walking speed recovery were considered to reduce the duration of hospitalization. Therefore, these indices can be used to assess the effectiveness of

  12. Effects of oral administration of Lonicera caerulea berries on UVB-induced damage in SKH-1 mice. A pilot study.

    PubMed

    Rajnochová Svobodová, Alena; Galandáková, Adéla; Palíková, Irena; Doležal, Dalibor; Kylarová, Dana; Ulrichová, Jitka; Vostálová, Jitka

    2013-10-01

    Solar ultraviolet radiation is a major environmental factor that has serious adverse effects on the structure and function of the skin. Although the UVB waveband (295-315 nm) represents only 5-10% of incoming UV light, it is very damaging to the skin. The aim of this study was to investigate the effect of Lonicera caerulea berries on UVB-induced damage to SKH-1 hairless mice. Mice were fed a L. caerulea berry-enriched diet (10%, w/w) for 14 days before a single UVB (1000 mJ cm(-2)) treatment. Effects on health status, antioxidant enzyme activity and expression, and DNA damage were evaluated. The bioavailability of L. caerulea phenolic components was also assessed. We found that feeding with L. caerulea berries prevented a decrease in catalase activity and stimulated NADPH quinone oxidoreductase-1, heme oxygenase-1, and gamma-glutamylcysteine synthetase catalytic and modulatory subunit expression in UVB exposed mice. Administration of the L. caerulea berry-enriched diet led to an increase in UVB-reduced interleukin-17 levels and a decrease in keratinocyte-derived chemokine protein expression that was enhanced after UVB treatment. Further, L. caerulea berries reduced UVB-induced DNA damage evaluated as number of single strand breaks, cyclobutane-pyrimidine dimer formation and H2AX phosphorylation, a marker of double strand breaks. Taken together, we provide evidence that oral administration of L. caerulea berries to mice affords at least partial protection from the adverse effects of a single UVB exposure via modulation of antioxidant enzyme activity/expression and reduction of DNA damage. PMID:23896761

  13. Effects of environmental noise on cognitive (dys)functions in schizophrenia: A pilot within-subjects experimental study.

    PubMed

    Wright, Bernice; Peters, Emmanuelle; Ettinger, Ulrich; Kuipers, Elizabeth; Kumari, Veena

    2016-05-01

    Cognitive impairment, particularly in attention, memory and executive function domains, is commonly present and associated with poor functional outcomes in schizophrenia. In healthy adults, environmental noise adversely affects many cognitive domains, including those known to be compromised in schizophrenia. This pilot study examined whether environmental noise causes further cognitive deterioration in a small sample of people with schizophrenia. Eighteen outpatients with schizophrenia on stable doses of antipsychotics and 18 age and sex-matched healthy participants were assessed on a comprehensive cognitive battery including measures of psychomotor speed, attention, executive functioning, working memory, and verbal learning and memory under three different conditions [quiet: ~30dB(A); urban noise: building site noise, 68-78dB(A); and social noise: background babble and footsteps from a crowded hall without any discernible words, 68-78dB(A)], 7-14days apart, with counter-balanced presentation of noise conditions across participants of both groups. The results showed widespread cognitive impairment in patients under all conditions, and noise-induced impairments of equal magnitude on specific cognitive functions in both groups. Both patient and healthy participant groups showed significant disruption of delayed verbal recall and recognition by urban and social noise, and of working memory by social noise, relative to the quiet condition. Performance under urban and social noise did not differ significantly from each other for any cognitive measure in either group. We conclude that noise has adverse effects on the verbal and working memory domains in schizophrenia patients and healthy participants. This may be particularly problematic for patients as it worsens their pre-existing cognitive deficits. PMID:27017491

  14. The influence of pharmacogenetics on fatty liver disease in the wistar and kyoto rats: a combined transcriptomic and metabonomic study.

    PubMed

    Griffin, Julian L; Scott, James; Nicholson, Jeremy K

    2007-01-01

    Although fatty liver disease is caused by a number of toxicological insults and the metabolic syndrome, the exact mechanisms by which many of these pathophysiological stimulii induce fatty liver are unknown. The rapid and profound steatosis caused by orotic acid, resulting from an impairment in the production of ApoB, has been investigated in the Wistar strain rat using a combined transcriptomic and metabonomic/metabolomic approach. Analysis of liver tissue from rats exposed to orotic acid for 1, 3, and 14 days was performed by DNA microarrays and high resolution 1H NMR spectroscopy based metabonomics of both tissue extracts and intact tissue (n = 3). Data were analyzed using a combination of ANOVA and principal components analysis, used as a data reduction tool to visualize the most perturbed transcripts and metabolites. Orotic acid produced a profound 8-fold increase in total lipids, and in particular increases in resonances associated with polyunsaturated fats (CH=CH and CH2CH=CH groups). This was accompanied by increases in the concentrations of trimethylamine-oxide (TMAO), betaine, choline, and phosphocholine, as well as a relative decrease in glucose and glycogen. At the transcriptional level, perturbations were detected in both oxidative stress and osmoregulation/pH homeostasis. However, this contrasts with a previous transcriptomic/metabolic study of fatty liver disease in a combined data set of Wistar (out-bred) and Kyoto (in-bred) strains of rats, with only 4 transcripts being found to be in common between the two analyses. This emphasizes the need to understand how strain background interacts with a given toxic lesion or genetic modification. PMID:17203948

  15. Effect of heat treatment on H2O2/HCl etched pure titanium dental implant: An in vitro study

    PubMed Central

    Zhang, Feng; Zhang, Chun-Fei; Yin, Mei-nv; Ren, Ling-Fei; Lin, Hai-sheng; Shi, Geng-sheng

    2012-01-01

    Summary Background Surface chemistry of dental implant plays an important role in osseointegration. Heat treatment might alter surface chemistry and result in different biological response. The aim of this study was to investigate the roles of heat treatment of H2O2/HCl-treated Ti implants in cell attachment, proliferation and osteoblastic differentiation. Material/Methods Sandblasted, dual acid-etched and H2O2/HCl heat-treated discs were set as the control group and sandblasted, dual acid-etched H2O2/HCl-treated discs were the test group. Both groups’ discs were sent for surface characterization. MC3T3-E1 cells were seeded on these 2 groups’ discs for 3 hours to 14 days, and then cell attachment, cell proliferation and cell differentiation were evaluated. Results Scanning electron microscope analysis revealed that the titanium discs in the 2 groups shared the same surface topography, while x-ray diffraction examination showed an anatase layer in the control group and titanium hydride diffractions in the test group. The cell attachment of the test group was equivalent to that of the control group. Cell proliferation was slightly stimulated at all time points in the control group, but the alkaline phosphatase (ALP) activity and osteocalcin (OC) production increased significantly in the test group compared with those in the control group at every time point investigated (p<0.05 or p<0.01). Moreover, the osteoblastic differentiation-related genes AKP-2, osteopontin (OPN) and OC were greatly up-regulated in the test group (p<0.05 or p<0.01). Conclusions The results implied that surface chemistry played an important role in cell response, and H2O2/HCl etched titanium surface without subsequent heat treatment might improve osseointegration response. PMID:22739726

  16. Predicting results of mycobacterial culture on sputum smear reversion after anti-tuberculous treatment: a case control study

    PubMed Central

    2010-01-01

    Background Little is currently known regarding sputum smear reversion (acid-fast smear becomes positive again after negative conversion) during anti-tuberculous treatment. This study aimed to evaluate its occurrence in patients with pulmonary tuberculosis (TB) and identify factors predicting results of mycobacterial culture for smear-reversion of sputum samples. Methods The retrospective review was performed in a tertiary referral center and a local teaching hospital in Taiwan. From 2000 to 2007, patients with smear-positive culture-confirmed pulmonary TB experiencing smear reversion after 14 days of anti-tuberculous treatment were identified. Results The 739 patients with smear-positive pulmonary TB had 74 (10%) episodes of sputum smear reversion that grew Mycobacterium tuberculosis in 22 (30%) (Mtb group). The remaining 52 episodes of culture-negative sputum samples were classified as the non-Mtb group. The anti-tuberculous regimen was modified after confirming smear reversion in 15 (20%). Fourteen episodes in the Mtb group and 15 in the non-Mtb group occurred during hospitalization. All were admitted to the negative-pressure rooms at the time of smear reversion. Statistical analysis showed that any TB drug resistance, smear reversion within the first two months of treatment or before culture conversion, and the absence of radiographic improvement before smear reversion were associated with the Mtb group. None of the smear reversion was due to viable M. tuberculosis if none of the four factors were present. Conclusions Sputum smear reversion develops in 10% of patients with smear-positive pulmonary TB, with 30% due to viable M. tuberculosis bacilli. Isolation and regimen modification may not be necessary for all drug-susceptible patients who already have radiographic improvement and develop smear reversion after two months of treatment or after sputum culture conversion. PMID:20205743

  17. Experimental studies on the pathogenicity of Mycoplasma ovipneumoniae and Mycoplasma arginini for the respiratory tract of goats.

    PubMed Central

    Goltz, J P; Rosendal, S; McCraw, B M; Ruhnke, H L

    1986-01-01

    Mycoplasma ovipneumoniae and Mycoplasma arginini were the species of Mollicutes most commonly isolated from 175 goats with respiratory disease in Ontario. The pathogenicity of M. ovipneumoniae, strain B321B and M. arginini, strain D53e, was assessed in goats following endobronchial inoculation. One out of three two year old goats developed fever after inoculation with a pure culture of strain B321B, and it had extensive subacute fibrinous pleuritis when necropsied three weeks later. Neither of the remaining goats had lesions in the respiratory tract. Mycoplasma ovipneumoniae was recovered from one of the animals four days after inoculation, but not at necropsy from any of the goats, at which time a marked humoral immune response with growth inhibiting antibodies was detected. In a second experiment three four to five week old goats were inoculated with the same strain and three other goats were given placebo treatment. One experimental goat developed fever and coughing, and it had extensive subacute fibrinous pleuritis in the right side and pneumonia. Another goat had focal pneumonia in the left diaphragmatic lobe. Microscopically there was subacute hyperplastic suppurative bronchiolitis, atelectasis and nonsuppurative alveolitis. The infected animals did not clear the mycoplasma and not all of them produced antibodies. Mycoplasma arginini, strain D53e, did not induce lesions in any of four goat kids within 14 days after inoculation but did cause transient elevations in rectal temperature, circulating monocytes, circulating neutrophils and blood fibrinogen. Mycoplasma arginini was infective and immunogenic for all inoculated animals and showed a particular affinity for the tonsil. Thus, this study provides the first evidence that M. ovipneumoniae is pathogenic for goats causing pneumonia and pleuritis.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. PMID:3742358

  18. Study of Carbon Nano-Tubes Effects on the Chondrogenesis of Human Adipose Derived Stem Cells in Alginate Scaffold

    PubMed Central

    Valiani, Ali; Hashemibeni, Batool; Esfandiary, Ebrahim; Ansar, Malek Masoud; Kazemi, Mohammad; Esmaeili, Nafiseh

    2014-01-01

    Background: Osteoarthritis is one of the most common diseases in middle-aged populations in the World and could become the fourth principal cause of disability by the year 2020. One of the critical properties for cartilage tissue engineering (TE) is the ability of scaffolds to closely mimic the extracellular matrix and bond to the host tissue. Therefore, TE has been presented as a technique to introduce the best combination of cells and biomaterial scaffold and to stimulate growth factors to produce a cartilage tissue resembling natural articular cartilage. The aim of study is to improve differentiation of adipose derived stem cells (ADSCs) into chondrocytes in order to provide a safe and modern treatment for patients suffering from cartilage damages. Methods: After functionalization, dispersions and sterilizing carbon nano-tubes (CNTs), a new type of nanocomposite gel was prepared from water-soluble CNTs and alginate. ADSCs seeded in 1.5% alginate scaffold and cultured in chondrogenic media with and without transforming growth factor-β1 (TGF-β1) for 7 and 14 days. The genes expression of sex determining region Y-box 9 (SOX9), types II and X collagens was assessed by real-time polymerase chain reaction and the amount of aggrecan (AGC) and type I collagen was measured by ELISA. Results: Our findings showed that the expression of essential cartilage markers, SOX9, type II collagen and AGC, in differentiated ADSCs at the concentration of 1 μg/ml CNTs in the presence of TGF-β1 were significantly increased in comparison with the control group (P < 0.001). Meanwhile, type X collagen expression and also type I collagen production were significantly decreased (P < 0.001). Conclusions: The results showed that utilized three-dimensional scaffold had a brilliant effect in promoting gene expression of chondrogenesis. PMID:25104993

  19. Efficacy of Vasa Avaleha and its granules on Tamaka Shwasa (bronchial asthma): Open-label randomized clinical study

    PubMed Central

    Paneliya, Ankit M.; Patgiri, Biswajyoti; Galib, R.; Prajapati, Pradeep Kumar

    2015-01-01

    Introduction: Bronchial asthma is one of the chronic inflammatory disorders of the respiratory tract causing a huge number of deaths annually. Increased industrialization and pollution are the exacerbating factors for this situation. In Ayurveda, this miserable condition is comparable with Tamaka Shwasa. Synthetic drugs provide instant symptomatic relief in cases of bronchial asthma but are known to develop certain adverse drug reactions. Considering this, the current suffering population is looking hopefully towards other systems of medicine such as Ayurveda for better relief. Ayurveda has a number of formulations to treat Tamaka Shwasa and is in practice with proven efficacy. Aims: To evaluate comparative clinical efficacy of Vasa Avaleha (VA) and its granules (GVA) in cases of Tamaka Shwasa. Materials and Methods: A total of 66 patients were registered and randomly grouped into A and B. Patients of Group A were treated with VA, while Group B with GVA at dose of 6 g twice a day with lukewarm water for the duration of 28 days. Follow-up was done after 14 days. The results were assessed in terms of clinical recovery, symptomatic relief, and pulmonary function improvement. Effect of the treatment was assessed based on subjective and objective parameters. Results: Significant improvement was observed in most of the cardinal and associated symptoms. Significant increase in peak expiratory flow rate, considerable decrease in absolute eosinophil count, and increased breath holding time were noticed. Withdrawal of modern emergency drugs, decreased frequency of attacks, improved quality of life were the major observations noticed in both groups. Conclusions: This study highlights the significance of traditional herbal formulations in noncommunicable diseases such as bronchial asthma, which can be used as an effective drug in place or along with modern drugs. PMID:27313413

  20. Does a toothpaste containing blue covarine have any effect on bleached teeth? An in vitro, randomized and blinded study.

    PubMed

    Bortolatto, Janaina Freitas; Dantas, Andrea Abi Rached; Roncolato, Ávery; Merchan, Hugo; Floros, Michael Christopher; Kuga, Milton Carlos; Oliveira Junior, Osmir Batista de

    2016-01-01

    The objective of this study was to analyze the effect of bleaching toothpastes, both conventional and those containing the new whitening agent Blue Covarine, on teeth previously bleached by conventional techniques (in-office and at-home). Squared bovine enamel/dentin blocks (6.0 x 6.0 x 2.0 mm) were randomly distributed in 6 groups (n = 15), according to the technique used to bleach them (in-office: HP35%; at-home: PC10%) and the type of bleaching toothpaste (none: control; Blue Covarine containing: BC; and without Blue Covarine: NBC). Experimental groups denominated HP35%, HP35%BC and HP35%NBC received in-office tooth bleaching before toothbrushing, and groups PC10%, PC10%BC and PC10%NBC were subjected to at-home tooth bleaching prior to toothbrushing. After bleaching treatment, groups HP35%BC, PC10%BC, HP35%NBC and PC10%NBC underwent daily tooth brushing in a brushing machine for 3 minutes (150 strokes/min, with a load of 375 g). Tooth color alteration was measured by reflectance spectroscopy (Vita EasyShade, Vident, Brea, CA, USA) at: T0 (baseline) - after in-office or at-home bleaching treatment; T1 - immediately after tooth brushing; T2 - 7 days and T3 - 14 days after tooth brushing. Data was analyzed by repeated measures mixed ANOVA and the Bonferroni post hoc test, with a significance level of 5%. Statistically significant differences were found between different experimental groups, evaluation times and for the interaction between them (p < 0.001). Tooth brushing using either bleaching toothpaste (conventional or with Blue Covarine) showed no color alteration on teeth previously bleached by in-office and at-home tooth bleaching. The use of bleaching toothpastes on previously bleached teeth did not produce a color alteration. PMID:26981757

  1. Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study.

    PubMed

    Benito, N; García-Vázquez, E; Horcajada, J P; González, J; Oppenheimer, F; Cofán, F; Ricart, M J; Rimola, A; Navasa, M; Rovira, M; Roig, E; Pérez-Villa, F; Cervera, C; Moreno, A

    2015-07-01

    There are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2-63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made. PMID:25882369

  2. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study

    PubMed Central

    Zullo, Angelo; Ridola, Lorenzo; Francesco, Vincenzo De; Gatta, Luigi; Hassan, Cesare; Alvaro, Domenico; Bellesia, Annamaria; de Nucci, Germana; Manes, Gianpiero

    2015-01-01

    Background The prevalence of resistance to clarithromycin and metronidazole has considerably increased, with a corresponding decrease in the eradication rate for Helicobacter pylori (H. pylori) infection. Primary resistance to amoxicillin is extremely low, and esomeprazole was found to exert a noteworthy antimicrobial activity in vitro against H. pylori. A dual therapy with high-dose of esomeprazole coupled with high-dose amoxicillin might be therefore an ideal first-line treatment for H. pylori eradication. We aimed to assess the efficacy of a first-line 10-day, high-dose dual therapy consisting of amoxicillin and esomeprazole to eradicate H. pylori infection. Methods Consecutive naïve H. pylori-infected patients, who underwent an upper endoscopy in 4 Italian hospitals due to dyspeptic symptoms and found to be infected at routine histological assessment, were invited to participate. Patients enrolled received a 10-day, high-dose dual therapy comprising esomeprazole (40 mg t.i.d) and amoxicillin (1 g t.i.d.). At least 4 weeks after the end of the treatment a 13C-urea breath test was performed to evaluate the eradication. Results A total of 56 patients agreed to participate in the study and were all followed-up. The overall eradication was 87.5% (95% CI=78.8•96.2), without a statistically significant difference among centres. Overall, 5 (8.9%; 1.5•16.4%) patients complained of side-effects. Conclusions The 10-day, high-dose dual therapy with esomeprazole and amoxicillin might be an effective and safe first-line regimen. The efficacy of a longer 14-day regimen should be tested. PMID:26423014

  3. Gene Expression Profiling in Liver and Testis of Rats to Characterize the Toxicity of Triazole Fungicides

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  4. GENE EXPRESSION PROFILING IN LIVER AND TESTIS OF RATS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES.

    EPA Science Inventory

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  5. [Treatment of mycosis fungoides with Zovirax (acyclovir). Study of 2 patients].

    PubMed

    Mahrle, G; Thiele, B; Steigleder, G K

    1985-04-01

    We report on two female patients suffering from mycosis fungoides, tumorous type but without systemic involvement, who have been treated with 400 mg Zovirax (Acyclovir) 3 times daily (about 15 mg/kg/day) for 12 days. The follow-up period amounted to 11 and 14 days, respectively. This therapy did not result in regression of the disease; one patient even showed progression of her skin tumors. PMID:4002770

  6. Investigation of Poultry Waste for Anaerobic Digestion: A Case Study

    NASA Astrophysics Data System (ADS)

    Salam, Christopher R.

    Anaerobic Digestion (AD) is a biological conversion technology which is being used to produce bioenergy all over the world. This energy is created from biological feedstocks, and can often use waste products from various food and agricultural processors. Biogas from AD can be used as a fuel for heating or for co-generation of electricity and heat and is a renewable substitute to using fossil fuels. Nutrient recycling and waste reduction are additional benefits, creating a final product that can be used as a fertilizer in addition to energy benefits. This project was conducted to investigate the viability of three turkey production wastes as AD feedstock: two turkey litters and a material separated from the turkey processing wastewater using dissolved air flotation (DAF) process. The DAF waste contained greases, oils and other non-commodity portions of the turkey. Using a variety of different process methods, types of bacteria, loading rates and food-to-microorganism ratios, optimal loading rates for the digestion of these three materials were obtained. In addition, the co-digestion of these materials revealed additional energy benefits. In this study, batch digestion tests were carried out to treat these three feedstocks, using mesophilic and thermophilic bacteria, using loading rates of 3 and 6 gVS/L They were tested separately and also as a mixture for co-digestion. The batch reactor used in this study had total and working volumes of 1130 mL and 500 mL, respectively. The initial organic loading was set to be 3 gVS/L, and the food to microorganism ratio was either 0.6 or 1.0 for different treatments based on the characteristics of each material. Only thermophilic (50 +/- 2ºC) temperatures were tested for the litter and DAF wastes in continuous digestion, but mesophilic and thermophilic batch digestion experiments were conducted. The optimum digestion time for all experiments was 14 days. The biogas yields of top litter, mixed litter, and DAF waste under

  7. COSMOS 2044: Lung morphology study, experiment K-7-28

    NASA Technical Reports Server (NTRS)

    Elliott, Ann R.; Mathieu-Costello, Odile; West, John B.

    1991-01-01

    Researchers examined the effect of microgravity during spaceflight on lung tissue. The ultrastructure of the left lungs of 5 Czechoslovakian Wister rats flown on the 13 day, 19+ hour Cosmos 2044 mission was examined and compared to 5 vivarium and 5 synchronous controls at 1-g conditions, and 5 rats exposed to 14 days of tail suspension. Pulmonary hemorrage and alveolar adema of unknown origin occurred to a greater extent in the flight, tail-suspended, and synchronous control animals, and in the dorsal regions of the lung when compared with the vivarium controls. The cause of these changes, which are possibly due to an increase in pulmonary vascular pressure, requires further investigation.

  8. Ovarian Tumor Cells Studied Aboard the International Space Station (ISS)

    NASA Technical Reports Server (NTRS)

    2001-01-01

    In August 2001, principal investigator Jeanne Becker sent human ovarian tumor cells to the International Space Station (ISS) aboard the STS-105 mission. The tumor cells were cultured in microgravity for a 14 day growth period and were analyzed for changes in the rate of cell growth and synthesis of associated proteins. In addition, they were evaluated for the expression of several proteins that are the products of oncogenes, which cause the transformation of normal cells into cancer cells. This photo, which was taken by astronaut Frank Culbertson who conducted the experiment for Dr. Becker, shows two cell culture bags containing LN1 ovarian carcinoma cell cultures.

  9. Teratologic studies of solvent-refined-coal-process materials

    SciTech Connect

    Hackett, P.L.; Sikov, M.R.; Springer, D.L.; Mahlum, D.D.; Kelman, B.J.

    1983-09-01

    The most striking effects observed following intragastric or inhalation exposure of pregnant rats to SRC materials were related to the fetal lungs: a dose-dependent decrease in weight and an increased incidence of small lungs. Whether the SRC materials was heavy distillate or a process development unit material (HPS) did not appear to influence fetal effects, but higher-boiling-range materials induced fetal responses at lower doses. The most sensitive period for production of small lungs and cleft palate was from 12 through 14 days gestation.

  10. Phase I study of capecitabine combined with radioembolization using yttrium-90 resin microspheres (SIR-Spheres) in patients with advanced cancer

    PubMed Central

    Cohen, S J; Konski, A A; Putnam, S; Ball, D S; Meyer, J E; Yu, J Q; Astsaturov, I; Marlow, C; Dickens, A; Cade, D N; Meropol, N J

    2014-01-01

    Background: This was a prospective single-centre, phase I study to document the maximum tolerated dose (MTD), dose-limiting toxicity (DLT), and the recommended phase II dose for future study of capecitabine in combination with radioembolization. Methods: Patients with advanced unresectable liver-dominant cancer were enrolled in a 3+3 design with escalating doses of capecitabine (375–1000 mg/m2 b.i.d.) for 14 days every 21 days. Radioembolization with 90Y-resin microspheres was administered using a sequential lobar approach with two cycles of capecitabine. Results: Twenty-four patients (17 colorectal) were enrolled. The MTD was not reached. Haematologic events were generally mild. Common grade 1/2 non-haematologic toxicities included transient transaminitis/alkaline phosphatase elevation (9 (37.5%) patients), nausea (9 (37.5%)), abdominal pain (7 (29.0%)), fatigue (7 (29.0%)), and hand-foot syndrome or rash/desquamation (7 (29.0%)). One patient experienced a partial gastric antral perforation with a capecitabine dose of 750 mg/m2. The best response was partial response in four (16.7%) patients, stable disease in 17 (70.8%) and progression in three (12.5%). Median time to progression and overall survival of the metastatic colorectal cancer cohort was 6.4 and 8.1 months, respectively. Conclusions: This combined modality treatment was generally well tolerated with encouraging clinical activity. Capecitabine 1000 mg/m2 b.i.d. is recommended for phase II study with sequential lobar radioembolization. PMID:24983373

  11. Effect of computerized cognitive training with virtual spatial navigation task during bed rest immobilization and recovery on vascular function: A pilot study

    PubMed Central

    Goswami, Nandu; Kavcic, Voyko; Marusic, Uros; Simunic, Bostjan; Rössler, Andreas; Hinghofer-Szalkay, Helmut; Pisot, Rado

    2015-01-01

    We investigated the effects of bed rest (BR) immobilization, with and without computerized cognitive training with virtual spatial navigation task (CCT), on vascular endothelium on older subjects. The effects of 14-day BR immobilization in healthy older males (n=16) of ages 53–65 years on endothelial function were studied using EndoPAT®, a noninvasive and user-independent method. From the group of 16 older men, 8 randomly received CCT during the BR, using virtual navigation tasks in a virtual environment with joystick device. In all the cases, EndoPAT assessments were done at pre- and post-BR immobilization as well as following 28 days of ambulatory recovery. The EndoPAT index increased from 1.53±0.09 (mean ± standard error of the mean) at baseline to 1.61±0.16 following immobilization (P=0.62) in the group with CCT. The EndoPAT index decreased from 2.06±0.13 (mean ± standard error of the mean) at baseline to 1.70±0.09 at the last day of BR study, day 14 (BR14) (P=0.09) in the control group. Additionally, there were no statistically significant differences between BR14 and at 28 days of follow-up (rehabilitation program) (R28). Our results show a trend of immobilization in older persons affecting the vasoconstrictory endothelial response. As the control subjects had a greater increase in EndoPAT index after R28 (+0.018) compared to subjects who had cognitive training (+0.11) (calculated from the first day of BR study), it is possible that cognitive training during BR does not improve endothelial function but rather contributes to slowing down the impairment of endothelial function. Finally, our results also show that EndoPAT may be a useful noninvasive tool to assess the vascular reactivity. PMID:25709419

  12. Randomized, double-blind study of the safety, tolerability, and efficacy of tafenoquine versus mefloquine for malaria prophylaxis in nonimmune subjects.

    PubMed

    Nasveld, Peter E; Edstein, Michael D; Reid, Mark; Brennan, Leonard; Harris, Ivor E; Kitchener, Scott J; Leggat, Peter A; Pickford, Philip; Kerr, Caron; Ohrt, Colin; Prescott, William

    2010-02-01

    This study represents the first phase III trial of the safety, tolerability, and effectiveness of tafenoquine for malaria prophylaxis. In a randomized (3:1), double-blinded study, Australian soldiers received weekly malaria prophylaxis with 200 mg tafenoquine (492 subjects) or 250 mg mefloquine (162 subjects) for 6 months on a peacekeeping deployment to East Timor. After returning to Australia, tafenoquine-receiving subjects received a placebo and mefloquine-receiving subjects received 30 mg primaquine daily for 14 days. There were no clinically significant differences between hematological and biochemical parameters of the treatment groups. Treatment-related adverse events for the two groups were similar (tafenoquine, 13.4%; mefloquine, 11.7%). Three subjects on tafenoquine (0.6%) and none on mefloquine discontinued prophylaxis because of possible drug-related adverse events. No diagnoses of malaria occurred for either group during deployment, but 4 cases (0.9%) and 1 case (0.7%) of Plasmodium vivax infection occurred among the tafenoquine and mefloquine groups, respectively, up to 20 weeks after discontinuation of medication. In a subset of subjects recruited for detailed safety assessments, treatment-related mild vortex keratopathy was detected in 93% (69 of 74) of tafenoquine subjects but none of the 21 mefloquine subjects. The vortex keratopathy was not associated with any effect on visual acuity and was fully resolved in all subjects by 1 year. Tafenoquine appears to be safe and well tolerated as malaria prophylaxis. Although the volunteers' precise exposure to malaria could not be proven in this study, tafenoquine appears to be a highly efficacious drug for malaria prophylaxis. PMID:19995933

  13. A Pilot Study Assessing the Safety and Latency-Reversing Activity of Disulfiram in HIV-1–Infected Adults on Antiretroviral Therapy

    PubMed Central

    Spivak, Adam M.; Andrade, Adriana; Eisele, Evelyn; Hoh, Rebecca; Bacchetti, Peter; Bumpus, Namandjé N.; Emad, Fatemeh; Buckheit, Robert; McCance-Katz, Elinore F.; Lai, Jun; Kennedy, Margene; Chander, Geetanjali; Siliciano, Robert F.; Siliciano, Janet D.; Deeks, Steven G.

    2014-01-01

    Background. Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4+ T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4+ T cells at concentrations achieved in vivo. Methods. We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1–infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4+ T cells. Results. Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). Conclusions. Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug. PMID:24336828

  14. Phase 1 Trial of Adalimumab in Focal Segmental Glomerulosclerosis (FSGS): II. Report of the FONT (Novel Therapies for Resistant FSGS) Study Group

    PubMed Central

    Joy, Melanie S.; Gipson, Debbie S.; Powell, Leslie; MacHardy, Jacqueline; Jennette, J. Charles; Vento, Suzanne; Pan, Cynthia; Savin, Virginia; Eddy, Allison; Fogo, Agnes B.; Kopp, Jeffrey B.; Cattran, Daniel; Trachtman, Howard

    2009-01-01

    Background Patients with primary focal segmental glomerulosclerosis (FSGS) resistant to current treatment regimens are at high risk of progression to end stage kidney disease. Antifibrotic agents, such as tumor necrosis factor α (TNF-α) antagonists, are a promising strategy to slow or halt the decline in renal function, based on preclinical and clinical data. Study Design Phase I clinical trial to assess the pharmacokinetics, tolerability, and safety of adalimumab, a human monoclonal antibody to TNF-α. Setting and Participants Ten patients (4 male and 6 female), age 16.8±9.0 yr, and estimated GFR 105±50 mL/min/1.73 m2, were studied as out-patients Intervention Adalimumab, 24 mg/m2 every 14 days for 16 weeks (total 9 doses) Outcomes Pharmacokinetic assessment, tolerability, and safety Measurements Estimated glomerular filtration rate, proteinuria, and pharmacokinetic assessment after initial dosing and steady state Results Pharmacokinetic evaluation indicated that the area under the curve was decreased by 54% (P<0.001) and clearance was increased by 160% (P<0.01) in patients with resistant FSGS compared to healthy controls and patients with rheumatoid arthritis. Adalimumab was well tolerated with no serious adverse events or infectious complications attributable to the drug. Proteinuria declined by ≥50% in 4 of 10 treated patients. Limitations Insufficient power to assess safety or efficacy of adalimumab therapy for patients with resistant FSGS Conclusions Pharmacokinetic assessment demonstrated increased clearance of adalimumab in patients with resistant primary FSGS and validated the need for evaluating the disposition of novel therapies in this disease to define appropriate dosing regimens. The study provides a rationale to evaluate efficacy of adalimumab as an antifibrotic agent for resistant FSGS in Phase II/III clinical trials. PMID:19932542

  15. Multicentre open-label randomised controlled trial to compare colistin alone with colistin plus meropenem for the treatment of severe infections caused by carbapenem-resistant Gram-negative infections (AIDA): a study protocol

    PubMed Central

    Dickstein, Yaakov; Leibovici, Leonard; Yahav, Dafna; Eliakim-Raz, Noa; Daikos, George L; Skiada, Anna; Antoniadou, Anastasia; Carmeli, Yehuda; Nutman, Amir; Levi, Inbar; Adler, Amos; Durante-Mangoni, Emanuele; Andini, Roberto; Cavezza, Giusi; Mouton, Johan W; Wijma, Rixt A; Theuretzbacher, Ursula; Friberg, Lena E; Kristoffersson, Anders N; Zusman, Oren; Koppel, Fidi; Dishon Benattar, Yael; Altunin, Sergey; Paul, Mical

    2016-01-01

    Introduction The emergence of antibiotic-resistant bacteria has driven renewed interest in older antibacterials, including colistin. Previous studies have shown that colistin is less effective and more toxic than modern antibiotics. In vitro synergy studies and clinical observational studies suggest a benefit of combining colistin with a carbapenem. A randomised controlled study is necessary for clarification. Methods and analysis This is a multicentre, investigator-initiated, open-label, randomised controlled superiority 1:1 study comparing colistin monotherapy with colistin–meropenem combination therapy for infections caused by carbapenem-resistant Gram-negative bacteria. The study is being conducted in 6 centres in 3 countries (Italy, Greece and Israel). We include patients with hospital-associated and ventilator-associated pneumonia, bloodstream infections and urosepsis. The primary outcome is treatment success at day 14, defined as survival, haemodynamic stability, stable or improved respiratory status for patients with pneumonia, microbiological cure for patients with bacteraemia and stability or improvement of the Sequential Organ Failure Assessment (SOFA) score. Secondary outcomes include 14-day and 28-day mortality as well as other clinical end points and safety outcomes. A sample size of 360 patients was calculated on the basis of an absolute improvement in clinical success of 15% with combination therapy. Outcomes will be assessed by intention to treat. Serum colistin samples are obtained from all patients to obtain population pharmacokinetic models. Microbiological sampling includes weekly surveillance samples with analysis of resistance mechanisms and synergy. An observational trial is evaluating patients who met eligibility requirements but were not randomised in order to assess generalisability of findings. Ethics and dissemination The study was approved by ethics committees at each centre and informed consent will be obtained for all patients. The

  16. EP3/FP dual receptor agonist ONO-9054 administered morning or evening to patients with open-angle glaucoma or ocular hypertension: results of a randomised crossover study

    PubMed Central

    Berlin, Michael S; Rowe-Rendleman, Cheryl; Ahmed, Ike; Ross, Douglas T; Fujii, Akifumi; Ouchi, Takafumi; Quach, Christine; Wood, Andrew; Ward, Caroline L

    2016-01-01

    Background/aims The novel prostaglandin E (EP) 3 and prostaglandin F (FP) receptor agonist ONO-9054 is effective in lowering intraocular pressure (IOP) in patients with ocular hypertension and open-angle glaucoma when administered once daily. This study compares the effects of morning (AM) versus evening (PM) dosing of ONO-9054 on tolerability and IOP lowering. Methods This was a single-centre, randomised, double-masked, two-sequence, placebo-controlled crossover study in 12 subjects with bilateral primary open-angle glaucoma or ocular hypertension. Two 14-day crossover regimens were separated by a 2-week washout: ONO-9054 (1 drop to each eye) in the morning (07:00) and vehicle in the evening (19:00) and vice versa. IOP was measured multiple times during select days. Ocular examinations also evaluated safety and tolerability. Results Mild ocular hyperaemia, reported by six subjects with PM dosing, was the most frequent adverse event. Mild to moderate dryness was also slightly more frequent after PM dosing. Maximum IOP reduction from baseline occurred on day 2 with decreases from baseline of −7.4 mm Hg (−30.8%) for AM dosing and −9.1 mm Hg, (−38.0%) for PM dosing; after 14 days, mean reduction in IOP was −6.8 mm Hg (−28.6%) for AM dosing and −7.5 mm Hg (−31.0%) for PM dosing. Conclusions PM dosing of ONO-0954 was associated with a slightly increased frequency of mild hyperaemia and mild to moderate dryness. Both dosing schedules provided sustained reduction in IOP. Trial registration number NCT01670266. PMID:26453641

  17. Phase 1 Study of ABT-751 in Combination With CAPIRI (Capecitabine and Irinotecan) and Bevacizumab in Patients With Advanced Colorectal Cancer.

    PubMed

    Rudek, Michelle A; Dasari, Arvind; Laheru, Daniel; He, Ping; Jin, Runyan; Walker, Rosalind; Taylor, Gretchen E; Jimeno, Antonio; Donehower, Ross C; Hidalgo, Manuel; Messersmith, Wells A; Purcell, W Thomas

    2016-08-01

    ABT-751 is an orally bioavailable sulfonamide with antimitotic properties. A nonrandomized phase 1 dose-escalation study of ABT-751 in combination with CAPIRI (capecitabine and irinotecan) and bevacizumab was conducted to define the maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics in patients with advanced colorectal cancer. Patients were treated with ABT-751 daily for 7 days (alone) and then began 21-day cycles of treatment with ABT-751 daily and capecitabine twice daily for 14 days plus irinotecan on day 1 intravenously. Bevacizumab was added as standard of care at 7.5 mg/kg on day 1 after the first 2 dose levels. Because of intolerance to the regimen, a reduced dose of ABT-751 was also explored with reduced-dose and full-dose CAPIRI with bevacizumab. ABT-751 and irinotecan pharmacokinetics, ABT-751 glucuronidation, and protein binding were explored. Twenty-four patients were treated over 5 dose levels. The maximum tolerated dose was ABT-751 125 mg combined with full-dose CAPIRI and bevacizumab 7.5 mg/kg on day 1. DLTs were hypokalemia, elevated liver tests, and febrile neutropenia. ABT-751 is metabolized by UGT1A8 and to a lesser extent UGT1A4 and UGT1A1. Irinotecan and APC exposure were increased, SN-38 exposure was similar, and SN-38 glucuronide exposure was decreased. Clinically relevant alterations in ABT-751 and irinotecan pharmacokinetics were not observed. Despite modest efficacy, the combination of ABT-751, CAPIRI, and bevacizumab will not be studied further in colorectal cancer. PMID:26632033

  18. Hospital-level variation in use of cardiovascular testing for adults with incident heart failure: Findings from the Cardiovascular Research Network PRESERVE Study

    PubMed Central

    Farmer, Steven A.; Lenzo, Justin; Magid, David J.; Gurwitz, Jerry H.; Smith, David H.; Hsu, Grace; Sung, Sue Hee; Go, Alan S.

    2014-01-01

    Objectives We aimed to characterize use of cardiovascular testing for patients with incident heart failure (HF) hospitalization participating in the NHLBI-sponsored Cardiovascular Research Network PRESERVE study. Background HF is a common cause of hospitalization, and testing and treatment patterns may differ substantially between providers. Testing choices have important implications for the cost and quality of care. Methods Crude and adjusted cardiovascular testing rates were calculated for each participating hospital. Cox proportional hazards regression models were used to examine hospital testing rates after adjustment for hospital-level patient case-mix. Results Of the 37,099 patients in the PRESERVE study, 5,878 patients were hospitalized with incident HF between 2005 and 2008. Of these, evidence of cardiovascular testing was available for 4,650 (79.1 %) over the time period between 14 days before the incident HF admission and ending six months following the incident discharge. We compared crude and adjusted cardiovascular testing rates at the hospital level because the vast majority of testing occurred during the incident HF hospitalization. Of patients for whom testing was performed, 4,085 (87.9%) had an echocardiogram, 4,345 (93.4%) had a systolic function assessment, and 1,714 (36.9%) had a coronary artery disease assessment. Crude and adjusted testing rates varied markedly across the profiled hospitals, for individual testing modalities (e.g., echocardiography, stress echocardiography, nuclear stress testing, and left heart catheterization) and for specific clinical indications (e.g., systolic function assessment and coronary artery disease assessment). Conclusions For patients with newly diagnosed heart failure, we did not observe widespread overuse of cardiovascular testing in the six months following incident HF hospitalization relative to existing HF guidelines. Variations in testing were greatest for assessment of ischemia, where testing guidelines

  19. Comparative study on biologic and immunologic characteristics of the pancreas islet cell between 24 degrees C and 37 degrees C culture in the rat.

    PubMed

    Kim, S C; Han, D J; Kim, I H; Woo, K O; We, Y M; Kang, S Y; Back, J H; Kim, Y H; Kim, J H; Lim, D G

    2005-10-01

    The aim of this study was to investigate the effect of culture at 24 degrees C on cell viability, cellular function, immunogenicity, and cytokine profiles of rat pancreatic islets. Pancreatic islets were isolated from Lewis rats and cultured at either 24 degrees C or 37 degrees C for 14 days. Islet recovery was counted as islet equivalents; islet viability was examined with fluorescent vital staining. Islet function was measured with a glucose stimulation test. Annexin V, and MHC class I and II expression were measured using flow cytometric assay for apoptosis and immunogenicity, respectively. Lymphocyte cell proliferation was examined with WST-1 proliferation assay. Cytokine profiles were analyzed with quantitative real time RT-PCR. All these parameters were measured on 1, 3, 5, 7 and 14 culture days after islet isolation. Islet recovery was higher in islets cultured at 24 degrees C than 37 degrees C without a change in viability. Insulin secretion after glucose stimulation was more effective in 24 degrees C culture conditions. Decreased apoptotic cell death was demonstrated in 24 degrees C cultured islets. Both MHC class I and II expression on islets and lymphocyte proliferation upon coculture with islets were less prominent in 24 degrees C cultured islets. TNF-alpha expression was lower in islets cultured at 24 degrees C than in islets cultured at 37 degrees C. Both IL-1beta and IL-10 cytokine expressions were similar under both culture conditions. This study demonstrated that cell recovery and function are increased in islets cultured at 24 degrees C than those at 37 degrees C with decreased antigenicity and proinflammatory cytokine expression. PMID:16298632

  20. [18F] fluoromisonidazole and [18F] fluorodeoxyglucose positron emission tomography in response evaluation after chemo-/radiotherapy of non-small-cell lung cancer: a feasibility study

    PubMed Central

    Gagel, Bernd; Reinartz, Patrick; Demirel, Cengiz; Kaiser, Hans J; Zimny, Michael; Piroth, Marc; Pinkawa, Michael; Stanzel, Sven; Asadpour, Branka; Hamacher, Kurt; Coenen, Heinz H; Buell, Ulrich; Eble, Michael J

    2006-01-01

    Background Experimental and clinical evidence suggest that hypoxia in solid tumours reduces their sensitivity to conventional treatment modalities modulating response to ionizing radiation or chemotherapeutic agents. The aim of the present study was to show the feasibility of determining radiotherapeutically relevant hypoxia and early tumour response by ([18F] Fluoromisonidazole (FMISO) and [18F]-2-fluoro-2'-deoxyglucose (FDG) PET. Methods Eight patients with non-small-cell lung cancer underwent PET scans. Tumour tissue oxygenation was measured with FMISO PET, whereas tumour glucose metabolism was measured with FDG PET. All PET studies were carried out with an ECAT EXACT 922/47® scanner with an axial field of view of 16.2 cm. FMISO PET consisted of one static scan of the relevant region, performed 180 min after intravenous administration of the tracer. The acquisition and reconstruction parameters were as follows: 30 min emission scanning and 4 min transmission scanning with 68-Ge/68-Ga rod sources. The patients were treated with chemotherapy, consisting of 2 cycles of gemcitabine (1200 mg/m2) and vinorelbine (30 mg/m2) followed by concurrent radio- (2.0 Gy/d; total dose 66.0 Gy) and chemotherapy with gemcitabine (300–500 mg/m2) every two weeks. FMISO PET and FDG PET were performed in all patients 3 days before and 14 days after finishing chemotherapy. Results FMISO PET allowed for the qualitative and quantitative definition of hypoxic sub-areas which may correspond to a localization of local recurrences. In addition, changes in FMISO and FDG PET measure the early response to therapy, and in this way, may predict freedom from disease, as well as overall survival. Conclusion These preliminary results warrant validation in larger trials. If confirmed, several novel treatment strategies may be considered, including the early use of PET to evaluate the effectiveness of the selected therapy. PMID:16515707

  1. The effect of kynurenic acid on the synthesis of selected cytokines by murine splenocytes – in vitro and ex vivo studies

    PubMed Central

    Siwicki, Andrzej K.; Wójcik, Roman M.; Turski, Waldemar A.; Kaczorek, Edyta

    2016-01-01

    Kynurenic acid (KYNA), a secondary product of the kynurenine pathway of tryptophan degradation, known mainly as an endogenous neuroprotectant, shows also immunotropic properties. Some quantities of KYNA are present in food and are effectively absorbed in the gastrointestinal tract. Since the spleen is an important target of dietary immunomodulators, the aim of the study was to determine the effect of exogenous KYNA on murine splenocytes. Splenocytes isolated from adult BALB/c mice were used in the study. Firstly, the effect of increasing KYNA concentrations (0-5 mM) on the viability, and proliferative and cytokine response (interleukin 1β [IL-1β], IL-6, IL-10, tumor necrosis factor α [TNF-α]) of murine splenocytes under in vitro conditions was determined. Then, proliferative and cytokine responses were determined in cells derived from animals receiving kynurenic acid in drinking water at concentrations of 2.5, 25, or 250 mg/l for 7-14 days. Cytokine levels were measured using commercial immunoassay (ELISA) kits, and cell viability and proliferation was determined with MTT reduction assay. Exogenous KYNA was characterised by a low level of cytotoxicity towards murine splenocytes, and was well tolerated by the animals receiving it in drinking water. As expected, it exhibited anti-inflammatory action towards the activated splenocytes, under both in vitro and ex vivo conditions. Surprisingly, however, KYNA itself influenced the activity of resting, non-stimulated cells, exerting an immunostimulant effect in vitro, and an immunosuppressive effect under ex vivo conditions. The obtained results indicate not only anti-inflammatory, but also more complex, immunomodulating properties of KYNA, which require more detailed investigation. PMID:27095921

  2. Studies on the antitumor activity and biochemical actions of cyclopentenyl cytosine against human colon carcinoma HT-29 in vitro and in vivo.

    PubMed

    Gharehbaghi, K; Zhen, W; Fritzer-Szekeres, M; Szekeres, T; Jayaram, H N

    1999-01-01

    Cyclopentenyl cytosine (CPEC) is cytotoxic to several tumor cell lines. CPEC inhibits CTP synthesis resulting in depletion of cytidylate pools. The aim of this study was to examine CPEC's cytotoxic and antitumor activity in vitro and in vivo against human colon carcinoma HT-29, and to relate its action on CTP synthesis. CPEC exhibits potent cytotoxicity in vitro to HT-29 cells with an LC50 (concentration that is lethal to the survival of 50% cell colonies) of 2.4 microM and 0.46 microM following 2 h and 24 h exposure, respectively. Incubation of cells with CPEC for 2 h resulted in a dose-dependent decrease in cytidylate pools. The in vivo antitumor activity of CPEC in athymic mice transplanted subcutaneously (s.c.) with 3 million HT-29 cells was examined. Antitumor activity of CPEC was elucidated in early-staged tumor, wherein CPEC (1.5 mg/kg, QD x 9 or 3 mg/kg, QOD x 9) was administered intraperitoneally (i.p.) 24 h after tumor implantation and it resulted in a significant reduction in tumor weight to 48% of control. The effect of CPEC on established solid tumors in vivo was examined in athymic mice transplanted s.c. 14 days earlier with HT-29 cells and treated i.p. with 1.5 mg/kg CPEC, QD x 5 for 4 courses, with a 10 day-interval between courses. This treatment resulted in a significant reduction in tumor weight (72%) in the treated group. HPLC analysis of HT-29 tumor obtained from mice after treatment with CPEC showed a depletion of the CTP concentration reaching a nadir at 8 h. In conclusion, the present studies demonstrate potent antitumor activity of CPEC against freshly transplanted and established human colon carcinoma which can be corroborated with the drug's biochemical actions. PMID:10069488

  3. Randomized controlled study of early medication change for non-improvers to antidepressant therapy in major depression--The EMC trial.

    PubMed

    Tadić, André; Wachtlin, Daniel; Berger, Mathias; Braus, Dieter F; van Calker, Dietrich; Dahmen, Norbert; Dreimüller, Nadine; Engel, Alice; Gorbulev, Stanislav; Helmreich, Isabella; Kaiser, Anne-Katrin; Kronfeld, Kai; Schlicht, Konrad F; Tüscher, Oliver; Wagner, Stefanie; Hiemke, Christoph; Lieb, Klaus

    2016-04-01

    Patients with Major Depressive Disorder (MDD) and no improvement after two weeks of antidepressant pharmacotherapy have a high risk of treatment failure. The aim of the study was to determine whether an early medication change (EMC) strategy is superior to a guideline-based treatment in MDD patients without improvement after two weeks of antidepressant pharmacotherapy. Eight-hundred-and-eighty-nine patients with MDD were enrolled, 879 patients received the SSRI escitalopram. Of those, 192 patients had no improvement, defined as a reduction of < 20% on the Hamilton Depression Rating Scale (HAMD-17) after 14 days of treatment, and were randomly assigned to open treatment with the EMC strategy (n = 97; venlafaxine XR for study days 15-56; in case of sustained non-improvement on day 28, lithium augmentation for days 29-56) or TAU (n = 95; escitalopram continuation; non-responders on day 28 were switched to venlafaxine XR for four weeks, i.e. days 29-56). The primary outcome was remission (HAMD-17 ≤ 7) after 8 weeks of treatment as assessed by blinded raters. Remission rates were 24% for EMC and 16% for TAU, which was not significantly different (p = 0.2056). Sensitivity analyses for the primary and secondary effectiveness endpoints consistently showed favorable results for patients randomized to EMC. The results confirm data from post-hoc analyses of clinical trials showing that early non-improvement identifies patients who likely need alternate interventions. However, the herein used two-step switch/augmentation strategy for this risk group was not more effective than the control intervention. Alternate strategies and other design aspects are discussed in order to support researchers addressing the same research question. PMID:26899588

  4. In Vitro and in Vivo Studies of Novel Poly(D,L-lactic acid), Superhydrophilic Carbon Nanotubes, and Nanohydroxyapatite Scaffolds for Bone Regeneration.

    PubMed

    Siqueira, Idalia A W B; Corat, Marcus Alexandre F; Cavalcanti, Bruno das Neves; Ribeiro Neto, Wilson Alves; Martin, Airton Abrahao; Bretas, Rosario Elida Suman; Marciano, Fernanda Roberta; Lobo, Anderson Oliveira

    2015-05-13

    Poly(D,L-lactide acid, PDLLA) has been researched for scaffolds in bone regeneration. However, its hydrophobocity and smooth surface impedes its interaction with biological fluid and cell adhesion. To alter the surface characteristics, different surface modification techniques have been developed to facilitate biological application. The present study compared two different routes to produce PDLLA/superhydrophilic vertically aligned carbon nanotubes:nanohydroxyapatite (PDLLA/VACNT-O:nHAp) scaffolds. For this, we used electrodeposition and immersion in simulated body fluid (SBF). Characterization by goniometry, scanning electron microscopy, X-ray diffraction, and infrared spectroscopy confirmed the polymer modifications, the in vitro bioactivity, and biomineralization. Differential scanning calorimetry and thermal gravimetric analyses showed that the inclusion of VACNT-O:nHA probably acts as a nucleating agent increasing the crystallization rate in the neat PDLLA without structural alteration. Our results showed the formation of a dense nHAp layer on all scaffolds after 14 days of immersion in SBF solution; the most intense carbonated nHAp peaks observed in the PDLLA/VACNT-O:nHAp samples suggest higher calcium precipitation compared to the PDLLA control. Both cell viability and alkaline phosphatase assays showed favorable results, because no cytotoxic effects were present and all produced scaffolds were able to induce detectable mineralization. Bone defects were used to evaluate the bone regeneration; the confocal Raman and histological results confirmed high potential for bone applications. In vivo study showed that the PDLLA/VACNT-O:nHAp scaffolds mimicked the immature bone and induced bone remodeling. These findings indicate surface improvement and the applicability of this new nanobiomaterial for bone regenerative medicine. PMID:25899398

  5. Investigating the water balance of on-farm techniques for improved crop productivity in rainfed systems: A case study of Makanya catchment, Tanzania

    NASA Astrophysics Data System (ADS)

    Makurira, H.; Savenije, H. H. G.; Uhlenbrook, S.; Rockström, J.; Senzanje, A.

    Water scarcity is a perennial problem in sub-Saharan agricultural systems where extreme rainfall events dominate agricultural seasons. Dry spell occurrences between and during seasons negatively impact on crop yields especially if such dry spells exceed 14 days. The impact of dry spells is felt more at smallholder farming scales where subsistence farming is the only source of livelihood for many households. This paper presents results from on-going research to improve rainfed water productivity in arid and semi-arid regions. The study site is the Makanya catchment in northern Tanzania where rainfall rarely exceeds 400 mm/season. Rainwater alone is not sufficient to support maize which is the preferred crop. The research introduced new soil and water conservation measures to promote water availability into the root zone. The introduced techniques include deep tillage, runoff diversion, fanya juus (infiltration trenches with bunds) and infiltration pits. The research aims at understanding the effectiveness of these interventions in increasing moisture availability within the root zone. Time domain reflectometry (TDR) was used to measure soil moisture twice weekly at 10 cm depth intervals up to depths of 2 m. Soil moisture fluctuated in the range 5-25% of volume with the beginning of the season recording the driest moisture levels and periods after good rainfall/runoff events recording the highest moisture levels. From the field observations made, a spreadsheet model was developed to simulate soil moisture variations during different maize growth stages. The results obtained show that the zones of greatest soil moisture concentrations are those around the trenches and bunds. Soil moisture is least at the centre of the plots. The study confirms the effectiveness of the introduced techniques to help concentrate the little available rainfall into green water flow paths. Indirect benefits from these improved techniques are the creation of fertile and moist zones around

  6. Homologous platelet-rich plasma for the treatment of knee osteoarthritis in selected elderly patients: an open-label, uncontrolled, pilot study

    PubMed Central

    Bottegoni, Carlo; Dei Giudici, Luca; Salvemini, Sergio; Chiurazzi, Enrico; Bencivenga, Rosella; Gigante, Antonio

    2016-01-01

    Objective: The objective of this study was to evaluate the safety and the effect of platelet-rich plasma (PRP) intra-articular injections obtained from blood donors (homologous PRP) on elderly patients with early or moderate knee osteoarthritis (OA) who are not candidates for autologous PRP treatment. Methods: A total of 60 symptomatic patients, aged 65–86 years, affected by hematologic disorders and early or moderate knee OA, were treated with 5 ml of homologous PRP intra-articular injections every 14 days for a total of three injections. Clinical evaluations before the treatment, and after 2 and 6 months were performed by International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome Score (KOOS) and Equal Visual Analogue Scale (EQ VAS) scores. Adverse events and patient satisfaction were recorded. Results: No severe complications were noted during the treatment and the follow-up period. A statistically significant improvement from basal evaluation to the 2-month follow-up visit was observed, whereas a statistically significant worsening from the 2-month to the 6-month follow-up visit was showed. The overall worst results were observed in patients aged 80 years or over and in those affected by minor bone attrition. It was found that 90% of patients were satisfied at the 6-month evaluation. Conclusions: Homologous PRP has an excellent safety profile but offers only a short-term clinical improvement in selected elderly patients with knee OA who are not candidates for autologous PRP treatment. Increasing age and developing degeneration result in a decreased potential for homologous PRP injection therapy. Further studies are needed to confirm these findings. PMID:27047571

  7. Effect of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharides and inflammatory cytokines: an in vitro study using a human colonic microbiota model.

    PubMed

    Rodes, Laetitia; Khan, Afshan; Paul, Arghya; Coussa-Charley, Michael; Marinescu, Daniel; Tomaro-Duchesneau, Catherine; Shao, Wei; Kahouli, Imen; Prakash, Satya

    2013-04-01

    Gut-derived lipopolysaccharides (LPS) are critical to the development and progression of chronic low-grade inflammation and metabolic diseases. In this study, the effects of probiotics Lactobacillus and Bifidobacterium on gut-derived lipopolysaccharide and inflammatory cytokine concentrations were evaluated using a human colonic microbiota model. Lactobacillus reuteri, L. rhamnosus, L. plantarum, Bifidobacterium animalis, B. bifidum, B. longum, and B. longum subsp. infantis were identified from the literature for their anti-inflammatory potential. Each bacterial culture was administered daily to a human colonic microbiota model during 14 days. Colonic lipopolysaccharides, and Gram-positive and negative bacteria were quantified. RAW 264.7 macrophage cells were stimulated with supernatant from the human colonic microbiota model. Concentrations of TNF-alpha, IL-1beta, and IL-4 cytokines were measured. Lipopolysaccharide concentrations were significantly reduced with the administration of B. bifidum (-46.45 +/- 5.65%), L. rhamnosus (-30.40 +/- 5.08%), B. longum (-42.50 +/- 1.28%), and B. longum subsp. infantis (-68.85 +/- 5.32%) (p < 0.05). Cell counts of Gram-negative and positive bacteria were distinctly affected by the probiotic administered. There was a probiotic strain-sp