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Sample records for single intraperitoneal administration

  1. Transient oxidative stress and inflammation after intraperitoneal administration of multiwalled carbon nanotubes functionalized with single strand DNA in rats

    Energy Technology Data Exchange (ETDEWEB)

    Clichici, Simona, E-mail: simonaclichici@yahoo.com [Department of Physiology, University of Medicine and Pharmacy, Cluj-Napoca (Romania); Biris, Alexandru Radu [National R and D Institute of Isotopic and Molecular Technologies, Cluj-Napoca (Romania); Tabaran, Flaviu [University of Agricultural Sciences and Veterinary Medicine, Cluj-Napoca (Romania); Filip, Adriana [Department of Physiology, University of Medicine and Pharmacy, Cluj-Napoca (Romania)

    2012-03-15

    Multi-walled carbon nanotubes (MWCNTs) are widely used for nanotechnology. Their impact on living organisms is, however, not entirely clarified. Oxidative stress and inflammation seem to be the key mechanisms involved in MWCNTs' cytotoxicity. Until present, pulmonary and skin models were the main tested experimental designs to assess carbon nanotubes' toxicity. The systemic administration of MWCNTs is essential, with respect for future medical applications. Our research is performed on Wistar rats and is focused on the dynamics of oxidative stress parameters in blood and liver and pro-inflammatory cytokines in liver, after single dose (270 mg l{sup −1}) ip administration of MWCNTs (exterior diameter 15–25 nm, interior diameter 10–15 nm, surface 88 m{sup 2} g{sup −1}) functionalized with single strand DNA (ss-DNA). The presence of MWCNTs in blood was assessed by Raman spectroscopy, while in liver histological examination and confocal microscopy were used. It was found that ss-DNA-MWCNTs induce oxidative stress in plasma and liver, with the return of the tested parameters to normal values, 6 h after ip injection of nanotubes, with the exception of reduced glutathione in plasma. The inflammatory cytokines (TNF-α, IL-1β) had a similar pattern of evolution. We also assessed the level of ERK1/2 and the phosphorylation of p65 subunit of NF-kB in liver that had a transient increase and returned to normal at the end of the tested period. Our results demonstrate that ss-DNA-MWCNTs produce oxidative stress and inflammation, but with a transient pattern. Given the fact that antioxidants modify the profile not only for oxidative stress, but also of inflammation, the dynamics of these alterations may be of practical importance for future protective strategies. -- Highlights: ► ss-DNA-MWCNTs ip administration induce oxidative stress in plasma and liver. ► ss-DNA-MWCNTs ip administration determine liver inflammation. ► ERK1/2 and p65 phosphorylated NF

  2. Characterisation and Safety of Intraperitoneal Perioperative Administration of Antibacterial Agents

    DEFF Research Database (Denmark)

    Fonnes, Siv; Holzknecht, Barbara Juliane; Arpi, Magnus

    2017-01-01

    Background Intraperitoneal drug administration applies treatment at the site of diseases with gynaecological, urological, or gastrointestinal origin. The objective of this systematic review was to investigate perioperative intraperitoneal administration of antibacterial agents to characterise...... event was discomfort or pain during administration, especially with use of oxytetracycline. Conclusion At least 12 different classes of antibacterial agents have been administered intraperitoneally during or after surgery as prophylaxis or treatment of intraabdominal infections. Intraperitoneal...... administration seems safe although use of oxytetracycline may cause discomfort or pain....

  3. In vivo efficacy of oral and intraperitoneal administration of extracts ...

    African Journals Online (AJOL)

    In vivo efficacy of oral and intraperitoneal administration of extracts of Warburgia ugandensis (Canellaceae) in experimental treatment of old world cutaneous leishmaniasis caused by Leishmania major .

  4. Intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα prevents radiation-induced fibrosis

    International Nuclear Information System (INIS)

    Nawroth, Isabel; Alsner, Jan; Behlke, Mark A.; Besenbacher, Flemming; Overgaard, Jens; Howard, Kenneth A.; Kjems, Jorgen

    2010-01-01

    Background and purpose: One of the most common and dose-limiting long-term adverse effects of radiation therapy is radiation-induced fibrosis (RIF), which is characterized by restricted tissue flexibility, reduced compliance or strictures, pain and in severe cases, ulceration and necrosis. Several strategies have been proposed to ameliorate RIF but presently no effective one is available. Recent studies have reported that tumor necrosis factor-α (TNFα) plays a role in fibrogenesis. Material and methods: Male CDF1 mice were radiated with a single dose of 45 Gy. Chitosan/DsiRNA nanoparticles targeting TNFα were intraperitoneal injected and late radiation-induced fibrosis (RIF) was assessed using a modification of the leg contracture model. Additionally, the effect of these nanoparticles on tumor growth and tumor control probability in the absence of radiation was examined in a C3H mammary carcinoma model. Results: We show in this work, that targeting TNFα in macrophages by intraperitoneal administration of chitosan/DsiRNA nanoparticles completely prevented radiation-induced fibrosis in CDF1 mice without revealing any cytotoxic side-effects after a long-term administration. Furthermore, such TNFα targeting was selective without any significant influence on tumor growth or irradiation-related tumor control probability. Conclusion: This nanoparticle-based RNAi approach represents a novel approach to prevent RIF with potential application to improve clinical radiation therapeutic strategies.

  5. [Intraperitoneal and intrathoracic administration of hydroxyapatite-carboplatin (HAp-CBDCA)].

    Science.gov (United States)

    Mohri, N; Mizuno, I; Akamo, Y; Takeyama, H; Manabe, T

    1999-10-01

    We have investigated the efficacy of intraperitoneal or intrathoracic administration of hydroxyapatite particles (HAp) loaded carboplatin (CBDCA). HAp-CBDCA (HAp; 200 mg, CBDCA; 4 mg) was administered intraperitoneally to rats with peritoneal carcinomatosis. The area under the curve of the ascitic platinum (Pt) increased significantly with rats given HAp-CBDCA, and the omental Pt levels in the HAp-CBDCA group remained higher and longer. Additionally, the HAp-CBDCA group showed a trend toward longer survival when compared with the CBDCA alone group. In clinical use, HAp-CBDCA (HAp; 5 g, CBDCA; 150 mg) was administered intrathoracically to a patient who had undergone esophagectomy. The Pt in serum was detected until 7 days after administration of HAp-CBDCA.

  6. EFFICACY OF INTRAPERITONEAL INTERFERON-α ADMINISTRATION FOR TREATMENT OF ENDOMETRIOSIS IN RATS

    Directory of Open Access Journals (Sweden)

    R. V. Pavlov

    2006-01-01

    Full Text Available Abstract. The article presents the results of intraperitoneal administration of recombinant rat interferon-α to twenty Wistar rats with experimentally induced endometriosis. The following criteria of treatment efficiency were applied: presence of ectopic endometrium in transplanted segments of cornu uteri, proliferative activity of endometrioid cells, features of vascularization and leucocyte infiltration within endometrial foci. It was shown that local application of interferon-α caused regression of endometrioid epithelial heterotopias in 50 per cent of the cases. If endometrioid epithelium was retained, its proliferative activity did significantly drop under interferon-α application. In all transplants derived from rats treated with interferon-α, the degree of vascularization is reduced, accompanied by increased leucocytic infiltration (due to lymphocytes, along with decreased contents of macrophages within leucocytic infiltrates.

  7. Distribution and pharmacokinetics of radiolabeled monoclonal antibody OC 125 after intravenous and intraperitoneal administration in gynecologic tumors

    International Nuclear Information System (INIS)

    Haisma, H.J.; Moseley, K.R.; Battaile, A.; Griffiths, T.C.; Knapp, R.C.

    1988-01-01

    Radiolabeled monoclonal antibodies may be useful for radioimmunotherapy of gynecologic tumors. Iodine 131-labeled F(ab')2 fragments of a monoclonal antibody, OC 125, with specificity for ovarian carcinoma, were used to study the distribution and pharmacokinetics of this antibody in patients with gynecologic tumors. The radiolabeled antibody was injected intravenously or intraperitoneally into 10 patients suspected of having ovarian cancer. Blood and urine samples were used for pharmacokinetic studies, and biopsy specimens were examined for the uptake of antibody. The serum half-life of the labeled antibody was 30 hours after intravenous administration, with 20% of the injected dose per liter detected at 24 hours. After intraperitoneal injection, the appearance of antibody in serum was slow, with a maximum level of 1.4% of the injected dose per liter at 24 hours. Urinary excretion of the radiolabeled antibody was similar for intravenous and intraperitoneal administration, with approximately 50% of the injected dose excreted after 48 hours. Intraperitoneal administration of the radiolabeled antibody resulted in a higher uptake of antibody in the tumor and a lower uptake of antibody in normal tissues. On the basis of this limited study, intraperitoneal administration of radiolabeled antibody is preferred over intravenous administration for radioimmunotherapy of ovarian cancer

  8. Association of Fluid Administration With Morbidity in Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Eng, Oliver S; Dumitra, Sinziana; O'Leary, Michael; Raoof, Mustafa; Wakabayashi, Mark; Dellinger, Thanh H; Han, Ernest S; Lee, Stephen J; Paz, I Benjamin; Lee, Byrne

    2017-12-01

    Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal cancers can be associated with significant complications. Randomized trials have demonstrated increased morbidity with liberal fluid regimens in abdominal surgery. To investigate the association of intraoperative fluid administration and morbidity in patients undergoing CRS/HIPEC. A retrospective analysis of information from a prospectively collected institutional database was conducted at a National Cancer Institute-designated comprehensive cancer center. A total of 133 patients from April 15, 2009, to June 23, 2016, with primary or secondary peritoneal cancers were included. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy. Morbidity associated with intraoperative fluid management calculated by the comprehensive complication index, which uses a formula combining all perioperative complications and their severities into a continuous variable from 0 to 100 in each patient. Of the 133 patients identified, 38% and 37% had diagnoses of metastatic appendiceal and colorectal cancers, respectively. Mean age was 54 (interquartile range [IQR], 47-64) years, and mean peritoneal cancer index was 13 (IQR, 7-18). Mitomycin and platinum-based chemotherapeutic agents were used in 96 (72.2%) and 37 (27.8%) of the patients, respectively. Mean intraoperative fluid (IOF) rate was 15.7 (IQR, 11.3-18.7) mL/kg/h. Mean comprehensive complication index (CCI) was 26.0 (IQR, 8.7-36.2). On multivariate analysis, age (coefficient, 0.32; 95% CI, 0.01-0.64; P = .04), IOF rate (coefficient, 0.97; 95% CI, 0.19-1.75; P = .02), and estimated blood loss (coefficient, 0.02; 95% CI, 0.01-0.03; P = .002) were independent predictors of increased CCI. In particular, patients who received greater than the mean IOF rate experienced a 43% increase in the CCI compared with patients who received less than the mean IOF rate (31.5 vs 22.0; P = .02). Intraoperative fluid

  9. In vivo distribution of lead in male and female rats after intraperitoneal and oral administration.

    Science.gov (United States)

    Nwokocha, C R; Ufearo, C S; Owu, D U; Idemudo, N C; Ojukwu, L C

    2012-03-01

    The resultant effects of lead exposure are seen in almost all the systems of the body and results in toxicity to many organs. Since toxicity depends on its degree of uptake, distribution and metabolism, the authors investigated the differential uptake, accumulation and distribution of lead in organs of males and female Wistar rats following various routes of administration. Group 1 served as control male and control female; group 2 males and females received 5 mg/kg body weight of lead intraperitoneally for 8 days while group 3 males and female rats were administered drinking water containing 100 ppm of lead acetate for 18 days. Tissues were collected for analysis of the lead content using atomic absorption spectroscopy. The relative retention of lead by the tissues was greater in rats exposed to lead by the i.p. route varying in the order of accumulation / uptake in males as lungs > spleen > stomach > kidney > blood > heart and in females as spleen > stomach > heart > kidney > blood > lungs (i.p. route) and (oral route) as for males kidney > lungs > stomach > blood > heart > spleen, and females as kidney > lungs > stomach > blood > heart > spleen. Male Wistar rats showed more accumulation with oral exposure in lungs, spleen and blood with values for kidney and stomach being significantly (p exposure for spleen and stomach tissues while values for the heart was significantly (p lead retention and the organ distribution varied depending upon the sex and route of lead administration.

  10. Absorption and tissue distribution of doxorubicin entrapped in liposomes following intravenous or intraperitoneal administration.

    Science.gov (United States)

    Rosa, P; Clementi, F

    1983-01-01

    Absorption and tissue distribution of free doxorubicin (Dxn) and Dxn entrapped into liposomes have been examined after intravenous (i.v.) or intraperitoneal (i.p.) injection into C57/B1/6 mice. Liposomal encapsulation of Dxn altered its plasma kinetics and tissue distribution. After i.v. administration Dxn in liposomes has a half-life longer than that of free Dxn and it is taken up mostly by tissues rich in reticuloendothelial cells, such as liver and spleen. In the heart and kidney liposomal Dxn reaches a lower concentration than free Dxn. After i.p. injection the tissue distribution of liposomal Dxn is drastically changed. We did not observe the first peak of high concentration in the tissues, the Dxn content in liver and spleen is decreased and its concentration in heart is even more reduced. The results of this study suggest that the route of administration of liposome-entrapped drugs may change both the kinetics of absorption and their tissue distribution and this could result in a different pharmacological effect.

  11. Excretion and metabolism of 1-nitropyrene in rats after oral or intraperitoneal administration

    International Nuclear Information System (INIS)

    Dutcher, J.S.; Sun, J.D.; Bechtold, W.E.; Unkefer, C.J.

    1985-01-01

    The metabolism and excretion of 1-nitropyrene (NP), a prevalent NPAH, by Fischer-344 rats after intraperitoneal (ip) or oral administration was studied. Radiolabeled NP was administered to rats (10 mg NP/kg body wt), and urine and feces were collected for 7 days. After ip administration of [ 14 C]NP, 60% of the radioactivity was found in the urine and 20% in the feces. Likewise, 55 and 35% of the orally administered 14 C was found in urine and feces, respectively. Both urine and feces were analyzed by high-pressure liquid chromatography for metabolites. The majority of the radioactivity in both urine and feces was associated with very polar metabolites, none accounting for more than 10% of the dose. Small amounts (less than 1% of the dose) of aminopyrene (AP), acetylaminopyrene, and NP were detected. A urinary metabolite (3-8% of the dose) was found that converted to acetylaminopyrene phenol (two isomers) when urine was heated overnight at 37 0 C at pH 4.5. More of this metabolite (2.2 times) as well as AP (1.8 times), was excreted after oral than after ip administration of NP. The NP metabolites found in this study demonstrate that reduction of the nitro group is a significant route of NP metabolism in rats. Since nitroreduction appears to be necessary in the activation of NPAHs to bacterial mutagens, this indicates that similar metabolic pathways are present in rats (catalyzed by mammalian and/or gut bacterial enzymes) and that activation of NPAHs to carcinogens or toxins by nitroreduction is possible. 29 references, 8 figures

  12. Curcumin loaded NLC induces histone hypoacetylation in the CNS after intraperitoneal administration in mice.

    Science.gov (United States)

    Puglia, Carmelo; Frasca, Giuseppina; Musumeci, Teresa; Rizza, Luisa; Puglisi, Giovanni; Bonina, Francesco; Chiechio, Santina

    2012-06-01

    The natural p300-specific histone acetyltransferase (HAT) inhibitor, curcumin (CUR), has been widely investigated for its potential therapeutic effect as an anticancer and anti-inflammatory agent. Notwithstanding this interesting pharmacological profile, CUR shows some drawbacks, such as poor absorption and a very fast metabolism and elimination, that limit its clinical use. Aim of the present study was to formulate CUR loaded nanostructured lipid carriers (NLC-CUR) in order to improve the bioavailability and stability of this compound after systemic administration with increased effects in the central nervous system (CNS). NLC-CUR were prepared and characterized on their physicochemical properties by PCS and DSC analyses. Thus, NLC-CUR were systemically injected and the effects in the CNS were compared with a CUR control formulation containing 0.05% DMSO (DMSO-CUR). Our results demonstrate that CUR is able to decrease histone acetylation in the CNS when included in NLCs. Western blot analysis shows that intraperitoneal injection of NLC-CUR (100mg/kg) in mice induces a marked hypoacetylation of histone 4 (H4) at lysine 12 (K12) in the spinal cord compared with control group. Notably, DMSO-CUR (100mg/kg) did not change the H4K12 acetylation level in the CNS. Our study suggests a novel approach to ameliorate the pharmacokinetics of CUR that allows a better permeation in the CNS. Copyright © 2012 Elsevier B.V. All rights reserved.

  13. Immunoglobulin E-mediated hypersensitivity reaction after intraperitoneal administration of vancomycin

    Directory of Open Access Journals (Sweden)

    Mun-Ju Hwang

    2015-03-01

    Full Text Available Intraperitoneal (IP vancomycin is widely used to treat Gram-positive peritonitis associated with peritoneal dialysis. There have been two cases of red man syndrome (RMS, a vancomycin-specific nonimmunologic reaction, associated with IP vancomycin. However, immune-mediated hypersensitivity reaction to IP vancomycin has not yet been reported. A 49 year old woman on continuous ambulatory peritoneal dialysis developed her first peritonitis episode. The patient was treated with IP vancomycin once/wk for 4 weeks. She experienced mild itching and flushing throughout her body for 1 day after the second treatment. Whenever vancomycin was administered, generalized urticaria and a prickling sensation developed, and the intensity increased gradually; however, these symptoms improved after vancomycin was discontinued. An allergic skin test was performed 6 weeks after the previous urticarial episode, and an intradermal skin test revealed a positive response to vancomycin. To our knowledge, this is the first case report of immunoglobulin E-mediated hypersensitivity reaction to IP vancomycin administration.

  14. Toxicokinetics of the ciguatoxin P-CTX-1 in rats after intraperitoneal or oral administration.

    Science.gov (United States)

    Bottein, Marie-Yasmine Dechraoui; Wang, Zhihong; Ramsdell, John S

    2011-06-18

    Ciguatoxins are voltage-gated selective algal toxins responsible for ciguatera fish poisoning. In this study we evaluate the toxicokinetics of one of the most common ciguatoxins found in the Pacific, the P-CTX-1, in rat after an oral or intraperitoneal (ip) dose of 0.26 μg/kg body weight. We report levels of ciguatoxin activity assessed over time in blood, urine and feces, and at 4 days in liver, muscle and brain, using the functional in vitro N2A cytotoxicity assay. Following exposure, the ciguatoxin activity exhibited a rapid systemic absorption that was followed by a bi-exponential decline, and data best fit a two-compartment model analysis. Maximum blood concentrations were reached at 1.97 and 0.43 h after the oral and ip dose, respectively. Ciguatoxin elimination from blood was slow with terminal half lives (t(½)β) estimated at 82 h for oral and 112 h for ip dosing. Ciguatoxin activity remained in liver, muscle and brain 96 h after ip and oral administration. While smaller amounts appeared in the urine, the main excretion route was feces, with peak rates reaching > 10 pg P-CTX-1 equivalents/h in both routes of administration. Assay guided fractionation showed the presence in the feces and liver of peaks of activity corresponding to the P-CTX-1 and to other less polar metabolites. In conclusion, biologically active ciguatoxins are detectable in blood, liver, muscle and brain, and continued to be excreted in urine and feces 4 days following exposure. Blood, as well as urine and feces may be useful matrices for low-invasive testing methods for ciguatera clinical cases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  15. Monte Carlo investigation of single cell beta dosimetry for intraperitoneal radionuclide therapy

    International Nuclear Information System (INIS)

    Syme, A M; Kirkby, C; Riauka, T A; Fallone, B G; McQuarrie, S A

    2004-01-01

    Single event spectra for five beta-emitting radionuclides (Lu-177, Cu-67, Re-186, Re-188, Y-90) were calculated for single cells from two source geometries. The first was a surface-bound isotropically emitting point source and the second was a bath of free radioactivity in which the cell was submerged. Together these represent a targeted intraperitoneal radionuclide therapy. Monoenergetic single event spectra were calculated over an energy range of 11 keV to 2500 keV using the EGSnrc Monte Carlo system. Radionuclide single event spectra were constructed by weighting monoenergetic single event spectra according to radionuclide spectra appropriate for each source geometry. In the case of surface-bound radioactivity, these were radionuclide beta decay spectra. For the free radioactivity, a continuous slowing down approximation spectrum was used that was calculated based on the radionuclide decay spectra. The frequency mean specific energy per event increased as the energy of the beta emitter decreased. This is because, at these energies, the stopping power of the electrons decreases with increasing energy. The free radioactivity produced a higher frequency mean specific energy per event than the corresponding surface-bound value. This was primarily due to the longer mean path length through the target for this geometry. This information differentiates the radionuclides in terms of the physical process of energy deposition and could be of use in the radionuclide selection procedure for this type of therapy

  16. Intraperitoneal administration of the globular adiponectin gene ameliorates diabetic nephropathy in Wistar rats.

    Science.gov (United States)

    Yuan, Fang; Liu, Ying-Hong; Liu, Fu-You; Peng, You-Ming; Tian, Jun-Wei

    2014-06-01

    The present study investigated the potential effects of the long-term expression of exogenous adiponectin (ADPN) on normal and diabetic kidneys. Type 2 diabetes mellitus models were induced by high-lipid and high-sucrose feeding plus intraperitoneal injection of streptozotocin. The recombinant plasmid pIRES2-EGFP-gAd, which is able to co-express globular ADPN (gAd) and enhanced green fluorescent protein (EGFP), was intraperitoneally injected into rat models mediated by Lipofectamine. In total, 32 Wistar rats were randomly assigned into four groups: the normal control group, the diabetes group, the diabetes group treated with pIRES2-EGFP-gAd and the diabetes group treated with pIRES2-EGFP. After 12 weeks, serum biochemistry and urine albumin levels were measured. The kidneys were collected to assess the generation of reactive oxygen species (ROS) and the renal pathological changes were observed by light microcopy. The protein expression of endothelial nitric oxide synthase (eNOS), transforming growth factor-β1 (TGF-β1) and phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were determined by an immunohistochemical staining method and western blot analysis. Intraperitoneal injection of the human gAd gene via Lipofectamine resulted in abundant ADPN protein in the kidney. In the diabetic rats, the delivery of the exogenous gAd gene ameliorated the progression of diabetic nephropathy (DN). ADPN attenuated urine albumin excretion in the diabetic rats. ADPN also mitigated glomerular mesangial expansion, reduced the generation of ROS and prevented interstitial fibrosis. In addition, the expression of gAd inhibited the renal expression of TGF-β1, promoted the protein expression of eNOS and activated the opening of the AMPK signaling pathway in the renal tissues of the diabetic rats. Despite the effects of ADPN on DN being controversial, these observations indicate that the supplementation of ADPN is beneficial in ameliorating DN in rats.

  17. Duration and degree of radioprotection by WR-2721 in mice following intraperitoneal, intramuscular and subcutaneous administration

    International Nuclear Information System (INIS)

    Kuna, P.

    1983-01-01

    An intramuscular dose of 300 mg S-2-(3-aminopropylamino)-ethyl-phosphothioic acid (WR-2721) per kg body weight, applied 15-120 minutes before whole-body #betta# irradiation, protected mice significantly from radiation death. The protective dose was 35% of the acute toxic dose. After intraperitoneal and subcutaneous injection, resp., the same protective dose was effective within a 90 minute interval. According to the LD/sub 50/30/ the most effective radioprotective dose in mice was 300 mg WR-2721/kg, applied intramuscularly

  18. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for the treatment of advanced epithelial and recurrent ovarian carcinoma: a single center experience.

    Science.gov (United States)

    Pavlov, Maja J; Ceranic, Miljan S; Latincic, Stojan M; Sabljak, Predrag V; Kecmanovic, Dragutin M; Sugarbaker, Paul H

    2017-09-07

    With standard treatment of epithelial ovarian cancer (EOC), prognosis is very poor. The aim of this study is to show early and late results in patients who underwent cytoreductive surgery and intraperitoneal chemotherapy. This was a retrospective single centre study. All patients with advanced and recurrent ovarian cancer treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) or modified early postoperative intraperitoneal chemotherapy (EPIC) were included in the study. In the period 1995-2014, 116 patients were treated, 55 with primary EOC and 61 with recurrent EOC. The mean age was 59 years (26-74). Statistically, median survival time was significantly longer in the group with primary advanced cancer of the ovary (41.3 months) compared to relapsed ovarian cancer (27.3 months). Survival for the primary EOC was 65 and 24% at 3 and 5 years, respectively. Survival for recurrent EOC was 33 and 16% at 3 and 5 years, respectively. Mortality was 1/116 (0.8%). Morbidity was 11/116 (9.5%). Peritoneal cancer index (PCI) was ≤20 in 59 (51%) patients and statistically, their average survival was significantly longer than in the group of 57 (49%) patients with PCI >20 (p = 0.014). In advanced or recurrent EOC, a curative therapeutic approach was pursued that combined optimal cytoreductive surgery and intraperitoneal chemotherapy. PCI and timing of the intervention (primary or recurrent) were the strongest independent prognostic factors.

  19. COMPUTER-ASSISTED SEMEN ANALYSIS OF RAT SPERMATOZOA AFTER AN INTRAPERITONEAL ADMINISTRATION OF INSECTICIDE DIAZINON

    Directory of Open Access Journals (Sweden)

    R. TOMAN

    2008-05-01

    Full Text Available The aim of this study was to reveal the effect of diazinon on the rat spermatozoa motility characteristics using the computer-assisted semen analysis (CASA. Motility, progressive motility, DAP, DCL, DSL, VAP, VCL, VSL, STR, LIN, WOB, ALH, and BCF after the diazinon i.p. administration of 20 mg/kg b.w. were evaluated. 36 hours after the diazinon administration, only slight decrease in VCL, DCL and increase in percentage of progressive motility in the diazinon-treated group. Significant decrease (P<0.01 was only observed in BCF in diazinon-treated group. Computer-assisted semen analysis (CASA of rat sperm motility showed that acute diazinon administration slightly affected the rat sperm motility which can be the first step in the decreased fertilization capacity caused by pesticides. Further investigation of reproductive effects of diazinon is needed.

  20. Dietary and Intraperitoneal Administration of Selenium Provide Comparable Protection in the 6-Hydroxydopamine Lesion Rat Model of Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Cecilia M. Fox

    2007-01-01

    Full Text Available Significant research implicates the involvement of free radicals in the manifestation of Parkinson's disease. The antioxidant, selenium is a vital dietary component for mammals. It is present in the active center of glutathione peroxidase, an antioxidant enzyme that scavenges peroxides and protects membrane lipids and macromolecules from oxidative insult. The purpose of this research was to determine an effective means of delivering selenium as well as an appropriate time frame for antioxidant administration that would elicit a protective response in rats challenged with an intranigral 6-hydroxydopamine (6-OHDA lesion. In the first part of this study, Fischer 344 rats were placed into one of four groups: selenium enhanced diet, control diet, intraperitoneal injection of selenium as Na2SeO3 or intraperitoneal injection of distilled water. All treatments were delivered prior to an intranigral 6-OHDA lesion. Animals were euthanized two weeks post lesion and their brains processed for tyrosine hydroxylase (TH immunocytochemistry. Average dopamine neuron survival in the substantia nigra of control animals was less than 22%; whereas nigral dopamine neuron survival in the selenium fed group was 49.7% and 56.0% in the selenium injected group. Based on these results, a subsequent study was designed utilizing the selenium enhanced diet method of antioxidant administration. To examine the neuroprotective effect of long-term selenium treatment, pregnant Fischer 344 rats were exposed to either selenium enhanced or control rat chow. Their pups were treated with the same diet as their mothers and lesioned with 6-OHDA at two months of age. Animals were euthanized and their brains were processed for TH immunocytochemistry. Nigral dopamine neuron survival for the selenium treated animals was significantly protective (59% when compared to the control chow fed animals (29.6%. However, when compared to the short-term exposure of selenium rat chow in the previous

  1. Intraperitoneal treatment with darbepoetin for children on peritoneal dialysis.

    NARCIS (Netherlands)

    Rijk, Y.; Raaijmakers, R.; Kar, N.C.A.J. van de; Schroder, C.

    2007-01-01

    To determine the efficacy and safety of intraperitoneal administration of darbepoetin in children with renal anemia on peritoneal dialysis, we conducted a single-arm, retrospective, two-centre study in which children were treated with intraperitoneal darbepoetin at the end of nightly intermittent

  2. Inhibition of Neuropathic Pain by a Single Intraperitoneal Injection of Diazepam in the Rat: Possible Role of Neurosteroids.

    Science.gov (United States)

    Chen, Shu-Ling; Zang, Ying; Zheng, Wen-Hui; Wei, Xu-Hong; Liu, Xian-Guo

    2016-02-29

    Diazepam binds with the same high affinity to the central benzodiazepine receptor (CBR) and the peripheral benzodiazepine receptor, which has been renamed translocator protein (TSPO). Both receptors could promote neurosteroid synthesis. In the present study, we investigated whether a single dose of diazepam could inhibit neuropathic pain induced by L5 spinal nerve ligation (L5 SNL), and whether CBR and TSPO mediated this effect. We found that a single intraperitoneal injection of diazepam 9 d after L5 SNL significantly depressed the established mechanical allodynia and thermal hyperalgesia, which persisted until the end of the experiments. Furthermore, the effects were mimicked by a single intraperitoneal injection of Ro5-4864, a specific TSPO agonist and pregnenolone, a neurosteroid precursor. In addition, we found that the inhibitory effect of diazepam was also completely blocked by pretreatment with a specific CBR antagonist, flumazenil. The effects of diazepam or Ro5-4864 on neuropathic pain were completely blocked by pretreatment with a neurosteroid synthesis inhibitor, aminoglutethimide (AMG). Finally, any one of the three drugs, diazepam, Ro5-4864 and pregnenolone, could reduce the activation of astrocytes and the production of interleukin-1beta (IL-1β) in the L5 spinal dorsal horn 14 d after L5 SNL. These results suggest that in addition to exerting effects on CBR, diazepam may inhibit neuropathic pain via TSPO, which promotes neurosteroid formation, subsequently reducing the activation of astrocytes and production of cytokines.

  3. Intraperitoneal administration of docosahexaenoic acid for 14days increases serum unesterified DHA and seizure latency in the maximal pentylenetetrazol model.

    Science.gov (United States)

    Trépanier, Marc-Olivier; Lim, Joonbum; Lai, Terence K Y; Cho, Hye Jin; Domenichiello, Anthony F; Chen, Chuck T; Taha, Ameer Y; Bazinet, Richard P; Burnham, W M

    2014-04-01

    Docosahexaenoic acid (DHA) is an omega-3 polyunsaturated fatty acid (n-3 PUFA) which has been shown to raise seizure thresholds following acute administration in rats. The aims of the present experiment were the following: 1) to test whether subchronic DHA administration raises seizure threshold in the maximal pentylenetetrazol (PTZ) model 24h following the last injection and 2) to determine whether the increase in seizure threshold is correlated with an increase in serum and/or brain DHA. Animals received daily intraperitoneal (i.p.) injections of 50mg/kg of DHA, DHA ethyl ester (DHA EE), or volume-matched vehicle (albumin/saline) for 14days. On day 15, one subset of animals was seizure tested in the maximal PTZ model (Experiment 1). In a separate (non-seizure tested) subset of animals, blood was collected, and brains were excised following high-energy, head-focused microwave fixation. Lipid analysis was performed on serum and brain (Experiment 2). For data analysis, the DHA and DHA EE groups were combined since they did not differ significantly from each other. In the maximal PTZ model, DHA significantly increased seizure latency by approximately 3-fold as compared to vehicle-injected animals. This increase in seizure latency was associated with an increase in serum unesterified DHA. Total brain DHA and brain unesterified DHA concentrations, however, did not differ significantly in the treatment and control groups. An increase in serum unesterified DHA concentration reflecting increased flux of DHA to the brain appears to explain changes in seizure threshold, independent of changes in brain DHA concentrations. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Plasma and brain pharmacokinetic profile of cannabidiol (CBD), cannabidivarine (CBDV), Δ⁹-tetrahydrocannabivarin (THCV) and cannabigerol (CBG) in rats and mice following oral and intraperitoneal administration and CBD action on obsessive-compulsive behaviour.

    Science.gov (United States)

    Deiana, Serena; Watanabe, Akihito; Yamasaki, Yuki; Amada, Naoki; Arthur, Marlene; Fleming, Shona; Woodcock, Hilary; Dorward, Patricia; Pigliacampo, Barbara; Close, Steve; Platt, Bettina; Riedel, Gernot

    2012-02-01

    Phytocannabinoids are useful therapeutics for multiple applications including treatments of constipation, malaria, rheumatism, alleviation of intraocular pressure, emesis, anxiety and some neurological and neurodegenerative disorders. Consistent with these medicinal properties, extracted cannabinoids have recently gained much interest in research, and some are currently in advanced stages of clinical testing. Other constituents of Cannabis sativa, the hemp plant, however, remain relatively unexplored in vivo. These include cannabidiol (CBD), cannabidivarine (CBDV), Δ(9)-tetrahydrocannabivarin (Δ(9)-THCV) and cannabigerol (CBG). We here determined pharmacokinetic profiles of the above phytocannabinoids after acute single-dose intraperitoneal and oral administration in mice and rats. The pharmacodynamic-pharmacokinetic relationship of CBD (120 mg/kg, ip and oral) was further assessed using a marble burying test in mice. All phytocannabinoids readily penetrated the blood-brain barrier and solutol, despite producing moderate behavioural anomalies, led to higher brain penetration than cremophor after oral, but not intraperitoneal exposure. In mice, cremophor-based intraperitoneal administration always attained higher plasma and brain concentrations, independent of substance given. In rats, oral administration offered higher brain concentrations for CBD (120 mg/kg) and CBDV (60 mg/kg), but not for Δ(9)-THCV (30 mg/kg) and CBG (120 mg/kg), for which the intraperitoneal route was more effective. CBD inhibited obsessive-compulsive behaviour in a time-dependent manner matching its pharmacokinetic profile. These data provide important information on the brain and plasma exposure of new phytocannabinoids and guidance for the most efficacious administration route and time points for determination of drug effects under in vivo conditions.

  5. A Comparative In Vivo Scrutiny of Biosynthesized Copper and Zinc Oxide Nanoparticles by Intraperitoneal and Intravenous Administration Routes in Rats.

    Science.gov (United States)

    C, Ashajyothi; K Handral, Harish; Kelmani R, Chandrakanth

    2018-04-03

    During the present time, anti-microbial features of copper (Cu) and zinc oxide (ZnO) nanoparticles (NPs) are extensively used to combat the growth of pathogenic microbes. CuNPs and ZnONPs are recurrently used in cosmetics, medicine and food additives, and their potential for toxic impacts on human and ecosystem is of high concern. In this study, the fate and toxicity of 16- to 96-nm-ranged biosynthesized copper (Bio-CuNPs) and zinc oxide (Bio-ZnONPs) was assessed in male Wistar rats. In vivo exposures of the two nanoparticles are achieved through two different administration routes namely, intraperitoneal (i/p) and intravenous (i/v) injections. The three different concentrations, no observable adverse effect concentration (NOAEC), inhibitory concentration (IC 50 ) and total lethal concentration (TLC), were appraised at the dose range of 6.1 to 19.82 μg/kg and 11.14 to 30.3 μg/kg for Bio-CuNPs and Bio-ZnONPs respectively, for both i/p and i/v routes on 14th and 28th day of observation. These dose ranges are considered based on the previous study of antibacterial dose on multidrug-resistant pathogenic bacteria. In this study, we investigated the toxic effect of Bio-CuNPs and Bio-ZnONPs on animal behaviour, animal mass, haematologic indices, organ indices and histopathology of liver, spleen, kidney and brain organs. We found that i/v and i/p administration of Bio-ZnONPs in three different doses did not cause mortality and body weight was slightly reduced up to second week of administration compared with the vehicle control group. At the dose ranges of 11-16 μg/kg (i/v) and 24-30 μg/kg (i/p), no significant changes were observed in the serum creatinine level as well as serum ALT, serum AST level and ALP level which were 40.7 mg/dl, 37.9 IU/L and 82.4 IU/L normal as compared to vehicle control on 14th and 28th day of observation. These findings are confirmed in liver, kidney and spleen indices and histopathology studies. Furthermore, liver and kidney injury

  6. Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain.

    Science.gov (United States)

    Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Yoshikawa, Yutaka; Yasui, Hiroyuki; Kanamura, Narisato; Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji; Fushiki, Shinji

    2010-08-20

    Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

  7. Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain

    International Nuclear Information System (INIS)

    Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Fushiki, Shinji; Yoshikawa, Yutaka; Yasui, Hiroyuki; Kanamura, Narisato; Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji

    2010-01-01

    Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

  8. Organ distribution of quantum dots after intraperitoneal administration, with special reference to area-specific distribution in the brain

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Shingo; Itoh, Kyoko; Yaoi, Takeshi; Tozawa, Takenori; Fushiki, Shinji [Department of Pathology and Applied Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Yoshikawa, Yutaka; Yasui, Hiroyuki [Department of Analytical and Bioinorganic Chemistry, Kyoto Pharmaceutical University, Kyoto (Japan); Kanamura, Narisato [Department of Dental Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto (Japan); Hoshino, Akiyoshi; Manabe, Noriyoshi; Yamamoto, Kenji, E-mail: sfushiki@koto.kpu-m.ac.jp [The International Clinical Research Center, Research Institute, International Medical Center of Japan, Tokyo (Japan)

    2010-08-20

    Quantum dots (QDs) are well known for their potential application in biosensing, ex vivo live-cell imaging and in vivo animal targeting. The brain is a challenging organ for drug delivery, because the blood brain barrier (BBB) functions as a gatekeeper guarding the body from exogenous substances. Here, we evaluated the distribution of bioconjugated QDs, i.e., captopril-conjugated QDs (QDs-cap) following intraperitoneal injection into male ICR mice as a model system for determining the tissue localization of QDs, employing ICP-MS and confocal microscopy coupled with spectrometric analysis. We have demonstrated that intraperitoneally administered QDs-cap were delivered via systemic blood circulation into liver, spleen, kidney and brain at 6 h after injection. QDs-cap were located predominantly inside the blood vessels in the liver, kidney and brain, but a few were distributed in the parenchyma, especially noteworthy in the brain. Careful studies on acute as well as chronic toxicity of QDs in the brain are required prior to clinical application to humans.

  9. Ciguatoxins and Maitotoxins in Extracts of Sixteen Gambierdiscus Isolates and One Fukuyoa Isolate from the South Pacific and Their Toxicity to Mice by Intraperitoneal and Oral Administration.

    Science.gov (United States)

    Munday, Rex; Murray, Sam; Rhodes, Lesley L; Larsson, Michaela E; Harwood, D Tim

    2017-06-30

    Ciguatoxins (CTXs), and possibly maitotoxins (MTXs), are responsible for Ciguatera Fish Poisoning, an important health problem for consumers of reef fish (such as inhabitants of islands in the South Pacific Ocean). The habitational range of the Gambierdiscus species is expanding, and new species are being discovered. In order to provide information on the potential health risk of the Gambierdiscus species, and one Fukuyoa species (found in the Cook Islands, the Kermadec Islands, mainland New Zealand, and New South Wales, Australia), 17 microalgae isolates were collected from these areas. Unialgal cultures were grown and extracts of the culture isolates were analysed for CTXs and MTXs by liquid chromatography tandem mass spectrometry (LC-MS/MS), and their toxicity to mice was determined by intraperitoneal and oral administration. An isolate of G. carpenteri contained neither CTXs nor MTXs, while 15 other isolates (including G. australes, G. cheloniae , G. pacificus , G. honu , and F. paulensis ) contained only MTX-1 and/or MTX-3. An isolate of G. polynesiensis contained both CTXs and MTX-3. All the extracts were toxic to mice by intraperitoneal injection, but those containing only MTX-1 and/or -3 were much less toxic by oral administration. The extract of G. polynesiensis was highly toxic by both routes of administration.

  10. Pulmonary injuries and cytokine levels after the intraperitoneal administration of pancreatic homogenates in rats Lesiones pulmonares y niveles de citoquinas tras la administración intraperitoneal de homogeneizado pancreático en ratas

    Directory of Open Access Journals (Sweden)

    G. Mozo

    2004-08-01

    Full Text Available Introduction: our objective was to investigate the effects of the administration of pancreatic homogenates, with or without enzymatic activation, to healthy animals regarding cytokine serum levels and the development of pulmonary distress. Material and methods: 106 male Wistar rats, divided into three groups, were studied: group A, intraperitoneal administration of homogenates activated with enterokinase; group B, homogenates without enterokinase; and group C, control group with administration of physiological saline solution. Each group was divided into 4 subgroups according to the time of sacrifice: 0, 2, 6 and 24 hours. We studied the pulmonary and pancreatic histology, serum parameters of renal and hepatic function, and serum levels of IL-1ß, IL-6 and TNFa. Results: there was no mortality in any group. Pancreatic disorders in A and B groups were noted at 24 hours. These two groups had statistically significant higher transaminase serum levels than those of the control group, as well as statistically significant higher creatinine levels in group A. IL-1ß showed a statistically significant higher level at 6 h in both groups, A and B, but was higher in group A, which also exhibited significant pulmonary histologic damage with respect to controls at 6 h. Conclusions: the higher IL-1ß level in group A may result from production by peritoneal macrophages under the influence of homogenate enzymatic activation. This may be the reason for lung damage.Introducción: nuestro objetivo es investigar, en animales sanos, los efectos de la administración de homogeneizado pancreático, con y sin activación enzimática, sobre los niveles séricos de citoquinas y el desarrollo de lesiones pulmonares. Material y métodos: se estudiaron 106 ratas Wistar macho divididas en 3 grupos: A: administración intraperitoneal de homogeneizado pancreático activado con enteroquinasa; B: homogeneizado sin enteroquinasa; y C: control, con la administración de suero

  11. Acute and subchronic toxicity of the antitumor agent rhodium (II citrate in Balb/c mice after intraperitoneal administration

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

    Full Text Available This study aimed to investigate potential acute and subchronic toxicity of rhodium (II citrate in female Balb/c mice after intraperitoneal injections. In the acute test, independent groups received five doses; the highest dose (107.5 mg/kg was equivalent to 33 times that used in our previous reports. The other doses were chosen as proportions of the highest, being 80.7 (75%, 53.8 (50%, 26.9 (25% or 13.8 mg/kg (12.5%. Animals were monitored over 38 days and no severe signs of toxicity were observed, according to mortality, monitoring of adverse symptoms, hematological, biochemical and genotoxic parameters. We conclude that the median lethal dose (LD50 could be greater than 107.5 mg/kg. In the subchronic test, five doses of Rh2Cit (80, 60, 40, 20 or 10 mg/kg were evaluated and injections were conducted on alternate days, totaling five applications per animal. Paclitaxel (57.5 mg/kg and saline solution were controls. Clinical observations, histopathology of liver, lung and kidneys and effects on hematological, biochemistry and genotoxic records indicated that Rh2Cit induced no severe toxic effects, even at an accumulated dose up to 400 mg/kg.We suggest Rh2Cit has great potential as an antitumor drug without presenting acute and subchronic toxicity.

  12. Effect of Intra CA1 and Intraperitoneal Administration of Opioid Receptor Modulating Agents on The Anxiolytic Properties of Nano and Conventional ZnO in Male Rats.

    Science.gov (United States)

    Torabi, Mozhgan; Kesmati, Mahnaz; Eshagh Harooni, Hooman; Varzi, Hosein Najafzadeh

    2014-01-01

    Nano components are today's new wonder material. However, the safety or toxicity of these components in humans is not yet clear. In a previous study we indicated that nano ZnO (nZnO) has a stronger anxiolytic effect compared to the conventional ZnO (cZnO). The present study was designed to evaluate the intraperitoneal administration of an opioidergic receptor agonist and antagonist of as well as the intra CA1 administration of an opioidergic receptor antagonist on the anxiolytic properties of nano and conventional ZnO in adult male Wistar rats. In this experimental study, rats received drugs via two modes of injection; intraperitoneal (IP.) and intra CA1 (intra hippocampus, CA1 area). Firstly, nZnO (5, 10, 20 mg/kg), cZnO (5, 10, 20 mg/kg), morphine 6 mg/kg, and naloxone 1 mg/kg were injected IP and naloxone 1µg/rat was injected intra CA1. Subsequently, morphine and na- loxone (IP and intra CA1) were co-injected with the effective dose of nZnO and cZnO. An elevated plus maze was used to evaluate anxiety related behavior and anxiety parameters 30 minutes after the second injection. The results indicated that the anxiolytic effects of nZnO 5 mg/kg and cZnO 10 mg/kg were equal. When injected intraperitoneally, naloxone increased anxiety but did not inhibit the anxiolytic effect of nZnO and cZnO. The anxiolytic effects of morphine potentiated the anxio- lytic effects of ZnO, particularly nZno. When introduced via intra CA1 injection naloxone alone had no effect on anxiety behaviors and did not inhibit the anxiolytic effect of nZnO. It seems that the opioidergic system activity involved in the anxiolytic effect of nano and conventional ZnO may operate through shared and unshared pathways.

  13. Intraperitoneal immunoconjugates

    International Nuclear Information System (INIS)

    Griffin, T.W.; Collins, J.; Bokhari, F.; Stochl, M.; Brill, A.B.; Ito, T.; Emond, G.; Sands, H.

    1990-01-01

    Intracavitary instillation of radioantibodies has been proposed as therapy for anatomically confined malignant disease. To evaluate this therapeutic strategy, a monoclonal antibody reactive with human transferrin receptor (7D3) was evaluated for localization in a human malignant mesothelioma transplanted i.p. in athymic nude mice. This antibody was purified and labeled with 131I, 125I, or 111In. Radiolabeled antibody was administered i.p. or i.v. to tumor-bearing mice. Three h after injection, the percentage of injected dose/g (ID/g) of tumor was higher in free-floating ascites tumor cells (31.0%/g tumor cell pellet) after i.p. injection than after i.v. injection (12.0%). However, localization of radiolabel in i.p. solid tumors was similar (5.37% ID/g i.p. versus 4.73% of ID/g i.v.), and by 24 h both routes of administration produced similar localization of radiolabel in both free-floating ascites cells and solid tumors. In contrast, uptake of radiolabel into liver, kidney, and to a lesser extent bone and bone marrow, was less with i.p. than with i.v. administration. In clinical studies with 111In and 90Y antibodies administered i.p. to patients with ovarian cancer, confined biodistribution of the radioantibody was again seen, although interpatient variability of rate of egress of the radiolabel was documented. Therefore, both preclinical and clinical data indicate that i.p. therapy with immunoconjugates may be advantageous for cancer confined to the peritoneal cavity. This advantage stems primarily from reduced localization of isotope in organs of catabolism or toxicity (liver, kidney, bone, and bone marrow), rather than greatly increased levels of isotope in tumor. Unresolved problems include degree of antibody penetration into solid tumors, microdosimetry, and radioantibody effectiveness for tumor killing

  14. Intra-peritoneal administration of interleukin-1 beta induces impaired insulin release from the perfused rat pancreas

    DEFF Research Database (Denmark)

    Wogensen, L; Helqvist, S; Pociot, F

    1990-01-01

    content in pancreata from IL-1 beta pre-treated rats was higher than in pancreata from saline-treated controls. In contrast to the inhibitory effect of in vivo administration of IL-1 beta on beta-cell function glucagon secretion was stimulated. These observations suggest that circulating IL-1 beta......-1 beta glucose-stimulated as well as IL-1 beta potentiated glucose-stimulated insulin release was almost completely abolished. Furthermore, a decline in insulin release was observed at 11 mmol/l D-glucose, in contrast to an increase in insulin release in controls. The total extractable insulin...

  15. Comparison of the Intraperitoneal, Retroorbital and per Oral Routes for F 18 FDG Administration as Effective Alternatives to Intravenous Administration in Mouse Tumor Models Using Small Animal PET/CT Studies

    International Nuclear Information System (INIS)

    Kim, Chulhan; Kim, In Hye; Kim, Seo il; Kim, Young Sang; Kang, Se Hun; Moon, Seung Hwan; Kim, Tae Sung; Kim, Seok ki

    2011-01-01

    We compared alternative routes for 18F fluorodeoxyglucose (FDG) administration, such as the retroorbital (RO), intraperitoneal (IP) and per oral (PO) routes, with the intravenous (IV) route in normal tissues and tumors of mice. CRL 1642 (ATCC, Lewis lung carcinoma) cells were inoculated in female BALB/c nu/nu mice 6 to 10 weeks old. When the tumor grew to about 9mm in diameter, positron emission tomography (PET) scans were performed after FDG administration via the RO, IP, PO or IV route. Additional serial PET scans were performed using the RO, IV or IP route alternatively from 5 to 29 days after the tumor cell injection. There was no significant difference in the FDG uptake in normal tissues at 60 min after FDG administration via RO, IP and IV routes. PO administration, however, showed delayed distribution and unwanted high gastrointestinal uptake. Tumoral uptake of FDG showed a similar temporal pattern and increased until 60 min after FDG administration in the RO, IP and IV injection groups. In the PO administration group, tumoral uptake was delayed and reduced. There was no statistical difference among the RO, IP and IV administration groups for additional serial PET scans. RO administration is an effective alternative route to IV administration for mouse FDG PET scans using normal mice and tumor models. In addition, IP administration can be a practical alternative in the late phase, although the initial uptake is lower than those in the IV and RO groups.

  16. Stability of Antibiotics for Intraperitoneal Administration in Extraneal 7.5% Icodextrin Peritoneal Dialysis Bags (STAB Study).

    Science.gov (United States)

    Ranganathan, Dwarakanathan; Naicker, Saiyuri; Wallis, Steven C; Lipman, Jeffrey; Ratanjee, Sharad K; Roberts, Jason A

    2016-01-01

    ♦ Patients with peritoneal dialysis (PD)-associated peritonitis may be advised to store PD-bags with pre-mixed antibiotics at home, although there is a paucity of antibiotic stability studies in the commonly used icodextrin solutions. The purpose of this study was to assess the stability of various antibiotics in PD-bags when stored at different temperatures over a 14-day period. ♦ 7.5% icodextrin PD-bags were dosed with gentamicin 20 mg/L (n = 9), vancomycin 1,000 mg/L (n = 9), cefazolin 500 mg/L (n = 9) and ceftazidime 500 mg/L (n = 9) as for intermittent dosing. Combinations of gentamicin/vancomycin (n = 9), cefazolin/ceftazidime (n = 9), and cefazolin/gentamicin (n = 9) were also tested. Nine drug-free bags were used as controls. Bags were stored in triplicate at 37°C, room-temperature (25°C), and refrigeration (4°C). Antibiotic concentrations were quantified at various time intervals using validated chromatography. Storage duration was considered unstable if the concentration of the antibiotic dropped ≤ 90% of the initial value. ♦ Gentamicin was stable for 14 days at all temperatures. Vancomycin was stable for 4 days at 37°C and for 14 days at both 25°C and 4°C. The gentamicin and vancomycin combination was stable for 4 days at 37°C and for 14 days at 25°C and 4°C. Cefazolin alone was stable for 24 hours at 37°C, 7 days at 25°C, and 14 days at 4°C. Ceftazidime alone was stable for only 6 hours at 37°C, 2 days at 25°C, and 14 days at 4°C. The cefazolin and ceftazidime combination was stable for 24 hours at 37°C, 2 days at 25°C, and 14 days at 4°C. The cefazolin and gentamicin combination was stable for 1 day at 37°C, 4 days at 25°C, and 14 days at 4°C. ♦ Antibiotics premixed in icodextrin PD-bags have varying stabilities with stability generally least at 37°C and best at 4(o)C, permitting storage for 14 days when refrigerated and prewarming to body temperature prior to administration. Further research confirming the sterility of

  17. Activity, toxicity and analysis of resistance of essential oil from Chenopodium ambrosioides after intraperitoneal, oral and intralesional administration in BALB/c mice infected with Leishmania amazonensis: a preliminary study.

    Science.gov (United States)

    Monzote, Lianet; Montalvo, Ana M; Scull, Ramón; Miranda, Migdalia; Abreu, Juan

    2007-01-01

    The World Health Organization has classified the leishmaniasis as a major tropical disease. Current therapy is toxic, expensive and cause several adverse effects. The majority of people in endemic areas of leishmaniasis depend of natural and traditional medicine. This study was developed to examine the activity of the essential oil from Chenopodium ambrosioides in BALB/c mice infected with Leishmania amazonensis. The infected animals received two cycle of treatment by different routes (intraperitoneal, oral or intralesional route). The intraperitoneal administration of the essential oil at dose of 30 mg/Kg prevented lesion development and decrease the parasite burden. Oral administration retarded the infection in the experimental model compared with untreated mice, although it was less effective that the intraperitoneal route. The administration by intralesional route did not show activity. Intraperitoneal and oral treatment at 30 mg/Kg with the essential oil had better antileishmanial effect that treatment with the reference drug, amphotericin B at 1 mg/Kg. Preliminarily, we examined the toxicity and the resistance after treatment. Signs of toxicity were evident only in the animals treated by intraperitoneal route. No resistance was detected in L. amazonensis isolates obtained from treated mice. These data clearly demonstrated that this natural product could be an alternative for the development of a new drug against cutaneous leishmaniasis based in the ethnomedical information.

  18. Preformulation and characterization of a lidocaine hydrochloride and dexamethasone sodium phosphate thermo-reversible and bioadhesive long-acting gel for intraperitoneal administration.

    Science.gov (United States)

    Arbelaez-Camargo, Diana; Suñé-Negre, Josep Maria; Roig-Carreras, Manel; García-Montoya, Encarna; Pérez-Lozano, Pilar; Miñarro-Carmona, Montserrat; Ticó-Grau, Josep Ramon

    2016-02-10

    The search for new formulations of anaesthetic agents that allow a localized administration and provide a prolonged effect is of great interest in the multimodal management of postoperative pain. The pre-formulation and characterization of a lidocaine and dexamethasone thermosensitive and bioadhesive long-acting gel for intraperitoneal administration was done as a tool in the management of pain in abdominal surgeries. The pre-formulation process was conducted by a systematic variation of the concentration of the different polymers, until setting it, in a suitable concentration that allowed an adequate gelation temperature. The poloxamer 407 (P407) was used as the main polymer; hydroxypropyl methylcellulose (HPMC) as the bioadhesive agent and polyvinyl pyrrolidone (PVP) to adjust the gelation temperature and physicochemical properties. The formulations were characterized by gelation temperature, pH, viscosity at 25°C and 37°C, gelation time, density and osmolality. Gelation temperature was decreased when increasing the concentration of hydroxypropyl methylcellulose and poloxamer 407, this effect was also observed when adding lidocaine hydrochloride and dexamethasone sodium phosphate to the formulations. The gelation temperature did not have statistically significant relation with the PVP concentration (P-value of 0.6797), even though, there is a tendency in the gelation temperature by varying it. Between the developed formulations, the 12.5/3.3/0.4% (P407/HPMC/PVP) formulation presents an appropriate gelation temperature, a suitable viscosity for administration by syringe, an adequate and stable pH and osmolality to prevent tissue damage and a correct gelation time that allowed the formation of a prolonged release implant. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. May intraperitoneal irrigation with Betadine improve cesarean delivery outcomes? Results of a 6 years' single centre experience.

    Science.gov (United States)

    Marino, Riccardo; Capriglione, Stella; Morosetti, Giulia; Di Angelo Antonio, Silvia; Miranda, Andrea; Pazzola, Marta; Lopez, Salvatore; Patrizi, Lodovico; Angioli, Roberto; Stella, Paolo

    2018-03-01

    Cesarean presents increased risk of adverse outcomes, such as endometritis, bacteremia, peritonitis, and maternal fever. This retrospective study aims to evaluate, for the first time in Literature, the effects Betadine washing versus normal saline washing after uterine closure in women undergoing cesarean delivery (CD) at ≥36 gestational weeks. Of the 2080 patients identified retrospectively for the analysis at Department of Obstetrics and Gynecology of San Camillo Hospital of Rome, 1042 were assigned to "Betadine group" and 1038 to "No Betadine group". There were no differences noted for maternal and obstetric characteristics. The outcomes of the present study were to evaluate the incidence of postoperative infections or fever; the reduction of blood white cells among preoperative and postoperative exams; mean and median time of intestinal recanalization, of postoperative ambulation and of 24-h post-CD pain, evaluated using VAS scale. Betadine group patients reported a statistically significant lower white cells increment, a lower mean time to ambulation and intestinal recanalization after CD and a lower 24-h post-CD pain and infections. Betadine intraperitoneal irrigation during CD seems to improve postoperative CD outcomes and patients' quality of life.

  20. Toxicity evaluation of methoxy poly(ethylene oxide)-block-poly(ε-caprolactone) polymeric micelles following multiple oral and intraperitoneal administration to rats.

    Science.gov (United States)

    Binkhathlan, Ziyad; Qamar, Wajhul; Ali, Raisuddin; Kfoury, Hala; Alghonaim, Mohammed

    2017-09-01

    Methoxy poly(ethylene oxide)- block -poly(ɛ-caprolactone) (PEO- b -PCL) copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO- b -PCL block copolymers and assess the toxic effects of drug-free PEO- b -PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip) administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO- b -PCL micelles, sixty animals were divided into two major groups: The first group received PEO- b -PCL micelles (100 mg/kg) by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen) were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  1. Toxicity evaluation of methoxy poly(ethylene oxide-block-poly(ε-caprolactone polymeric micelles following multiple oral and intraperitoneal administration to rats

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

    Full Text Available Methoxy poly(ethylene oxide-block-poly(ɛ-caprolactone (PEO-b-PCL copolymers are amphiphilic and biodegradable copolymers designed to deliver a variety of drugs and diagnostic agents. The aim of this study was to synthesize PEO-b-PCL block copolymers and assess the toxic effects of drug-free PEO-b-PCL micelles after multiple-dose administrations via oral or intraperitoneal (ip administration in rats. Assembly of block copolymers was achieved by co-solvent evaporation method. To investigate the toxicity profile of PEO-b-PCL micelles, sixty animals were divided into two major groups: The first group received PEO-b-PCL micelles (100 mg/kg by oral gavage daily for seven days, while the other group received the same dose of micelles by ip injections daily for seven days. Twenty-four hours following the last dose, half of the animals from each group were sacrificed and blood and organs (lung, liver, kidneys, heart and spleen were collected. Remaining animals were observed for further 14 days and was sacrificed at the end of the third week, and blood and organs were collected. None of the polymeric micelles administered caused any significant effects on relative organ weight, animal body weight, leucocytes count, % lymphocytes, liver and kidney toxicity markers and organs histology. Although the dose of copolymers used in this study is much higher than those used for drug delivery, it did not cause any significant toxic effects in rats. Histological examination of all the organs confirmed the nontoxic nature of the micelles.

  2. Clinical features of pulmonary emboli in patients following cytoreductive surgery (peritonectomy) and hyperthermic intraperitoneal chemotherapy (hipec), a single centre experience.

    Science.gov (United States)

    Vukadinovic, V; Chiou, J D; Morris, D L

    2015-05-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) can be complicated by pulmonary emboli (PE). Patients are at high risk due to surgery, underlying malignancy, immobility and indwelling lines. This paper aims to identify clinically significant signs and symptoms preceding acute PE in post CRS-HIPEC patients, assess the PE investigative approach in this population and the significance of PE on patient management. 25 cases with a positive and 50 controls with a negative CTPA for PE were isolated from the peritonectomy database at St George Hospital Sydney, January 2006 to July 2013. Vital signs, patient symptoms, adjunct investigation findings and patient outcomes were collected and graphed in Microsoft Excel. P values and 95% confidence intervals were calculated using GraphPad Prism version 6. 25 of 562 (4.4%) CRS-HIPEC patients were diagnosed with acute PE. Raised body temperature was the only statistically significant clinical finding that differentiated cases from controls (p value 0.02). Arterial blood gas results did not correlate with PE (p values 0.62; 0.29; 0.55, 0.84). Troponin, ECG and CXR were not routinely conducted. CXR and CTPA findings were similar between cases and controls (Table 4). PE patients required lower supplementary oxygen and escalation of care. Body temperature is the only statistically significant clinical finding observed with PE. We recommend a standardised investigative approach consisting of troponin, ECG and CXR. PE in CRS-HIPEC does not cause significant cardio-respiratory dysfunction, or escalation of care. PE rates are higher than other major surgeries, thus we propose a trial with increased chemical prophylaxis in CRS-HIPEC patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Particulate 1,3-beta-D-Glucan, Carboxymethylglucan and Sulfoethylglucan-Influence of Their Oral or Intraperitoneal Administration on Immunological Respondence of Mice

    Czech Academy of Sciences Publication Activity Database

    Mucksová, J.; Babíček, K.; Pospíšil, Miloslav

    2001-01-01

    Roč. 46, č. 6 (2001), s. 559-563 ISSN 0015-5632 Institutional research plan: CEZ:AV0Z5020903 Keywords : influence * intraperitoneal * immunological Subject RIV: EE - Microbiology, Virology Impact factor: 0.776, year: 2001

  4. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

    OpenAIRE

    Ke Yang; Shi-Wei Chen; Xin-Yan Dou; Zhi-Rui Zhang; Xin Jin; Hong-Min Zhang

    2018-01-01

    AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total). The c...

  5. A single intraperitoneal injection of bovine fetuin-A attenuates bone resorption in a murine calvarial model of particle-induced osteolysis.

    Science.gov (United States)

    Jablonski, Heidrun; Polan, Christina; Wedemeyer, Christian; Hilken, Gero; Schlepper, Rüdiger; Bachmann, Hagen Sjard; Grabellus, Florian; Dudda, Marcel; Jäger, Marcus; Kauther, Max Daniel

    2017-12-01

    Particle-induced osteolysis, which by definition is an aseptic inflammatory reaction to implant-derived wear debris eventually leading to local bone destruction, remains the major reason for long-term failure of orthopedic endoprostheses. Fetuin-A, a 66kDa glycoprotein with diverse functions, is found to be enriched in bone. Besides being an important inhibitor of ectopic calcification, it has been described to influence the production of mediators of inflammation. Furthermore, a regulatory role in bone metabolism has been assigned. In the present study, the influence of a single dose of bovine fetuin-A, intraperitoneally injected in mice subjected to particle-induced osteolysis of the calvaria, was analyzed. Twenty-eight male C57BL/6 mice, twelve weeks of age, were randomly divided into four groups. Groups 2 and 4 were subjected to ultra-high molecular weight polyethylene (UHMWPE) particles placed on their calvariae while groups 1 and 3 were sham-operated. Furthermore, groups 3 and 4 received a single intraperitoneal injection of 20mg bovine fetuin-A while groups 1 and 2 were treated with physiologic saline. After 14days calvarial bone was qualitatively and quantitatively assessed using microcomputed tomography (μCT) and histomorphometrical approaches. Application of fetuin-A led to a reduction of particle-induced osteolysis in terms of visible osteolytic lesions and eroded bone surface. The reduction of bone thickness and bone volume, as elicited by UHMWPE, was alleviated by fetuin-A. In conclusion, fetuin-A was found to exert an anti-resorptive effect on particle-induced osteolysis in-vivo. Thus, fetuin-A could play a potentially osteoprotective role in the treatment of bone metabolic disorders. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    M Boering

    2016-06-01

    Full Text Available Aims Elevated sex hormone-binding globulin (SHBG concentrations have been described in patients with type 1 diabetes mellitus (T1DM, probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII, or subcutaneous (SC, influences SHBG concentrations among T1DM patients. Methods Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13 years, diabetes duration 23 (±11 years, and hemoglobin A1c (HbA1c 8.7 (±1.1 (72 (±12 mmol/mol. As secondary outcomes, testosterone, 17-β-estradiol, luteinizing hormone (LH, and follicle-stimulating hormone (FSH were analyzed. Results Estimated mean change in SHBG was −10.3nmol/L (95% CI: −17.4, −3.2 during CIPII and 3.7nmol/L (95% CI: −12.0, 4.6 during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was −6.6nmol/L (95% CI: −17.5, 4.3; −12.7nmol/L (95% CI: −25.1, −0.4 for males and −1.7nmol/L (95% CI: −24.6, 21.1 for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; −15.8nmol/L (95% CI: −24.2, −7.5 and −8.3nmol/L (95% CI: −14.4, −2.2, respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2 among males. Conclusions SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

  7. A single intraperitoneal injection of endotoxin in rats induces long-lasting modifications in behavior and brain protein levels of TNF-α and IL-18

    Directory of Open Access Journals (Sweden)

    Bossù Paola

    2012-05-01

    Full Text Available Abstract Background Systemic inflammation might cause neuronal damage and sustain neurodegenerative diseases and behavior impairment, with the participation of pro-inflammatory cytokines, like tumor necrosis factor (TNF-α and interleukin (IL-18. However, the potential contribution of these cytokines to behavioral impairment in the long-term period has not been fully investigated. Methods Wistar rats were treated with a single intraperitoneal injection of LPS (5 mg/kg or vehicle. After 7 days and 10 months, the animal behavior was evaluated by testing specific cognitive functions, as mnesic, discriminative, and attentional functions, as well as anxiety levels. Contextually, TNF-α and IL-18 protein levels were measured by ELISA in defined brain regions (that is, frontal cortex, hippocampus, striatum, cerebellum, and hypothalamus. Results Behavioral testing demonstrated a specific and persistent cognitive impairment characterized by marked deficits in reacting to environment modifications, possibly linked to reduced motivational or attentional deficits. Concomitantly, LPS induced a TNF-α increase in the hippocampus and frontal cortex (from 7 days onward and cerebellum (only at 10 months. Interestingly, LPS treatment enhanced IL-18 expression in these same areas only at 10 months after injection. Conclusions Overall, these results indicate that the chronic neuroinflammatory network elicited by systemic inflammation involves a persistent participation of TNF-α accompanied by a differently regulated contribution of IL-18. This leads to speculation that, though with still unclear mechanisms, both cytokines might take part in long-lasting modifications of brain functions, including behavioral alteration.

  8. Corneal pharmacokinetics of the 2% diacerein eye drops between multiple administration and single administration

    Directory of Open Access Journals (Sweden)

    Ke Yang

    2018-04-01

    Full Text Available AIM: To compare the pharmacokinetic differences of the 2% diacerein eye drops between conjunctival sac multiple administration and single administration in the cornea, and to provide the experimental basis for clinicians to use the conjunctival sac multiple administration.METHODS: Male Kunming mice were randomly divided into the multiple administration group and the single administration group. The multiple administration group were given diacerein eye drop every 2min(3 times in total. The concentrations of the metabolites of diacerein in the cornea were measured by high performance liquid chromatography after given eye drop 5, 15, 30, 60, 120, and 180min. The pharmacokinetic parameters were calculated by pharmacokinetic software(DAS2.1.1. RESULTS: The metabolites of diacerein, rhein, was detected in the cornea at each time point. The concentration of the metabolite of diacerein in the cornea was 318.678±40.88, 210.02±25.66, 188.83±31.74, 112.24±11.70, 90.28±22.01 and 57.67±13.71μg/g after given eye drop 5, 15, 30, 60, 120, and 180min in the multiple administration group. The concentration in the single administration group was 145.17±19.29, 97.95±10.49, 71.18±18.70, 39.11±2.44, 18.10±2.34 and 9.08±2.04μg/g respectively. The concentration of rhein in the cornea was the highest at 5min after the administration in the two groups. The concentration of the multiple administration group was higher than that in the single administration group at 5, 15, 30, 60, 120, and 180min(PCONCLUSION: Compared with the single administration, the conjunctival sac multiple administration has the advantages of high drug concentration and long duration. Therefor the conjunctival sac multiple administration is a more effective method to treat acute infectious corneal diseases.

  9. Structural Changes of the Testis and Changes in Semen Quality Parameters Caused by Intraperitoneal and Peroral Administration of Selenium in Rats

    Directory of Open Access Journals (Sweden)

    Michal Cabaj

    2012-05-01

    Full Text Available The aim of this study was to find the structural changes in the testis and semen quality parameters of rat after a singleintraperitoneal and repeated peroral selenium administration. Rats were killed 36 hours following the intraperitonealadministration of selenium selenite (2 mg.kg-1 b.w.; 98% purity and after 90 days of the peroral repeatedadministration of selenium in drinking water (5 mg.l-1. Testis samples were evaluated by histological andmorphometrical methods in light microscopy. Evaluation of semen samples were examined with CASA method. 36hours after the selenium i.p. administration, damage of cellular associations, release of necrotised epithelial cells totubule lumen and fibrotisation and extension of interstitium were observed. Morphometry methods have shown thereduction of seminiferous epithelium volume (P<0.001, extension of interstitium (P<0.001 and increased area ofintraepithelial spaces (P<0.01. In p.o. group similar but more intense changes were noted; in addition, occasionalldegeneration of seminiferous tubuli and rarely total damage in histoarchitecture of seminiferous epithelium wereobserved. CASA analysis revealed significant decrease in all parameters except the concentration of spermatozoa.Additionally, we suppose that p.o. dose 5 mg.l-1 sodium selenite in drinking water is minimum lethal dose level foryoung rats. Selenium after i.p. and p.o. administration causes damage of seminiferous epithelium and interstitium. Itleads to changes in relative proportion of functional tissues of the testis. Reduced spermatogenesis and harmfuleffects in semen parameters are characteristic especially for peroral repeated (subchronic administration. Thesechanges are time- and dose-dependent. In both dosage methods subfertility or infertility can appear.

  10. Effect of Intraperitoneal Administration of Hydroalcoholic and Hexanic Extract of Heated Female Cannabis Sativa Flowertops on Anxiety Behavior, Motor Coordination and Locomotor Activity in the Male Rats

    Directory of Open Access Journals (Sweden)

    B Farhadi Moghadam

    2016-01-01

    Full Text Available Introduction: Decarboxylated phytocannabinoids activates CB1 receptors of endocannabinoid system in the central nervous system. Endocannabinoid system interacts with dopaminergic and serotoninergic systems, which seems to be effective on the behavior processes. Therefore, this study aimed to investigate the effect of hydroalcoholic and hexanic extract of heated female Cannabis sativa flowertops containing decarboxylated cannabinoids on anxiety, motor coordination and locomotor activity. Methods: In this experimental study, adult male Wistar rats were randomly (200 to 250 g used in two groups(n=7 of control and sham (administration of the solution vehicle (Tween 80, ethanol and saline with 1:1:8 proportions. IP administration of hydroalcoholic extract (50mg/kg dosage, and hexanic extract (50mg/kg dosage were applied. The elevated plus maze, open field and rotarod apparatus were used in order to measure the anxiety, locomotor activity and motor coordination in each group, respectively. Moreover, the data analysis was carried out by one-way ANOVA and Neumann-keuls post-hoc test. Results: The study results indicated that IP administration of hexanic extract (50mg/kg dosage significantly reduced the numbers of entries into the open arms (P<0.05 as well as time of stay in the open arms (P<0.01 in evaluated plus maze. Furthermore, motor activity (P <0.01 and time coordination (P <0.001 were reported to significantly reduce. Conclusion: The study findings revealed thst administration of hexanic extract has probably more decarboxylated cannabinoids than hydroalcoholic extract resulting in a decrease in the motor activity and time of motor coordination, yet an increase in anxiety via activation of CB1 receptors.

  11. Rhabdomyolysis associated with single-dose intravenous esomeprazole administration

    Science.gov (United States)

    Jeon, Dae-Hong; Kim, Yire; Kim, Min Jeong; Cho, Hyun Seop; Bae, Eun Jin; Chang, Se-Ho; Park, Dong Jun

    2016-01-01

    Abstract Background: Proton pump inhibitors are usually safe, although serious adverse effects can occur. We report the first case of rhabdomyolysis associated with single-dose intravenous esomeprozole administration. Methods: A 45-year-old Korean male visited our emergency room because of persistent lower chest discomfort that started 10 hours before. He had been diagnosed with diabetes and coronary heart disease, but discontinued oral hypoglycemic agents 1 month earlier. He continued to take medications for coronary heart disease. There was no abnormality on an electrocardiogram or in cardiac enzymes. Initial laboratory findings did not show abnormalities for muscle enzymes. Esomeprozole 40 mg was administrated intravenously for the control of his ambiguous chest discomfort. Then, 12 hours later, he complained of abrupt severe right buttock pain. An area of tender muscle swelling 8 cm in diameter was seen on his right buttock area. Creatine kinase and lactate dehydrogenase were elevated to 40,538 and 1326 U/L, respectively. A bone scan using 20 mCi of 99mTc-hydroxymethylene diphosphonate was compatible with rhabdomyolysis. Results: His muscular symptoms, signs, and laboratory findings improved markedly with conservative management, including hydration and urine alkalinization. He is being followed in the outpatient department with no evidence of recurrence. Conclusion: We should keep in mind that single-dose intravenous administration of esomeprazole can induce rhabdomyolysis. PMID:27442680

  12. Systemic Toxicity of Intraperitoneal Vancomycin

    OpenAIRE

    Kumar, Teerath; Teo, Iris; McCormick, Brendan B.

    2016-01-01

    Intraperitoneal vancomycin is used for empiric treatment of peritoneal dialysis peritonitis. It is dosed intermittently and a high systemic concentration is often achieved. Despite this, there are very few reports of systemic toxicity from intraperitoneal vancomycin. We report the course of a patient who developed a drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome after three weeks of intraperitoneal vancomycin. We review the literature and conclude that this is the firs...

  13. Intraperitoneal administration of a tumor-associated antigen SART3, CD40L, and GM-CSF gene-loaded polyplex micelle elicits a vaccine effect in mouse tumor models.

    Directory of Open Access Journals (Sweden)

    Kouichi Furugaki

    Full Text Available Polyplex micelles have demonstrated biocompatibility and achieve efficient gene transfection in vivo. Here, we investigated a polyplex micelle encapsulating genes encoding the tumor-associated antigen squamous cell carcinoma antigen recognized by T cells-3 (SART3, adjuvant CD40L, and granulocyte macrophage colony-stimulating factor (GM-CSF as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC. Intraperitoneally administrated polyplex micelles were predominantly found in the lymph nodes, spleen, and liver. Compared with mock controls, the triple gene vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer cells, of which long-term surviving mice showed complete rejection when re-challenged with CT26 tumors. Moreover, the DNA vaccine inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung tumors in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+ DCs and CD4+/CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ T cells by neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. In conclusion, a SART3/CD40L+GM-CSF gene-loaded polyplex micelle can be applied as a novel vaccine platform to elicit tumor rejection immunity regardless of the recipient MHC haplotype.

  14. Restless Legs Syndrome After Single Low Dose Quetiapine Administration.

    Science.gov (United States)

    Soyata, Ahmet Z; Celebi, Fahri; Yargc, Lutfi I

    2016-01-01

    Restless legs syndrome is an underdiagnosed sensori-motor disorder and psychotropic drugs are one of the main secondary causes of the illness. The most common psychotropic agents that cause restless legs syndrome are antidepressants; however, antipsychotics have also been reported to induce restless legs syndrome. The prevalence, vulnerability factors and the underlying mechanism of antipsychotic-induced restless legs syndrome are unclear. A possible explanation is that dopaminergic blockade is the main precipitator of the syndrome. Quetiapine-induced restless legs syndrome is another point of interest because of its low binding to D2 receptors. We herein report the case of a restless legs syndrome that emerged after a single low dose quetiapine administration.

  15. Sick Sinus Syndrome After a Single Oral Administration of Garenoxacin

    Directory of Open Access Journals (Sweden)

    Chiyo Sugiyama, MD

    2010-01-01

    Full Text Available This report presents the case of a 60-year-old female who demonstrated sick sinus syndrome after a single administration of Garenoxacin (GRNX. She was administered GRNX for an upper respiratory infection and 10 minutes thereafter, she suddenly felt palpitation and numbness of both arms. She was transferred to the hospital 2 hours after taking GRNX. An electrocardiogram showed bradycardia with junctional escape beats and the longest sinus arrest was 4 seconds. She was treated with a temporary pacemaker and 21 hours after the administration of GRNX her sinus node function was observed to have completely improved. GRNX-induced sick sinus syndrome was suspected because her clinical course was compatible with the concentration of GRNX and her other cardiological assessments, including an electrophysiologic study (EPS which were conducted on the 9th day of the admission, were normal. GRNX has less effect on the QT interval than other quinolone agents. However, physicians should be aware of the risk of sick sinus syndrome because GRNX is frequently prescribed in outpatient clinics.

  16. Administração intraperitoneal da mistura com excesso enantiomérico de 50% de bupivacaína (S75-R25 para analgesia pós-operatória em colecistectomias videolaparoscópicas Administración intraperitoneal de la mezcla con exceso enantiomérico de 50% de bupivacaína (S75-R25 para analgesia postoperatoria en colecistectomías videolaparoscópicas Intraperitoneal administration of 50% enantiomeric excess (S75-R25 bupivacaine in postoperative analgesia of laparoscopic cholecystectomy

    Directory of Open Access Journals (Sweden)

    João Batista Santos Garcia

    2007-08-01

    40 pacientes sometidos a colecistectomía videolaparoscópica divididos en dos grupos: GI (n = 20 que recibió 80 mL de solución de bupivacaína S75-R25 a 0,125% intraperitoneal al final de la operación; y GII (n = 20 que recibió 80 mL de solución fisiológica a 0,9%. Los dos grupos recibieron 40 mg de tenoxican y 30 mg.kg-1 de dipirona, por vía venosa, poco antes del final de la operación. La analgesia en el postoperatorio (PO se hizo con tramadol. Se evaluaron las puntuaciones de dolor en reposo, al sentarse y en la maniobra de Valsalva, según la escala numérica al despertar y 2, 4, 8, 12 y 24 horas en el PO; la presencia de dolor en el hombro; el tiempo para la primera solicitación del analgésico y su consumo acumulativo. RESULTADOS: Hubo una diferencia estadística significativa entre los puntajes de dolor a las 12 horas en el PO con el paciente en reposo (GI BACKGROUND AND OBJECTIVES: The analgesic effect of intraperitoneal administration of local anesthetics after laparoscopic cholecystectomy is a controversial issue, and the results described vary from considerable pain relief to little reduction in pain. The objective of this study was to evaluate the efficacy of the intraperitoneal administration of 50% enantiomeric excess bupivacaine (S75-R25 for the postoperative pain relief of laparoscopic cholecystectomy. METHODS: A randomized, double blind, placebo controlled study was conducted with 40 patients undergoing laparoscopic cholecystectomy, who were divided in two groups: GI (n = 20 received 80 mL of intraperitoneal 0,125% S75-R25 bupivacaine at the end of the procedure; and GII (n = 20 received 80 mL of intraperitoneal normal saline. Both groups received 40 mg of tenoxicam and 30 mg.kg-1 of intravenous dypirone shortly before the end of the surgery. Tramadol was used for postoperative analgesia (PO. Pain scores were evaluated at rest, sitting up, and during the Valsalva maneuver, according to a numeric scale upon waking up and 2, 4, 8, 12, and 24

  17. A suicide involving intraperitoneal injection of pentobarbital.

    Science.gov (United States)

    Hangartner, Sarah; Steiner, Jasmin; Dussy, Franz; Moeckli, Regula; Gerlach, Kathrin; Briellmann, Thomas

    2016-09-01

    We present an unusual case of suicide by intraperitoneal injection of pentobarbital, an overdose of zolpidem and the intake of diazepam, ethanol and other psychoactive substances. The autopsy and specimen collection were conducted in a 10 to 18 h postmortem interval. The toxicological analysis revealed a significantly higher pentobarbital concentration in femoral blood compared to cardiac blood (36 vs. 15 mg/L). On the contrary, zolpidem and diazepam concentrations in cardiac blood (2700 and 590 µg/L) were found to be significantly higher than in femoral blood (1500 and 230 µg/L). These findings point to a postmortem redistribution with a distinct gradient from areas of high drug concentrations in the gastrointestinal tract (zolpidem and diazepam) and the injection site (pentobarbital) to peripheral tissue. Ethanol concentration was 0.95 ‰ which amplified the CNS depression. The choice of this unusual suicide method was associated with the deceased's former job as a veterinarian's assistant. In veterinary medicine, the intraperitoneal injection of a lethal dose of pentobarbital is quite commonly performed to euthanise small animals. Intraperitoneal injection is rare as route of administration in humans.

  18. Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism

    DEFF Research Database (Denmark)

    Joffe, P; Ladefoged, S D; Cintin, C

    1994-01-01

    ,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS......: Following oral administration of 1 alpha-OHD3, a decrease in serum alkaline phosphatase was seen when levels at 1 and 6 h were compared to baseline (P trend in serum Ca2+ throughout the study (P

  19. Plasma concentrations of clonazepam after single rectal administration.

    Science.gov (United States)

    Rylance, G W; Poulton, J; Cherry, R C; Cullen, R E

    1986-01-01

    Clonazepam was administered rectally to six children aged 1.4 to 4.7 years in a dose of 0.05 mg/kg and to five children aged 1.4 to 4.1 years in a dose of 0.1 mg/kg. Plasma concentrations indicate that it is rapidly absorbed, and it may therefore be an alternative to rectal administration of diazepam in continuing convulsions. PMID:3954443

  20. Intraperitoneal explosion following gastric perforation

    OpenAIRE

    K. Mansfield, Scott; Roderick Borrowdale, Roderick Borrowdale

    2017-01-01

    The object of this study is to report a rare case of explosion during laparotomy where diathermy ignited intraperitoneal gas from a spontaneous stomach perforation. Fortunately, the patient survived but the surgeon experienced a finger burn. A literature review demonstrates other examples of intraoperative explosion where gastrointestinal gases were the fuel source. Lessons learned from these cases provide recommendations to prevent this potentially lethal event from occurring.

  1. Intraperitoneal explosion following gastric perforation.

    Science.gov (United States)

    Mansfield, Scott K; Borrowdale, Roderick

    2014-04-01

    The object of this study is to report a rare case of explosion during laparotomy where diathermy ignited intraperitoneal gas from a spontaneous stomach perforation. Fortunately, the patient survived but the surgeon experienced a finger burn. A literature review demonstrates other examples of intraoperative explosion where gastrointestinal gases were the fuel source. Lessons learned from these cases provide recommendations to prevent this potentially lethal event from occurring. Copyright © 2012. Published by Elsevier B.V.

  2. Intraperitoneal explosion following gastric perforation

    Directory of Open Access Journals (Sweden)

    Scott K. Mansfield

    2014-04-01

    Full Text Available The object of this study is to report a rare case of explosion during laparotomy where diathermy ignited intraperitoneal gas from a spontaneous stomach perforation. Fortunately, the patient survived but the surgeon experienced a finger burn. A literature review demonstrates other examples of intraoperative explosion where gastrointestinal gases were the fuel source. Lessons learned from these cases provide recommendations to prevent this potentially lethal event from occurring.

  3. Intraperitoneal pressure in peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Vicente Pérez Díaz

    2017-11-01

    Full Text Available The measure of intraperitoneal pressure in peritoneal dialysis is easy and provides clear therapeutic benefits. However it is measured only rarely in adult peritoneal dialysis units. This review aims to disseminate the usefulness of measuring intraperitoneal pressure. This measurement is performed in supine before initiating the drain of a manual exchange with “Y” system, by raising the drain bag and measuring from the mid-axillary line the height of the liquid column that rises from the patient. With typical values of 10–16 cm H2O, intraperitoneal pressure should never exceed 18 cm H2O. With basal values that depend on body mass index, it increases 1–3 cm H2O/L of intraperitoneal volume, and varies with posture and physical activity. Its increase causes discomfort, sleep and breathing disturbances, and has been linked to the occurrence of leaks, hernias, hydrothorax, gastro-esophageal reflux and enteric peritonitis. Less known and valued is its ability to decrease the effectiveness of dialysis significantly counteracting ultrafiltration and decreasing solute clearance to a smaller degree. Because of its easy measurement and potential utility, should be monitored in case of ultrafiltration failure to rule out its eventual contribution in some patients. Although not yet mentioned in the clinical practice guidelines for PD, its clear benefits justify its inclusion among the periodic measurements to consider for prescribing and monitoring peritoneal dialysis. Resumen: La medida de la presión intraperitoneal en diálisis peritoneal es muy sencilla y aporta claros beneficios terapéuticos. Sin embargo, su monitorización todavía no se ha generalizado en las unidades de diálisis peritoneal de adultos. Esta revisión pretende divulgar su conocimiento y la utilidad de su medida. Se realiza en decúbito antes de iniciar el drenaje de un intercambio manual con bolsa en Y, elevando la bolsa de

  4. Blastomogenic effect of Cs137, Sr90 and Ca45 in single and chronic administration

    International Nuclear Information System (INIS)

    Zapol'skaya, N.A.; Fedorova, A.V.; Borisova, V.V.

    1978-01-01

    The blastomogenic actions of 137 Cs, 90 Sr, and 45 Ca were considered in experiments on white rats, and it was found that the site and type of tumor were determined by the organotropism of the radionuclide. With chronic administration of radionuclides, the tumor rate was low as compared to single-occasion administration

  5. Pharmacokinetics of diclofenac in pigs after intramuscular administration of a single dose

    OpenAIRE

    Pejčić Zorica; Pokrajac Milena; Jezdimirović Milanka

    2006-01-01

    The pharmacokinetics of diclofenac was studied in 10 clinically normal male Yorkshire pigs, following intramuscular (i.m) administration of a single dose of diclofenac-sodium (2.5 mg/kg body weight). Diclofenac serum concentrations were determined by high pressure- liquid-chromatography (HPLC), with UV detection (226 nm). Following i.m. administration all individual diclofenac serum levels best fitted the one-compartment open model for extravascular administration. The maximal diclofenac seru...

  6. Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei.

    Science.gov (United States)

    Horvath, Philipp; Beckert, Stefan; Struller, Florian; Königsrainer, Alfred; Königsrainer, Ingmar

    2016-08-06

    To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy (HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared. Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort (n = 32) received Mitomycin C (MMC)-based HIPEC intraperitoneally (35 mg/m² for 90 min) and the second cohort (n = 10) received a bi-directional therapy consisting of oxaliplatin (OX) (300 mg/m(2) for 30 min) intraperitoneally and 5-fluorouracil (5-FU) 400 mg/m² plus folinic acid 20 mg/m² intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC (completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery (CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group (10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients (33%) required medical treatment. Patients affected by leukopenia were predominantly female (7/10 patients) and older than 50 years (8/10 patients). The length of hospital stay tended to be higher in the MMC-group without reaching statistical significance (22.5 ± 11 vs 16.5 ± 3.5 d). Length of operation (08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger post-HIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMC-based HIPEC protocols primarily

  7. Biodistribution of Intraperitoneally-administered {sup 125}I-labeled IgG in Mouse

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sooyong; Dho, So Hee; Cho, Eunha; Lee, Soyoung; Jung, Sunghee; Lim, Jaecheong [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-10-15

    The use of radiolabeled antibodies is one of the most effective strategies to diagnose and treat cancers. However, it is hindered by the relatively low delivery to tumors following intravenous administration, in particular, cancers in peritoneal cavity. Intraperitoneal administration of radiolabeled antibodies results in significantly higher exposure to the peritoneal cavity than does intravenous administration. Therefore, intraperitoneal administration of the radiolabeled antibodies can be more effective to diagnose and treat cancers in peritoneal cavity such as ovarian and colonic cancers. This study was performed to determine the biodistribution pattern of intraperitoneally-administered radiolabeled antibodies. The {sup 125}I-labeled IgG was rapidly absorbed into the blood and organs, and the radioactivities were dropped in 24 hr p.i. These results suggest that the intraperitoneal administration of the radiolabeled antibodies can be an effective way to treat diseases in the peritoneal cavity.

  8. Pharmacokinetic study of single and multiple oral administrations of 2 mg dienogest in healthy Korean women.

    Science.gov (United States)

    Shin, Donghoon; Lee, SeungHwan; Lim, Kyoung Soo; Park, Joong Shin; Shin, Sang-Goo; Jang, In-Jin; Yu, Kyung-Sang

    2013-06-01

    The progestin dienogest was developed for oral contraception, endometriosis treatment and menopause management. Dienogest's pharmacokinetics have been primarily studied in Caucasian women. This study evaluated the single- and multiple-dose pharmacokinetics of dienogest in Korean women. Sixteen healthy Korean adult women received a single administration of 2 mg dienogest, followed by multiple once-daily administrations for 14 days. The single-dose administration and the final dose of the multiple administrations were each followed by blood sampling over 60 h. The mean (SD) maximum serum concentration after multiple doses of dienogest was slightly increased compared with that after a single dose [from 51.6 (9.6) to 56.6 (11.9) ng/mL], as was the area under the concentration-time curves (AUC)0-24h [from 503 (56.3) to 613 (90.7) ng ∙ h/mL]. The linearity factor calculated by AUCs of single and multiple doses is 1.00 ± 0.14, and the terminal half-life remained unchanged when single dosing and multiple dosing were compared. The present study described the single- and multiple-dose pharmacokinetic profiles of dienogest in Korean women and showed linear pharmacokinetics of dienogest at steady state. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration.

    Science.gov (United States)

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer K A; Nuernberger, Martin C

    2014-03-07

    Fluralaner is a novel systemic insecticide and acaricide. The purpose of these studies was to investigate the pharmacokinetic properties of fluralaner in Beagle dogs following single oral or intravenous (i.v.) administration. Following the oral administration of 12.5, 25 or 50 mg fluralaner/kg body weight (BW), formulated as chewable tablets or i.v. administration of 12.5 mg fluralaner/kg BW, formulated as i.v. solution to 24 Beagles, plasma samples were collected until 112 days after treatment. Plasma concentrations of fluralaner were measured using HPLC-MS/MS. Pharmacokinetic parameters were calculated by non-compartmental methods. After oral administration, maximum plasma concentrations (C(max)) were reached within 1 day on average. Fluralaner was quantifiable in plasma for up to 112 days after single oral and i.v. treatment. The apparent half-life of fluralaner was 12-15 days and the mean residence time was 15-20 days. The apparent volume of distribution of fluralaner was 3.1 L/kg, and clearance was 0.14 L/kg/day. Fluralaner is readily absorbed after single-dose oral administration, and has a long elimination half-life, long mean residence time, relatively high apparent volume of distribution, and low clearance. These pharmacokinetic characteristics help to explain the prolonged activity of fluralaner against fleas and ticks on dogs after a single oral dose.

  10. Pharmacokinetics of fluralaner in dogs following a single oral or intravenous administration

    OpenAIRE

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer KA; Nuernberger, Martin C

    2014-01-01

    Background Fluralaner is a novel systemic insecticide and acaricide. The purpose of these studies was to investigate the pharmacokinetic properties of fluralaner in Beagle dogs following single oral or intravenous (i.v.) administration. Methods Following the oral administration of 12.5, 25 or 50 mg fluralaner/kg body weight (BW), formulated as chewable tablets or i.v. administration of 12.5 mg fluralaner/kg BW, formulated as i.v. solution to 24 Beagles, plasma samples were collected until 112...

  11. [Postoperative intraperitoneal complications in colon cancer surgery].

    Science.gov (United States)

    Erokhina, E A; Topuzov, É G; Topuzov, É É

    2014-01-01

    The authors studied the clinical characteristics and terms of the development of postoperative intraperitoneal complications in patients undergoing colon cancer surgery. It was stated, that the diversity of clinical data depended on complication characteristics. Results of investigation allowed defining of the most dangerous terms of intraperitoneal complications and risk factors.

  12. Acute effect of oral, intraperitoneal, and intravenous 1 alpha-hydroxycholecalciferol on markers of bone metabolism

    DEFF Research Database (Denmark)

    Joffe, P; Ladefoged, S D; Cintin, C

    1994-01-01

    , significant decreases of intact PTH were observed in the oral and i.v. group. No changes in serum phosphate and serum PICP levels were observed over time after oral, i.p., and i.v. delivery of 1 alpha-OHD3. However, serum PIIINP following oral and i.p. administration of 1 alpha-OHD3 decreased at 1 and 6 h (P......,25-(OH)2D3 was measured. DESIGN: Single doses of 1 alpha-OHD3 (80 ng/kg body wt) were given in randomized cross-over fashion, orally, intraperitoneally (i.p.) and intravenously (i.v.) on three occasions. Blood was sampled at 0, 1, 6, 12, and 24 h after administration of 1 alpha-OHD3. MAIN RESULTS...

  13. Changes in growth hormone (GH) messenger RNA (GH mRNA) expression in the rat anterior pituitary after single interferon (IFN) alpha administration

    International Nuclear Information System (INIS)

    Romanowski, W.; Braczkowski, R.; Nowakowska-Zajdel, E.; Muc-Wierzgon, M.; Zubelewicz-Szkodzinska, B.; Kosiewicz, J.; Korzonek, I.

    2006-01-01

    Introduction: Interferon a (IFN-a) is a cytokine with pleiotropic effects which, via different pathways, influences the secretion of certain cytokines and hormones. Growth hormone (GH) secreted from the pituitary has physiological effects on various target tissues. The question is how IFN-a administered in various types of disease influences GH secretion. This study investigated the acute effect of IFN-a on GH mRNA expression in the rat anterior pituitary. Objective: The aim of the study was to measure the cellular expression of GH mRNA by in situ hybridisation in the anterior pituitary after a single administration of IFN-a. Material and methods: Rats were administered an intraperitoneal injection of IFN-a or saline. The rat pituitaries were taken 2 and 4 hours after IFN/saline administration and kept frozen until in situ hybridisation histochemistry. A 31 - base 35S -labelled oligonucleotide probe complementary to part of the exonic mRNA sequence coding for GH mRNA was used. All control and experimental sections were hybridised in the same hybridisation reaction. Results: Acute administration of interferon a increased GH mRNA expression in the anterior pituitary in the 4-hour group in comparison with the control group, and there was no difference between the control group and the 2-hour rats. Conclusion: A single IFN-a administration was found to exert an influence on anterior pituitary GH mRNA expression. These observations may pave the way for presenting a possible new action of IFN-a. (author) GH mRNA, anterior pituitary, interferon

  14. Comparison of Giemsa Staining, Intraperitoneal Injection and Oral

    Directory of Open Access Journals (Sweden)

    Sajad Rashidi

    2014-02-01

    Full Text Available Background: Toxoplasma gondii is one of the most common protozoan parasites in humans and animals in all countries of the world. The aim of this study was to detect Toxoplasma parasite in the brain of wild rats in Tehran using smear preparation, Giemsa staining, Intraperitoneal injection and oral administration to Souri mice. Materials and Methods: Forty rats were collected from different areas of Tehran. Smears were prepared from rat brains on glass slides and stained using Giemsa. In the second method, a cell suspension was prepared from rat brain and was given orally and injected intraperitoneally into Souri mice. In peritoneal method, peritoneum of the mice was examined for parasites. In oral method, the titer of Toxoplasma antibody in sera of Souri mice was determined using Toxoplasma IgG antibody kit and anti-mouse conjugate of Sigma company. Results: All results were negative in Giemsa staining method. In the second method, the results were negative and no parasites were observed in peritoneum of Souri mice. In oral administration method, after ingestion of suspensions by Souri mice and measuring the IgG titer, 50% of them showed a positive titer after one month. Conclusion: In detection of Toxoplasma gondii, the method of smear preparation on glass slides followed by Giemsa staining, and intraperitoneal injection of brain suspensions to Souri mice are of less value in comparison with oral administration of suspensions and determining the titer of IgG in sera of Souri mice.

  15. COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATE

    Science.gov (United States)

    COMPARATIVE METABOLISM OF ARSENIC IN MICE AFTER A SINGLE OR REPEATED ORAL ADMINISTRATION OF ARSENATEMichael F. Hughes*1, Elaina M. Kenyon1, Brenda C. Edwards1, Carol T. Mitchell1, Luz Maria Del Razo2 and David J. Thomas11US EPA, ORD, NHEERL, ETD, PKB, Research Triangle Pa...

  16. Pharmacokinetics of terbinafine after oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Evans, Erika E; Emery, Lee C; Cox, Sherry K; Souza, Marcy J

    2013-06-01

    To determine pharmacokinetics after oral administration of a single dose of terbinafine hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 6 healthy adult Hispaniolan Amazon parrots. A single dose of terbinafine hydrochloride (60 mg/kg) was administered orally to each bird, which was followed immediately by administration of a commercially available gavage feeding formula. Blood samples were collected at the time of drug administration (time 0) and 0.25, 0.5, 1, 2, 4, 8, 12, and 24 hours after drug administration. Plasma concentrations of terbinafine were determined via high-performance liquid chromatography. Data from 1 bird were discarded because of a possible error in the dose of drug administered. After oral administration of terbinafine, the maximum concentration for the remaining 5 fed birds ranged from 109 to 671 ng/mL, half-life ranged from 6 to 13.5 hours, and time to the maximum concentration ranged from 2 to 8 hours. No adverse effects were observed. Analysis of the results indicated that oral administration of terbinafine at a dose of 60 mg/kg to Amazon parrots did not result in adverse effects and may be potentially of use in the treatment of aspergillosis. Additional studies are needed to determine treatment efficacy and safety.

  17. Acute administration of single oral dose of grape seed polyphenols restores blood pressure in a rat model of metabolic syndrome: role of nitric oxide and prostacyclin.

    Science.gov (United States)

    Pons, Zara; Margalef, Maria; Bravo, Francisca I; Arola-Arnal, Anna; Muguerza, Begoña

    2016-03-01

    The aims of this study were to evaluate the antihypertensive effectiveness of different doses of grape seed polyphenols in cafeteria diet-fed hypertensive rats (CHRs) and to establish the mechanism involved in the blood pressure (BP) lowering effect of these compounds in this experimental model of metabolic syndrome (MS). Male 8-week-old Wistar rats were fed cafeteria or standard (ST) diet for 10 weeks. After this, the antihypertensive effect of a single oral administration of a polyphenol grape seed extract (GSPE) was tested at different doses (250, 375 and 500 mg/kg) in CHRs. BP was recorded before and 2, 4, 6, 8, 24 and 48 h post-administration. The hypotensive effect of GSPE was also proved in ST diet-fed rats. Additionally, in other experiment, CHRs were orally administered 375 mg/kg GSPE. Four hours post-administration, the rats were intraperitoneally administrated 30 mg/kg NG-nitro-L-arginine methyl ester (L-NAME) or 5 mg/kg indomethacin [inhibitors of nitric oxide (NO) and prostacyclin synthesis, respectively]. BP was recorded initially and 6 h post-administration. GSPE produced a decrease in SBP and DBP, the most effective dose (375 mg/kg) showing an antihypertensive effect in CHRs similar to the drug captopril, and did not affect BP of ST diet-fed rats. The antihypertensive effect was completely abolished by L-NAME and partially inhibited by indomethacin. GSPE acts as an antihypertensive agent in a rat model of hypertension associated with MS. The change in endothelium-derived NO availability is one of the mechanisms involved in the antihypertensive effect of GSPE in CHRs. Additionally, endothelial prostacyclin contributes to the effect of GSPE on arterial BP.

  18. Effect of Intraperitoneal Bupivacaine on Postoperative Pain in the Gynecologic Oncology Patient.

    Science.gov (United States)

    Rivard, Colleen; Vogel, Rachel Isaksson; Teoh, Deanna

    2015-01-01

    To evaluate if the administration of intraperitoneal bupivacaine decreased postoperative pain in patients undergoing minimally invasive gynecologic and gynecologic cancer surgery. Retrospective cohort study (Canadian Task Force classification II-3). University-based gynecologic oncology practice operating at a tertiary medical center. All patients on the gynecologic oncology service undergoing minimally invasive surgery between September 2011 and June 2013. Starting August 2012, intraperitoneal administration of .25% bupivacaine was added to all minimally invasive surgeries. These patients were compared with historical control subjects who had surgery between September 2011 and July 2012 but did not receive intraperitoneal bupivacaine. One-hundred thirty patients were included in the study. The patients who received intraperitoneal bupivacaine had lower median narcotic use on the day of surgery and the first postoperative day compared with those who did not receive intraperitoneal bupivacaine (day 0: 7.0 mg morphine equivalents vs 11.0 mg, p = .007; day 1: .3 mg vs 1.7 mg, p = .0002). The median patient-reported pain scores were lower on the day of surgery in the intraperitoneal bupivacaine group (2.7 vs 3.2, p = .05) CONCLUSIONS: The administration of intraperitoneal bupivacaine was associated with improved postoperative pain control in patients undergoing minimally invasive gynecologic and gynecologic cancer surgery and should be further evaluated in a prospective study. Copyright © 2015 AAGL. Published by Elsevier Inc. All rights reserved.

  19. Pharmacokinetics and selected pharmacodynamics of cobalt following a single intravenous administration to horses.

    Science.gov (United States)

    Knych, H K; Arthur, R M; Mitchell, M M; Holser, I; Poppenga, R; Smith, L L; Helm, M N; Sams, R A; Gaskill, C L

    2015-07-01

    Cobalt has been used by human athletes due to its purported performance-enhancing effects. It has been suggested that cobalt administration results in enhanced erythropoiesis, secondary to increased circulating erythropoietin (EPO) concentrations leading to improvements in athletic performance. Anecdotal reports of illicit administration of cobalt to horses for its suspected performance enhancing effects have led us to investigate the pharmacokinetics and pharmacodynamic effects of this compound when administered in horses, so as to better regulate its use. In the current study, 18 horses were administered a single intravenous dose of cobalt chloride or cobalt gluconate and serum and urine samples collected for up to 10 days post administration. Cobalt concentrations were measured using inductively coupled plasma mass spectrometry (ICP-MS) and pharmacokinetic parameters determined. Additional blood samples were collected for measurement of equine EPO concentrations as well as to assess any effects on red blood cell parameters. Horses were observed for adverse effects and heart rate monitored for the first 4 h post administration. Cobalt was characterized by a large volume of distribution (0.939 L/kg) and a prolonged gamma half-life (156.4 h). Cobalt serum concentrations were still above baseline values at 10 days post administration. A single administration of cobalt had no effect on EPO concentrations, red blood cell parameters or heart rate in any of the horses studied and no adverse effects were noted. Based on the prolonged gamma half-life and prolonged residence time, regulators should be able to detect administration of a single dose of cobalt to horses. Copyright © 2014 John Wiley & Sons, Ltd.

  20. Hypotonic intraperitoneal cisplatin chemotherapy for peritoneal carcinomatosis in mice.

    OpenAIRE

    Kondo, A.; Maeta, M.; Oka, A.; Tsujitani, S.; Ikeguchi, M.; Kaibara, N.

    1996-01-01

    The intraperitoneal (i.p.) administration of cisplatin (CDDP) is one of the most effective therapies for cancers that are confined to the abdominal cavity. However, the effect of fluid osmolarity on the therapeutic efficacy of i.p. administration of CDDP has not been well established. In the current study, hypotonic (154 mosmol 1-1), isotonic (308 mosmol 1-1) and hypertonic (616 mosmol 1-1) solutions of CDDP were prepared for an evaluation of their therapeutic efficacy in an experimental syst...

  1. Biological fate of a single administration of 191Pt in rats following different routes of exposure

    International Nuclear Information System (INIS)

    Moore, W. Jr.; Hysell, D.; Crocker, W.; Stara, J.

    1975-01-01

    The retention, tissue distribution, and excretion of 191 Pt in adult rats was determined following oral, intravenous (IV), and intratracheal administration. The highest retention was obtained following IV dosing, and lowest retention (less than 0.5 percent) occurred after oral dosing. Tissues containing the highest concentrations of 191 Pt following IV administration were the kidney, adrenal, spleen, and liver. Following a single oral dose, almost all of the 191 Pt was excreted in the feces due to nonabsorption, whereas after IV dosing, similar quantities were excreted in both the urine and feces. Following IV dosing of pregnant rats, 191 Pt was found in all the fetuses; however, the amount was small

  2. Administration

    DEFF Research Database (Denmark)

    Bogen handler om den praksis, vi kalder administration. Vi er i den offentlige sektor i Danmark hos kontorfolkene med deres sagsmapper, computere, telefoner,, lovsamlinger,, retningslinier og regneark. I bogen udfoldes en mangfoldighed af konkrete historier om det administrative arbejde fra...... forskellige områder i den offentlige sektor. Hensigten er at forstå den praksis og faglighed der knytter sig til det administrative arbejde...

  3. Pharmacokinetics of meloxicam in rabbits after oral administration of single and multiple doses.

    Science.gov (United States)

    Fredholm, Daniel V; Carpenter, James W; KuKanich, Butch; Kohles, Micah

    2013-04-01

    To determine the pharmacokinetics of meloxicam (1 mg/kg) in rabbits after oral administration of single and multiple doses. 6 healthy rabbits. A single dose of meloxicam (1 mg/kg, PO) was administered to the rabbits. After a 10-day washout period, meloxicam (1 mg/kg, PO) was administered to rabbits every 24 hours for 5 days. Blood samples were obtained from rabbits at predetermined intervals during both treatment periods. Plasma meloxicam concentrations were determined, and noncompartmental pharmacokinetic analysis was performed. The mean peak plasma concentration and area under the plasma concentration-versus-time curve extrapolated to infinity after administration of a single dose of meloxicam were 0.83 μg/mL and 10.37 h•μg/mL, respectively. After administration of meloxicam for 5 days, the mean peak plasma concentration was 1.33 μg/mL, and the area under the plasma concentration-versus-time curve from the time of administration of the last dose to 24 hours after that time was 18.79 h•μg/mL. For single- and multiple-dose meloxicam experiments, the mean time to maximum plasma concentration was 6.5 and 5.8 hours and the mean terminal half-life was 6.1 and 6.7 hours, respectively. Plasma concentrations of meloxicam for rabbits in the present study were proportionally higher than those previously reported for rabbits receiving 0.2 mg of meloxicam/kg and were similar to those determined for animals of other species that received clinically effective doses. A dose of 1 mg/kg may be necessary to achieve clinically effective circulating concentrations of meloxicam in rabbits, although further studies are needed.

  4. Continuous intraperitoneal insulin infusion in the treatment of type 1 diabetes mellitus: Glycaemia and beyond

    OpenAIRE

    van Dijk, Peter R.

    2015-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As compared to the most commonly used forms of insulin administration -injections and an externally placed pump- which deliver insulin in the subcutaneous (SC) tissue, CIPII delivers the insulin in the intraperitoneal space. CIPII using an implantable pump is an unique treatment which has been available for more than 30 year...

  5. Modified single prolonged stress reduces cocaine self-administration during acquisition regardless of rearing environment.

    Science.gov (United States)

    Hofford, Rebecca S; Prendergast, Mark A; Bardo, Michael T

    2018-02-15

    Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in cocaine self-administration and HPA markers. Regardless of rearing condition, rats exposed to modSPS had greater corticosterone (CORT) release and reduced cocaine self-administration during initial acquisition compared to non-stressed controls. In addition, during initial acquisition, rats that received both Iso rearing and modSPS showed a more rapid increase in cocaine self-administration across sessions compared to Enr and Std rats exposed to modSPS. Following initial acquisition, a dose response analysis showed that Iso rats were overall most sensitive to changes in cocaine unit dose; however, modSPS had no effect on the cocaine dose response curve. Further, there was no effect of either modSPS or differential rearing on expression of glucocorticoid receptor (GR) in hypothalamus, medial prefrontal cortex, amygdala, or nucleus accumbens. By using modSPS in combination with Iso housing, this study identified unique contributions of each stressor to acquisition of cocaine self-administration. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Administration

    OpenAIRE

    2009-01-01

    Cet imposant volume constitue un registre des cours magistraux tenus par l’auteur à l’École supérieure allemande des sciences administratives de Spire, enrichis des résultats de travaux scientifiques menés principalement à l'Institut Allemand de Recherche en Administration Publique (Deutsches Forschungsinstitut für öffentliche Verwaltung Speyer, FÖV). Il s’agit donc d’une entreprise au long cours, destinée à apporter un nouvel éclairage (quasi ?) exhaustif sur l’administration publique : son ...

  7. Comparative pharmacokinetics of fluralaner in dogs and cats following single topical or intravenous administration.

    Science.gov (United States)

    Kilp, Susanne; Ramirez, Diana; Allan, Mark J; Roepke, Rainer Ka

    2016-05-31

    Bravecto™ Chewable Tablets for Dogs, containing fluralaner as active ingredient, is an innovative treatment for flea and tick infestations that provides safe, rapid and long acting efficacy after a single oral administration in dogs. Topically applied fluralaner provides similar safe, rapid and long acting efficacy, both in dogs and in cats. The pharmacokinetic profile of fluralaner was evaluated in dogs and in cats following either topical or intravenous administration. Twenty four dogs and 24 cats received three different topical doses, with the mid-dose based on the respective minimum recommended dose, and one intravenous dose. Plasma samples were collected for 112 days and fluralaner concentrations were quantified using a validated high performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS) method. Pharmacokinetic parameters were calculated using non-compartmental methods. In dogs, fluralaner was readily absorbed from the topical administration site into the skin, subjacent tissues and blood. Fluralaner plasma concentrations showed an apparent plateau between ~ day 7 and 63, with individual tmax seen within this time period. After the plasma plateau, concentrations declined slowly and were quantifiable for more than 12 weeks. In cats, fluralaner was readily systemically absorbed from the topical administration site, reaching maximum concentrations (Cmax) in plasma between 3 and 21 days post administration, after which concentrations declined slowly, and were also quantifiable for more than 12 weeks. Systemic exposure, as shown by Cmax and the area under the concentration versus time curve from time 0 to the last measurable concentration (AUC(0→t)) increased proportionally with dose in both species. Following intravenous administration fluralaner showed a relatively high apparent volume of distribution (Vz), a low plasma clearance (Cl), a long terminal half-life (t1/2) and a long mean residence time (MRT); thereby demonstrating

  8. Quality of bevacizumab (Avastin®) repacked in single-use glass vials for intravitreal administration.

    Science.gov (United States)

    Sugimoto, Michelle A A; Toledo, Vicente de Paulo Coelho Peixoto de; Cunha, Mariem Rodrigues Ribeiro; Carregal, Virginia M; Jorge, Rodrigo; Leão, Pedro; Fialho, Sílvia Ligorio; Silva-Cunha, Armando

    2017-01-01

    Avastin® (bevacizumab) is an anti-vascular endothelial growth factor (VEGF) monoclonal antibody given as an off-label drug by intravitreal administration for treatment of ocular diseases. The drug's clinical application and its cost-benefit profile has generated demand for its division into single-use vials to meet the low volume and low-cost doses necessary for intraocular administration. However, the safety of compounding the drug in single-use vials is still under discussion. In this study, the stability and efficacy of Avastin® repacked in individual single-use glass vials and glass ampoules by external compounding pharmacies were evaluated. Polyacrylamide gel electrophoresis (PAGE), size-exclusion chromatography (SEC), dynamic light scattering (DLS), and turbidimetry were selected to detect the formation of aggregates of various sizes. Changes in bevacizumab biological efficacy were investigated by using an enzyme-linked immunosorbent assay (ELISA). Repacked and reference bevacizumab showed similar results when analyzed by PAGE. By SEC, a slight increase in high molecular weight aggregates and a reduction in bevacizumab monomers were observed in the products of the three compounding pharmacies relative to those in the reference bevacizumab. A comparison of repacked and reference SEC chromatograms showed that the mean monomer loss was ≤1% for all compounding pharmacies. Protein aggregates in the nanometer- and micrometer-size ranges were not detected by DLS and turbidimetry. In the efficacy assay, the biological function of repacked bevacizumab was preserved, with <3% loss of VEGF binding capacity relative to that of the reference. The results showed that bevacizumab remained stable after compounding in ampoules and single-use glass vials; no significant aggregation, fragmentation, or loss of biological activity was observed.

  9. Intraperitoneal stone migration during percutaneos nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Akif Diri

    2014-12-01

    Full Text Available Percutaneos nephrolithotomy (PNL is the standard care for renal stones larger than 2 cm. The procedure has some major and minor complications. Renal pelvis laceration and stone migration to the retroperitoneum is one of the rare condition. We report the first case of intraperitoneal stone migration during PNL.

  10. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC have been established as treatment options for patients with peritoneal metastases or peritoneal mesothelioma. However, this novel treatment strategy remains associated with a large percentage of local-regional treatment failures. These treatment failures are attributed to the inadequacy of HIPEC to maintain a surgical complete response. Management strategies to supplement CRS and HIPEC are indicated. A simplified approach to the intraoperative placement of an intraperitoneal port for adjuvant bidirectional chemotherapy (ABC was devised. Four different chemotherapy treatment plans were utilized depending upon the primary site of the malignancy. Thirty-one consecutive patients with an intraoperative placement of the intraperitoneal port were available for study. The incidence of adverse events that caused an early discontinuation of the bidirectional chemotherapy occurred in 75% of the 8 patients who had an incomplete cytoreduction and in 0% of patients who had a complete cytoreduction. All of the patients who had complete cytoreduction completed at least 5 of the scheduled 6 bidirectional chemotherapy treatments. Adjuvant bidirectional chemotherapy is possible following a major cytoreductive surgical procedure using a simplified method of intraoperative intraperitoneal port placement.

  11. Selected oxidative stress parameters after single and repeated administration of octabromodiphenyl ether to rats

    Directory of Open Access Journals (Sweden)

    Elżbieta Bruchajzer

    2014-10-01

    Full Text Available Objectives: Octabromodiphenyl ether (OctaBDE was used as a flame retardant applied mostly in the manufacture of plastics utilized in the electrical and electronic industries. Owing to its long half-life and being regarded as an environmental pollutant, OctaBDE, like other polybrominated diphenyl ethers, has been classified as a persistent organic pollutant (POP. This study was carried out to assess the effects of oxidative stress (redox homeostasis induced in rats by OctaBDE. Material and Methods: Female Wistar rats exposed intragastrically to OctaBDE at single (25, 200 or 2000 mg/kg b.w., or repeated (0.4, 2, 8, 40 or 200 mg/kg/day doses during 7–28 days were used in the experiment. Selected oxidative stress parameters were determined in the liver and blood serum. Results: Administration (single or repeated of OctaBDE to rats resulted in the impaired redox homeostasis, as evidenced by the increased levels of reduced (GSH and oxidized (GSSG glutathione in the liver, the reduced total antioxidant status (TAS in serum and the increased concentration of malondialdehyde (MDA in the liver. After multiple doses of OctaBDE, elevated activity of glutathione transferase (GST in the liver was also noted. Conclusions: After repeated administration of OctaBDE at the lowest dose (0.4 mg/kg/day, changes were observed in the parameters (MDA, TAS, GSSG indicative of oxidative stress.

  12. Plasma pharmacokinetics of selamectin after a single topical administration in the American bullfrog (Rana catesbeiana).

    Science.gov (United States)

    D'Agostino, Jennifer J; West, Gary; Boothe, Dawn M; Jayanna, Prashanth K; Snider, Timothy; Hoover, John P

    2007-03-01

    Parasitism is common in wild and captive amphibians; however, pharmacologic data are lacking for anthelmintic drugs. This study was developed to determine the plasma pharmacokinetics of selamectin after topical administration in bullfrogs. Thirty-two adult American bullfrogs (Rana catesbeiana) were randomly assigned into eight groups of four with each group representing a different collection time point. Seven groups received selamectin (6 mg/ kg) topically and the remaining group served as the untreated control group. One group of frogs was euthanized and blood samples immediately collected on days 0 (control), 1, 5, 10, 15, 20, 25, and 30. Plasma was analyzed for selamectin using high performance liquid chromatography with fluorescence detection. Individual samples were analyzed, then data were reported as the mean of the four frogs at each time point. A histologic evaluation of the lung, liver, kidney, and skin tissues was performed and none of the frogs showed histologic evidence of toxicity due to selamectin administration. The mean peak plasma concentration was 162.5 +/- 42.3 ng/ml, area under the curve was 2,856 ng day/ml, mean residence time was 12.2 days, and disappearance half-life was 1.87 days. Based on the plasma pharmacokinetics, bullfrogs appear to absorb selamectin very efficiently, concentrations reach high levels in the plasma, and there were no apparent histologic effects from single dose administration.

  13. Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats

    Directory of Open Access Journals (Sweden)

    Evon S. Ereifej

    2017-01-01

    Full Text Available Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225–250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose. Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol.

  14. Status Epilepticus due to Intraperitoneal Injection of Vehicle Containing Propylene Glycol in Sprague Dawley Rats.

    Science.gov (United States)

    Ereifej, Evon S; Meade, Seth M; Smith, Cara S; Chen, Keying; Kleinman, Nanette; Capadona, Jeffrey R

    2017-01-01

    Published reports of status epilepticus due to intraperitoneal injection containing propylene glycol in rats are sparse. In fact, there are no reports specifying a maximum safe dose of propylene glycol through intraperitoneal administration. We report here a case of unexpected seizures in Sprague Dawley rats after receiving an intraperitoneal injection containing propylene glycol. Nine-week-old, 225-250 gram male rats were reported to experience tremor progressing to seizures within minutes after given injections of resveratrol (30 mg/kg) dissolved in a 40 : 60 propylene glycol/corn oil vehicle solution by direct intraperitoneal (IP) slow bolus injection or via a preplaced intraperitoneal catheter. The World Health Organization suggests a maximum dose of 25 mg/kg/day of propylene glycol taken orally and no more than 25 mg/dL in blood serum, whereas the animals used in our study got a calculated maximum 0.52 g/kg (25 times lower dose). Blood tests from the seizing rat support a diagnosis of hemolysis and lactic acidosis which may have led to the seizures, all of which appeared to be a consequence of the propylene glycol administration. These findings are consistent with oral and intravenous administration of propylene glycol toxicity as previously reported in other species, including humans. To our knowledge, this report represents the first published case of status epilepticus due to an IP injection containing propylene glycol.

  15. 76 FR 67192 - Administration on Children, Youth and Families Announces the Award of Five Single-Source...

    Science.gov (United States)

    2011-10-31

    ... training and supports for Tribal middle managers in child welfare. There are five traineeship universities... DEPARTMENT OF HEALTH AND HUMAN SERVICES Administration for Children and Families Administration on Children, Youth and Families Announces the Award of Five Single-Source Expansion Supplement Grants To...

  16. A single administration of LFA-1 antibody confers prolonged allograft survival.

    Science.gov (United States)

    Talento, A; Nguyen, M; Blake, T; Sirotina, A; Fioravanti, C; Burkholder, D; Gibson, R; Sigal, N H; Springer, M S; Koo, G C

    1993-02-01

    C57BL/6 (B6) thyroid gland transplanted to the left kidney capsule of an allogeneic (BALB/c) host was typically rejected in 14 days. A single administration of 500 micrograms of an antibody to the adhesion molecule, leucocyte function-associated antigen (LFA-1, CD11a), prevented all thyroid allograft rejection for at least 70 days. Fifty percent of the treated recipients retained intact allografts for 470 days. However, the same treatment with anti-CD11a could not protect a sensitized BALB/c mouse from rejecting a second B6 thyroid allograft. Production of donor-specific alloantibodies elicited by allograft rejection was also inhibited in this system. In this transplant model, the Ab therapy is more efficacious than that of FK506, administered daily for 14 days at 15 mg/kg. These results demonstrate the remarkable effect of an anti-LFA-1 antibody in promotion of allograft survival.

  17. Oxytetracycline hydrochloride in the horse: serum, synovial, peritoneal and urine concentrations after single dose intravenous administration.

    Science.gov (United States)

    Brown, M P; Stover, S M; Kelly, R H; Farver, T B; Knight, H D

    1981-03-01

    Six adult mares were given a single intravenous injection of oxytetracycline HCl (50 mg/ml) at a dosage of 5 mg/kg. Serum, synovial fluid, peritoneal fluid, and urine oxytetracycline concentrations were measured serially over a 48-h period. The highest measured serum oxytetracycline concentration was 8.01 mcg/ml at 1/2 h. Oxytetracycline was detected in synovial fluid and peritoneal fluid, which obtained mean peak oxytetracycline concentrations of 4.43 mcg/ml and 4.20 mcg/ml, at 1/2 h and 1 h, respectively. These concentrations steadily declined in parallel with serum concentrations and were not measurable at 48 h. Urine oxytetracycline concentration was relatively high, with a peak concentration of 1565.2 mcg/ml at 1/2 h after drug administration.

  18. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    Science.gov (United States)

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

  19. Continuous intraperitoneal insulin infusion in the treatment of type 1 diabetes mellitus : Glycaemia and beyond

    NARCIS (Netherlands)

    van Dijk, Peter R.

    2015-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a last-resort treatment option for selected patients with type 1 diabetes mellitus (T1DM). As compared to the most commonly used forms of insulin administration -injections and an externally placed pump- which deliver

  20. Ninety-day readmissions after degenerative cervical spine surgery: A single-center administrative database study.

    Science.gov (United States)

    Akamnonu, Chibuikem; Cheriyan, Thomas; Goldstein, Jeffrey A; Errico, Thomas J; Bendo, John A

    2015-01-01

    Unplanned hospital readmissions result in significant clinical and financial burdens to patients and the healthcare system. Readmission rates and causes have been investigated using large administrative databases which have certain limitations in data reporting and coding. The objective of this study was to provide a description of 90 day post-discharge readmissions following surgery for common degenerative cervical spine pathologies at a large-volume tertiary hospital. The study also compared the readmission rates of patients who underwent anterior- and posterior-approach procedures. The administrative records from a single-center, high-volume tertiary institution were queried using ICD-9 codes for common cervical pathology over a three year period to determine the rate and causes of readmissions within the 90 days following the index surgery. A total of 768 patients underwent degenerative cervical spine surgery during the three year study period. Within 90 days of discharge, 24 (3.13%) patients were readmitted; 16 (2.06%) readmissions were planned for lumbar surgery; 8 (1.04%) readmissions were unplanned. 640 patients underwent procedures involving an anterior approach and 128 patients underwent procedures involving a posterior approach. There were 14 (2.17%) planned readmissions in the anterior group and 2 (1.5%) in the posterior group. The unplanned readmission rate was 0.63% (4 patients) and 3.13% (4 patients) in the anterior and posterior groups, respectively. (p=0.0343). The 90 day post-discharge unplanned readmission rate that followed elective degenerative cervical spine surgery was 1.04%. The unplanned readmission rate associated with posterior-approach procedures (3.13%) was significantly higher than that of anterior-approach procedures (0.63%). IV.

  1. PHARMACOKINETICS OF A SINGLE DOSE OF METRONIDAZOLE AFTER RECTAL ADMINISTRATION IN CAPTIVE ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

    Science.gov (United States)

    Sander, Samantha J; Siegal-Willott, Jessica L; Ziegler, Jessie; Lee, Elizabeth; Tell, Lisa; Murray, Suzan

    2016-03-01

    Metronidazole is a nitroimidazole antibacterial and antiprotozoal drug with bacteriocidal activity against a broad range of anaerobic bacteria. It is a recognized treatment for elephants diagnosed with anaerobic bacterial infection or protozoal disease or exhibiting signs of colonic impaction, diarrhea, and colic. This study evaluated the pharmacokinetics of rectally administered metronidazole (15 mg/kg) in five adult female Asian elephants (Elephas maximus). Serum samples were collected from each animal for 96 hr after rectal administration of metronidazole. Serum concentrations of metronidazole and its primary metabolite, hydroxymetronidazole, were measured via ultraperformance liquid chromatography. Data were analyzed via a noncompartmental pharmacokinetic approach. Results indicated that serum levels of metronidazole were quantifiable at the 0.25 hr time point and absent in all elephants by the 96 hr time point. The serum peak concentration (mean ± SD, 13.15 ± 2.59 μg/ml) and area under the curve from time 0 to infinity (mean ± SD, 108.79 ± 24.77 hr × μg/ml) were higher than that reported in domestic horses after similar usage. Concurrently, the time of maximum serum concentration (mean ± SD, 1.2 ± 0.45 hr) and terminal elimination half-life (harmonic mean ± pseudo-SD, 7.85 ± 0.93 hr) were longer when compared to equine reports. Rectal administration of metronidazole was well tolerated and rapidly absorbed in all study elephants. Based on the findings in this study, metronidazole administered at a single dose of 15 mg/kg per rectum in the Asian elephant is likely to result in serum concentrations above 4 μg/ml for 8 hr and above 2 μg/ml for 24 hr after treatment is administered. Dosing recommendations should reflect the mean inhibitory concentration of metronidazole for each pathogen.

  2. Pharmacokinetics and pharmacodynamic effects of amiodarone in plasma of ponies after single intravenous administration

    International Nuclear Information System (INIS)

    Trachsel, D.; Tschudi, P.; Portier, C.J.; Kuhn, M.; Thormann, W.; Scholtysik, G.; Mevissen, M.

    2004-01-01

    Atrial fibrillation is a well-known heart disease in horses. The common therapy consists of administration of quinidine. More potent antiarrhythmic drugs have become available for human therapy and the use of these as alternatives to quinidine for equine antiarrhythmic therapy is a matter of interest. Amiodarone (AMD) is used in human medicine for treatment of many arrhythmias, including atrial fibrillation. Its disposition in horses has not yet been investigated. The purpose of this study was to measure the effect of single intravenous doses of amiodarone (5 and 7 mg/kg) on the surface electrocardiogram (ECG) of healthy minishetland ponies during the first 2 days after drug administration and to calculate pharmacokinetic parameters with a physiologically based pharmacokinetic model (PBPK) using amiodarone and desethylamiodarone (DAMD) plasma levels that were determined by high-performance liquid chromatography (HPLC). As expected for a K + -channel-blocker, the main effect on the measured ECG could be seen on the ventricular complex, as the QT interval and the T wave showed statistically significant alterations. The doses investigated were well tolerated clinically. Results from the pharmacokinetic model were found to compare well with literature data of rats, dogs, and humans. It showed a rapid distribution in the tissue, beginning with the rapidly perfused tissue, like the heart, followed by slowly perfused tissues, and finally an accumulation in fat. The half-life for total elimination was calculated to be 16.3 days with 99% eliminated by 97 days. The model predicts that approximately 96% of amiodarone is eliminated as desethylamiodarone in urine, 2% eliminated as desethylamiodarone in bile, and 2% as other metabolites

  3. Pharmacokinetics of meloxicam after intramuscular and oral administration of a single dose to American flamingos (Phoenicopertus ruber).

    Science.gov (United States)

    Boonstra, Jennifer L; Cox, Sherry K; Martin-Jimenez, Tomas

    2017-03-01

    OBJECTIVE To determine pharmacokinetics after IM and oral administration of a single dose of meloxicam to American flamingos (Phoenicopertus ruber). ANIMALS 14 adult flamingos. PROCEDURES Flamingos were allocated to 2 groups. Each group received a dose of meloxicam (1 mg/kg) by the IM or oral route. After a 4-week washout period, groups received meloxicam via the other route of administration. Plasma meloxicam concentrations were measured with high-performance liquid chromatography. Data for each bird were analyzed. Estimated values of selected pharmacokinetic parameters were compared by use of a linear mixed-effects ANOVA. Pooled concentration-time profiles for each route of administration were analyzed to examine the influence of body weight on pharmacokinetics. RESULTS Mean ± SD maximum plasma concentration was 1.00 ± 0.88 μg/mL after oral administration. This was approximately 15% of the mean maximum plasma concentration of 5.50 ± 2.86 μg/mL after IM administration. Mean time to maximum plasma concentration was 1.33 ± 1.32 hours after oral administration and 0.28 ± 0.17 hours after IM administration. Mean half-life of the terminal phase after oral administration (3.83 ± 2.64 hours) was approximately twice that after IM administration (1.83 ± 1.22 hours). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the extent and rate of meloxicam absorption were less after oral administration than after IM administration. Intramuscular administration resulted in a short period during which mean plasma concentrations met or exceeded reported efficacious analgesic concentrations in other species, whereas oral administration did not. These results suggested that higher doses may be required for oral administration.

  4. Pharmacokinetics after oral and intravenous administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Souza, Marcy J; Sanchez-Migallon Guzman, David; Paul-Murphy, Joanne R; Cox, Sherry K

    2012-08-01

    To determine pharmacokinetics after IV and oral administration of a single dose of tramadol hydrochloride to Hispaniolan Amazon parrots (Amazona ventralis). 9 healthy adult Hispaniolan Amazon parrots (3 males, 5 females, and 1 of unknown sex). Tramadol (5 mg/kg, IV) was administered to the parrots. Blood samples were collected from -5 to 720 minutes after administration. After a 3-week washout period, tramadol (10 and 30 mg/kg) was orally administered to parrots. Blood samples were collected from -5 to 1,440 minutes after administration. Three formulations of oral suspension (crushed tablets in a commercially available suspension agent, crushed tablets in sterile water, and chemical-grade powder in sterile water) were evaluated. Plasma concentrations of tramadol and its major metabolites were measured via high-performance liquid chromatography. Mean plasma tramadol concentrations were > 100 ng/mL for approximately 2 to 4 hours after IV administration of tramadol. Plasma concentrations after oral administration of tramadol at a dose of 10 mg/kg were 100 ng/mL for approximately 6 hours after administration. Oral administration of the suspension consisting of the chemical-grade powder resulted in higher plasma tramadol concentrations than concentrations obtained after oral administration of the other 2 formulations; however, concentrations differed significantly only at 120 and 240 minutes after administration. Oral administration of tramadol at a dose of 30 mg/kg resulted in plasma concentrations (> 100 ng/mL) that have been associated with analgesia in Hispaniolan Amazon parrots.

  5. Metabolism and distribution of guanosine given intraperitoneally: implications for spinal cord injury.

    Science.gov (United States)

    Jiang, Shucui; Fischione, Gemma; Giuliani, Patricia; Guiliani, Patricia; Romano, Silvia; Caciagli, Francesco; Di Iorio, Patrizia; Diiorio, Patrizia

    2008-06-01

    Intraperitoneal administration of guanosine to rats with chronic spinal cord injury stimulates remyelination and functional recovery. If guanosine produced its effects in the nervous system, it should enter it and elevate endogenous concentrations. [(3)H]-guanosine (8 mg/kg) was administered intraperitoneally to rats and its distribution and concentration in different sites determined. Guanosine rapidly entered all tissues; its concentration peaked at about 15 minutes except in adipose tissue and CNS where it continued to rise for 30 minutes. Its chief metabolic product in all sites was guanine with over twice as much guanine as guanosine present in CNS after 30 minutes.

  6. Efficacy of intramuscular and intraperitoneal deferoxamine for aluminum chelation.

    Science.gov (United States)

    Molitoris, B A; Alfrey, P S; Miller, N L; Hasbargen, J A; Kaehney, W D; Alfrey, A C; Smith, B J

    1987-04-01

    As intravenous administration of deferoxamine is difficult in home dialysis patients we set out to determine the efficacy of intramuscular (i.m.) and intraperitoneal (i.p.) deferoxamine for removal of aluminum. Patients with serum aluminum levels greater than 90 micrograms/liter were studied in a paired fashion with each patient serving as their own control. Serum and peritoneal fluid aluminum were determined using flameless atomic absorption. In hemodialysis patients 2 g of intravenous deferoxamine increased serum aluminum from 124.7 +/- 32.4 to 415 +/- 192.4 micrograms/liter. One g of deferoxamine given intravenously or intramuscularly resulted in 76.8 +/- 35.3% and 70.4 +/- 23.2%, respectively, of the 2 g i.v. response. The rate at which serum aluminum increased following i.v. deferoxamine infusion was biphasic, with an initial rapid phase lasting 139 minutes followed by a much slower phase. The volume of distribution of aluminum following deferoxamine administration was 12.6 +/- 1.61 and the half life (t1/2) for aluminum removal during hemodialysis was 9.0 +/- 2.0 hours. The increase in serum aluminum following deferoxamine was not due to chelation of erythrocyte aluminum as erythrocyte aluminum remained constant over 24 hours. In patients on continuous ambulatory peritoneal dialysis, 2 g intravenous deferoxamine resulted in the removal of 560 +/- 267 micrograms of aluminum over 24 hours while 2 g deferoxamine given intraperitoneally gave 91 +/- 13% of the intravenous response. Aluminum clearance over 48 hours was twice that for 24 hours for both i.v. and i.p. deferoxamine.(ABSTRACT TRUNCATED AT 250 WORDS)

  7. 77 FR 41415 - Single-Ingredient, Immediate-Release Drug Products Containing Oxycodone for Oral Administration...

    Science.gov (United States)

    2012-07-13

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0563... Labeled for Human Use; Enforcement Action Dates; Correction AGENCY: Food and Drug Administration, HHS... contain oxycodone hydrochloride for oral administration and are labeled for human use, and persons who...

  8. Pharmacokinetics of meloxicam after intravenous, intramuscular, and oral administration of a single dose to Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Molter, Christine M; Court, Michael H; Cole, Gretchen A; Gagnon, David J; Hazarika, Suwagmani; Paul-Murphy, Joanne R

    2013-03-01

    To compare pharmacokinetics after IV, IM, and oral administration of a single dose of meloxicam to Hispaniolan Amazon parrots (Amazona ventralis). 11 healthy parrots. Cohorts of 8 of the 11 birds comprised 3 experimental groups for a crossover study. Pharmacokinetics were determined from plasma concentrations measured via high-performance liquid chromatography after IV, IM, and oral administration of meloxicam at a dose of 1 mg/kg. Initial mean ± SD plasma concentration of 17.3 ± 9.0 μg/mL was measured 5 minutes after IV administration, whereas peak mean concentration was 9.3 ± 1.8 μg/mL 15 minutes after IM administration. At 12 hours after administration, mean plasma concentrations for IV (3.7 ± 2.5 μg/mL) and IM (3.5 ± 2.2 μg/mL) administration were similar. Peak mean plasma concentration (3.5 ± 1.2 μg/mL) was detected 6 hours after oral administration. Absolute systemic bioavailability of meloxicam after IM administration was 100% but was lower after oral administration (range, 49% to 75%). Elimination half-lives after IV, IM, and oral administration were similar (15.9 ± 4.4 hours, 15.1 ± 7.7 hours, and 15.8 ± 8.6 hours, respectively). Pharmacokinetic data may provide useful information for use of meloxicam in Hispaniolan Amazon parrots. A mean plasma concentration of 3.5 μg/mL would be expected to provide analgesia in Hispaniolan Amazon parrots; however, individual variation may result in some birds having low plasma meloxicam concentrations after IV, IM, or oral administration. After oral administration, meloxicam concentration slowly reached the target plasma concentration, but that concentration was not sustained in most birds.

  9. Pharmacokinetics of MMB4 DMS in rats, rabbits, and dogs following a single IV administration.

    Science.gov (United States)

    Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

    2013-01-01

    Organophosphorus (OP) nerve agents pose tremendous threats to both military and civilian populations. The substance 1,1'-methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) is being developed as a replacement for the currently fielded 2-pyridine aldoxime, or pralidoxime (2-PAM) as a treatment for OP nerve agent-induced toxicity. The present study characterized pharmacokinetic (PK) profiles of MMB4 in male and female Sprague-Dawley rats, New Zealand White rabbits, and beagle dogs given a single intravenous (IV) administration of MMB4 dimethanesulfonate (DMS) at 55, 25, and 15 mg/kg dose, respectively. The plasma MMB4 concentration versus time profiles were biphasic for all species tested and fit a 2-compartment model with first-order elimination. There were no overt sex-related differences in the calculated PK parameters. For the rat, rabbit, and dog, the average systemic exposure parameters predicted Cmax (µg/mL) and AUC∞ (µg·h/mL) were 273 and 71.0, 115 and 48.1, and 87.4 and 39.6; the average volume of distribution (mL/kg) values to the central and peripheral compartments were 207 and 143, 242 and 172, and 198 and 213; and the average elimination half-life (hour) and clearance (mL/h/kg) values were 0.18 and 778, 0.29 and 577, and 0.32 and 430, respectively, when the PK parameters for males and females were combined. The current study revealed a similarity in the volume of distribution to the central compartment for MMB4 among the 3 species tested while demonstrating species-related differences in the elimination half-life and clearance of MMB4.

  10. Superovulation with a single administration of FSH in aluminum hydroxide gel: a novel superovulation method for cattle.

    Science.gov (United States)

    Kimura, Koji

    2016-10-18

    Superovulation (SOV) is a necessary technique to produce large numbers of embryos for embryo transfer. In the conventional methods, follicular stimulating hormone (FSH) is administered to donor cattle twice daily for 3 to 4 days. As this method is labor intensive and stresses cattle, improving this method has been desired. We previously developed a novel and simple SOV method, in which the intramuscular injection of a single dose of FSH in aluminum hydroxide gel (AH-gel) induced the growth of multiple follicles, ovulation and the production of multiple embryos. Here we show that AH-gel can efficiently adsorb FSH and release it effectively in the presence of BSA, a major interstitial protein. When a single intramuscular administration of the FSH and AH-gel mixture was performed to cattle, multiple follicular growth, ovulation and embryo production were induced. However, the treatments caused indurations at the administration sites in the muscle. To reduce the muscle damage, we investigated alternative administration routes and different amounts of aluminum in the gel. By administering the FSH in AH-gel subcutaneously rather than intramuscularly, the amount of aluminum in the gel could be reduced, thus reducing the size of the induration. Moreover, repeated administrations of FSH with AH-gel did not affect the superovulatory response. These results indicate that a single administration of FSH with AH-gel is an effective, novel and practical method for SOV treatment.

  11. Population pharmacokinetics of a single dose of meloxicam after oral and intramuscular administration to captive lesser flamingos (Phoeniconaias minor).

    Science.gov (United States)

    Zordan, Martín A; Papich, Mark G; Pich, Ashley A; Unger, Katy M; Sánchez, Carlos R

    2016-12-01

    OBJECTIVE To determine the pharmacokinetics of a single dose of meloxicam after IM and oral administration to healthy lesser flamingos (Phoeniconaias minor) by use of a population approach. ANIMALS 16 healthy captive lesser flamingos between 1 and 4 years of age. PROCEDURES A single dose of meloxicam (0.5 mg/kg) was administered IM to each bird, and blood samples were collected from birds at 3 (n = 13 birds), 2 (2), or 1 (1) selected point between 0 and 13 hours after administration, with samples collected from birds at each point. After a 15-day washout period, the same dose of meloxicam was administered PO via a red rubber tube and blood samples were collected as described for IM administration. Pharmacokinetic values were determined from plasma concentrations measured by high-performance liquid chromatography. RESULTS Plasma drug concentrations after IM administration of meloxicam reached a mean ± SD maximum value of 6.01 ± 3.38 μg/mL. Mean area under the concentration-versus-time curve was 17.78 ± 2.79 μg•h/mL, and mean elimination half-life was 1.93 ± 0.32 hours. Plasma concentrations after oral administration reached a mean maximum value of 1.79 ± 0.33 μg/mL. Mean area under the curve was 22.16 ± 7.17 μg•h/mL, and mean elimination half-life was 6.05 ± 3.53 hours. CONCLUSIONS AND CLINICAL RELEVANCE In lesser flamingos, oral administration of meloxicam resulted in higher bioavailability and a longer elimination half-life than did IM administration, but the maximum plasma concentration was low and may be insufficient to provide analgesia in flamingos. Conversely, IM administration achieved the desired plasma concentration but would require more frequent administration.

  12. Guideline adherence to chemotherapy administration safety standards: a survey on nurses in a single institute

    OpenAIRE

    Kim, Kidong; Lee, Hee Sook; Kim, Younha; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Ryu, Sang-Young

    2011-01-01

    Objective Little is known about the guideline adherence of nurses to chemotherapy administration guidelines. We determined the guideline adherence of nurses to the Chemotherapy Administration Safety Standards and the relationship between demographic characteristics and guideline adherence. Methods Survey sheets containing two questions on demographic characteristics and 16 questions on the guideline adherence of nurses regarding chemotherapy administration were distributed to all in-patient d...

  13. CT evaluation of the intraperitoneal fluid distribution

    Energy Technology Data Exchange (ETDEWEB)

    Wojtowicz, J.; Rzymski, K.; Czarnecki, R.

    1982-07-01

    The intraperitoneal distribution of fluid and its detectability with a CT scanning were investigated in 13 patients during infusion of dialysate for peritoneal dialysis. An ascending pattern of spread i.e. from the lesser pelvis through the inframesocolic compartment to the supramesocolic compartment prevailed. Accumulation of fluid in the perihepatic space and in Morison's pouch as a function of fluid volume is at best approximated by a parabolic curve. Fifty to two hundred fifty ml. of fluid were detectable with a CT scanning in supine position in the majority of cases within the perihepatic space and Morison's pouch. The lowest amount of fluid detectable in the peritoneal cavity - 25 ml. was found between the anterior abdominal wall and bowel loops in right decubitus.

  14. The nucleic acid metabolism in rat liver after single and long-term administration of tritium oxide

    International Nuclear Information System (INIS)

    Shorokhova, V.B.

    1984-01-01

    It was shown that after a single administration of tritiUm oxide in a dose of 22.2 MBq/g body mass the liver mass increased, the concentration of nucleic acids decreased and the biosynthesjs rate increased dUring a one-month observation. By the end of the observation period (the first year) the parameters under study were normalized. The long-term administration of tritium oxide in daily doses of 0.37, 0.925 and 1.85 MBq/g body mass caused changes in the nucleac acid metabolism which were less manifest (at early times), than in the case of a single injection. At the same time, the long-term administration of tritium oxide in the dose of 0.925 MBq/g caused a substantial disturbance of the nucleic acid metabolism at later times (after 2-9 months)

  15. Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

    International Nuclear Information System (INIS)

    Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

    2016-01-01

    Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

  16. Cannabinoid Disposition After Human Intraperitoneal Use: An Insight Into Intraperitoneal Pharmacokinetic Properties in Metastatic Cancer.

    Science.gov (United States)

    Lucas, Catherine J; Galettis, Peter; Song, Shuzhen; Solowij, Nadia; Reuter, Stephanie E; Schneider, Jennifer; Martin, Jennifer H

    2018-01-06

    Medicinal cannabis is prescribed under the provision of a controlled drug in the Australian Poisons Standard. However, multiple laws must be navigated in order for patients to obtain access and imported products can be expensive. Dose-response information for both efficacy and toxicity pertaining to medicinal cannabis is lacking. The pharmacokinetic properties of cannabis administered by traditional routes has been described but to date, there is no literature on the pharmacokinetic properties of an intraperitoneal cannabinoid emulsion. A cachectic 56-year-old female with stage IV ovarian cancer and peritoneal metastases presented to hospital with fevers, abdominal distension and severe pain, vomiting, anorexia, dehydration and confusion. The patient reported receiving an intraperitoneal injection, purported to contain 12 g of mixed cannabinoid (administered by a deregistered medical practitioner) two days prior to presentation. Additionally, cannabis oil oral capsules were administered in the hours prior to hospital admission. THC concentrations were consistent with the clinical state but not with the known pharmacokinetic properties of cannabis nor of intraperitoneal absorption. THC concentrations at the time of presentation were predicted to be ~60 ng/mL. Evidence suggests that blood THC concentrations >5 ng/mL are associated with substantial cognitive and psychomotor impairment. The predicted time for concentrations to drop pharmacokinetic properties of the case suggest that there is a large amount unknown about cannabis pharmacokinetic properties. The pharmacokinetic properties of a large amount of a lipid soluble compound given intraperitoneally gave insights into the absorption and distribution of cannabinoids, particularly in the setting of metastatic malignancy. Copyright © 2018 Elsevier HS Journals, Inc. All rights reserved.

  17. No significant effects of single intravenous, single oral and subchronic oral administration of acetylcholinesterase inhibitors on striatal [{sup 123}I]FP-CIT binding in rats

    Energy Technology Data Exchange (ETDEWEB)

    Knol, R.J.J.; Booij, J. [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands); Graduate School of Neurosciences, Amsterdam (Netherlands); Bruin, K. de; Eck-Smit, B.L.F. van [University of Amsterdam, Department of Nuclear Medicine, Academic Medical Center, Amsterdam (Netherlands)

    2008-03-15

    [{sup 123}I]FP-CIT SPECT is a valuable diagnostic tool to discriminate Lewy body dementia from Alzheimer's dementia. To date, however, it is uncertain whether the frequently used acetylcholinesterase inhibitors (AChEIs) by demented patients, have an effect on [{sup 123}I]FP-CIT binding to dopamine transporters (DATs). Earlier animal studies showed a decline of DAT availability after acute intravenous injection of AChEIs. The aim of this study was to investigate effects of single intravenous, single oral and subchronic oral administration of AChEIs on DAT availability in the rat brain as measured by [{sup 123}I]FP-CIT. Biodistribution studies were performed in Wistar rats (n = 5-16 per group). Before [{sup 123}I]FP-CIT injection, rats were injected intravenously with a single dose of the AChEI rivastigmine (2.5 mg/kg body weight) or donepezil (0.5 mg/kg), the DAT-blocker methylphenidate (10 mg/kg) or saline. A second group was orally treated with a single dose of rivastigmine or donepezil (2.5 mg/kg), methylphenidate (10 mg/kg) or saline before injection of [{sup 123}I]FP-CIT. Studies were also performed in rats that were orally treated during 14 consecutive days with either rivastigmine (1 mg/kg daily), donepezil (1.5 mg/kg daily), methylphenidate (2.5 mg/kg) or saline. Brain parts were assayed in a gamma counter, and specific striatum/cerebellum ratios were calculated for the [{sup 123}I]FP-CIT binding to DATs. No significant effects of either single intravenous, single oral or subchronic oral administration of AChEIs on striatal FP-CIT binding could be detected. Single pretreatment with methylphenidate resulted in an expected significantly lower striatal FP-CIT binding. We conclude that in rats, single intravenous and single or subchronic oral administration of the tested AChEIs does not lead to an important alteration of [{sup 123}I]FP-CIT binding to striatal DATs. Therefore, it is unlikely that these drugs will induce large effects on the interpretation of

  18. Quantifying rates of glucose production in vivo following an intraperitoneal tracer bolus.

    Science.gov (United States)

    Wang, Sheng-Ping; Zhou, Dan; Yao, Zuliang; Satapati, Santhosh; Chen, Ying; Daurio, Natalie A; Petrov, Aleksandr; Shen, Xiaolan; Metzger, Daniel; Yin, Wu; Nawrocki, Andrea R; Eiermann, George J; Hwa, Joyce; Fancourt, Craig; Miller, Corin; Herath, Kithsiri; Roddy, Thomas P; Slipetz, Deborah; Erion, Mark D; Previs, Stephen F; Kelley, David E

    2016-12-01

    Aberrant regulation of glucose production makes a critical contribution to the impaired glycemic control that is observed in type 2 diabetes. Although isotopic tracer methods have proven to be informative in quantifying the magnitude of such alterations, it is presumed that one must rely on venous access to administer glucose tracers which therein presents obstacles for the routine application of tracer methods in rodent models. Since intraperitoneal injections are readily used to deliver glucose challenges and/or dose potential therapeutics, we hypothesized that this route could also be used to administer a glucose tracer. The ability to then reliably estimate glucose flux would require attention toward setting a schedule for collecting samples and choosing a distribution volume. For example, glucose production can be calculated by multiplying the fractional turnover rate by the pool size. We have taken a step-wise approach to examine the potential of using an intraperitoneal tracer administration in rat and mouse models. First, we compared the kinetics of [U- 13 C]glucose following either an intravenous or an intraperitoneal injection. Second, we tested whether the intraperitoneal method could detect a pharmacological manipulation of glucose production. Finally, we contrasted a potential application of the intraperitoneal method against the glucose-insulin clamp. We conclude that it is possible to 1) quantify glucose production using an intraperitoneal injection of tracer and 2) derive a "glucose production index" by coupling estimates of basal glucose production with measurements of fasting insulin concentration; this yields a proxy for clamp-derived assessments of insulin sensitivity of endogenous production. Copyright © 2016 the American Physiological Society.

  19. A comparative bioavailability study of two ibuprofen formulations after single-dose administration in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Metta S.S. Wiria

    2007-09-01

    Full Text Available This study was aimed to investigate the bioequivalence of ibuprofen 125 mg suppository formulation (Ibukal®, test formulation from PT. Kalbe Farma, Tbk., Jakarta and the ibuprofen suppository comparative formulation (Proris®, from PT. Pharos Indonesia, Jakarta in 12 healthy volunteers. The pharmacokinetic parameters used in this study were the area under the concentration-time curve from time zero to hour 10 (AUC0-t, the area under the concentration-time curve from time zero to infinite (AUC0-inf, the maximum concentration (Cmax, and the time needed to reach the maximum concentration (tmax. The study was designed as a random cross-over fashion, single-blinded which included 12 healthy adult volunteers. The volunteers were fasted overnight and in the morning they received a suppository of the test drug (Ibukal® or a suppository of the comparative drug (Proris®. Blood samples were withdrawn on hour 0 (control, 20 min; 40 min; 1; 1.5; 2; 2.5; 3; 4; 6; 8; and 10 time points after the administration of the drug. Following a wash-out period of 1 week, this procedure was repeated using the other drug. The serum concentration of the drug was determined by means of high-performance liquid chromatography with ultraviolet detection. The results of the study showed that, the mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the test drug were, respectively, 28.59(3.37 μg.h.mL-1, 30.47(3.56 μg.h.mL-1, 8.24(1.44 μg/mL, and 1.33(0.44 h. The mean (SD of AUC0-t, AUC0-inf, Cmax and tmax of the comparative drug were, respectively, 28.13(8.14 μg.h.mL-1, 30.56(8.05 μg.h.mL-1, 8.27(2.88 μg/mL, and 1.79(0.33 h. The geometric means ratio of the test to the comparative drug were 104.38% (CI 90%: 90.38-120.54% for AUC0-t, 101.97% (CI 90%: 89.51-116.16% for AUC0-inf, and 104.02% (CI 90%: 85.73-126.16% for Cmax. There was no side effect of the drug detected in this study. From the results we can conclude that the 125 mg of ibuprofen suppository of PT Kalbe Farma

  20. Pharmacokinetics, Safety and Tolerability of Single Oral or Intravenous Administration of 200 mg Tedizolid Phosphate in Adolescents.

    Science.gov (United States)

    Bradley, John S; Flanagan, Shawn D; Arrieta, Antonio C; Jacobs, Richard; Capparelli, Edmund; Prokocimer, Philippe

    2016-06-01

    Tedizolid is a novel oxazolidinone antibacterial US FDA approved for treatment of acute bacterial skin and skin structure infections in adults. This study assessed the pharmacokinetics, safety and tolerability of tedizolid phosphate in adolescents (12-17 years old) after administration of a single intravenous (IV) or oral dose. In this multicenter, open-label study, a single IV infusion (N = 10) or oral dose (N = 10) of 200 mg tedizolid phosphate was administered to adolescents already receiving antibacterial treatment for presumed or documented infection. Blood and urine samples were collected predose and over 24 hours. Tedizolid pharmacokinetics was generally similar after IV or oral administration of 200 mg tedizolid phosphate. Mean (standard deviation) half-life values were similar for oral and IV routes, 8.3 (2.0) and 6.6 (0.7) hours, respectively. Absolute oral bioavailability of tedizolid (90% confidence interval) was 88.8% (70.4%-112.1%). Geometric mean ratio (90% confidence interval) of area under the concentration-time curve values for adolescents relative to values previously reported for adults after 200 mg of single-dose IV or oral administration were 0.847 (0.736-0.975). Tedizolid was well tolerated. Overall pharmacokinetics of tedizolid was similar after administration of a single oral or IV 200 mg dose, and bioavailability was high. Exposure profiles were similar to those in adults. With clinical outcomes based on area under the concentration-time curve/minimum inhibitory concentration and current susceptibility of Gram-positive pathogens, results suggest that the 200 mg daily regimen of tedizolid phosphate can be extended to adolescents for clinical trials, and that dose adjustment may not be required when switching routes.

  1. Pharmacokinetics of voriconazole after oral administration of single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis).

    Science.gov (United States)

    Sanchez-Migallon Guzman, David; Flammer, Keven; Papich, Mark G; Grooters, Amy M; Shaw, Shannon; Applegate, Jeff; Tully, Thomas N

    2010-04-01

    To determine the pharmacokinetics and safety of voriconazole administered orally in single and multiple doses in Hispaniolan Amazon parrots (Amazona ventralis). 15 clinically normal adult Hispaniolan Amazon parrots. Single doses of voriconazole (12 or 24 mg/kg) were administered orally to 15 and 12 birds, respectively; plasma voriconazole concentrations were determined at intervals via high-pressure liquid chromatography. In a multiple-dose trial, voriconazole (18 mg/kg) or water was administered orally to 6 and 4 birds, respectively, every 8 hours for 11 days (beginning day 0); trough plasma voriconazole concentrations were evaluated on 3 days. Birds were monitored daily, and clinicopathologic variables were evaluated before and after the trial. Voriconazole elimination half-life was short (0.70 to 1.25 hours). In the single-dose experiments, higher drug doses yielded proportional increases in the maximum plasma voriconazole concentration (C(max)) and area under the curve (AUC). In the multiple-dose trial, C(max), AUC, and plasma concentrations at 2 and 4 hours were decreased on day 10, compared with day 0 values; however, there was relatively little change in terminal half-life. With the exception of 1 voriconazole-treated parrot that developed polyuria, adverse effects were not evident. In Hispaniolan Amazon parrots, oral administration of voriconazole was associated with proportional kinetics following administration of single doses and a decrease in plasma concentration following administration of multiple doses. Oral administration of 18 mg of voriconazole/kg every 8 hours would require adjustment to maintain therapeutic concentrations during long-term treatment. Safety and efficacy of voriconazole treatment in this species require further investigation.

  2. Biodistribution of BPA and BSH after single, repeated and simultaneous administrations for neutron-capture therapy of cancer

    Energy Technology Data Exchange (ETDEWEB)

    Ichikawa, H. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)], E-mail: ichikawa@pharm.kobegakuin.ac.jp; Taniguchi, E. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fukumori, Y. [Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586 (Japan)

    2009-07-15

    The effect of administration mode of L-BPA and BSH on the biodistribution in the melanoma-bearing hamsters was investigated. In single intravenous (i.v.) administration, BSH (100 mg BSH/kg) showed no significant retention of {sup 10}B in all the tissues, including tumors, while long-term retention of {sup 10}B in the tumor, muscle and brain was observed with L-BPA (500 mg BPA/kg). The dose escalation of L-BPA and the simultaneous single administration of L-BPA and BSH were not so effective at increasing boron accumulation in tumor after bolus i.v. injection. The boron concentration in tumor was 41 {mu}g B/g after single bolus i.v. injection even at the dose of 1000 mg BPA/kg. In contrast, two sequential bolus i.v. injections of L-BPA with the dose of 500 mg BPA/kg each was found to be effective at increasing {sup 10}B accumulation in the tumor; the maximum {sup 10}B concentration in the tumor reached 52 {mu}g B/g at 3 h after the second i.v. injection.

  3. Guideline adherence to chemotherapy administration safety standards: a survey on nurses in a single institute.

    Science.gov (United States)

    Kim, Kidong; Lee, Hee Sook; Kim, Younha; Kim, Beob-Jong; Kim, Moon-Hong; Choi, Seok-Cheol; Ryu, Sang-Young

    2011-03-31

    Little is known about the guideline adherence of nurses to chemotherapy administration guidelines. We determined the guideline adherence of nurses to the Chemotherapy Administration Safety Standards and the relationship between demographic characteristics and guideline adherence. Survey sheets containing two questions on demographic characteristics and 16 questions on the guideline adherence of nurses regarding chemotherapy administration were distributed to all in-patient departments in our hospital in which chemotherapy was performed. All clinical nurses in the department were recommended to respond. Of 202 nurses, 123 responses were collected (61% response rate). The guideline adherence rate was >70% for 15 of 16 questions, but 55% of respondents indicated that there was no competency monitoring for nurses. Nurses with >7 years of clinical nursing experience felt more competent in performing cardiopulmonary resuscitation (CPR) than nurses with guideline adherence rate of nurses with respect to chemotherapy administration was high, with the exception of the absence of a competency monitoring for nurses. A significant number of nurses with <7 years of clinical nursing experience felt incompetent in performing CPR.

  4. ASPECTOS CLÍNICOS DA INFUSÃO INTRAPERITONEAL EM BOVINOS

    Directory of Open Access Journals (Sweden)

    Wilmar Sachetin Marçal

    2015-12-01

    Full Text Available The maintenance and the proper concentration of ions are essential for homeostasis in animals. Some diseases such as hypocalcemia, hypoglycemia, diarrhea among others, commonly affect cattle, leading to eletrolute an acid base imbalances. Fluid therapy is done as a therapeutic method. This paper is intended to evaluate the use of intraperitoneal administrations of crystalloid solutions and other drugs as an effective and safe way for rehydration therapy of the sick animals.

  5. Intraperitoneal Paclitaxel Is Useful as Adjuvant Chemotherapy for Advanced Gastric Cancer with Serosal Exposure

    Directory of Open Access Journals (Sweden)

    Joji Kitayama

    2014-01-01

    Full Text Available Background: Intraperitoneal administration of paclitaxel (PTX can elicit a marked clinical response in peritoneal metastases of gastric cancer. Methods: In this study, we retrospectively analyzed the clinical outcome of 17 patients who underwent R0 resection with D2 dissection for advanced gastric cancer with macroscopic serosal exposure and received intraperitoneal PTX as adjuvant therapy. Results: A pathological study revealed that the depth of invasion of the primary tumor was pT4a or pT4b in 10 cases, and that the pN stage was more than pN2 in 8 cases. Genetic analysis of peritoneal lavage fluid was performed in 14 cases, all of which were positive for carcinoembryonic antigen mRNA. In these patients, PTX was intraperitoneally administered at 20-60 mg/m2 with oral S-1 for 3-36 months after surgery. In a median follow-up period of 66 months, recurrence occurred in the liver and peritoneum in 2 (11.7% and 1 (5.9% patients, respectively, and no nodal recurrence was observed. Five-year overall survival and disease-free survival were 88.2 and 82.3%, respectively. Conclusion: Since these patients are considered to be a high-risk group for peritoneal recurrence, this result strongly suggests that adjuvant chemotherapy including intraperitoneal PTX is a promising protocol to improve the outcome of patients with advanced gastric cancer with serosal exposure.

  6. Effect of exposure routes on the relationships of lethal toxicity to rats from oral, intravenous, intraperitoneal and intramuscular routes.

    Science.gov (United States)

    Ning, Zhong H; Long, Shuang; Zhou, Yuan Y; Peng, Zi Y; Sun, Yi N; Chen, Si W; Su, Li M; Zhao, Yuan H

    2015-11-01

    The lethal toxicity values (log 1/LD(50)) of 527 aliphatic and aromatic compounds in oral, intravenous, intramuscular and intraperitoneal routes were used to investigate the relationships of log 1/LD(50) from different exposure routes. Regression analysis shows that the log 1/LD(50) values are well correlated between intravenous and intraperitoneal or intramuscular injections. However, the correlations between oral and intravenous or intraperitoneal routes are relatively poor. Comparison of the average residuals indicates that intravenous injection is the most sensitive exposure route and oral administration is the least sensitive exposure route. This is attributed to the difference in kinetic process of toxicity testing. The toxic effect of a chemical can be similar or significantly different between exposure routes, depending on the absorption rates of chemicals into blood. Inclusion of hydrophobic parameter and fractions of ionic forms can improve the correlations between intravenous and intraperitoneal or oral routes, but not between intraperitoneal and oral routes. This is due to the differences of absorption rate in different exposure environments from different routes. Several factors, such as experimental uncertainty, metabolism and toxic kinetics, can affect the correlations between intravenous and intraperitoneal or oral routes. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Comparative single-dose pharmacokinetics of rasagiline in minipigs after oral dosing or transdermal administration via a newly developed patch.

    Science.gov (United States)

    Lin, Yu; Zou, Yanye; Lin, Jialiang; Zhang, Tao; Deng, Jie

    2013-08-01

    1. A rasagiline transdermal patch was developed for the treatment of early and advanced Parkinson's disease. Relevant pharmacokinetic parameters of rasagiline obtained after transdermal administration to minipigs were compared with those of rasagiline after oral administration. 2. A total of 18 minipigs were randomly divided into three groups (six animals for each group). A single dose of 1 mg rasagiline tablet was orally administrated to one group. Meanwhile, single dose of 1.25 and 2.5 mg (2 and 4 cm(2)) rasagiline patches were given (at the postauricular skin) to the other two groups, respectively. The pharmacokinetic parameters such as plasma half-life (t1/2), time to peak plasma-concentration (Tmax), mean residence time (MRT), area under the curve (AUC(0-t)) were significantly (p rasagiline (1.25 mg patch: 11.8 ± 6.5 h, 2.5 mg patch: 12.5 ± 4.7 h) in minipig following transdermal administration was significantly prolonged as compared with that following the oral administration (1 mg tablet: 4.7 ± 2.5 h). The dose-normalized relative bioavailability of rasagiline patch in minipig were 178.5% and 156.4%, respectively, for 1.25 and 2.5 mg patches compared with 1 mg rasagiline tablet. The prolonged t1/2 and increased bioavailability of rasagiline patch suggested a possible longer dosing interval compared with oral tablet.

  8. Comparative toxicokinetics of MMB4 DMS in rats, rabbits, dogs, and monkeys following single and repeated intramuscular administration.

    Science.gov (United States)

    Hong, S Peter; Gibbs, Seth T; Kobs, Dean J; Hawk, Michael A; Croutch, Claire R; Osheroff, Merrill R; Johnson, Jerry D; Burback, Brian L

    2013-01-01

    1,1'-Methylenebis[4-[(hydroxyimino)methyl]-pyridinium] (MMB4) dimethanesulfonate (DMS) is a bisquaternary pyridinium aldoxime that reactivates acetylcholinesterase inhibited by organophosphorus nerve agent. Time courses of MMB4 concentrations in plasma were characterized following 7-day repeated intramuscular (IM) administrations of MMB4 DMS to male and female Sprague-Dawley rats, New Zealand White rabbits, beagle dogs (single dose only), and rhesus monkeys at drug dose levels used in earlier toxicology studies. In general, there were no significant differences in MMB4 toxicokinetic (TK) parameters between males and females for all the species tested in these studies. After a single IM administration to rats, rabbits, dogs, and monkeys, MMB4 DMS was rapidly absorbed, resulting in average T max values ranging from 5 to 30 minutes. Although C max values did not increase dose proportionally, the overall exposure to MMB4 in these preclinical species, as indicated by area under the curve (AUC) extrapolated to the infinity (AUC∞) values, increased in an approximately dose-proportional manner. The MMB4 DMS was extensively absorbed into the systemic circulation after IM administration as demonstrated by greater than 80% absolute bioavailability values for rats, rabbits, and dogs. Repeated administrations of MMB4 DMS for 7 days did not overtly alter TK parameters for MMB4 in rats, rabbits, and monkeys (150 and 300 mg/kg/d dose groups only). However, C max and AUC values decreased in monkeys given 450 and 600 mg/kg IM doses of MMB4 DMS following repeated administrations for 7 days. Based on the TK results obtained from the current study and published investigations, it was found that the apparent volume of distribution and clearance values were similar among various preclinical species, except for the rat.

  9. 77 FR 2024 - Federal Housing Administration (FHA) Single-Family Mortgage Insurance: Elimination of Requests...

    Science.gov (United States)

    2012-01-13

    ... utilizing the appeals process has gone from 105 for the 2008 loan limits to zero for the 2011 loan limits...) Single-Family Mortgage Insurance: Elimination of Requests for Alternative Mortgage Limits AGENCY: Office... amounts. HUD currently sets the area- based loan limits on a yearly basis and permits appeals of these...

  10. Pharmacokinetics, Safety, and Tolerability of Tedizolid Phosphate After Single-dose Administration in Healthy Korean Male Subjects.

    Science.gov (United States)

    Kim, Yun; Kim, Anhye; Lee, SeungHwan; Choi, Sung-Hak; Lee, Dae Young; Song, Ji-Su; Lee, Howard; Jang, In-Jin; Yu, Kyung-Sang

    2017-09-01

    Tedizolid phosphate is a next-generation oxazolidinone prodrug that is transformed into the active moiety tedizolid. Its indication is acute bacterial skin and skin structure infections caused by gram-positive species, including methicillin-resistant Staphylococcus aureus. Although tedizolid phosphate has been marketed in Korea, no data on the pharmacokinetic (PK) properties or tolerability of tedizolid phosphate in Korean subjects are available. This study was designed to evaluate the PK properties, oral bioavailability, and tolerability with a single-dose oral and intravenous administration of tedizolid phosphate in healthy Korean male subjects. A block-randomized, double-blind, placebo-controlled, single-dose study was conducted in 3 groups (200, 400, and 600 mg; 10 subjects in each group). In the second part of the study, subjects from the 200-mg group received administration orally and intravenously (1-hour infusion) via 2-way crossover for the evaluation of absolute bioavailability. There was a 7-day washout period between treatments in the absolute bioavailability part of the study. Serial blood samples for PK analysis were collected for up to 72 hours. Tolerability was assessed by analysis of adverse events. Thirty healthy Korean subjects completed the study and were included in the PK and tolerability analyses. Tedizolid phosphate was rapidly converted into tedizolid. After a single oral dose, the T max of tedizolid was observed to be 1.5 to 2.5 hours, and the plasma concentration-time curve of tedizolid showed a 2-phase elimination pattern, with a half-life of ~11 hours. Dose-dependent increases were observed in the AUC last value (29,441-78,062 μg · h/L) and in the C max value ( 2679-6980 μg/L) with the administration of tedizolid phosphate 200 to 600 mg PO. The absolute bioavailability of tedizolid was 95.2% (90% CI, 92.7%-97.8%) in the 200-mg administration group. There were no serious adverse events or clinically significant changes in the

  11. Intraperitoneal Vancomycin Plus Either Oral Moxifloxacin or Intraperitoneal Ceftazidime for the Treatment of Peritoneal Dialysis-Related Peritonitis: A Randomized Controlled Pilot Study.

    Science.gov (United States)

    Xu, Rong; Yang, Zhikai; Qu, Zhen; Wang, Huan; Tian, Xue; Johnson, David W; Dong, Jie

    2017-07-01

    Intraperitoneal administration of antibiotics is recommended as a first treatment for managing peritoneal dialysis (PD)-related peritonitis. However, the efficacy of oral administration of quinolones has not been well studied. Randomized controlled pilot study. 80 eligible patients with PD-related peritonitis from Peking University First Hospital (40 in each arm). Intraperitoneal vancomycin, 1g, every 5 days plus oral moxifloxacin, 400mg, every day (treatment group) versus intraperitoneal vancomycin, 1g, every 5 days plus intraperitoneal ceftazidime, 1g, every day (control group). The primary end point was complete resolution of peritonitis, and secondary end points were primary or secondary treatment failure. PD effluent white blood cell count. Baseline demographic and clinical characteristics of the 2 groups were comparable. There were 24 and 22 Gram-positive organisms, 6 and 7 Gram-negative organisms, 9 and 10 culture-negative samples, and 1 and 1 fungal sample in the treatment and control groups, respectively. Complete resolution of peritonitis was achieved in 78% and 80% of cases in the treatment and control groups, respectively (OR, 0.86; 95% CI, 0.30-2.52; P=0.8). There were 3 and 1 cases of relapse in the treatment and control groups, respectively. Primary and secondary treatment failure rates were not significantly different (33% vs 20% and 10% vs 13%, respectively). In each group, there was 1 peritonitis-related death and 6 transfers to hemodialysis therapy. During the 3-month follow-up period, 7 and 3 successive episodes of peritonitis occurred in the treatment and control groups, respectively. Only 2 adverse drug reactions (mild nausea and mild rash, respectively) were observed in the 2 groups. Sample size was relatively small and the eligibility ratio was low. Also, the number of peritonitis episodes was low, limiting the power to detect a difference between groups. This pilot study suggests that intraperitoneal vancomycin with oral moxifloxacin is a

  12. Effects of single and repeated administration of 1,2,3,4-tetrahydroisoquinoline analogs on the binding of [11C]raclopride to dopamine D2 receptors in the mouse brain

    International Nuclear Information System (INIS)

    Ishiwata, K.; Senda, M.; Saitoh, T.; Taguchi, K.; Toda, J.; Sano, T.; Koyanagi, Y.

    2001-01-01

    We investigated the effects of intraperitoneal injection of 1,2,3,4-tetrahydroisoquinoline (TIQ) analogs and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on the binding of [ 11 C]raclopride to striatal dopamine D 2 receptors in mice. The binding of [ 11 C]raclopride, but not of [ 11 C]N-methylspiperone or [ 11 C]nemonapride with higher affinity, to the receptors was significantly decreased immediately after TIQ injection. Neither a dopamine transporter blocker induced such effect nor TIQ affected the dopamine transporter-radioligand binding. Among the compounds investigated, including parkinsonism-inducing TIQ and (R/S)-1-benzyl-TIQ, parkinsonism-preventing (R)- and (S)-1-methyl-TIQ, and probable N-methylated metabolites of TIQ and 1-methyl-TIQ, TIQ and (S)-1-methyl-TIQ had the strongest effect on the binding of [ 11 C]raclopride, and N-methylated derivatives showed less of an effect than the respective parent compounds. The decrease in the binding of [ 11 C]raclopride continued for 7 hours and was followed by an increase until 10 days after the single and subchronic administration of TIQ. These findings suggest that TIQ analogs profoundly stimulated dopamine release which resulted in the competitive inhibition of the binding of [ 11 C]raclopride to dopamine D 2 receptors, but did not induce degeneration of the receptors. (author)

  13. Administration of single-dose GnRH agonist in the luteal phase in ICSI cycles: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Oliveira João

    2010-09-01

    Full Text Available Abstract Background The effects of gonadotrophin-releasing hormone agonist (GnRH-a administered in the luteal phase remains controversial. This meta-analysis aimed to evaluate the effect of the administration of a single-dose of GnRH-a in the luteal phase on ICSI clinical outcomes. Methods The research strategy included the online search of databases. Only randomized studies were included. The outcomes analyzed were implantation rate, clinical pregnancy rate (CPR per transfer and ongoing pregnancy rate. The fixed effects model was used for odds ratio. In all trials, a single dose of GnRH-a was administered at day 5/6 after ICSI procedures. Results All cycles presented statistically significantly higher rates of implantation (P Conclusions These findings demonstrate that the luteal-phase single-dose GnRH-a administration can increase implantation rate in all cycles and CPR per transfer and ongoing pregnancy rate in cycles with GnRH antagonist ovarian stimulation protocol. Nevertheless, by considering the heterogeneity between the trials, it seems premature to recommend the use of GnRH-a in the luteal phase. Additional randomized controlled trials are necessary before evidence-based recommendations can be provided.

  14. Pharmacokinetics and egg residues after oral administration of a single dose of meloxicam in domestic chickens (Gallus domesticus).

    Science.gov (United States)

    Souza, Marcy J; Bergman, Joan B; White, Molly S; Gordon, Kristen I; Gerhardt, Lillian E; Cox, Sherry K

    2017-08-01

    OBJECTIVE To determine the pharmacokinetics of meloxicam in domestic hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg). ANIMALS 8 healthy adult White Leghorn hens. PROCEDURES Hens were administered 1 mg of meloxicam/kg PO once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma, egg whites (albumen), and egg yolks were analyzed by high-performance liquid chromatography. RESULTS The half-life, maximum concentration, and time to maximum concentration of meloxicam in plasma samples were 2.8 hours, 7.21 μg/mL, and 2 hours, respectively. Following meloxicam administration, the drug was not detected after 4 days in egg whites and after 8 days in egg yolks. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that meloxicam administered at a dose of 1 mg/kg PO in chickens appears to maintain plasma concentrations equivalent to those reported to be therapeutic for humans for 12 hours. The egg residue data may be used to aid establishment of appropriate drug withdrawal time recommendations.

  15. Repeated Intraperitoneal alpha-Radioimmunotherapy of Ovarian Cancer in Mice

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger

    2010-01-01

    The aim of this study was to investigate the therapeutic efficacy of alpha-radioimmunotherapy of ovarian cancer in mice using different fractionated treatment regimens. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. Methods....... Nude mice were intraperitoneally inoculated with ~1 x 10(7) cells of the cell line NIH:OVCAR-3. Four weeks later 6 groups of animals were given 400 kBq (211)At-MX35 F(ab')(2) as a single or as a repeated treatment of up to 6 times (n = 18 in each group). The fractionated treatments were given every...... seventh day. Control animals were treated with unlabeled MX35 F(ab')(2) (n = 12). Eight weeks posttreatment the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Results. The tumor-free fractions (TFFs) of the animals, defined as the fraction of animals...

  16. Serum Antibodies Protect against Intraperitoneal Challenge with Enterotoxigenic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Xinghong Yang

    2011-01-01

    Full Text Available To assess whether anticolonization factor antigen I (CFA/I fimbriae antibodies (Abs from enterotoxigenic Escherichia coli (ETEC can protect against various routes of challenge, BALB/c mice were immunized with a live attenuated Salmonella vaccine vector expressing CFA/I fimbriae. Vaccinated mice elicited elevated systemic IgG and mucosal IgA Abs, unlike mice immunized with the empty Salmonella vector. Mice were challenged with wild-type ETEC by the oral, intranasal (i.n., and intraperitoneal (i.p. routes. Naïve mice did not succumb to oral challenge, but did to i.n. challenge, as did immunized mice; however, vaccinated mice were protected against i.p. ETEC challenge. Two intramuscular (i.m. immunizations with CFA/I fimbriae without adjuvant conferred 100% protection against i.p. ETEC challenge, while a single 30 μg dose conferred 88% protection. Bactericidal assays showed that ETEC is highly sensitive to anti-CFA/I sera. These results suggest that parenteral immunization with purified CFA/I fimbriae can induce protective Abs and may represent an alternative method to elicit protective Abs for passive immunity to ETEC.

  17. Single-dose ethanol administration activates the hypothalamic-pituitary-adrenal axis: exploration of the mechanism of action.

    Science.gov (United States)

    Thiagarajan, A B; Mefford, I N; Eskay, R L

    1989-10-01

    Activation of the hypothalamic-pituitary-adrenal axis (HPAA) by single-dose ethanol administration, which achieved moderately high blood ethanol levels, was explored in naive rats in order to determine the mechanism of ethanol's activation of the stress axis. Adult male rats received a single dose (3.2 g/kg body weight-1 of a 12% solution of ethanol in physiological saline. The plasma concentration of immunoreactive (ir) adrenocorticotropic hormone (ACTH), beta-endorphin (BE) and corticosterone (CS) was determined by radioimmunoassay, whereas, plasma concentrations of epinephrine (E) and norepinephrine (NE) were quantified following reverse-phase liquid chromatographic separation and amperometric detection. Ethanol induced maximal plasma ACTH levels within minutes, which declined toward basal levels by 60 min, whereas, plasma concentration of CS rose rapidly and remained elevated at 60 min. Plasma ACTH and CS levels in saline-treated control animals did not vary significantly at any time point. Consistent with co-release of ACTH from corticotrophs, the plasma concentration of ir-BE increased 5-fold at 15 min and declined towards basal levels at 60 min after-ethanol challenge. Plasma E increased 10- to 20-fold as compared to saline controls or preinjection levels and returned to preinjection levels by 90 min, in a manner similar to ethanol-induced changes in proopiomelanocortin-derived peptides and CS. Removal of the adrenal medulla and thus the source of E prior to ethanol administration, did not attenuate activation of the HPAA. Passive immunoneutralization of arginine vasopressin (AVP), using a high-titer AVP antiserum and a protocol which was found to block ether-induced ACTH secretion by 40% in adult male rats, failed to even partially block ethanol-induced ACTH or CS secretion. The results of this study indicate that neither adrenal medulla-derived E nor AVP are significant regulators or coregulators of corticotroph secretions following a moderately high

  18. Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

    Science.gov (United States)

    Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

    2017-01-01

    To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

  19. Continuous intraperitoneal insulin infusion versus subcutaneous insulin therapy in the treatment of type 1 diabetes: effects on glycemic variability

    NARCIS (Netherlands)

    van Dijk, Peter R.; Groenier, Klaas H.; DeVries, J. Hans; Gans, Reinold O. B.; Kleefstra, Nanno; Bilo, Henk J. G.; Logtenberg, Susan J. J.

    2015-01-01

    As continuous intraperitoneal insulin infusion (CIPII) results in a more physiologic action of insulin than subcutaneous (SC) insulin administration, we hypothesized that CIPII would result in less glycemic variability (GV) than SC insulin therapy among type 1 diabetes mellitus (T1DM) patients. Data

  20. [The main aspects of vesical risk in intraperitoneal surgery].

    Science.gov (United States)

    Tode, V; Voinea, F; Marin, O

    2001-01-01

    They are described the main aspects of vezical risk in intraperitoneal surgery: subembilical celiostomy, haernios surgery, rectal surgery, gynecological surgery. It is shown few aspects of our experience in the treatment of haernias, vesicovaginal fistules secondary to total hysterectomy.

  1. Comparison of efficacy of intraperitoneal instillation of bupivacaine ...

    African Journals Online (AJOL)

    Comparison of efficacy of intraperitoneal instillation of bupivacaine alone with bupivacaine – fentanyl and bupivacaine –tramadol combination for alleviation of post-operative pain following laparoscopic cholecystectomy: a randomized prospective study.

  2. Pharmacokinetics and Safety of Tedizolid after Single and Multiple Intravenous/Oral Sequential Administrations in Healthy Chinese Subjects.

    Science.gov (United States)

    Chen, Rui; Shen, Kai; Chang, Xinying; Tanaka, Toshiaki; Li, Li; Hu, Pei

    2016-08-01

    Tedizolid phosphate is a new antibacterial agent under investigation for the treatment of Gram-positive infections in China. This study was conducted to assess the pharmacokinetic (PK) properties, oral bioavailability, and safety of once daily tedizolid phosphate 200 mg in Chinese subjects to support its further clinical development in China. This Phase I single-center study, conducted in 16 healthy Chinese male subjects, consisted of a single-dose administration, 1:1 randomized, two-way, intravenous (IV)/oral (PO) crossover of tedizolid phosphate 200 mg (Part 1) and, after a 7-day washout, a nonrandomized, multiple-dose, 7-day tedizolid phosphate 200 mg once daily administration (IV for 3 days, PO for 4 days; Part 2). Blood samples were collected for up to 72 hours after single dosing and for up to 2 hours on Day 3 and 72 hours on Day 7 of multiple dosing to determine PK parameters. Adverse events (AEs) were recorded throughout the entire study. The Cmax and AUC of tedizolid (the active moiety of tedizolid phosphate) were 3.02 µg/mL and 30.50 µg • h/mL after single IV dosing of tedizolid phosphate, and 2.25 µg/mL and 26.10 µg • h/mL after single PO dosing, respectively, and the mean half-life was 10.1 hours for both administration routes. The oral bioavailability of tedizolid was 85.5%. PK parameters of tedizolid were similar after single and multiple dosing of tedizolid phosphate, indicating no time dependency. Only minor accumulation of tedizolid was observed after multiple dosing (expressed as accumulation ratios RAAUC: 1.18 for PO dosing, and RACmax: 1.16 and 1.05 for IV and PO dosing, respectively). Steady state of tedizolid was reached after about 3 days, and trough concentrations remained constant when switching from IV to PO dosing. Tedizolid phosphate was well tolerated with 6 subjects (37.5%) in Part 1 and 5 subjects (31.3%) in Part 2 experiencing an AE; all AEs but one were related to the study drug assessed by the investigator. All AEs were of

  3. Behandling af peritoneal karcinose med laparoskopisk intraperitoneal kemoterapi under tryk

    DEFF Research Database (Denmark)

    Graversen, Martin; Pfeiffer, Per; Mortensen, Michael Bau

    2016-01-01

    Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment option in patients with peritoneal carcinomatosis (PC). PIPAC has proven efficacious in the treatment of PC from ovarian, colon and gastric cancer. PIPAC has a favourable profile regarding safety for patients and occupati......Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new treatment option in patients with peritoneal carcinomatosis (PC). PIPAC has proven efficacious in the treatment of PC from ovarian, colon and gastric cancer. PIPAC has a favourable profile regarding safety for patients...

  4. Pharmacokinetics and bioequivalence study of aniracetam after single-dose administration in healthy Chinese male volunteers.

    Science.gov (United States)

    Tian, Yuan; Zhang, Jing-Jing; Feng, Shu-Dan; Zhang, Zun-Jian; Chen, Yun

    2008-01-01

    The pharmacokinetics of aniracetam (CAS 72432-10-1) in Chinese healthy male volunteers was investigated for the first time. Twenty male volunteers were enrolled into this open, randomized, single blind two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg (2 x 200 mg/capsule) aniracetam as a test or reference formulation with a 3-day washout period between the two preparations. The plasma concentrations of aniracetam were analyzed by a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. The pharmacokinetic parameters of the test and reference formulations were estimated as follows: The maximum plasma concentrations (Cmax) were 8.75 +/- 7.82 and 8.65 +/- 8.70 ng/mL, Tmax were 0.4 +/- 0.1 and 0.4 +/- 0.1 h, and plasma elimination half-lives (t(1/2)) were 0.47 +/- 0.16 and 0.49 +/- 0.24 h, respectively. The AUC(0-t) values demonstrated nearly identical bioavailability of aniracetam from the examined formulations. AUC(0-2.5) values were 4.53 +/- 6.62 and 4.76 +/- 6.65 ng h/mL, the areas under the plasma concentration-time curve (AUC(0-infinity) were 4.62 +/- 6.66 and 4.85 +/- 6.71 ng h/mL for the test and reference formulation, respectively. No statistical differences were observed for Cmax, and AUC(0-infinity) for aniracetam. The 90% confidence limits calculated for AUC and Cmax of aniracetam were within the standard bioequivalence range (80%-125% for AUC and Cmax). Therefore, the aniracetam test formulation can be regarded as bioequivalent to the aniracetam reference formulation.

  5. [Anaphylaxis needing adrenaline administration during anesthesia: a 7-year single-institution study].

    Science.gov (United States)

    Kayashima, Kenji; Sozen, Reiko

    2013-10-01

    Adrenaline is the key treatment for acute anaphylaxis; however, it is difficult to use it appropriately in terms of dosage and timing. If used incorrectly, adrenaline can cause cardiac infarction, stroke, recurrence and other problems. We collected data of suspected anaphylaxis from records in our anesthesia department between April 2005 and March 2012. All cases where the skin of patients turned red and blood pressure decreased continuously were included. We analyzed the usage of adrenaline in these cases. Six (0.034%) suspected anaphylaxis cases were analyzed from a total of 27,597 anesthesia cases. Adrenaline was administered subcutaneously in 2 cases, intravenously in 3 cases, and with and infused in 1 case. In the 4 cases with intravenous administration, the median dose was 0.52 (range : 0.02-1.6) mg. Following decreased and unstable blood pressure, adrenaline was initiated after a median of 12.5 (5-25) min, and blood pressure returned to normal after 20 (5-95) min. Patients were extubated 19 (4-24) hours after observation of anomalous blood pressure. No aftereffects or recurrences were observed. Adrenaline was administered appropriately in terms of dosage, but timing should have been earlies in 3 of 6 cases.

  6. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects

    Directory of Open Access Journals (Sweden)

    Handan Bardak

    2016-01-01

    Full Text Available No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC, total trefoil (TF, total spherical aberration (TSA, and total higher order aberration (HOA were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France. The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p>0.05. A significant increase was observed in TF and HOA measurements following coffee intake (p=0.029 and p=0.009, resp.. Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

  7. Effect of Single Administration of Coffee on Pupil Size and Ocular Wavefront Aberration Measurements in Healthy Subjects.

    Science.gov (United States)

    Bardak, Handan; Gunay, Murat; Mumcu, Ugur; Bardak, Yavuz

    2016-01-01

    No study has so far evaluated the impact of coffee drinking on ocular wavefront aberration (OWA) measurements. This study presents novel findings regarding the OWA of the eye following coffee intake. We aimed to evaluate the acute changes in pupil size and OWA of the eye after single administration of coffee. A total of 30 otherwise healthy participants were included in this prospective study. All subjects drank a cup of coffee containing 57 mg caffeine. Measurements of pupil size, total coma (TC), total trefoil (TF), total spherical aberration (TSA), and total higher order aberration (HOA) were performed before and at 5 minutes, at 30 minutes, and at 4 hours after coffee drinking using a wavefront aberrometer device (Irx3, Imagine Eyes, Orsay, France). The mean age of the study population was 20.30 ± 2.74 years. Pupil size did not show a significant change during the measurements (p > 0.05). A significant increase was observed in TF and HOA measurements following coffee intake (p = 0.029 and p = 0.009, resp.). Single administration of coffee results in significant increase in TF and total HOAs in healthy subjects without any effect on pupil diameter. Ultrastructural changes in the cornea following coffee intake might be of relevance to the alterations in ocular aberrations in healthy subjects.

  8. The delayed lung responses to single and repeated intratracheal administration of pure cobalt and hard metal powder in the rat.

    Science.gov (United States)

    Lasfargues, G; Lardot, C; Delos, M; Lauwerys, R; Lison, D

    1995-05-01

    Epidemiological and clinical studies suggest that inhalation of cobalt metal dust (Co) mixed with tungsten carbide particles (WC), but not of cobalt dust alone, may cause interstitial pulmonary lesions (hard metal disease). In previous experimental studies in the rat, we have demonstrated the greater acute pulmonary toxicity of a WC-Co mixture compared to Co or WC alone. The present study was undertaken to compare in the same animal model the delayed lung response after intratracheal administration of Co or WC-Co particles (cobalt particle 6.3 wt%). The responses were also compared with those obtained after treatment with arsenic trioxide and crystalline silica used a reference materials producing an acute toxic insult and a progressive fibrogenic response, respectively. Cellular (total and differential counts) and biochemical parameters (LDH, N-acetyl-beta-D-glucosaminidase, total protein, albumin, fibronectin, and hyaluronic acid) were measured in bronchoalveolar lavage fluid following single and repeated intratracheal instillations. The results indicate that the delayed lung response observed after WC-Co is different from that after cobalt metal alone. A single intratracheal dose of WC-Co (1, 5, or 10 mg/100 g body wt) induced an acute alveolitis which persisted for at least 1 month. Four months after a single instillation of WC-Co, no clear histological lung fibrosis could however be evidenced, indicating a reversibility of the lesions. The effects of cobalt (0.06, 0.3, or 0.6 mg/100 g body wt) or tungsten carbide alone (1, 5, 10 mg/ 100 g body wt) were very modest, if any. Following repeated intratracheal instillations (four administrations at 1-month interval), increased lung hydroxyproline content and histopathological evidence of interstitial fibrosis were observed after WC-Co (4 x 1 mg/100 g body wt), but not after administration of each component separately, i.e., Co (4 x 0.06 mg/100 g body wt) or WC (4 x 1 mg/100 g body wt). The mechanism of the fibrotic

  9. Therapeutic response to single intravenous bolus administration of formate dehydrogenase in methanol-intoxicated rats.

    Science.gov (United States)

    Muthuvel, Arumugham; Rajamani, Rathinam; Sheeladevi, Rathinasamy

    2006-02-20

    Methanol remains to be a major public and environmental health hazard. Formic acid is the toxic metabolite responsible for the metabolic acidosis observed in methanol poisoning in humans, in non-human primates and in folate-depleted rodents. Cytochrome oxidase inhibition by formate leads to lactic acid accumulation, which contributes significantly to metabolic acidosis. Toxic effects in human beings are characterized by formic acidemia, metabolic acidosis, ocular toxicity, nervous system depression, blindness, coma and death. Elimination of formate is one of the principles of management in methanol poisoning. Hemodialysis facility is not readily available in all the places, in developing countries like India. Formate dehydrogenase (EC 1.2.1.2) acts directly over formate and converts formate into CO(2) in the presence of NAD. Effect of single intravenous bolus infusion of formate dehydrogenase, obtained from Candida boidinii; in methanol-intoxicated folate deficient rat model was evaluated. Folate depletion induced by methotrexate (MTX) treatment. Carbicarb (Carb) (equimolar solution of sodium carbonate and sodium bicarbonate) was used to treat metabolic acidosis. Experimental design consists of seven groups, namely Saline control, methanol control, MTX control, Enzyme control, MTX-methanol control, MTX-methanol-Carb and MTX-methanol-Carb-Enz group. Male wistar rats treated with MTX (0.3mg/kg) for a week, were injected (i.p.) with methanol (4 gm/kg), 12h latter, Carbicarb solution was infused, following this enzyme was infused (i.v.) in bolus. Blood samples were collected every 15 min for an hour from the cannulated left jugular vein and blood methanol, formate were estimated, respectively, with HPLC and fluorimetric assay. Blood pH, blood gases pO(2), pCO(2) and bicarbonate were monitored with blood gas analyzer in order to evaluate acid base status of the animal. Results obtained show that there is significant elimination of formate within 15 min. It may be

  10. Meloxicam pharmacokinetics using nonlinear mixed-effects modeling in ferrets after single subcutaneous administration.

    Science.gov (United States)

    Chinnadurai, S K; Messenger, K M; Papich, M G; Harms, C A

    2014-08-01

    This study was designed to investigate the pharmacokinetics of meloxicam, an oxicam class, nonsteroidal anti-inflammatory drug (NSAID), in ferrets. We determined the pharmacokinetic properties of a single subcutaneous dose of meloxicam (0.2 mg/kg) in nine male and nine female ferrets. Blood samples were collected by venipuncture of the cranial vena cava into heparinized syringes. Plasma meloxicam concentrations were determined by high-pressure liquid chromatography (HPLC). Pharmacokinetic variables were calculated using nonlinear mixed-effects modeling to take advantage of the population-based sampling scheme and to minimize sample volume collected per animal. Maximum plasma concentration, volume of distribution per absorption, and elimination half-life were 0.663 μg/mL, 0.21 L, and 11.4 h, respectively, for females and 0.920 μg/mL, 0.35 L, and 17.8 h, respectively, for males. Significant differences were found in each of the above parameters between male and female ferrets. Systemic clearance per absorption was not affected by gender and was 13.4 mL/h. Analgesic efficacy was not evaluated, but plasma meloxicam concentrations achieved in these animals are considered effective in other species. Sex differences in the pharmacokinetic behavior of meloxicam should be taken into consideration when treating ferrets. © 2014 John Wiley & Sons Ltd.

  11. Topiramate modulates trigeminal pain processing in thalamo-cortical networks in humans after single dose administration.

    Science.gov (United States)

    Hebestreit, Julia M; May, Arne

    2017-01-01

    Migraine is the sixth most common cause of disability in the world. Preventive migraine treatment is used to reduce frequency, severity and duration of attacks and therefore lightens the burden on the patients' quality of life and reduces disability. Topiramate is one of the preventive migraine treatments of proven efficacy. The mechanism of action underlying the preventive effect of topiramate in migraine remains largely unknown. Using functional magnetic resonance imaging (fMRI) we examined the central effects of a single dose of topiramate (100mg) on trigeminal pain in humans, compared to placebo (mannitol). In this prospective, within subject, randomized, placebo-controlled and double-blind study, 23 healthy participants received a standardized nociceptive trigeminal stimulation and control stimuli whilst being in the scanner. No differences in the subjective intensity ratings of the painful stimuli were observed between topiramate and placebo sessions. In contrast, topiramate significantly decreased the activity in the thalamus and other pain processing areas. Additionally, topiramate increased functional coupling between the thalamus and several brain regions such as the bilateral precuneus, posterior cingulate cortex and secondary somatosensory cortex. These data suggest that topiramate exhibits modulating effects on nociceptive processing in thalamo-cortical networks during trigeminal pain and that the preventive effect of topiramate on frequent migraine is probably mediated by an effect on thalamo-cortical networks.

  12. Administration of follitropin alfa and lutropin alfa combined in a single injection: a feasibility assessment

    Directory of Open Access Journals (Sweden)

    Agostinetto Rita

    2009-05-01

    Full Text Available Abstract Background Gonadotrophins are routinely administered in assisted reproductive technology (ART treatment protocols. Recombinant human follicle-stimulating hormone (r-hFSH; follitropin alfa and recombinant human luteinizing hormone (r-hLH; lutropin alfa can be administered individually or in a fixed combination. The ability to vary the FSH to LH dose ratio in a single injection without compromising the bioactivity of either gonadotrophin or generating losses of active principle is important for physicians and patients alike. Methods This study investigated whether follitropin alfa (GONAL-f (R, as lyophilized powder for reconstitution or solution from the GONAL-f (R (filled-by-mass [FbM] Prefilled Pen, could be used to reconstitute Pergoveris TM (follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder. In Ratio Groups 1 and 2, the r-hFSH:r-hLH ratio was 3:1; in Ratio Groups 3 and 4, the ratios of r-hFSH:r-hLH were 5:1 and 8:1, respectively. The protein content and bioactivity of each mixed solution were evaluated. The r-hFSH and r-hLH content was determined using reverse-phase high performance liquid chromatography. The biological activity of r-hFSH and r-hLH was assessed using the Steelman-Pohley and Van Hell in vivo bioassays in rats, respectively. Results Follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder could be successfully mixed with follitropin alfa 75 IU FbM solution that was either reconstituted from lyophilized powder or injected directly from the prefilled pen to create solutions with ratios of r-hFSH and r-hLH from 3:1 to 8:1. The measured content of r-hFSH and r-hLH corresponded favourably with the target protein content in Ratio Groups 1–4. The in vivo target and measured bioactivity of r-hFSH and r-hLH were also closely matched in all Ratio Groups. Conclusion Follitropin alfa lyophilized powder or solution can be accurately mixed with follitropin alfa/lutropin alfa 150 IU/75 IU lyophilized powder to

  13. [Intraperitoneal photodynamic therapy for peritoneal metastasis of epithelial ovarian cancer. Limits and future prospects].

    Science.gov (United States)

    Azaïs, H; Mordon, S; Collinet, P

    2017-04-01

    High peritoneal recurrence rate in advanced epithelial ovarian cancer after complete macroscopic cytoreductive surgery and platinum-based chemotherapy, raises the issue of peritoneal microscopic disease management and requires the development of additional locoregional treatment strategies. Photodynamic therapy is an effective treatment already applied in other medical and surgical indications. After administration of a photosensitizer which accumulates in cancer cells, illumination with a light of adequate wavelength may induce photochemical reaction between photosensitizer and tissue oxygen which lead to reactive oxygen species production and cytotoxic phenomenon. Photodynamic therapy's ability to treat superficial lesions disseminated on large area makes it an excellent candidate to insure destruction of microscopic peritoneal metastases in addition to macroscopic cytoreductive surgery in order to decrease peritoneal recurrence rate. Development of intraperitoneal photodynamic therapy has been limited by its poor tolerance related to the lack of specificity of photosensitizers and the location of the metastases in proximity to adjacent intraperitoneal organs. Our aim is to review clinical data concerning intraperitoneal photodynamic therapy and epithelial ovarian cancer to identify the limits of this strategy and to provide solutions which may be applied to solve these barriers and enable safe and effective treatment. Targeted photosensitizers and innovative illumination solutions are mandatory to continue research in this field and to consider the feasibility of clinical trials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  14. Intraperitoneal implantation of life-long telemetry transmitters in otariids

    Directory of Open Access Journals (Sweden)

    Haulena Martin

    2008-12-01

    Full Text Available Abstract Background Pinnipeds, including many endangered and declining species, are inaccessible and difficult to monitor for extended periods using externally attached telemetry devices that are shed during the annual molt. Archival satellite transmitters were implanted intraperitoneally into four rehabilitated California sea lions (Zalophus californianus and 15 wild juvenile Steller sea lions (Eumetopias jubatus to determine the viability of this surgical technique for the deployment of long-term telemetry devices in otariids. The life history transmitters record information throughout the life of the host and transmit data to orbiting satellites after extrusion following death of the host. Results Surgeries were performed under isoflurane anesthesia and single (n = 4 or dual (n = 15 transmitters were inserted into the ventrocaudal abdominal cavity via an 8.5 to 12 cm incision along the ventral midline between the umbilicus and pubic symphysis or preputial opening. Surgeries lasted 90 minutes (SD = 8 for the 19 sea lions. All animals recovered well and were released into the wild after extended monitoring periods from 27 to 69 days at two captive animal facilities. Minimum post-implant survival was determined via post-release tracking using externally attached satellite transmitters or via opportunistic re-sighting for mean durations of 73.7 days (SE = 9.0, Z. californianus and 223.6 days (SE = 71.5, E. jubatus. Conclusion The low morbidity and zero mortality encountered during captive observation and post-release tracking periods confirm the viability of this surgical technique for the implantation of long-term telemetry devices in otariids.

  15. Short term changes in melatonin and cortisol serum levels after a single administration of estrogen to menopausal women.

    Science.gov (United States)

    Kerdelhué, Bernard; Andrews, Mason C; Zhao, Yueqin; Scholler, Robert; Jones, Howard W

    2006-10-01

    It has been well-documented that serum melatonin levels are insensitive to estrous or menstrual ovarian steroid variations in the female rat or the human. However, a negative coupling has been already demonstrated between the nocturnal serum melatonin peak and serum E2 concentration during the late premenopausal period in the woman. The objection of the present study was designed to determine if diurnal serum melatonin values can be also lowered by a single administration of estrogen. We performed a detailed analysis of variations of serum estradiol, LH, FSH, melatonin and cortisol after one single I.M. injection of 2 mg of a conjugated estrogen, delestrogen (estradiol valerate) in 0.1 ml of oil. A 15 ml blood collection was done at 8:00 a.m. before the injection, and at 8:30 a.m., 9:00 a.m., 10:00 a.m., 12:00 noon, and 4:00 p.m. 17beta-estradiol, LH and FSH were determined by microparticle enzyme immunoassays kits. Melatonin determination was made using a RIA kit and cortisol was assayed by a RIA method. A significant rise in serum 17beta-estradiol was already seen by one hour after the injection of estradiol valerate. Then, an almost linear increase was observed up to at last eight hours after the injection of estradiol valerate. A significant decrease in serum LH was not seen before four hours after the injection of estradiol valerate. Overall, there was a trend toward a decline in serum melatonin and cortisol concentration. The decreasing trend of cortisol serum level was tested as significant over time (pmelatonin. Overall, these results show that after menopause an acute administration of estrogen during the early diurnal period of the day leads to a significant rapid decrease in cortisol serum values, but to only a partial non significant decrease in melatonin serum values.

  16. Benefits of Preventive Administration of Chlorella sp. on Visceral Pain and Cystitis Induced by a Single Administration of Cyclophosphamide in Female Wistar Rat.

    Science.gov (United States)

    Hidalgo-Lucas, Sophie; Rozan, Pascale; Guérin-Deremaux, Laetitia; Baert, Blandine; Violle, Nicolas; Saniez-Degrave, Marie-Hélène; Bisson, Jean-François

    2016-05-01

    Chlorella sp. is a green microalgae containing nutrients, vitamins, minerals, and chlorophyll. In some communities, Chlorella sp. is a traditional medicinal plant used for the management of inflammation-related diseases. In a rat model, ROQUETTE Chlorella sp. (RCs) benefits were investigated on visceral pain and associated inflammatory parameters related to cystitis both induced by cyclophosphamide (CYP). RCs was orally administered every day from day 1-16 (250 and 500 mg/kg body weight). Six hours after an intraperitoneal injection of 200 mg/kg body weight of CYP, body temperature, general behavior, food intake, and body weight were recorded. Twenty-four hours after CYP injection, rats were tested in two behavioral tests, an open field and the aversive light stimulus avoidance conditioning test, to evaluate the influence of pain on general activity and learning ability of rats. After euthanasia, bladders were weighed, their thickness was scored, and the urinary hemoglobin was measured. RCs orally administered at the two dosages significantly reduced visceral pain and associated inflammatory parameters related to cystitis both induced by CYP injection, and improved rat behavior. To conclude, RCs demonstrated beneficial effects against visceral pain and cystitis.

  17. Ketoprofen pharmacokinetics of R- and S-isomers in juvenile loggerhead sea turtles (Caretta caretta) after single intravenous and single- and multidose intramuscular administration.

    Science.gov (United States)

    Thompson, K A; Papich, M G; Higgins, B; Flanagan, J; Christiansen, E F; Harms, C A

    2018-04-01

    Ketoprofen is a nonsteroidal anti-inflammatory and analgesic agent that nonselectively inhibits cyclooxygenase, with both COX-1 and COX-2 inhibition. Recent studies on COX receptor expression in reptiles suggest that nonselective COX inhibitors may be more appropriate than more selective inhibitors in some reptiles, but few pharmacokinetic studies are available. The goal of this study was to determine single- and multidose (three consecutive days) pharmacokinetics of racemic ketoprofen administered intravenously and intramuscularly at 2 mg/kg in healthy juvenile loggerhead turtles (Caretta caretta). The S-isomer is the predominant isomer in loggerhead sea turtles, similar to most mammals, despite administration of a 50:50 racemic mixture. Multidose ketoprofen administration demonstrated no bioaccumulation; therefore, once-daily dosing will not require dose adjustment over time. S-isomer pharmacokinetic parameters determined in this study were C max of 10.1 μg/ml by IM injection, C 0 of 13.4 μg/ml by IV injection, AUC of 44.7 or 69.4 μg*hr/ml by IM or IV injection, respectively, and T½ of 2.8 or 3.6 hr by IM or IV injection, respectively. Total ketoprofen plasma concentrations were maintained for at least 12 hr above concentrations determined to be effective for rats and humans. A dose of 2 mg/kg either IM or IV every 24 hr is likely appropriate for loggerhead turtles. © 2017 John Wiley & Sons Ltd.

  18. Effect of sorbitol, single, and multidose activated charcoal administration on carprofen absorption following experimental overdose in dogs.

    Science.gov (United States)

    Koenigshof, Amy M; Beal, Matthew W; Poppenga, Robert H; Jutkowitz, L Ari

    2015-01-01

    To compare the effectiveness of single dose activated charcoal, single dose activated charcoal with sorbitol, and multidose activated charcoal in reducing plasma carprofen concentrations following experimental overdose in dogs. Randomized, four period cross-over study. University research setting. Eight healthy Beagles. A 120 mg/kg of carprofen was administered orally to each dog followed by either (i) a single 2 g/kg activated charcoal administration 1 hour following carprofen ingestion (AC); (ii) 2 g/kg activated charcoal with 3.84 g/kg sorbitol 1 hour following carprofen ingestion (ACS); (iii) 2 g/kg activated charcoal 1 hour after carprofen ingestion and repeated every 6 hours for a total of 4 doses (MD); (iv) no treatment (control). Plasma carprofen concentrations were obtained over a 36-hour period following carprofen ingestion for each protocol. Pharmacokinetic modeling was performed and time versus concentration, area under the curve, maximum plasma concentration, time to maximum concentration, and elimination half-life were calculated and compared among the groups using ANOVA followed by Tukey's multiple comparisons test. Activated charcoal, activated charcoal with sorbitol (ACS), and multiple-dose activated charcoal (MD) significantly reduced the area under the curve compared to the control group. AC and MD significantly reduced the maximum concentration when compared to the control group. MD significantly reduced elimination half-life when compared to ACS and the control group. There were no other significant differences among the treatment groups. Activated charcoal and ACS are as effective as MD in reducing serum carprofen concentrations following experimental overdose in dogs. Prospective studies are warranted to evaluate the effectiveness of AC, ACS, and MD in the clinical setting. © Veterinary Emergency and Critical Care Society 2015.

  19. Targeting Visceral Fat by Intraperitoneal Delivery of Novel AAV Serotype Vector Restricting Off-Target Transduction in Liver

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2017-09-01

    Full Text Available It is challenging to genetically manipulate fat in adults. We demonstrate that intraperitoneal (i.p. injection of an engineered adeno-associated virus (AAV serotype Rec2 leads to high transduction of multiple visceral fat depots at a dose of 1 to 2 orders lower than commonly used doses for systemic gene delivery. To target adipose tissue, we develop a single AAV vector harboring two expression cassettes: one using the CBA promoter to drive transgene expression and one using the liver-specific albumin promoter to drive a microRNA-targeting WPRE sequence that only exists in this AAV vector. This dual-cassette vector achieves highly selective transduction of visceral fat while severely restricting off-target transduction of liver. As proof of efficacy, i.p. administration of an adipose-targeting Rec2 vector harboring the leptin gene corrects leptin deficiency, obesity, and metabolic syndromes of ob/ob mice. This study provides a powerful tool to genetically manipulate fat for basic research and gene therapies of genetic and acquired diseases.

  20. Complications of continuous intraperitoneal insulin infusion with an implantable pump

    NARCIS (Netherlands)

    van Dijk, Peter R; Logtenberg, Susan J. J.; Groenier, Klaas H; Haveman, Jan Willem; Kleefstra, Nanno; Bilo, Henk J. G.

    2012-01-01

    AIM: To monitor the course of continuous intraperitoneal insulin infusion (CIPII) and to gain more insight into possible complications. METHODS: A retrospective, longitudinal observational cohort study in patients with type 1 diabetes mellitus (T1DM) was performed. Only patients with "brittle" T1DM

  1. Continuous intraperitoneal insulin infusion in patients with 'brittle' diabetes

    DEFF Research Database (Denmark)

    DeVries, J H; Eskes, S A; Snoek, Frank J

    2002-01-01

    AIMS: To evaluate the effects of continuous intraperitoneal insulin infusion (CIPII) using implantable pumps on glycaemic control and duration of hospital stay in poorly controlled 'brittle' Dutch diabetes patients, and to assess their current quality of life. METHODS: Thirty-three patients were...

  2. From intraperitoneal onlay mesh repair to preperitoneal onlay mesh repair.

    Science.gov (United States)

    Yang, George Pei Cheung

    2017-05-01

    Laparoscopic repair for ventral and incisional hernias was first reported in the early 1990s. It uses intraperitoneal only mesh placement to achieve a tension-free repair of the hernia. However, in recent years, there has been greater concern about long-term complication involving intraperitoneal mesh placement. Many case reports and case series have found evidence of mesh adhesion, mesh fistulation, and mesh migration into hollow organs including the esophagus, small bowel, and large bowel, resulting in various major acute abdominal events. Subsequent management of these complications may require major surgery that is technically demanding and difficult; in such cases, laparotomy and bowel resection have often been performed. Because of these significant, but not common, adverse events, many surgeons favor open sublay repair for ventral and incisional hernias. Investigators are therefore searching for a laparoscopic approach for ventral and incisional hernias that might overcome the mesh-induced visceral complications seen after intraperitoneal only mesh placement repair. Laparoscopic preperitoneal onlay mesh is one such approach. This article will explore the fundamental of intraperitoneal only mesh placement and its problems, the currently available peritoneal visceral-compatible meshes, and upcoming developments in laparoscopic ventral and incisional hernia repair. The technical details of preperitoneal onlay mesh, as well as its potential advantages and disadvantages, will also be discussed. © 2017 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and John Wiley & Sons Australia, Ltd.

  3. The role of intraperitoneally administered vitamin C during ...

    African Journals Online (AJOL)

    The effects of daily intraperitoneally administered doses of 100 mg/kg bd. wt. vitamin C on levels of some endogenous antioxidants as well as hepatic and renal function were investigated in a group of rabbits infected with a strain of Trypanosoma congolense (strain number: BS2/TC /SP28/P4). Values of parameters ...

  4. Effects of intraperitoneal nitroglycerin on the strength and healing ...

    African Journals Online (AJOL)

    Background: Ischemic conditions in the intestine result in deterioration of anastomosis healing process. In this study, our aim was to evaluate the possible effects of intraperitoneal nitroglycerin on the intestinal anastomosis healing and anastomosis burst pressures in rats with ischemia and reperfusion injury (I/R). Materials ...

  5. Time-course measurements of drug concentrations in hair and toenails after single administrations of pharmaceutical products.

    Science.gov (United States)

    Kuwayama, Kenji; Miyaguchi, Hajime; Iwata, Yuko T; Kanamori, Tatsuyuki; Tsujikawa, Kenji; Yamamuro, Tadashi; Segawa, Hiroki; Inoue, Hiroyuki

    2017-04-01

    Hair and nails are often used to prove long-term intake of drugs in forensic drug testing. The aim of this study was to evaluate the effectiveness of drug testing using hair and nails and the feasibility of determining when drugs were ingested by measuring the time-courses of drug concentrations in hair and toenails after single administrations of various drugs. Healthy subjects ingested four pharmaceutical products containing eight active ingredients in single doses. Hair and toenails were collected at predetermined intervals, and drug concentrations in hair and nails were measured for 12 months. The administered drugs and their main metabolites were extracted using micropulverized extraction with a stainless steel bullet and were analyzed using liquid chromatography/tandem mass spectrometry. Acidic compounds such as ibuprofen and its metabolites were not detected in both specimens. Acetaminophen, a weakly acidic compound, was detected in nails more frequently than in hair. The maximum concentration of allyl isopropyl acetylurea, a neutral compound, in nails was significantly higher than in hair. Nails are an effective specimen to detect neutral and weakly acidic compounds. For fexofenadine, a zwitterionic compound, and for most basic compounds, the maximum concentrations in hair segments tended to be higher than those in nails. The hair segments showing the maximum concentrations varied between drugs, samples, and subjects. Drug concentrations in hair segments greatly depended on the selection of the hair. Careful interpretation of analytical results is required to predict the time of drug intake. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  6. Administration of toltrazuril during experimental coccidiosis in mule ducks: comparison of the efficacy of a single administration at two different endogenous stages.

    Science.gov (United States)

    Reynaud, M C; Chauve, C M; Gastellu, J; Gounel, J M

    1999-03-15

    An experimental Eimeria mulardi coccidiosis was reproduced in mule ducks. A single dose of toltrazuril (7 mg per kg) was administered at two different endogenous stages: Day 2 (first meronts) or Day 5 (last meronts and gamonts). The efficacy of the drug was assessed on four criteria (body weight, oocyst counts, macroscopic lesions, and presence of the meronts and gamonts). To have a curative effect, a single dose of toltrazuril should be administered early on. However, a single treatment on Day 5 had a prophylactic effect.

  7. Iatrogenic Cushing's syndrome and secondary adrenal insufficiency after a single intra-articular administration of triamcinolone acetonide in HIV-infected patients treated with ritonavir.

    Science.gov (United States)

    Yombi, J C; Maiter, D; Belkhir, L; Nzeusseu, A; Vandercam, B

    2008-12-01

    The development of an iatrogenic Cushing's syndrome (ICS) followed by secondary adrenal failure remains an exceptional event after a single dose administration of a synthetic glucocorticoid. Medical attention has been drawn recently on the possible impact of ritonavir-based antiretroviral regimens on the systemic deleterious effects of a chronic administration of corticosteroids in HIV-infected patients. Three HIV-infected patients treated by a ritonavir-boosted protease inhibitor (PI) regimen received a single intra-articular injection of 40 mg triamcinolone acetonide in our university hospital. The three patients rapidly developed signs and symptoms of ICS followed by secondary adrenal insufficiency. Special attention must be paid when a single administration of corticosteroids has to be given in HIV-positive patients under ritonavir-boosted antiretroviral treatment, as these patients are at risk of developing early cushingoid features and a prolonged suppression of their hypothalamic-pituitary-adrenal axis.

  8. PHARMACOKINETICS OF CEFTIOFUR CRYSTALLINE FREE ACID STERILE SUSPENSION IN GREEN IGUANAS ( IGUANA IGUANA) AFTER SINGLE INTRAMUSCULAR ADMINISTRATION.

    Science.gov (United States)

    Sadar, Miranda J; Hawkins, Michelle G; Taylor, Ian T; Byrne, Barbara A; Tell, Lisa A

    2018-03-01

    The objective of this study was to establish the pharmacokinetic parameters of ceftiofur crystalline free acid (CCFA) for a single intramuscular injection in green iguanas ( Iguana iguana). Six green iguanas received an injection of 5 mg/kg CCFA into the triceps muscle. Using high-performance liquid chromatography, concentrations of ceftiofur free acid equivalents in plasma samples collected at predetermined time points were evaluated up to 21 days following drug administration. Noncompartmental pharmacokinetic analysis was applied to the data. The observed maximum plasma concentration (C max obs ) was 2.765 ± 0.864 μg/mL, and the time of observed maximum concentration (T max obs ) was 6.1 ± 9.2 hr. The area under the curve (0 to infinity) was 239.3 ± 121.1 μg·hr/mL. No significant adverse drug reactions were clinically observed, and no visible injection site reactions were noted. Minimum inhibitory concentrations of bacterial isolates from iguanas were used to establish a target plasma concentration of 2.0 μg/mL. Based on the results from this study, a potential dosing interval for ceftiofur crystalline free acid administered at 5 mg/kg intramuscularly for iguanas maintained at a temperature of 30°C would be 24 hr based on a target plasma concentration of 2 μg/mL; however, multidose studies still need to be performed.

  9. Influence of fullerenol C60(OH24 on enzime status in serum of rats after single dose administration of doxorubicine

    Directory of Open Access Journals (Sweden)

    Govedarica Biljana Č.

    2008-01-01

    Full Text Available The antracycline antibiotics have one of the widest areas of use in oncology. The most investigated mechanisms of their antineoplastic activity include: interactions of these antibiotics with DNA, inhibition of topoisomerase II and production of free radicals. However, the side effects of doxorubicin, especially cardiotoxicity, are the limiting factor of its use in cancer therapy. The aim of this research was to investigate the influence of fullerenol С60(ОH24 as a cytoprotector in single doze administration of doxorubicin on the activity of enzymes in serum (CK, AST, ALT, LDH and a-HBDH in rats in in vivo system. Activity of enzymes (CK, LDH, HBDH, AST, and ALT in serume was measured with standard commercial methods. The results of analysis of the samples treated with the combination of fullerenol and doxorubicin show no difference in enzyme activity in comparison with the control group. The results indicate the possibility of using fullerenol as a protector in the therapy with doxorubicin in malign neoplasm.

  10. Pharmacokinetics of toltrazuril and its metabolites, toltrazuril sulfoxide and toltrazuril sulfone, after a single oral administration to pigs.

    Science.gov (United States)

    Lim, Jong-Hwan; Kim, Myoung-Seok; Hwang, Youn-Hwan; Song, In-Bae; Park, Byung-Kwon; Yun, Hyo-In

    2010-08-01

    Toltrazuril (TZR) is a triazine-based antiprotozoal agent. Following a single oral administration of TZR at 10 and 20 mg/kg to male pigs, the mean TZR concentration in plasma peaked at 4.24 and 8.18 microg/ml at 15.0 and 12.0 hr post-dose, respectively. TZR absorbed was rapidly converted to the short-lived intermediary metabolite toltrazuril sulfoxide (TZR-SO), and then metabolized to the reactive toltrazuril sulfone (TZR-SO2). TZR-SO2 was actually more slowly eliminated, with average half-lives of 231 and 245 hr, compared with TZR (48.7 and 68.9 hr) or TZR-SO (51.9 and 53.2 hr) in the 10 and 20 mg/kg groups, respectively. This study demonstrates that TZR metabolizes to TZR-SO2 having a long-terminal half-life, enabling the persistent clinical efficacy in the treatment of I. suis infection. In contrast, special consideration should be given to the residual of TZR-SO2.

  11. Intraperitoneal distribution of 32P-chromic phosphate suspension in the dog

    International Nuclear Information System (INIS)

    Tewfik, H.H.; Gruber, H.; Tewfik, F.A.; Lifshitz, S.G.

    1979-01-01

    Intraperitoneal administration of radioactive chromic phosphate suspension is receiving renewed attention as a therapeutic treatment to limit metastatic dissemination of ovarian carcinoma. Our study utilized mongrel dogs to approximate the uptake and distribution of 3.0 millicuries 32 P-chromic phosphate suspension administered intraperitoneally (IP). Lymph nodes, omentum, retroperitoneum, peritoneum, diaphragm, abdominal wall muscle, pleura, spleen, liver, kidneys, lung, small intestine, and blood were sampled for liquid scintillation counting and autoradiography. Whole blood showed the least activity (1800 cpm/100 lambda at day one, declining to 2800 cpm/100 lambda by day 16). Omentum and diaphragm maintained the greatest concentrations (183 x 10 6 dpm/g and 4 x 10 6 dpm/g respectively). These initial high values were 100 times greater than the highest values found for the small intestine, abdominal wall muscle, mediastinal and retroperitoneal lymph nodes and pleura. The peritoneum increased in specific activity until day three (5.9 x 10 6 dpm/g) and then rapidly declined. Our results show that following IP administration to the dog, 32 P suspension is associated with the serous membranes of the peritoneal cavity (most notably omentum, diaphragm, peritoneum, and retroperitoneum). This distribution could be valuable in adjuvant tumor therapy since serosal surfaces of the peritoneum (both visceral and parietal) and the omentum are the most common sites of tumor metastases associated with ovarian carcinoma

  12. Pharmacokinetics of the Protein Microbicide 5P12-RANTES in Sheep following Single-Dose Vaginal Gel Administration.

    Science.gov (United States)

    McBride, John W; Dias, Nicola; Cameron, David; Offord, Robin E; Hartley, Oliver; Boyd, Peter; Kett, Vicky L; Malcolm, R Karl

    2017-10-01

    5P12-RANTES, a chemokine analogue that potently blocks the HIV CCR5 coreceptor, is being developed as both a vaginal and rectal microbicide for prevention of sexual transmission of HIV. Here, we report the first pharmacokinetic data for 5P12-RANTES following single-dose vaginal gel administration in sheep. Aqueous gel formulations containing low (1.24-mg/ml), intermediate (6.18-mg/ml), and high (32.0-mg/ml; suspension-type gel) concentrations of 5P12-RANTES were assessed via rheology, syringeability, and in vitro release testing. Following vaginal gel administration to sheep, 5P12-RANTES concentrations were measured in vaginal fluid, vaginal tissue, and serum over a 96-h period. All gels showed non-Newtonian pseudoplastic behavior, with the high-concentration gels exhibiting a greater viscosity and cohesive structure than the intermediate- and low-concentration gels. In in vitro release testing, >90% 5P12-RANTES was released from the low- and intermediate-concentration gels after 72 h. For the high-concentration gel, ∼50% 5P12-RANTES was detected, attributed to protein denaturation during lyophilization and/or subsequent solvation of the protein within the gel matrix. In sheep, 5P12-RANTES concentrations in vaginal fluid, vaginal tissue, and serum increased in a dose-dependent manner. The highest concentrations were measured in vaginal fluid (10 5 to 10 7 ng/ml), followed by vaginal tissue (10 4 to 10 6 ng/ml). Both of these concentration ranges are several orders of magnitude above the reported half-maximal inhibitory concentrations. The lowest concentration was measured in serum (<10 2 ng/ml). The 5P12-RANTES pharmacokinetic data are similar to those reported previously for other candidate microbicides. These data, coupled with 5P12-RANTES's potency at picomolar concentrations, its strong barrier to resistance, and the full protection that it was observed to provide in a rhesus macaque vaginal challenge model, support the continued development of 5P12-RANTES as

  13. Pharmacokinetics of Tedizolid Following Oral Administration: Single and Multiple Dose, Effect of Food, and Comparison of Two Solid Forms of the Prodrug

    OpenAIRE

    Flanagan, Shawn D; Bien, Paul A; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2013-01-01

    Objectives The single- and multiple-dose pharmacokinetics (PK) of tedizolid were examined after oral administration of tedizolid phosphate disodium (TPD), including the effect of food on PK. The relative bioavailability of TPD to the free acid tedizolid phosphate was determined to bridge the results of these and other studies to the solid form of the prodrug selected for further development. Design Randomized placebo-controlled, double-blind single- and multiple-ascending dose studies and ran...

  14. The role of resuscitation promoting factors in pathogenesis and reactivation of Mycobacterium tuberculosis during intra-peritoneal infection in mice

    Directory of Open Access Journals (Sweden)

    Kana Bavesh D

    2007-12-01

    Full Text Available Abstract Background Mycobacterium tuberculosis can enter into a dormant state which has resulted in one third of the world's population being infected with latent tuberculosis making the study of latency and reactivation of utmost importance. M. tuberculosis encodes five resuscitation promoting factors (Rpfs that bear strong similarity to a lysozyme-like enzyme previously implicated in reactivation of dormant bacteria in vitro. We have developed an intraperitoneal infection model in mice, with immune modulation, that models chronic infection with similar properties in mouse lungs as those observed in the murine aerosol infection model. We have assessed the behavior of mutants that lack two or three rpf genes in different combinations in our intraperitoneal model. Methods C57Bl/6 mice were intraperitonealy infected with H37Rv wild type M. tuberculosis or mutant strains that lacked two or three rpf genes in different combinations. After 90 days of infection aminoguanidine (AG or anti-TNFα antibodies were administrated. Organ bacillary loads were determined at various intervals post infection by plating serial dilutions of organ homogenates and enumerating bacteria. Results We found that the rpf triple and double mutants tested were attenuated in their ability to disseminate to mouse lungs after intraperitoneal administration and were defective in their ability to re-grow after immunosuppression induced by administration of aminoguanidine and anti-TNFα antibodies. Conclusion Rpf proteins may have a significant physiological role for development of chronic TB infection and its reactivation in vivo.

  15. Sex-dependent behavioral changes in rat offspring after in utero administration of a single low dose PBDE 47

    Energy Technology Data Exchange (ETDEWEB)

    Kuriyama, S.N.; Talsness, C.E.; Chahoud, I. [Charite Univ. Medical School Berlin (Germany). Inst. of Clinical Pharmacology and Toxicology, Dept. Toxicology, Campus Benjamin Franklin

    2004-09-15

    change which could manifest itself in an irreversible fashion at later time points in life. We administered a single dose to gravid dams on gestation day 6 of either 140 {mu}g/kg BW or 700 {mu}g/kg BW of the congener, 2,2'4,4'-tetrabromo diphenyl ether (PBDE 47). These doses are pertinent to human exposure levels because a study by She et al. found a mean level of 33.3 {mu}g PBDE 47 /kg fat in human breast adipose tissue with a range from 7.01 to 196 {mu}g PBDE 47 /kg fat (10). In this study, peri-pubertal behavior effects were evaluated in rat offspring after in utero administration of low dose PBDE 47.

  16. Pharmacokinetics of betamethasone after single-dose intramuscular administration of betamethasone phosphate and betamethasone acetate to healthy subjects.

    Science.gov (United States)

    Salem, Isam I; Najib, Naji M

    2012-01-01

    Betamethasone is used for its antiinflammatory and immunosuppressive effects in disorders of many organ systems. However, the pharmacokinetic properties of betamethasone in plasma after intramuscular injection of betamethasone sodium phosphate and betamethasone acetate dual-acting suspension need further investigation. The main aim of this study was to determine the pharmacokinetic parameters of betamethasone, betamethasone acetate, and betamethasone phosphate after the administration of a single intramuscular dose of the dual-acting suspension to healthy human volunteers. Two different studies were conducted in healthy males. Volunteers were judged healthy based on their medical history, physical examination, and laboratory test results. Before confinement, all volunteers were tested for freedom from alcohol and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg of betamethasone acetate was administered by intramuscular injection. Blood sampling covered 48 hours. The plasma samples obtained in the second study were stabilized to enable pharmacokinetic profiling of betamethasone esters. Twenty-four healthy males with mean (SD) age of 27 (6.62) years participated in each study. No incidences of serious adverse events were recorded during the studies. Six mild adverse events were reported in 2 subjects in the second study. One subject suffered from pain at the injection site and insomnia, and another subject complained of heartburn and drowsiness. Betamethasone phosphate appeared to be readily absorbed with a mean AUC(0-t) of 96.01 ng/h/mL and an AUC(0-∞) of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration reached a mean t(½) of 12.92 hours. Betamethasone acetate was not detected in the volunteers' plasma in either study (total of 2208 plasma samples). The observed pharmacokinetic parameters suggested that the acetate ester, and not the

  17. Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.

    Directory of Open Access Journals (Sweden)

    Rege N

    1989-10-01

    Full Text Available The hypothesis that macrophages appear to play a pivotal role in the development of intraperitoneal adhesions and that modulation of macrophage activity, therefore, is likely to provide a tool for prevention of adhesions, was tested in the present study. Effect of Asparagus racemosus, an indigenous agent with immunostimulant properties, was evaluated in an animal model of intraperitoneal adhesions induced by caecal rubbing. Animals were sacrificed 15 days following surgery. The peritoneal macrophages were collected to assess their activity. At the same time, peritoneal cavity was examined for the presence of adhesions, which were graded. A significant decrease was observed in the adhesion scores attained by animals receiving Asparagus racemosus. This was associated with significant increase in the activity of macrophages (70.1 +/- 2.52, compared to that in surgical controls (53.77 +/- 10.8. These findings support our hypothesis and provide a novel approach for the prevention and management of post-operative adhesions.

  18. [Nursing care for ovarian cancer patients with intraperitoneal chemotherapy].

    Science.gov (United States)

    Lu, Yu-Ying; Chou, Ju-Fen; Tsao, Lee-Ing; Liang, Shu-Yuan; Wu, Shu-Fang

    2015-02-01

    Ovarian cancer, known as a "silent killer", is the leading cause of gynecologic cancer death. Standard treatments for ovarian cancer are debulking surgery combined with platinum chemotherapy drugs to prolong the survival of patients. According to clinical trials run by the American Society of Gynecologic Oncology, patients who received intraperitoneal (IP) chemotherapy survived longer on average than patients who received intravenous chemotherapy alone. Thus, intraperitoneal chemotherapy is a new potential approach for treating ovarian cancer patients. However, the toxicities and undesirable complications of IP chemotherapy are the major challenges of this treatment approach. This article helps nurses recognize the toxicities and complications of IP chemotherapy and may be used as reference for future revisions to patient care guidelines.

  19. Intraperitoneal fluid collection: CT characteristics in determining the causes

    International Nuclear Information System (INIS)

    Kim, Mi Young; Suh, Chang Hae; Chung, Won Kyun; Kim, Chong Soo; Choi, Ki Chul

    1995-01-01

    Abdominal CT scans in patients with intraperitoneal fluid were retrospectively studied to identify characteristic features useful for differential diagnosis of various causes. One hundred and seventy patients with intraperitoneal fluid collection were classified as categories of hepatic disease, carcinomatosis, and infectious disease. We analyzed sites of fluid collection, the presence of peritoneal thickening, omental and mesenteric fat infiltration, and lymph node enlargement. Intraperitoneal fluid was present in subhepatic space, subphrenic space, paracolic gutter, mesentery, and fossa of the gallbladder in decreasing order of frequency. Fluid in the gallbladder fossa was the most frequent in hepatic disease. The fluid collection in subhepatic and subphrenic space was less frequent in infectious disease. Peritoneal thickening was noted in infectious diseases, and carcinomatosis. Omental fat infiltration and enlarged lymph nodes were the most frequent in carcinomatosis (58% and 44%, respectively), whereas, mesenteric fat infiltration and enlarged lymph nodes were the most common in infectious diseases (61%, and 26%, respectively). The location of peritoneal fluid collection showed some lesion specific characteristics, and CT features of fat infiltration and enlarged lymph nodes of peritoneum, omentum, and mesentery were helpful for differential diagnosis between carcinomatosis and infectious diseases

  20. Serial Changes of the Splenic Volume after Traumatic Intraperitoneal Hemorrhage

    International Nuclear Information System (INIS)

    Park, Hyun Jin; Lee, Young Hwan; Jung, Kyung Jae

    2010-01-01

    We wanted to evaluate the serial changes of the splenic volume in patients with traumatic intraperitoneal hemorrhage. 20 consecutive patients with traumatic intraperitoneal hemorrhage and who underwent initial CT, early follow-up CT within 30 days and late follow- up CT examinations thereafter were included in this study. The volume of the spleen on each CT examination was measured and the relative splenic volume (RSV) on the initial and early follow-CT examinations was calculated on the basis of the splenic volume on the late follow-up CT. The hemoperitoneum score was calculated on the basis of the size of the intraperitoneal hemorrhage. The average RSVs of the initial and early follow-up CT were 62.0% and 133.3%, respectively, and all the patients showed an increase of the splenic and relative splenic volumes on the early follow-up CT, as compared with those on the initial CT. Initial splenic contraction was seen in 18 patients (90.0%) and early splenomegaly was seen in 14 patients (70.0%). Patients with initial splenic contraction and early splenomegaly were the most common (12 patient, 60.0%). Initial physiologic splenic contraction was seen in most of the patients with hemoperitoneum, and thereafter early splenomegaly was commonly seen before normalization of the splenic volume

  1. Preventing intraperitoneal adhesions with ethyl pyruvate and hyaluronic acid/carboxymethylcellulose: a comparative study in an experimental model.

    Science.gov (United States)

    Caglayan, E Kıyak; Caglayan, K; Erdogan, N; Cinar, H; Güngör, B

    2014-10-01

    To compare the effectiveness of ethyl pyruvate (EP) with that of hyaluronic acid+carboxymethyl cellulose (Seprafilm) for the prevention of intraperitoneal adhesions. Seprafilm has been shown to be effective in many experimental and clinical studies. Thirty rats were divided into three groups at random, and uterine horn abrasion was performed by laparotomy. One group received no treatment (control group), one group received a single intraperitoneal dose of EP 50mg/kg (EP group), and a 2×1-cm patch of Seprafilm was applied in the third group (Seprafilm group). All rats were killed 14 days after surgery. Macroscopic and histopathological evaluation were performed by a surgeon and a pathologist who were blinded to group allocation. Histopathologically, inflammation, fibroblastic activity, foreign body reaction, collagen proliferation, vascular proliferation, Masson-Trichrome score, matrix metalloproteinase-2 score and vascular endothelial growth factor score were studied. Median macroscopic intraperitoneal adhesion scores for the control, EP and Seprafilm groups were 2.8, 1.2 and 1.1, respectively. Multiple comparisons between groups showed a significant difference (p0.05). After histopathological evaluation, significant differences in all parameters were found between the groups (p0.0167). In comparison with the untreated control group, EP and Seprafilm were found to reduce the formation of intraperitoneal adhesions. No significant difference was found between EP and Seprafilm. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Treatment of gastric peritoneal carcinomatosis by combining complete surgical resection of lesions and intraperitoneal immunotherapy using catumaxomab

    International Nuclear Information System (INIS)

    Goéré, Diane; Gras-Chaput, Nathalie; Aupérin, Anne; Flament, Caroline; Mariette, Christophe; Glehen, Olivier; Zitvogel, Laurence; Elias, Dominique

    2014-01-01

    The peritoneum is one of the most frequent sites of recurrent gastric carcinoma after curative treatment, despite the administration of pre- and/or postoperative systemic chemotherapy. Indeed, the prognosis of peritoneal carcinomatosis from gastric carcinoma continues to be poor, with a median survival of less than one year with systemic chemotherapy. Whereas the prognosis of peritoneal carcinomatosis from colorectal cancer has changed with the development of locally administered hyperthermic intraperitoneal chemotherapy (HIPEC), survival results following carcinomatosis from gastric cancer remain disappointing, yielding a 5-year survival rate of less than 20%. Innovative surgical therapies such as intraperitoneal immunotherapy therefore need to be developed for the immediate postoperative period after complete cytoreductive surgery. In a recent randomised study, a clinical effect was obtained after intraperitoneal infusion of catumaxomab in patients with malignant ascites, notably from gastric carcinoma. Catumaxomab, a nonhumanized chimeric antibody, is characterized by its unique ability to bind to three different types of cells: tumour cells expressing the epithelial cell adhesion molecule (EpCAM), T lymphocytes (CD3) and also accessory cells (Fcγ receptor). Because the peritoneum is an immunocompetent organ and up to 90% of gastric carcinomas express EpCAM, intraperitoneal infusion of catumaxomab after complete resection of all macroscopic disease (as defined in the treatment of carcinomatosis from colorectal cancer) could therefore efficiently treat microscopic residual disease. The aim of this randomized phase II study is to assess 2-year overall survival after complete resection of limited carcinomatosis synchronous with gastric carcinoma, followed by an intraperitoneal infusion of catumaxomab with different total doses administered in each of the 2 arms. Close monitoring of peri-opertive mortality, morbidity and early surgical re-intervention will be done

  3. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats.

    Science.gov (United States)

    Ardiansyah; Ohsaki, Yusuke; Shirakawa, Hitoshi; Koseki, Takuya; Komai, Michio

    2008-04-23

    We studied the effects of a single oral administration of ferulic acid (FA) on the blood pressure (BP) and lipid profile in stroke-prone spontaneously hypertensive rats (SHRSP). Male 12-week-old SHRSP were administered FA (9.5 mg/kg of body weight) and distilled water as the control (C) (1 mL) via a gastric tube. The hypotensive effect of FA was observed at the lowest value after 2 h administration. A decrease in the angiotensin-1-converting enzyme (ACE) activity in the plasma corresponded well with the reduction of BP. Plasma total cholesterol and triglyceride levels were lower after 2 h administration. The mRNA expression of genes involved in lipid and drug metabolism was downregulated in the FA group. These results suggest that oral administration of FA appears beneficial in improving hypertension and hyperlipidemia.

  4. Intraperitoneal microdialysis in the postoperative surveillance of infants undergoing surgery for congenital abdominal wall defect

    DEFF Research Database (Denmark)

    Risby, Kirsten; Pedersen, Mark Ellebæk; Jakobsen, Marianne S

    2015-01-01

    PURPOSE: This study aims to investigate the safety and clinical implication of intraperitoneal microdialysis (MD) in newborns operated on for congenital abdominal wall defect. PATIENTS AND METHODS: 13 infants underwent intraperitoneal microdialysis (9 with gastroschisis and 4 with omphalocele). MD...

  5. Intraperitoneal delivery of monoclonal antibodies: enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

    International Nuclear Information System (INIS)

    Wahl, R.L.; Fisher, S.

    1987-01-01

    Radiolabeled monoclonal antibodies (MAb) delivered intraperitoneally expose cells in contact with peritoneal fluid to considerably higher levels of MAb than if the MAb dose were given intravenously. This regional delivery advantage for intact MAb is present mainly due to the relatively slow exit of MAb from the peritoneal fluid to the blood. Eventually, following i.p. injection, blood levels of MAb rise resulting in exposure of the animal to high systemic MAb levels and potential toxicity. In this series of experiments, systemic exposure was minimized by the administration of unlabeled goat polyclonal anti-mouse antibody intravenously from 1 1/2 to 6 h following i.p. MAb injection. This maneuver results in the formation of immune complexes with their subsequent clearance and dehalogenation by the reticuloendothelial system, thus minimizing systemic MAb exposure. This approach, of increasing systemic clearance of MAb, did not alter intraperitoneal MAb levels and thus significantly increased the regional delivery advantage to the peritoneal cavity by 70-100%. This approach provides an immunologic rationale for the further enhancement of MAb delivery to i.p. foci of malignant disease and may have diagnostic and therapeutic utility. (author)

  6. Political administration

    OpenAIRE

    Åkerstrøm Andersen, Niels

    2000-01-01

    One of the major discussions of the 1990s has been about the relation between politics and administration. The themes of the discussions have been many and varied. It has been suggested that the level of politics should concentrate on the general political outlining and entrust the remaining to the administration. It has been criticised that politicians make their decisions on the basis of single cases, which ought to be an administrative matter entirely. It has been a theme that efficient op...

  7. Influence of single and repeated cannabidiol administration on emotional behavior and markers of cell proliferation and neurogenesis in non-stressed mice.

    Science.gov (United States)

    Schiavon, Angélica Pupin; Bonato, Jéssica Mendes; Milani, Humberto; Guimarães, Francisco Silveira; Weffort de Oliveira, Rúbia Maria

    2016-01-04

    Therapeutic effects of antidepressants and atypical antipsychotics may arise partially from their ability to stimulate neurogenesis. Cannabidiol (CBD), a phytocannabinoid present in Cannabis sativa, presents anxiolytic- and antipsychotic-like effects in preclinical and clinical settings. Anxiolytic-like effects of repeated CBD were shown in chronically stressed animals and these effects were parallel with increased hippocampal neurogenesis. However, antidepressant-like effects of repeated CBD administration in non-stressed animals have been scarcely reported. Here we investigated the behavioral consequences of single or repeated CBD administration in non-stressed animals. We also determined the effects of CBD on cell proliferation and neurogenesis in the dentate gyrus (DG) and subventricular zone (SVZ). Single CBD 3mg/kg administration resulted in anxiolytic-like effect in mice submitted to the elevated plus maze (EPM). In the tail suspension test (TST), single or repeated CBD administration reduced immobility time, an effect that was comparable to those of imipramine (20 mg/kg). Moreover, repeated CBD administration at a lower dose (3 mg/kg) increased cell proliferation and neurogenesis, as seen by an increased number of Ki-67-, BrdU- and doublecortin (DCX)-positive cells in both in DG and SVZ. Despite its antidepressant-like effects in the TST, repeated CBD administration at a higher dose (30 mg/kg) decreased cell proliferation and neurogenesis in the hippocampal DG and SVZ. Our findings show a dissociation between behavioral and proliferative effects of repeated CBD and suggest that the antidepressant-like effects of CBD may occur independently of adult neurogenesis in non-stressed Swiss mice. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats

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    Gisele Alborghetti Nai

    2015-02-01

    Full Text Available BACKGROUND AND OBJECTIVE: Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. METHODS: 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0 mg/kg; group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. RESULTS: The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (p 0.05. CONCLUSION: No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated.

  9. [Evaluation of genotoxicity induced by repetitive administration of local anaesthetics: an experimental study in rats].

    Science.gov (United States)

    Nai, Gisele Alborghetti; de Oliveira, Mariliza Casanova; de Oliveira Tavares, Graziela; Pereira, Laís Fabrício Fonseca; Soares, Nádia Derli Salvador Lemes; Silva, Patrícia Gatti

    2015-01-01

    Previous studies regarding the effects of some local anaesthetics have suggested that these agents can cause genetic damage. However, they have not been tested for genotoxicity related to repetitive administration. The aim of this study was to evaluate the genotoxic potential of local anaesthetics upon repetitive administration. 80 male Wistar rats were divided into: group A - 16 rats intraperitoneally injected with lidocaine hydrochloride 2%; group B - 16 rats IP injected with mepivacaine 2%; group C - 16 rats intraperitoneally injected with articaine 4%; group D - 16 rats IP injected with prilocaine 3% (6.0mg/kg); group E - 8 rats subcutaneously injected with a single dose of cyclophosphamide; and group F - 8 rats intraperitoneally injected with saline. Eight rats from groups A to D received a single dose of anaesthetic on Day 1 of the experiment; the remaining rats were dosed once a day for 5 days. The median number of micronuclei in the local anaesthetics groups exposed for 1 or 5 days ranged from 0.00 to 1.00, in the cyclophosphamide-exposed group was 10.00, and the negative control group for 1 and 5 days was 1.00 and 0.00, respectively (plocal anaesthetic groups (p=0.0001), but not between the negative control group and the local anaesthetic groups (p>0.05). No genotoxicity effect was observed upon repetitive exposure to any of the local anaesthetics evaluated. Copyright © 2013 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  10. Liquid Paraffin vs Hyaluronic Acid in Preventing Intraperitoneal Adhesions.

    Science.gov (United States)

    Kataria, Hanish; Singh, Vinod Prem

    2017-12-01

    Adhesion formation after abdominal and pelvic operations remains a challenging problem. Role of adjuvant barriers have been studied but there is no comparative study between liquid paraffin and hyaluronic acid as a barrier method. Hence, we planned to compare the effectiveness of 0.4 % hyaluronic acid and liquid paraffin in the prevention of postoperative intraperitoneal adhesions in rats. This prospective, randomized and controlled study was conducted in 60 adult Wistar albino rats. Surgical trauma by caecal abrasion and 1 g talcum powder was used in the rat model to induce adhesion formation. After trauma, 3 ml normal saline was instilled in the peritoneal cavity in control group ( n  = 20), 3 ml liquid paraffin was instilled in experimental group A ( n  = 20) and 3 ml 0.4 % hyaluronic acid was instilled in experimental group B ( n  = 20). Two weeks after laparotomy, repeat laparotomy was performed and the adhesions were scored according to Zuhlke classification. Liquid paraffin and hyaluronic acid both reduce the extent and grade of adhesions both macroscopically ( p  = 0.018, p  = 0.017) and microscopically ( p  = 0.019, p  = 0.019) respectively. Although there was significant reduction in adhesions by hyaluronic acid at certain specific sites as compared with liquid paraffin, its overall effectiveness in preventing postoperative intraperitoneal adhesions is not significantly different from liquid paraffin ( p  = 0.092, p  = 0.193) respectively. The presence of liquid paraffin and hyaluronic acid in the peritoneal cavity reduce postoperative intraperitoneal adhesions significantly in rats. However, there is no overall significant difference in the effectiveness of two groups. Dosage and safety of these chemicals in human beings remains to be established.

  11. Safety of ferric carboxymaltose immediately after infliximab administration, in a single session, in inflammatory bowel disease patients with iron deficiency: a pilot study.

    Directory of Open Access Journals (Sweden)

    Xavier Cortes

    Full Text Available To obtain preliminary safety and efficacy data on intravenous (IV administration of infliximab (IFX and ferric carboxymaltose (FCM to inflammatory bowel disease (IBD patients in a single treatment session.A two-phase non-interventional, observational, prospective pilot study was performed to evaluate safety and efficacy of FCM given immediately after IFX. IBD patients were recruited consecutively in the outpatient clinic in two groups. Control group patients (n = 12 received FCM on a separate day from IFX. Subsequently, single-session group patients (n = 33 received FCM after IFX on the same day. All patients received 5mg/kg IFX and 1000mg FCM for iron-restricted anemia (IRA or 500mg FCM for iron deficiency without anemia. Safety assessment was performed by recording adverse events (AEs during and immediately after infusion, 30 minutes afterwards, and via follow-up at 7 days and 8 weeks. For efficacy assessment, hematological parameters were assessed prior to FCM infusion (pre-FCM and after 8 weeks. Economic impact of FCM given immediately after IFX was assessed.All 45 patients (35 Crohn´s disease, 10 ulcerative colitis received IFX 5mg/kg. 21 patients received 500mg FCM and 24 received 1000mg. FCM administration immediately after IFX corrected iron deficiency or IRA as shown by increases in hematological parameters. No AEs were reported during the safety evaluation at the end of FCM or IFX administration, 30 minutes, 7 days and 8 weeks afterwards, in either control or single-session groups. Total cost per patient for single-session administration was 354.63€; for patients receiving IFX and FCM on separate days, it was 531.94€, giving a 177.31€ per-patient cost saving.Single-session administration of FCM after IFX was safe and effective in IBD patients and can offer a good cost-benefit ratio and improve treatment adherence. To our knowledge, this study is the first to evaluate FCM and IFX administration in a single treatment session.

  12. What's new in intraperitoneal test on Kevlar (asbestos substitute)?

    Science.gov (United States)

    Brinkmann, O A; Müller, K M

    1989-09-01

    The intraperitoneal test is a suitable experimental method for studying the different patterns of morphological reaction to foreign body substances of various kinds and concentrations as well as their transport within and elimination from the organism, Kevlar fibres are synthetic aromatic polyamid (aramid) fibres which, investigated by means of the intraperitoneal test in Wistar rats, show distinct pathogenetic reaction patterns: 1. In the early stage after application, the formation of multinucleated giant cells with phagocytosis of the amber-coloured Kevlar fibres, and an inflammatory reaction are foremost features. 2. The typical feature of the second stage is the development of granulomas with central necrosis indicating the cytotoxic nature of Kevlar fibres. 3. The third stage is dominated by the mesenchymal activation with capsular structures of collagenous fibres. Besides granulomatous foci, a slight submesothelial fibrosis is observed. 4. Fragments of Kevlar fibres are drained through lymphatic pathways and stored in lymph nodes where they lead to inflammatory reactions. 5. The reactive granulomatous changes in the greater omentum of rats are accompanied by proliferative mesothelial changes which, in one cases, even led to the development of a multilocular mesothelioma.

  13. Active protection against rotavirus infection of mice following intraperitoneal immunization.

    Science.gov (United States)

    McNeal, M M; Sheridan, J F; Ward, R L

    1992-11-01

    Active immunity to rotavirus has been demonstrated following oral inoculation with live virus but little is known about the effects of parenteral immunization. In this study, adult mice were immunized by intraperitoneal (ip) inoculation with live rotaviruses and later orally challenged with murine rotavirus (EDIM) to measure active immunity against infection. Three doses of EDIM (8 micrograms/dose) given intraperitoneally (ip) provided full protection against EDIM infection, whether administered with or without Freund's adjuvant. Only partial protection was found when the quantity of immunogen was reduced to protection of all mice. Significant protection was also observed after inoculation with one or three doses (2 micrograms/dose) of heterologous rotaviruses. Protection provided by the heterologous strains did not correlate with neutralizing antibody to EDIM, which indicated that neutralizing antibody to the challenge virus was not required for protection. uv-Inactivated EDIM also provided significant protection against EDIM, thus demonstrating that viral replication was not required for protection. These results suggest that parenteral immunization may be an effective method to vaccinate against rotavirus disease.

  14. Safe Veress Needle Intraperitoneal Placement and Safer Laparoscopic Entry.

    Science.gov (United States)

    Vilos, George; Vilos, Angelos; Jacob, George P; Abu-Rafea, Basim; Ternamian, Artin

    2018-02-06

    Fifty percent of laparoscopic bowel and vascular injuries occur at the time of entry. These serious complications can lead to significant morbidity and even mortality. This video demonstrates 3 techniques that have been developed to minimize the risk of these injuries during entry. Step-by-step description of 3 techniques that can be used as a highly reliable and safe method of obtaining intraperitoneal entry during laparoscopy. Caudal displacement of the umbilicus before insertion of the veress needle allows for a median displacement of 6 cm between the site of entry and the common iliac vessels. An entry pressure of less than 9 mm Hg is suggestive of successful intraperitoneal entry. The left upper quadrant should be used in specific cases instead of the umbilicus as the point of entry for the veress needle. The use of a visualized trocarless cannula instead of a conventional primary trocar for entry after insufflation allows for real-time recognition of injury and converts linear penetrating force to radial torque. These 3 techniques can help decrease the risk and improve intraoperative recognition of serious bowel and vascular injuries during laparoscopy. Copyright © 2018 American Association of Gynecologic Laparoscopists. Published by Elsevier Inc. All rights reserved.

  15. Effects of single and combined administration of fermented barley extract and gamma-aminobutyric acid on the development of atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Hokazono, Hideki; Omori, Toshiro; Ono, Kazuhisa

    2010-01-01

    We examined the effects single and combined administration of fermented barley extract P (FBEP), prepared from barley-shochu distillery by-products, and gamma-aminobutyric acid (GABA) on the development of atopic dermatitis (AD)-like skin lesions in NC/Nga mice. Single administration of FBEP and GABA dose-dependently reduced the development of AD-like skin lesions in mice. GABA reduced the development of AD-like skin lesions by suppressing serum immunoglobulin E (IgE) and splenocyte interleukin (IL)-4 production, while FBEP reduced skin lesions without affecting the IgE or cytokine production. However, in mice with induced AD-like skin lesions, combined administration of FBEP and GABA decreased serum IgE levels and splenic cell IL-4 production, and increased splenic cell interferon-gamma production. These results suggest that combined administration of FBEP and GABA alleviated AD-like skin lesions in the NC/Nga mice by adjusting the Th1/Th2 balance to a Th1-predominant immune response.

  16. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Zheng, Zhaozhu; Chen, Dongye; Wang, Xiaoqin; Shi, Fuxin; Yu, Dehong; Wu, Hao

    2015-01-01

    This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA) stealth nanoparticles loaded with dexamethasone (DEX). DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs) had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4), 5 days in artificial perilymph (pH 7.4), and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM) of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8 kHz frequencies when compared to the control of free DEX formulation. Histological analyses indicated that the administration of DEX-NPs did not induce local inflammatory responses. Therefore, prolonged delivery of DEX by PEG-PLA nanoparticles through local RWM diffusion (administration) significantly protected the hair cells and auditory function in guinea pigs from cisplatin toxicity, as determined at both histological and functional levels, suggesting the potential therapeutic benefits in clinical applications.

  17. A comparative study of calcium absorption following a single serving administration of calcium carbonate powder versus calcium citrate tablets in healthy premenopausal women

    Directory of Open Access Journals (Sweden)

    Haiyuan Wang

    2014-04-01

    Full Text Available Background: Calcium is an essential mineral often taken as a daily, long-term nutritional supplement. Data suggests that once-daily dosing is important with regard to long-term compliance of both drugs and nutritional supplements. Objective: This study was undertaken to compare the bioavailability of a single serving of two calcium supplements in healthy, premenopausal women. Design: A two-period, crossover bioavailability study of a single serving of calcium citrate tablets (two tablets=500 mg calcium versus a single serving of calcium carbonate powder (one packet of powder=1,000 mg calcium was performed in healthy women aged between 25 and 45. All subjects were on a calcium-restricted diet 7 days prior to testing and fasted for 12 h before being evaluated at 0, 1, 2, and 4 h after oral administration of the test agents. Blood measurements for total and ionized calcium and parathyroid hormone were performed and adverse events were monitored. Results: Twenty-three women were evaluable with a mean age of 33.2±8.71. Results showed that administration of a single serving of a calcium carbonate powder resulted in greater absorption in total and ionized calcium versus a single serving of calcium citrate tablets at 4 h (4.25±0.21 vs. 4.16±0.16, p=0.001. There were minimal side effects and no reported serious adverse events. Conclusions: This study shows that a single serving of a calcium carbonate powder is more bioavailable than a single serving of calcium citrate tablets. This may be beneficial for long-term compliance.

  18. Pharmacokinetic Properties and Tolerability of Cycloserine Following Oral Administration in Healthy Chinese Volunteers: A Randomized, Open-Label, Single- and Multiple-Dose 3-Way Crossover Study.

    Science.gov (United States)

    Zhou, Huili; Wu, Guolan; Hu, Xingjiang; Zhu, Meixiang; Zhai, You; Liu, Jian; Shentu, Jianzhong; Wu, Lihua

    2015-06-01

    A new generic formulation of cycloserine has been developed in China but the pharmacokinetic properties of cycloserine in the Chinese population have not been reported. The aim of our study was to evaluate the pharmacokinetic properties and tolerability of single and multiple oral administrations of cycloserine capsules in healthy Chinese volunteers. This open-label, single- and multiple-dose 3-way crossover study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of cycloserine (250, 500, or 1000 mg) in separate trial periods, with a 1-week washout between periods. Those allocated to the 250-mg dose continued into the multiple-dose phase, in which they received 250 mg BID for 5 consecutive days. During the single-dose phase, blood samples were collected at regular intervals from 0 to 72 hours after drug administration and the concentrations of cycloserine were determined using LC-MS/MS. During the multiple-dose phase, blood samples were obtained before drug administration on Days 4, 5, and 6 to determine the Cmin at steady state. On Day 6, blood samples were also collected from 0 to 72 hours after drug administration. Pharmacokinetic parameters were estimated using noncompartmental methods. Tolerability was determined using clinical evaluation and monitoring of adverse events. The study enrolled 12 healthy Chinese volunteers (6 men: mean [SD] age = 23.0 [2.6] years, weight = 60.2 [6.2] kg, height = 170.0 [3.0] cm, and body mass index = 20.7 [1.7]; 6 women: mean [SD] age = 25.3 [1.4] years, weight = 51.5 [3.3] kg, height = 160.0 [4.0] cm, and body mass index = 20.1 [0.9]). After administration of a single dose, cycloserine was rapidly absorbed, reaching peak plasma concentrations approximately 0.84 hours after oral administration, and t½ in plasma was about 13.0 hours. The geometric mean (SD) Cmax value increased in proportion to cycloserine dose, from 19.42 (5.89) to 84.76 (21.74) mg/L, and the geometric mean (SD) AUC0

  19. Effects of single cortisol administrations on human affect reviewed: Coping with stress through adaptive regulation of automatic cognitive processing

    NARCIS (Netherlands)

    Putman, P.L.J.; Roelofs, K.

    2011-01-01

    The human stress hormone cortisol may facilitate effective coping after psychological stress. In apparent agreement, administration of cortisol has been demonstrated to reduce fear in response to stressors. For anxious patients with phobias or posttraumatic stress disorder this has been ascribed to

  20. Enhancing the Predictive Potential of Personality: Isolating Multiple Components of Trait Expression via a Single Administration Design

    Science.gov (United States)

    2015-03-01

    55 4.1 Government and Public Administration 35 2.6 Community and Social Service 29 2.1 Manufacturing 29 2.1 Hospitality and Tourism 25 1.8...beauty salon or barber shop . 34. Manage a department within a large company. 35. Start your own business. 36. Negotiate business contracts. 37

  1. CELL RESPONSE TO INTRAPERITONEAL PDMS/HAP COMPOSITE IMPLANT

    Directory of Open Access Journals (Sweden)

    Perica Vasiljević

    2005-07-01

    Full Text Available Siloxane polimers have been widely used in biomedicine and pharmacy due to their biocompatibility. Hydroxyapatite (HAp is a natural constituent of bones, and therefore widely used in maxillofacial and orthopedic surgery. HAp itself is amorphous and without elasticity, so its characteristics can be improved when combined with organic polymers. We evaluated the interaction of cells and composites made of polydimethylsiloxane (PDMS and HAp by scanning electron microscopy (SEM 10 days after their intraperitoneal implantation into Balb/c mice. Two composites which were different in the quantity of HAp were analyzed. Both of them showed high adhesive characteristics for different cell types. The erythrocytes in cell clusters could be seen on the surface of the composite with higher quantity of HAp.

  2. Neutron-Activatable Nanoparticles for Intraperitoneal Radiation Therapy.

    Science.gov (United States)

    Hargrove, Derek; Lu, Xiuling

    2017-01-01

    Intraperitoneal internal radiation therapy is a cancer treatment option that is employed in situations where surgical resection, systemic chemotherapy, and external beam radiotherapy are not amenable for patients. However, exposure of noncancerous tissues to radiation continues to be a hindrance to safe and effective treatment of patients. In addition, reducing prolonged radiation exposure of personnel during preparation of internal radiation therapy agents makes their manufacture complicated and hazardous. Developments in nanotechnology have provided a platform for targeted treatments that combine dual imaging and treatment capabilities all in one package, while also being robust enough to withstand the intense stresses faced during neutron activation. Here, we describe a method for synthesizing neutron activatable mesoporous silica nanoparticles for use in radiotherapy of metastatic peritoneal cancers while limiting personal exposure to radioactive materials, limiting the leakage of radioactive isotopes caused by nanoparticle degradation during neutron activation, and increasing cancer tissue specificity of radiation.

  3. Reproducibility of intraperitoneal 2-deoxy-2-[18F]-fluoro-D-glucose cerebral uptake in rodents through time

    International Nuclear Information System (INIS)

    Marsteller, Douglas A.; Barbarich-Marsteller, Nicole C.; Fowler, Joanna S.; Schiffer, Wynne K.; Alexoff, David L.; Rubins, Daniel J.; Dewey, Stephen L.

    2006-01-01

    Introduction: One strength of small animal imaging is the ability to obtain longitudinal measurements within the same animal, effectively reducing the number of animals needed and increasing statistical power. However, the variability of within-rodent brain glucose uptake after an intraperitoneal injection across an extended time has not been measured. Methods: Small animal imaging with 2-deoxy-2-[ 18 F]-fluoro-D-glucose ( 18 FDG) was used to determine the variability of a 50-min brain 18 FDG uptake following an intraperitoneal injection over time in awake male and female Sprague-Dawley rodents. Results: After determining the variability of an intraperitoneal injection in the awake rat, we found that normalization of brain 18 FDG uptake for (1) injected dose and body weight or (2) body weight, plasma glucose concentration and injected dose resulted in a coefficient of variation (CV) of 15%. However, if we normalized regional uptake to whole brain to compare relative regional changes, the CV was less than 5%. Normalized cerebral 18 FDG uptake values were reproducible for a 2-week period in young adult animals. After 1 year, both male and female animals had reduced whole-brain uptake, as well as reduced regional hippocampal and striatal 18 FDG uptake. Conclusion: Overall, our results were similar to findings in previous rodent and human clinical populations; thus, using a high throughput study with intraperitoneal 18 FDG is a promising preclinical model for clinical populations. This is particularly relevant for measuring changes in brain function after experimental manipulation, such as long-term pharmacological administration

  4. Adenosine 2A receptor agonism: A single intrathecal administration attenuates motor paralysis in experimental autoimmune encephalopathy in rats

    NARCIS (Netherlands)

    Loram, L.C.; Strand, K.A.; Taylor, F.R.; Sloane, E.; van Dam, A.M.; Rieger, J.; Maier, S.F.; Watkins, L.R.

    2015-01-01

    A single intrathecal dose of adenosine 2A receptor (A2AR) agonist was previously reported to produce a multi-week reversal of allodynia in two different models of neuropathic pain in addition to downregulating glial activation markers in the spinal cord. We aimed to determine whether a

  5. A proposal of Brazilian Society of Surgical Oncology for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil: pseudomixoma peritonei, appendiceal tumors and malignant peritoneal mesothelioma

    Directory of Open Access Journals (Sweden)

    Thales Paulo Batista

    Full Text Available ABSTRACT Cytoreductive surgery plus hypertermic intraperitoneal chemotherapy has emerged as a major comprehensive treatment of peritoneal malignancies and is currently the standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome as well as malignant peritoneal mesothelioma. Unfortunately, there are some worldwide variations of the cytoreductive surgery and hypertermic intraperitoneal chemotherapy techniques since no single technique has so far demonstrated its superiority over the others. Therefore, standardization of practices might enhance better comparisons between outcomes. In these settings, the Brazilian Society of Surgical Oncology considered it important to present a proposal for standardizing cytoreductive surgery plus hypertermic intraperitoneal chemotherapy procedures in Brazil, with a special focus on producing homogeneous data for the developing Brazilian register for peritoneal surface malignancies.

  6. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: a randomized controlled trial.

    Science.gov (United States)

    Song, Taejong; Kim, Mi Kyoung; Kim, Mi-La; Jung, Yong Wook; Yun, Bo Seong; Seong, Seok Ju

    2016-02-01

    Can a two-dose methotrexate treatment protocol improve the treatment success rate compared with a single-dose protocol in women with an ectopic pregnancy? The two-dose protocol was not superior to the single-dose protocol for the treatment of ectopic pregnancy. Although the two-dose methotrexate protocol for ectopic pregnancy was recently introduced to combine the efficacy and convenience of the fixed multi-dose and single-dose protocols, studies comparing the success rates, treatment satisfaction and acceptability of the single-dose and two-dose treatment protocols for ectopic pregnancy are currently lacking. A randomized trial was conducted on 92 participants with tubal ectopic pregnancy, between May 2013 and April 2015. Patients who were diagnosed with tubal ectopic pregnancy and who elected to undergo systemic methotrexate treatment were randomly assigned to follow either the single-dose (n = 46) or two-dose protocol (n = 46). The primary outcome measure was treatment success without surgical intervention. The secondary outcome measures were the incidence of methotrexate-associated side effects, β-human chorionic gonadotrophin (β-hCG) resolution time, cost of care received and treatment satisfaction. There were no differences in baseline characteristics between the groups. The success rates between the single-dose and two-dose groups did not show a significant difference [82.6 versus 87.0%; relative risk (RR) 0.95; 95% confidence interval (CI) 0.80-1.13]. However, the success rate in a subgroup of participants with a pretreatment β-hCG level of >5000 mIU/ml appeared to be higher in the two-dose group than in the single-dose group (80.0 versus 58.8%), although the difference was not statistically significant. No significant differences in methotrexate-associated side effects, cost or treatment satisfaction were observed between the groups. The two-dose group required a lower number of days for the β-hCG level to decrease to ectopic pregnancy. None. www

  7. Pharmacokinetics of tedizolid following oral administration: single and multiple dose, effect of food, and comparison of two solid forms of the prodrug.

    Science.gov (United States)

    Flanagan, Shawn D; Bien, Paul A; Muñoz, Kelly A; Minassian, Sonia L; Prokocimer, Philippe G

    2014-03-01

    The single- and multiple-dose pharmacokinetics (PK) of tedizolid were examined after oral administration of tedizolid phosphate disodium (TPD), including the effect of food on PK. The relative bioavailability of TPD to the free acid tedizolid phosphate was determined to bridge the results of these and other studies to the solid form of the prodrug selected for further development. Randomized placebo-controlled, double-blind single- and multiple-ascending dose studies and randomized open-label, crossover food effect and relative bioavailability studies. Clinical Research Units. Healthy subjects. Study TR701-101 enrolled 40 subjects in single-ascending dose (200-1200 mg TPD or placebo) and 40 subjects in 21-day multiple-ascending dose (200, 300, or 400 mg TPD once/day; 600 mg linezolid twice/day; or placebo) arms. Study TR701-103 was a food-effect study in 12 subjects administered 600 mg TPD. Study TR701-108 was a relative bioavailability study in 12 subjects administered 150-mg tedizolid equivalents as TPD or tedizolid phosphate. Plasma concentrations of the prodrug tedizolid phosphate, its active moiety tedizolid, and/or linezolid were collected. After administration of 200 to 600 mg TPD, tedizolid values increased approximately dose proportionally in area under the concentration-time curve (AUC) and maximum plasma concentration (Cmax ). Tedizolid half-life values were approximately 2-fold greater compared with linezolid. TPD administration with food delayed tedizolid absorption and reduced Cmax relative to the fasted state but did not alter AUC. Minimal accumulation was predicted and observed for tedizolid, whereas observed accumulation of linezolid exceeded predictions based on single-dose PK. Comparable PK of tedizolid was observed following oral administration of either TPD or tedizolid phosphate. In the multiple-ascending dose study, 3 of 24 tedizolid subjects were withdrawn under prespecified stopping rules (one each of elevated alanine

  8. Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats.

    Science.gov (United States)

    Akiyama, Yasuki; Yoshimura, Mitsuhiro; Nishimura, Kazuaki; Nishimura, Haruki; Sonoda, Satomi; Ueno, Hiromichi; Mitojima, Yasuhito; Saito, Reiko; Maruyama, Takashi; Nonaka, Yuki; Hashimoto, Hirofumi; Uezono, Yasuhito; Hirata, Keiji; Ueta, Yoichi

    2017-08-26

    Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. Nesfatin-1/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central nesfatin-1/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (180-220 g). Cumulative food intake was remarkably suppressed for at least 24 h and body weight was significantly smaller at 24 h after i.p. administration of cisplatin compared to control group. At 90 min after i.p. administration, they were perfused, followed by carrying out double-immunohistochemistry for Fos and nesfatin-1/NucB2. The percentage of nesfatin-1/NucB2 immunoreactive neurons expressing Fos was marked increased in the hypothalamus and brainstem after i.p. administration of cisplatin. Intracerebroventricularlly administered nesfatin-1/NucB2-antisense resulted in a significant attenuation of decreased food intake for 2 h after i.p. administration of cisplatin compared to nesfatin-1/NucB2-missense treated group. These results suggest that i.p. administration of cisplatin activated, at least in part, nesfatin-1/NucB2 neuron in the CNS and may exert anorexigenic effects in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Superovulation with a single administration of FSH in aluminum hydroxide gel: a novel superovulation method for cattle

    OpenAIRE

    KIMURA, Koji

    2016-01-01

    Superovulation (SOV) is a necessary technique to produce large numbers of embryos for embryo transfer. In the conventional methods, follicular stimulating hormone (FSH) is administered to donor cattle twice daily for 3 to 4 days. As this method is labor intensive and stresses cattle, improving this method has been desired. We previously developed a novel and simple SOV method, in which the intramuscular injection of a single dose of FSH in aluminum hydroxide gel (AH-gel) induced the growth of...

  10. Acute effects of a single, oral dose of d9-tetrahydrocannabinol (THC) and cannabidiol (CBD) administration in healthy volunteers.

    Science.gov (United States)

    Martin-Santos, R; Crippa, J A; Batalla, A; Bhattacharyya, S; Atakan, Z; Borgwardt, S; Allen, P; Seal, M; Langohr, K; Farré, M; Zuardi, A W; McGuire, P K

    2012-01-01

    Animal and humans studies suggest that the two main constituents of cannabis sativa, delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) have quite different acute effects. However, to date the two compounds have largely been studied separately. To evaluate and compare the acute pharmacological effects of both THC and CBD in the same human volunteers. A randomised, double-blind, cross-over, placebo controlled trial was conducted in 16 healthy male subjects. Oral THC 10 mg or CBD 600 mg or placebo was administered in three consecutive sessions, at one-month interval. Physiological measures and symptom ratings were assessed before, and at 1, 2 and 3 hours post drug administration. The area under the curve (AUC) between baseline and 3 hours, and the maximum absolute change from baseline at 2 hours were analysed by one-way repeated measures analysis of variance, with drug condition (THC or CBD or placebo) as the factor. Relative to both placebo and CBD, administration of THC was associated with anxiety, dysphoria, positive psychotic symptoms, physical and mental sedation, subjective intoxication (AUC and effect at 2 hours: p CBD and placebo on any symptomatic, physiological variable. In healthy volunteers, THC has marked acute behavioural and physiological effects, whereas CBD has proven to be safe and well tolerated.

  11. Randomised clinical trial on the effect of a single oral administration of l-tryptophan, at three dose rates, on reaction speed, plasma concentration and haemolysis in horses.

    Science.gov (United States)

    Noble, Glenys K; Li, Xiuhua; Zhang, Dagong; Sillence, Martin N

    2016-07-01

    Tryptophan (TRP) is marketed as a calmative for horses despite reservations about its efficacy. The aim of this study was to measure the effect of oral TRP administration on the reaction speed of horses. Sixty mature horses were used in a two stage randomised, blind, cross-over study, receiving a placebo and an oral dose of TRP (30, 60 or 120 mg/kg body weight), before undergoing a reaction speed test. Blood samples were taken up to 96 h after TRP administration, to identify signs of acute haemolytic anaemia. Plasma TRP concentrations were increased (P reaction speed of horses when startled. There was no evidence of alterations in clinical pathology parameters in 432 blood samples. While the safety of these doses of TRP can be confirmed, there was no evidence to suggest that a single dose of TRP is an effective calmative for horses. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Toxicokinetics of bisphenol A in female DA/Han rats after a single i.v. and oral administration.

    Science.gov (United States)

    Upmeier, A; Degen, G H; Diel, P; Michna, H; Bolt, H M

    2000-10-01

    Bisphenol A [BPA; 2,2-bis-(4-hydroxyphenyl)-propane] is a monomer used in the manufacture of resins with a wide range of applications, e.g. plastic coatings in the food packaging industry. BPA has been shown to have a weak oestrogenic activity in vitro and in vivo. Despite its low oestrogenic potency there is concern that, as a consequence of slow clearance, BPA might reach biologically significant levels in humans and animals exposed to environmental levels. To address this concern, we assessed the kinetic behaviour of BPA in female DA/Han rats. Groups of female rats received 10 mg BPA/kg body weight intravenously or 10 or 100 mg BPA/kg body weight orally (by gavage). Blood samples were collected at different time-points and plasma was prepared. Free BPA in the samples was isolated by fluid-fluid extraction. BPA was measured by GC-MS which allowed the reliable determination of BPA concentrations as low as approximately 10 ng/ml plasma. Immediately after i.v. administration, the BPA plasma concentration was in the range of about 15 microg/ml and decreased rapidly within the first hour (to 700 ng/ml). The levels declined further (100 ng/ml at 2 h), and after 24 h the analytical detection limit was reached. BPA was detected in plasma as early as 10 min after gavage administration, indicating rapid initial uptake from the gastrointestinal tract. Absorption of BPA was variable. In animals receiving 10 mg/kg, maximal plasma levels were reached after 1.5 h (31 ng/ ml) and 6 h (40 ng/ml). In animals receiving 100 mg/kg, plasma levels reached maxima around 30 min (150 ng/ml) and 3 h (134 ng/ml) after administration. After 48 h BPA was at or below the detection limit in both dose groups. Fluctuations in the BPA plasma concentrations over time point to the possibility of enterohepatic recirculation and protracted absorption from the gastrointestinal tract. Using the area under the concentration-time curves (AUCs), low bioavailabilities of 16.4% and 5.6% were calculated for

  13. Single systemic administration of Ag85B of mycobacteria DNA inhibits allergic airway inflammation in a mouse model of asthma

    Directory of Open Access Journals (Sweden)

    Karamatsu K

    2012-12-01

    Full Text Available Katsuo Karamatsu,1,2 Kazuhiro Matsuo,3 Hiroyasu Inada,4 Yusuke Tsujimura,1 Yumiko Shiogama,1,2 Akihiro Matsubara,1,2 Mitsuo Kawano,5 Yasuhiro Yasutomi1,21Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, 2Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, 3Department of Research and Development, Japan BCG Laboratory, Tokyo, 4Department of Pathology, Suzuka University of Medical Science, Suzuka, 5Department of Microbiology and Molecular Genetics, Mie University Graduate School of Medicine, Tsu, JapanAbstract: The immune responses of T-helper (Th and T-regulatory cells are thought to play a crucial role in the pathogenesis of allergic airway inflammation observed in asthma. The correction of immune response by these cells should be considered in the prevention and treatment of asthma. Native antigen 85B (Ag85B of mycobacteria, which cross-reacts among mycobacteria species, may play an important biological role in host–pathogen interaction since it elicits various immune responses by activation of Th cells. The current study investigated the antiallergic inflammatory effects of DNA administration of Ag85B from Mycobacterium kansasii in a mouse model of asthma. Immunization of BALB/c mice with alum-adsorbed ovalbumin followed by aspiration with aerosolized ovalbumin resulted in the development of allergic airway inflammation. Administration of Ag85B DNA before the aerosolized ovalbumin challenge protected the mice from subsequent induction of allergic airway inflammation. Serum and bronchoalveolar lavage immunoglobulin E levels, extent of eosinophil infiltration, and levels of Th2-type cytokines in Ag85B DNA-administered mice were significantly lower than those in control plasmid-immunized mice, and levels of Th1- and T-regulatory-type cytokines were enhanced by Ag85B

  14. Influence of activated charcoal on the pharmacokinetics of moxifloxacin following intravenous and oral administration of a 400 mg single dose to healthy males

    Science.gov (United States)

    Stass, H; Kubitza, D; Möller, J-G; Delesen, H

    2005-01-01

    Aims To evaluate the extent to which enterohepatic recycling circulation contributes to moxifloxacin bioavailability in healthy, males by administration of activated charcoal and to evaluate the efficacy of activated charcoal administration in decreasing systemic concentrations of moxifloxacin in the event of overdose. Methods Nine healthy males, mean age 34 years (range 23–45 years) participated in a single centre, randomized, nonplacebo-controlled, three way crossover study. The pharmacokinetics of moxifloxacin in plasma and urine were determined for up to 96 h following a 400 mg single dose randomly administered on three separate occasions with a minimum washout phase of 1 week. Treatment A was 400 mg moxifloxacin IV as a 1 h infusion, treatment B was 400 mg moxifloxacin IV as a 1 h infusion with oral activated charcoal (5 g directly before the start of the infusion, 5 g immediately after the end of the infusion, and 10 g at 2, 4 and 8 h after the start of the infusion), treatment C was 400 mg oral moxifloxacin with activated charcoal (10 g 15 min before and at 2, 4 and 8 h after drug administration). The subjects underwent a series of clinical and laboratory tests. Results Single 400 mg doses of moxifloxacin (PO and/or IV) were safe and well tolerated. The bioavailability of moxifloxacin was significantly decreased when given with charcoal (AUC = 35.5 (IV reference) vs 5.40 (PO) vs 28.5 (IV) mg l−1 h). Concurrently peak concentrations were lowered Cmax = 3.38 (IV reference) vs 0.62(PO) vs 2.97 (IV) mg l−1) by approximately 85% (P activated charcoal may be useful in treating moxifloxacin overdose by preventing its absorption. PMID:15842551

  15. Comparison of simultaneous and sequential administration of fentanyl-propofol for surgical abortion: a randomized single-blinded controlled trial.

    Science.gov (United States)

    Gao, Wei; Sha, Baoyong; Zhao, Yuan; Fan, Zhe; Liu, Lin; Shen, Xin

    2017-08-01

    Propofol lipid emulsion (PLE) is a nanosized sedative, and it is used with a combination of salted antalgic prodrug, fentanyl citrate (FC). To illustrate the synergistic effect of mixing, we compared the sedation/analgesia resulting from simultaneous and sequential administration in surgically induced abortion (No. ChiCTR-IPC-15006153). Simultaneous group showed lower bispectral index, blood pressure, and heart rate, when cannula was inserted into the uterus. It also showed less frequency of hypertension, sinus tachycardia, movement, pain at the injection site, and additional FC. Therefore, premixing of PLE and FC enhanced the sedation and analgesia; stabilized the hemodynamics; lessened the incidence of movement and injection pain; and reduced the requirement of drugs.

  16. Pregnancy success of lactating Holstein cows after a single administration of a sustained-release formulation of recombinant bovine somatotropin

    Directory of Open Access Journals (Sweden)

    Gutiérrez CG

    2008-06-01

    Full Text Available Abstract Background Results regarding the use of bovine somatotropin for enhancing fertility in dairy cattle are variable. Here, the hypothesis was tested that a single injection of a sustained-release preparation of bovine somatotropin (bST during the preovulatory period would improve pregnancy success of lactating dairy cows at first service. Results The first experiment was conducted in a temperate region of Mexico. Cows inseminated following natural estrus or timed artificial insemination were given a single injection of bST or a placebo injection at insemination (n = 100 cows per group. There was no significant difference between bST and control groups in the proportion of inseminated cows diagnosed pregnant (29 vs 31% pregnant. The second experiment was performed during heat stress in Florida. Cows were subjected to an ovulation synchronization regimen for first insemination. Cows treated with bST received a single injection at 3 days before insemination. Controls received no additional treatment. As expected, bST did not increase vaginal temperature. Treatment with bST did not significantly increase the proportion of inseminated cows diagnosed pregnant although it was numerically greater for the bST group (24.2% vs 17.8%, 124–132 cows per group. There was a tendency (p = 0.10 for a smaller percent of control cows to have high plasma progesterone concentrations (≥ 1 ng/ml at Day 7 after insemination than for bST-treated cows (72.6 vs 81.1%. When only cows that were successfully synchronized were considered, the magnitude of the absolute difference in the percentage of inseminated cows that were diagnosed pregnant between bST and control cows was reduced (24.8 vs 22.4% pregnant for bST and control. Conclusion Results failed to indicate a beneficial effect of bST treatment on fertility of lactating dairy cows.

  17. Population pharmacokinetics of methadone hydrochloride after a single intramuscular administration in adult Japanese sika deer (Cervus nippon nippon).

    Science.gov (United States)

    Scala, Christopher; Marsot, Amélie; Limoges, Marie-Josée; Locatelli, Yann; Simon, Nicolas; Alvarez, Jean-Claude

    2015-03-01

    To assess the population pharmacokinetics of methadone in deer. Prospective non-randomized experimental trial. Twelve healthy adult sika deer (nine males and three females). Deer received intramuscular administration of racemic methadone hydrochloride at 0.5 mg kg(-1) or 1 mg kg(-1) . Plasma methadone and its metabolite 2-Ethylidene-1,5-Dimethyl-3,3-Diphenyl-Pyrolidine (EDDP) concentrations were determined by validated liquid chromatography coupled to tandem mass spectrometry methods, at times 0, 30 minutes, 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours. Population pharmacokinetics analysis was undertaken using a non-linear mixed effects modelling (NONMEM). A two-compartment linear disposition model best described observed time-concentration profiles of methadone and EDDP. Population parameter estimates of methadone were elimination clearance (17.3 L hour(-1) ), metabolic clearance (34.6 L hour(-1) ), volume of distribution of compartment 1 (216.0 L) and volume of distribution of compartment 2 (384.0 L). Population parameter estimates of EDDP were elimination clearance (121.0 L hour(-1) ), volume of distribution of compartment 3 (1.08 L) and volume of distribution of compartment 4 (499.5 L). The total clearance and total volume of distribution of methadone and EDDP were 51.9 L hour(-1) , 121.0 L hour (-1) , 600.0 L and 500.6 L, respectively. The methadone terminal elimination half-life was 8.19 hours. No adverse effects were observed after methadone administration. Following intramuscular injection, methadone was characterized by a large total volume of distribution, high systemic clearance and intermediate terminal half-life in sika deer. © 2014 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  18. Intravenous avidin chase improved localization of radiolabeled streptavidin in intraperitoneal xenograft pretargeted with biotinylated antibody

    International Nuclear Information System (INIS)

    Zhang Meili; Sakahara, Harumi; Yao Zhengsheng; Saga, Tsuneo; Nakamoto, Yuhi; Sato, Noriko; Nakada, Hiroshi; Yamashina, Ikuo; Konishi, Junji

    1997-01-01

    In the present study, we examined the effect of avidin administered intravenously (i.v.) on the biodistribution of radiolabeled streptavidin in mice bearing intraperitoneal (IP) xenografts pretargeted with biotinylated antibody. Tumors were established in nude mice by IP inoculation of LS180 human colon cancer cells. Monoclonal antibody MLS128, which recognizes Tn antigen on mucin, was biotinylated and injected IP into the IP tumor-bearing mice. Radioiodinated streptavidin was administered IP or i.v. 48 h after pretargeting of biotinylated antibody. Avidin was administered i.v. 30 min prior to streptavidin injection. The localization of radioiodinated streptavidin in the tumor pretargeted with biotinylated antibody was significantly higher than that without pretargeting and that of radioiodinated MLS128 by the one-step method. Avidin administration significantly accelerated the clearance of radioiodinated streptavidin in blood and other normal tissues and increased the tumor-to-blood radioactivity ratio regardless of administration route of streptavidin. The i.v. avidin chase improved tumor localization of radiolabeled streptavidin in the IP xenografts pretargeted with biotinylated antibody

  19. Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

    Science.gov (United States)

    Shamsi, Milad; Sedaghatkish, Amir; Dejam, Morteza; Saghafian, Mohsen; Mohammadi, Mehdi; Sanati-Nezhad, Amir

    2018-11-01

    Intraperitoneal (IP) chemotherapy has revived hopes during the past few years for the management of peritoneal disseminations of digestive and gynecological cancers. Nevertheless, a poor drug penetration is one key drawback of IP chemotherapy since peritoneal neoplasms are notoriously resistant to drug penetration. Recent preclinical studies have focused on targeting the aberrant tumor microenvironment to improve intratumoral drug transport. However, tumor stroma targeting therapies have limited therapeutic windows and show variable outcomes across different cohort of patients. Therefore, the development of new strategies for improving the efficacy of IP chemotherapy is a certain need. In this work, we propose a new magnetically assisted strategy to elevate drug penetration into peritoneal tumor nodules and improve IP chemotherapy. A computational model was developed to assess the feasibility and predictability of the proposed active drug delivery method. The key tumor pathophysiology, including a spatially heterogeneous construct of leaky vasculature, nonfunctional lymphatics, and dense extracellular matrix (ECM), was reconstructed in silico. The transport of intraperitoneally injected magnetic nanoparticles (MNPs) inside tumors was simulated and compared with the transport of free cytotoxic agents. Our results on magnetically assisted delivery showed an order of magnitude increase in the final intratumoral concentration of drug-coated MNPs with respect to free cytotoxic agents. The intermediate MNPs with the radius range of 200-300 nm yield optimal magnetic drug targeting (MDT) performance in 5-10 mm tumors while the MDT performance remains essentially the same over a large particle radius range of 100-500 nm for a 1 mm radius small tumor. The success of MDT in larger tumors (5-10 mm in radius) was found to be markedly dependent on the choice of magnet strength and tumor-magnet distance while these two parameters were less of a concern in small tumors

  20. Comparative pharmacokinetics and bioavailability of tylosin tartrate and tylosin phosphate after a single oral and i.v. administration in chickens.

    Science.gov (United States)

    Ji, L-W; Dong, L-L; Ji, H; Feng, X-W; Li, D; Ding, R-L; Jiang, S-X

    2014-06-01

    The pharmacokinetics and oral bioavailability of tylosin tartrate and tylosin phosphate were carried out in broiler chickens according to a principle of single dose, random, parallel design. The two formulations of tylosin were given orally and intravenously at a dose level of 10 mg/kg b.w to chicken after an overnight fasting (n = 10 chickens/group). Serial blood samples were collected at different time points up to 24 h postdrug administration. A high performance liquid chromatography method was used for the determination of tylosin concentrations in chicken plasma. The tylosin plasma concentration's time plot of each chicken was analyzed by the 3P97 software. The pharmacokinetics of tylosin was best described by a one-compartmental open model 1st absorption after oral administration. After intravenous administration the pharmacokinetics of tylosin was best described by a two-compartmental open model, and there were no significant differences between tylosin tartrate and tylosin phosphate. After oral administration, there were significant differences in the Cmax (0.18 ± 0.01, 0.44 ± 0.09) and AUC (0.82 ± 0.05, 1.57 ± 0.25)between tylosin phosphate and tylosin tartrate. The calculated oral bioavailability (F) of tylosin tartrate and tylosin phosphate were 25.78% and 13.73%, respectively. Above all, we can reasonably conclude that, the absorption of tylosin tartrate is better than tylosin phosphate after oral administration. © 2013 John Wiley & Sons Ltd.

  1. Open, intraperitoneal, ventral hernia repair: lessons learned from laparoscopy.

    Science.gov (United States)

    Ponsky, Todd A; Nam, Arthur; Orkin, Bruce A; Lin, Paul P

    2006-03-01

    Recent literature suggests that laparoscopic repair of ventral hernias may have very low recurrence rates. However, laparoscopy may not be feasible in certain situations. We describe an open technique that uses the tension-free retrofascial principles of laparoscopic repair without the need for subcutaneous flaps. Through an incision in the hernia, the peritoneum is entered and adhesions are taken down. A piece of DualMesh (W.L. Gore & Associates, Inc, Newark, Del) is trimmed to fit with a 5-cm circumferential overlap. A vertical incision is made in the mid portion of the mesh. The mesh is fixed in an intraperitoneal retrofascial position using GORE-TEX sutures (W.L. Gore & Associates, Inc). The sutures are brought through the abdominal wall using a laparoscopic suture passer and tied into place on one side of the mesh. That side is then tacked to the posterior fascia with a spiral tacking device. The other side is sutured into place in a similar fashion and then tacked to the fascia by passing the spiral tacking device through the incision in the mesh. The mesh incision is closed with a running GORE-TEX suture. The overlying tissues are closed in layers.

  2. Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced conditioned place preference

    Directory of Open Access Journals (Sweden)

    Robin eVoigt

    2012-01-01

    Full Text Available Re-exposure to cues repeatedly associated with methamphetamine (Meth can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the long-term maintenance of Meth-induced conditioned place preference (CPP when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a ‘reinforced re-exposure’ to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP on day 20; however, rats administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber did not demonstrate CPP. These results indicate a context-dependent effect of mirtazapine, and that the ability of mirtazapine to disrupt the long-term maintenance of CPP is greatest when the atypical antidepressant is tested with a combination of Meth injection and contextual cues.

  3. Concurrent administration of donepezil HCl and sertraline HCl in healthy volunteers: assessment of pharmacokinetic changes and safety following single and multiple oral doses

    Science.gov (United States)

    Nagy, Christa F; Kumar, Dinesh; Perdomo, Carlos A; Wason, Suman; Cullen, Edward I; Pratt, Raymond D

    2004-01-01

    Aim This study evaluated the safety and pharmacokinetics (PK) of donepezil HCl and sertraline HCl when administered separately and in combination. Methods This was a randomized, open-label, three-period crossover study. In consecutive dosing periods separated by washout periods of ≥3 weeks, healthy volunteers received either oral donepezil HCI 5 mg once daily for 15 days, oral sertraline HCl 50 mg once daily for 5 days followed by 10 days of once-daily sertraline HCl 100 mg, or the simultaneous administration of oral donepezil HCl and sertraline HCl. Plasma donepezil and sertraline concentrations were determined by high performance liquid chromatography/mass spectrometry. Safety was evaluated by physical and laboratory evaluations and the monitoring of adverse events (AEs). Results A total of 19 volunteers (16 male and three female) were enrolled. Three male subjects withdrew from the study prematurely due to AEs (one case of nausea/stomach cramps and one case of eosinophilia during combination treatment, and one upper respiratory tract infection during treatment with sertraline HCl alone). In subjects who completed all three treatment periods (n = 16), the concurrent administration of donepezil HCl and sertraline HCl did not alter the steady-state (day 15) PK parameters of donepezil HCl. A small (<12%) but statistically significant (P = 0.02) increase in donepezil Cmax was seen after single doses of sertraline HCl and donepezil HCl on day 1 but this was not thought to be clinically meaningful. No significant differences in the tmax or AUC0–24 h of donepezil were observed between the donepezil HCl only or donepezil HCl plus sertraline HCl groups on day 1. No significant changes in sertraline PK parameters were observed either on day 1 (single dose) or on day 15 (steady state) when sertraline HCl was co-administered with donepezil HCl. Generally, the concurrent administration of donepezil HCl and sertraline HCl was well tolerated, with no serious AEs reported

  4. A single dose of dexamethasone encapsulated in polyethylene glycol-coated polylactic acid nanoparticles attenuates cisplatin-induced hearing loss following round window membrane administration

    Directory of Open Access Journals (Sweden)

    Sun CL

    2015-05-01

    Full Text Available Changling Sun,1,3,* Xueling Wang,1,* Zhaozhu Zheng,2 Dongye Chen,1 Xiaoqin Wang,2 Fuxin Shi,1 Dehong Yu,1 Hao Wu11Department of Otolaryngology–Head and Neck Surgery, Xinhua Hospital, Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, 2National Engineering Laboratory for Modern Silk, Soochow University, Suzhou, 3Department of Otolaryngology–Head and Neck Surgery, Affiliated Hospital of Jiangnan University, The Fourth People’s Hospital of Wuxi City, Wuxi, People’s Republic of China*These authors have contributed equally to this workAbstract: This study aimed to investigate the sustained drug release properties and hearing protection effect of polyethylene glycol-coated polylactic acid (PEG-PLA stealth nanoparticles loaded with dexamethasone (DEX. DEX was fabricated into PEG-PLA nanoparticles using an emulsion and evaporation technique, as previously reported. The DEX-loaded PEG-PLA nanoparticles (DEX-NPs had a hydrodynamic diameter of 130±4.78 nm, and a zeta potential of -26.13±3.28 mV. The in vitro release of DEX from DEX-NPs lasted 24 days in phosphate buffered saline (pH 7.4, 5 days in artificial perilymph (pH 7.4, and 1 day in rat plasma. Coumarin 6-labeled NPs placed onto the round window membrane (RWM of guinea pigs penetrated RWM quickly and accumulated to the organs of Corti, stria vascularis, and spiral ganglion cells after 1 hour of administration. The DEX-NPs locally applied onto the RWM of guinea pigs by a single-dose administration continuously released DEX in 48 hours, which was significantly longer than the free DEX that was cleared out within 12 hours after administration at the same dose. Further functional studies showed that locally administrated single-dose DEX-NPs effectively preserved outer hair cells in guinea pigs after cisplatin insult and thus significantly attenuated hearing loss at 4 kHz and 8

  5. Plasma concentrations of buprenorphine following a single subcutaneous administration of a sustained release formulation of buprenorphine in sheep.

    Science.gov (United States)

    Zullian, Chiara; Lema, Pablo; Lavoie, Melissa; Dodelet-Devillers, Aurore; Beaudry, Francis; Vachon, Pascal

    2016-07-01

    The goal of the present study was to evaluate the potential use of slow release buprenorphine in sheep. Twelve adult female sheep (6 Dorset and 6 Suffolk, 12 months of age) were used for this project and were divided into 2 experimental groups (n = 6/group comprising 3 Dorset and 3 Suffolk sheep). Sustained release (SR) buprenorphine was administered subcutaneously in the scapular region at a concentration of 0.1 mg/kg body weight (BW) for group 1 and of 0.05 mg/kg BW for group 2. Following blood collections at selected time points, plasma concentrations of buprenorphine was performed by tandem liquid chromatograph-mass spectrometry. Mean buprenorphine concentration was above 0.1 ng/mL at 48 h up to 192 h post-injection for group 1 and it was above 0.1 ng/mL at 48 h up to 72 h post-injection for group 2. In conclusion, a long lasting potential analgesic plasma level of buprenorphine is attained following a single subcutaneous injection of 0.1 mg/kg BW of SR buprenorphine in sheep. However the effective analgesic plasma threshold still needs to be determined in sheep.

  6. Effect of food on the pharmacokinetics of rosuvastatin after administration of a single oral dose in dogs.

    Science.gov (United States)

    Baek, I-H; Kwon, K-I; Kim, M-S

    2013-03-01

    Rosuvastatin is a highly effective inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and is used for the treatment of patients with hyperlipidemia. We examined the effect of food on the pharmacokinetics of rosuvastatin by administering it while fasting and after intake of low-fat and high-fat meals. We administered a single 10-mg oral dose of rosuvastatin while fasting and after intake of a low-fat and high-fat meal in a parallel design. The plasma concentrations of rosuvastatin were measured using liquid chromatography tandem mass spectrometry (LC-MS/MS), and the pharmacokinetics of rosuvastatin was analyzed using both noncompartmental and compartmental models. The values of area under the curve at 24 h (AUC 24 h ) and peak plasma concentration (C max) in fed conditions were significantly lower than the corresponding values in the fasting conditions. In addition, consumption of a high-fat meal significantly delayed the time required to achieve the maximum concentration (T max) of rosuvastatin. Both the models sufficiently explained the effect of food on the pharmacokinetics of rosuvastatin and showed that the volume of distribution (V c) was increased and absorption rate constant (K a) was decreased in fed dogs. These findings suggest that food intake affects both the rate and extent of absorption of rosuvastatin, and that rosuvastatin should be administered on an empty stomach to avoid food effect. © Georg Thieme Verlag KG Stuttgart · New York.

  7. THE EFFECT OF SINGLE NICKEL AND COMBINED NICKEL AND ZINC PERORAL ADMINISTRATION ON HAEMATOLOGICAL PARAMETERS IN RABBITS

    Directory of Open Access Journals (Sweden)

    Jana Emrichová

    2013-06-01

    Full Text Available The aim of this study was to determine the effect of single nickel (NiCl2 and nickel in combination with zinc (ZnCl2 on selected haematological parameters of rabbits: white blood cell, red blood cell, haemoglobin, haematocrit, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, platelets, mean platelet volume, red cell distribution width, lymphocytes, monocytes, eosinophils, neutrophils, basophils. Twenty rabbits of broiler line Californian were used in this experiment. The animals were divided into the five groups, four animals in each ones (control group K and experimental groups E1, E2, E3 and E4. Animals were fed ad libitum using KKV1 feeding mixture (FM with or without nickel and zinc addition for 90 days follows: group E1 received 17.5 g of NiCl2.100 kg-1 FM; group E2 35 g NiCl2.100 kg-1 FM; group E3 17.5 g NiCl2 + 30 g ZnCl2.100 kg-1 FM and group E4 35 g NiCl2 + 30 g ZnCl2.100 kg-1 FM. The parameters were analysed using Advia – 120. Blood was collected into tubes containing anticoagulant agents K – EDTA. Statistical analyse showed a significant changes (P 0.05. Nickel has negative effect on some haematological parameters, but zinc can eliminates its influence.

  8. Effect of exercise on turnover and fate of 4-14C$-cholesterol administered intraperitoneally and orally to rats

    International Nuclear Information System (INIS)

    Fukuda, Nobuhiro; Tsuge, Yasuyuki; Sugano, Michihiro

    1979-01-01

    The fate of [4- 14 C]-cholesterol administered intraperitoneally or orally was compared in exercised (treadmill running for 14 days) and sedentary rats. Plasma triglyceride, phospholipid and cholesterol decreased in exercised rats and this reduction lasted at least for 10 days after exercise was terminated. When rats received [4- 14 C]-cholesterol intraperitoneally or orally, the turnover rate of serum cholesterol was considerably higher in exercised rats at the time shortly after the administration of the label. The radioactivity remaining in the liver was consistently lower in exercised rats, whereas that in extrahepatic tissues was the same between two groups. Excretion into feces of the label as total steroids was moderately enhanced by exercise. This effect was almost entirely ascribed to the increase in output of the label shortly after the administration. These results suggest that the mechanism responsible for cholesterol lowering effect of exercise is mainly attributable to the increase in turnover of cholesterol in the hepato-plasmic system. The moderate increase in fecal output of endogenous steroids may be the reflection of the increased turnover. (author)

  9. Efficacy and safety of selenium nanoparticles administered intraperitoneally for the prevention of growth of cancer cells in the peritoneal cavity.

    Science.gov (United States)

    Wang, Xin; Sun, Kang; Tan, Yanping; Wu, Shanshan; Zhang, Jinsong

    2014-07-01

    Peritoneal implantation of cancer cells, particularly postoperative seeding metastasis, frequently occurs in patients with primary tumors in the stomach, colon, liver, and ovary. Peritoneal carcinomatosis is associated with poor prognosis. In this work, we evaluated the prophylactic effect of intraperitoneal administration of selenium (Se), an essential trace element and a putative chemopreventive agent, on peritoneal implantation of cancer cells. Elemental Se nanoparticles were injected into the abdominal cavity of mice, into which highly malignant H22 hepatocarcinoma cells had previously been inoculated. Se concentrations in the cancer cells and tissues, as well as the efficacy of proliferation inhibition and safety, were evaluated. Se was mainly concentrated in cancer cells compared to Se retention in normal tissues, showing at least an order of magnitude difference between the drug target cells (the H22 cells) and the well-recognized toxicity target of Se (the liver). Such a favorable selective distribution resulted in strong proliferation suppression without perceived host toxicity. The mechanism of action of the Se nanoparticle-triggered cytotoxicity was associated with Se-mediated production of reactive oxygen species, which impaired the glutathione and thioredoxin systems. Our results suggest that intraperitoneal administration of Se is a safe and effective means of preventing growth of cancer cells in the peritoneal cavity for the above-mentioned high-risk populations. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. A single intranasal administration of virus-like particle vaccine induces an efficient protection for mice against human respiratory syncytial virus.

    Science.gov (United States)

    Jiao, Yue-Ying; Fu, Yuan-Hui; Yan, Yi-Fei; Hua, Ying; Ma, Yao; Zhang, Xiu-Juan; Song, Jing-Dong; Peng, Xiang-Lei; Huang, Jiaqiang; Hong, Tao; He, Jin-Sheng

    2017-08-01

    Human respiratory syncytial virus (RSV) is an important pediatric pathogen causing acute viral respiratory disease in infants and young children. However, no licensed vaccines are currently available. Virus-like particles (VLPs) may bring new hope to producing RSV VLP vaccine with high immunogenicity and safety. Here, we constructed the recombinants of matrix protein (M) and fusion glycoprotein (F) of RSV, respectively into a replication-deficient first-generation adenoviral vector (FGAd), which were used to co-infect Vero cells to assemble RSV VLPs successfully. The resulting VLPs showed similar immunoreactivity and function to RSV virion in vitro. Moreover, Th1 polarized response, and effective mucosal virus-neutralizing antibody and CD8 + T-cell responses were induced by a single intranasal (i.n.) administration of RSV VLPs rather than intramuscular (i.m.) inoculation, although the comparable RSV F-specific serum IgG and long-lasting RSV-specific neutralizing antibody were detected in the mice immunized by both routes. Upon RSV challenge, VLP-immunized mice showed increased viral clearance but decreased signs of enhanced lung pathology and fewer eosinophils compared to mice immunized with formalin-inactivated RSV (FI-RSV). In addition, a single i.n. RSV VLP vaccine has the capability to induce RSV-specific long-lasting neutralizing antibody responses observable up to 15 months. Our results demonstrate that the long-term and memory immune responses in mice against RSV were induced by a single i.n. administration of RSV VLP vaccine, suggesting a successful approach of RSV VLPs as an effective and safe mucosal vaccine against RSV infection, and an applicable and qualified platform of FGAd-infected Vero cells for VLP production. Copyright © 2017. Published by Elsevier B.V.

  11. The Effect of Nicotine Administration on Physical and Psychological Signs of Withdrawal Syndrome Induced by Single or Frequent Doses of Morphine in Rats

    Directory of Open Access Journals (Sweden)

    Mohammad Allahtavakoli

    2012-07-01

    Full Text Available Introduction. Morphine addiction and morphine withdrawal syndrome are the two main problems of today’s human society. The present study has investigated the effects of nicotine on the strength of physical and psychological dependency in single and repeated doses morphine administrated rats. Materials and methods. Male Wistar rats were subjected to morphine consumption with single or frequent dose protocols. In the single dose protocol, rats received only one dose of morphine and 24hrs later they also received one dose of nicotine 30 min prior to injection of naloxone. In the repeated dose protocol, rats received incremental doses of morphine for 7 days and 24hr after the last dose (the 8th day were given naloxone. However, the nicotine regimen of this group was injected 15 min before the morphine injection, for 4 days, from the 4th to the 7th day. Five minutes after naloxone injection, each rat′s behavior was captured for 30 min, and then physical and psychological signs of withdrawal syndrome were recorded. Data were analyzed by ANOVA followed by Tukey tests and p<0.05 was considered as significant difference. Findings. Results showed that the injection of frequent and single doses of morphine lead to morphine dependency. In single dose protocol, nicotine consumption attenuated the signs of withdrawal syndrome, especially weight of excrement and total withdrawal score. In frequent dose protocol, in addition to these effects, nicotine induced weight loss and place aversion. Conclusion. The inhibitory effects of nicotine on signs of withdrawal syndrome may involve a dopaminergic portion of the central nervous system and is mediated by central nicotinic receptors. There is also a cross-dependence between nicotine and morphine.

  12. Tamoxifen Forms DNA Adducts In Human Colon After Administration Of A Single [14C]-Labeled Therapeutic Dose.

    Energy Technology Data Exchange (ETDEWEB)

    Brown, K; Tompkins, E M; Boocock, D J; Martin, E A; Farmer, P B; Turteltaub, K W; Ubick, E; Hemingway, D; Horner-Glister, E; White, I H

    2007-05-23

    Tamoxifen is widely prescribed for the treatment of breast cancer and is also licensed in the U.S. for the prevention of this disease. However, tamoxifen therapy is associated with an increased occurrence of endometrial cancer in women and there is also evidence that it may elevate the risk of colorectal cancer. The underlying mechanisms responsible for tamoxifen-induced carcinogenesis in women have not yet been elucidated but much interest has focussed on the role of DNA adduct formation. We investigated the propensity of tamoxifen to bind irreversibly to colorectal DNA when given to ten women as a single [{sup 14}C]-labeled therapeutic (20 mg) dose, {approx}18 h prior to undergoing colon resections. Using the sensitive technique of accelerator mass spectrometry, coupled with HPLC separation of enzymatically digested DNA, a peak corresponding to authentic dG-N{sup 2}-tamoxifen adduct was detected in samples from three patients, at levels ranging from 1-7 adducts/10{sup 9} nucleotides. No [{sup 14}C]-radiolabel associated with tamoxifen or its major metabolites was detected. The presence of detectable CYP3A4 protein in all colon samples suggests this tissue has the potential to activate tamoxifen to {alpha}-hydroxytamoxifen, in addition to that occurring in the systemic circulation, and direct interaction of this metabolite with DNA could account for the binding observed. Although the level of tamoxifeninduced damage displayed a degree of inter-individual variability, when present it was {approx}10-100 times higher than that reported for other suspect human colon carcinogens such as PhIP. These findings provide a mechanistic basis through which tamoxifen could increase the incidence of colon cancers in women.

  13. An Open-label, Single-dose, Pharmacokinetic Study of Factor VIII Activity After Administration of Moroctocog Alfa (AF-CC) in Male Chinese Patients With Hemophilia A.

    Science.gov (United States)

    Liu, Hongzhong; Wu, Runhui; Hu, Pei; Sun, Feifei; Xu, Lihong; Liang, Yali; Nepal, Sunil; Qu, Peng Roger; Huard, Francois; Korth-Bradley, Joan M

    2017-07-01

    Hemophilia A represents up to 80% of all hemophilia cases in China. In patients with this condition, bleeding can be prevented and controlled by administering clotting factor VIII (FVIII). Since their initial availability, recombinant FVIII products have undergone several iterations to enhance their safety. Moroctocog alfa albumin-free cell culture (AF-CC) is among the third generation of recombinant FVIII products and received regulatory approval in China in August 2012. The present study characterizes the single-dose pharmacokinetic parameters of FVIII activity (FVIII:C) after administration of moroctocog alfa (AF-CC) in male Chinese patients with hemophilia A. This multicenter, open-label, single-dose study enrolled 13 male Chinese patients diagnosed with severe hemophilia A (FVIII:C hemophilia A. The pharmacokinetic profile in older patients was similar to that previously reported with recombinant FVIII products in studies with a predominantly white population; younger patients had reduced exposure to FVIII:C. The single doses of moroctocog alfa (AF-CC) were well tolerated; 2 cases of transient, low-titer FVIII inhibitor development were observed. ClinicalTrials.gov identifier: NCT02461992. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

  14. Chronic vitamin C administration induces thermal hyperalgesia in ...

    African Journals Online (AJOL)

    Against a backdrop of neurological effects, the effects of acute and chronic administration of vitamin C (600mg/kg) on pain processing were investigated in male rats. Chronic administration of vitamin C induced significant thermal hyperalgesia while acute administration had no effect. In addition, the intraperitoneal ...

  15. [Nootropic and analgesic effects of Semax following different routes of administration].

    Science.gov (United States)

    Manchenko, D M; Glazova, N Iu; Levitskaia, N G; Andreeva, L A; Kamenskiĭ, A A; Miasoedov, N F

    2010-10-01

    Heptapeptide Semax (MEHFPGP) is the fragment of ACTH(4-10) analogue with prolonged neurotropic activity. The aim of the present work was to study the Semax effects on learning capability and pain sensitivity in white rats following intraperitoneal and intranasal administration in different doses. Semax nootropic effects were studied in the test of acquisition of passive avoidance task. Pain sensitivity was estimated in Randall-Selitto paw-withdrawal test. It was shown that Semax exerts nootropic and analgesic activities following intraperitoneal administration. Analysis of dependence of these effects on dose resulted in different dose-response curves. Following intranasal administration, Semax was more potent in learning improvement compared to intraperitoneal administration. The peptide failed to affect the animal pain sensitivity following intranasal administration as opposed to intraperitoneal administration. The data obtained suggest different mechanisms and brain structures involved in realization of the nootropic and analgesic effects of Semax.

  16. Factors associated with thromboembolic events following cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Rottenstreich, Amihai; Kalish, Yosef; Kleinstern, Geffen; Yaacov, Almog Ben; Dux, Joseph; Nissan, Aviram

    2017-12-01

    We investigated the risk factors, incidence, and role of thromboprophylaxis in the development of thrombosis following cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). We reviewed data of patients with CRS/HIPEC in three hospitals. Overall, 192 patients underwent CRS/HIPEC during 2007-2016. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h before surgery until discharge) was provided for all patients; and 116 (60.4%) also received an extended course of enoxaparin for 2-4 weeks after discharge. Twenty-six patients experienced thrombotic complications (13.5%) including portal-splenic-mesenteric venous thrombosis (n = 11, 5.7%), pulmonary embolism (n = 10, 5.2%), and deep vein thrombosis (n = 5, 2.6%); most (n = 21, 80.8%) occurred after hospital discharge. Univariate analysis identified Peritoneal Cancer Index, intraoperative transfusion requirement, operative blood loss, operative time, lengths of hospital, and intensive care unit stay, and lack of administration of anticoagulation at discharge as significantly associated with thrombosis. With multivariate analysis, only the lack of anticoagulation therapy at discharge remained significantly associated with thrombosis (P = 0.0001). Thromboembolic complications are common following CRS/HIPEC. As significantly lower rates of thrombosis were found in patients who received an extended course of anticoagulation, we support its use for at least 2 weeks after discharge. © 2017 Wiley Periodicals, Inc.

  17. Lipopolysaccharide contamination of beta-lactoglobulin affects the immune response against intraperitoneally and orally administered antigen

    DEFF Research Database (Denmark)

    Pedersen, Susanne Brix; Kjær, T.M.R.; Barkholt, Vibeke

    2004-01-01

    Microbial components in the environment are potent activators of the immune system with capacity to shift the active immune response towards priming of Th1 and/or Th2 cells. Lipopolysaccharide (LPS), a cell-wall component of Gram- negative bacteria, is extensively present in food products like cow......'s milk. It is not well established, however, how this presence of LPS affects oral tolerance induction. Methods: We studied the effect of LPS contamination in a commercial preparation of the cow milk protein beta-lactoglobulin (beta-LG) on antigen-specific immune responses. IgG1/IgG2a production upon...... intraperitoneal immunization without adjuvant was measured, and oral tolerance induction against beta-LG after administration of either an aqueous solution or water-in-oil (w/o) emulsion of beta-LG was evaluated. Results: LPS contamination of beta-LG provoked a beta-LG-specific IgG2a lresponse, as well...

  18. Toxicities, complications, and clinical encounters during intraperitoneal chemotherapy in 17 women with ovarian cancer.

    Science.gov (United States)

    Sun, Virginia; Otis-Green, Shirley; Morgan, Robert; Wakabayashi, Mark; Hakim, Amy; Callado, Maria Elenita; Yang, Eunice; Ferrell, Betty; Grant, Marcia

    2013-06-01

    Intraperitoneal (IP) chemotherapy is a viable and superior treatment to standard intravenous (IV) chemotherapy in women with small volume residual ovarian cancer following optimal debulking. Despite this clinical advantage, widespread adoption of the treatment regimen has been hampered by concerns related to toxicities and complications. The purpose of this descriptive study was to describe nursing implications related to toxicities, complications and clinical encounters in 17 women with ovarian cancer who received IP chemotherapy. Women with ovarian cancer who received IP chemotherapy at one NCI-designated comprehensive cancer center were accrued. Data related to IP chemotherapy summary, clinical encounters and admissions were obtained through comprehensive chart audits. Common treatment-related toxicities included nausea and vomiting, fatigue, hypomagnesia, pain, neuropathy, anemia, and constipation. Reasons for dose-modifications were multi-factorial, and were primarily related to catheter complications and chemotherapy toxicities. The number of clinical encounters was high, and they were primarily related to admissions for inpatient IP chemotherapy and follow-up clinic visits. Treatment-related toxicities and complications were common in women with ovarian cancer who received IP chemotherapy. Use of IP chemotherapy results in multiple clinical encounters, such as outpatient clinic visits and inpatient admissions. Nursing is a critical part of the interdisciplinary approach in caring for women treated with IP chemotherapy. Interdisciplinary teams with high levels of knowledge and skills related to IP chemotherapy administration are needed to manage treatment-related toxicities and complications, and support multiple clinical encounters during treatment. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Absorbed Doses and Risk Estimates of {sup 211}At-MX35 F(ab'){sub 2} in Intraperitoneal Therapy of Ovarian Cancer Patients

    Energy Technology Data Exchange (ETDEWEB)

    Cederkrantz, Elin [Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Andersson, Håkan [Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Bernhardt, Peter; Bäck, Tom [Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Hultborn, Ragnar [Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Jacobsson, Lars [Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Jensen, Holger [PET and Cyclotron Unit, Department of Clinical Physiology and Nuclear Medicine, Copenhagen University Hospital, Copenhagen (Denmark); Lindegren, Sture [Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Ljungberg, Michael [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Magnander, Tobias; Palm, Stig [Department of Radiation Physics, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden); Albertsson, Per, E-mail: per.albertsson@oncology.gu.se [Department of Oncology, Institute for Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg (Sweden)

    2015-11-01

    Purpose: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence, intraperitoneal (i.p.) targeted α therapy has been proposed as an adjuvant treatment for minimal residual disease after successful primary treatment. In the present study, we calculated absorbed and relative biological effect (RBE)-weighted (equivalent) doses in relevant normal tissues and estimated the effective dose associated with i.p. administration of {sup 211}At-MX35 F(ab'){sub 2}. Methods and Materials: Patients in clinical remission after salvage chemotherapy for peritoneal recurrence of ovarian cancer underwent i.p. infusion of {sup 211}At-MX35 F(ab'){sub 2}. Potassium perchlorate was given to block unwanted accumulation of {sup 211}At in thyroid and other NIS-containing tissues. Mean absorbed doses to normal tissues were calculated from clinical data, including blood and i.p. fluid samples, urine, γ-camera images, and single-photon emission computed tomography/computed tomography images. Extrapolation of preclinical biodistribution data combined with clinical blood activity data allowed us to estimate absorbed doses in additional tissues. The equivalent dose was calculated using an RBE of 5 and the effective dose using the recommended weight factor of 20. All doses were normalized to the initial activity concentration of the infused therapy solution. Results: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. Conclusion: Intraperitoneal {sup 211}At

  20. The stimulatory effect of single-dose pre-irradiation administration of indomethacin and diclofenac on haemopoietic recovery in the spleen of gamma-irradiated mice

    International Nuclear Information System (INIS)

    Kozubik, A.; Pospisil, M.; Netikova, J.

    1989-01-01

    The aim of the work was to examine the effect of the single-dose pre-irradiation administration of non-steroid anti-inflammatory drugs, i.e. indomethacin (0.15 mg/mouse) and diclofenac (0.6 mg/mouse) on the recovery of haemopoiesis in the spleen of whole-body irradiated male mice (CBA x C57BL/10)F 1 . It was shown that the administation of these substances 1-24 h prior to sublethal irradiation stimulates the recovery of the proliferation activity of the spleen and the formation of endogenous spleen colonies. These results can be explained as the inhibitory effect of the substances administered on biosynthesis of prostaglandins. (author)

  1. Estudo da ação inflamatória aguda do tiopental intraperitoneal em ratos Acute inflammatory action of tiopental intraperitoneal in rats

    Directory of Open Access Journals (Sweden)

    A.B. Carregaro

    2005-04-01

    Full Text Available Determinou-se a ação inflamatória aguda do tiopental intraperitoneal (IP utilizando-se 72 ratos, divididos em grupo-tratado (40mg/kg de tiopental a 2,5% IP e grupo-controle (0,25ml de solução fisiológica IP. Para determinar o processo inflamatório, colheu-se o lavado peritoneal às 2, 6, 12, 24 e 48h após a inoculação. Os animais foram anestesiados com isoflurano e submetidos à eutanásia por secção dos vasos cervicais. Administraram-se 5ml de solução fisiológica heparinizada por via IP e, após homogeneização, divulsionou-se o peritôneo e colheu-se a amostra. Determinaram-se a dosagem de proteínas plasmáticas (PP, a contagem global (CGL e a diferencial (CDL de leucócitos. Não foi observada diferença na PP entre os grupos em nenhum momento exceto às 2h. Entre os momentos, a dosagem foi superior às 6 e 12h nos dois grupos. Não houve diferença entre os grupos para a CGL. Entre os momentos, a CGL diferiu dos demais às 6h em ambos os grupos. Verificou-se o mesmo perfil para a CDL entre os grupos exceto para os eosinófilos às 6h. Entre os momentos, os valores foram diferentes em relação aos neutrófilos em ambos os grupos, às 6 e 12h. Observou-se reação inflamatória aguda no processo provavelmente desencadeada pela ação mecânica da injeção. A eosinofilia observada no grupo-tratado após 6h sugere uma certa ação irritante do tiopental.The acute inflammatory action of thiopental intraperitoneal (IP in rats was studied. Seventy two animals were divided in treated (40mg/kg of thiopental, 2.5% IP and control (0.25ml of saline solution IP rats. In order to evaluate the inflammatory process, peritoneal fluid was taken at 2h, 6h, 12h, 24h e 48h after drug administration. The animals were anesthetized with isoflurane and submitted to euthanasia through cervical vessels section. Five millilitres of heparinized saline solution were injected IP, homogenized by abdomen massage and then withdrawn. Plasma protein (PP

  2. Comparison of the Local Tolerability to 5 Long-acting Drug Nanosuspensions with Different Stabilizing Excipients, Following a Single Intramuscular Administration in the Rat.

    Science.gov (United States)

    Chamanza, Ronnie; Darville, Nicolas; van Heerden, Marjolein; De Jonghe, Sandra

    2018-01-01

    To investigate the effects of common nanosuspension-stabilizing excipients on the nature and temporal evolution of histopathological changes at intramuscular (i.m.) administration sites, 5 groups of 39 male rats per group received a single injection of 1 of the 5 analogous crystalline drug nanosuspensions containing 200 mg/ml of an antiviral compound with particle sizes of ±200 nm and identical vehicle compositions, except for the type of nanosuspension stabilizer. The investigated stabilizers were poloxamer 338, poloxamer 407, d-α-tocopherol polyethylene glycol 1,000-succinate (TPGS), polysorbate 80, and polysorbate 80 combined with egg phosphatidylglycerol. Histopathology and immunohistochemistry revealed progressive inflammatory changes at the i.m. administration sites and the draining lymph nodes that differed according to the time point of sacrifice and the type of stabilizer. Although the overall time course of inflammatory changes was similar across the groups, differences in the nature, severity, and timing of the inflammatory response were observed between animals injected with poloxamer- or TPGS-containing nanosuspensions and those injected with formulations containing polysorbate 80. A more severe and prolonged active inflammatory phase, the presence of multinucleate giant cells, prolonged macrophage infiltration of the formulation depot, and more persistent histiocytic infiltrates in the lymph nodes were observed in the polysorbate 80-containing nanosuspension groups. Such vehicle-mediated effects could influence the overall tolerability profile of long-acting nanosuspensions.

  3. Generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder.

    Science.gov (United States)

    Tabaru, A; Endou, M; Miura, Y; Otsuki, M

    1996-11-01

    We report a case of generalized peritonitis caused by spontaneous intraperitoneal rupture of the urinary bladder. A 74-year-old female was admitted with abdominal pain and biochemical findings of acute renal failure (ARF). She had recently complained of macrohematuria. She had a past history of radiotherapy for uterine cervical cancer and Parkinson's disease treated with levodopa and amantadine. We diagnosed this case as intraperitoneal rupture of the bladder by cystogram. Biochemical findings of ARF might have resulted from urine reabsorption. Intraperitoneal rupture of the bladder should be considered in all cases of peritonitis, especially in patients with urological symptoms and features of ARF.

  4. Segmental-dependent membrane permeability along the intestine following oral drug administration: Evaluation of a triple single-pass intestinal perfusion (TSPIP) approach in the rat.

    Science.gov (United States)

    Dahan, Arik; West, Brady T; Amidon, Gordon L

    2009-02-15

    In this paper we evaluate a modified approach to the traditional single-pass intestinal perfusion (SPIP) rat model in investigating segmental-dependent permeability along the intestine following oral drug administration. Whereas in the traditional model one single segment of the intestine is perfused, we have simultaneously perfused three individual segments of each rat intestine: proximal jejunum, mid-small intestine and distal ileum, enabling to obtain tripled data from each rat compared to the traditional model. Three drugs, with different permeabilities, were utilized to evaluate the model: metoprolol, propranolol and cimetidine. Data was evaluated in comparison to the traditional method. Metoprolol and propranolol showed similar P(eff) values in the modified model in all segments. Segmental-dependent permeability was obtained for cimetidine, with lower P(eff) in the distal parts. Similar P(eff) values for all drugs were obtained in the traditional method, illustrating that the modified model is as accurate as the traditional, throughout a wide range of permeability characteristics, whether the permeability is constant or segment-dependent along the intestine. Three-fold higher statistical power to detect segmental-dependency was obtained in the modified approach, as each subject serves as his own control. In conclusion, the Triple SPIP model can reduce the number of animals utilized in segmental-dependent permeability research without compromising the quality of the data obtained.

  5. Enhanced local bioavailability of single or compound drugs delivery to the inner ear through application of PLGA nanoparticles via round window administration.

    Science.gov (United States)

    Cai, Hui; Wen, Xingxing; Wen, Lu; Tirelli, Nicola; Zhang, Xiao; Zhang, Yue; Su, Huanpeng; Yang, Fan; Chen, Gang

    2014-01-01

    In this paper, the potential of poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) for carrying single or compound drugs traversing the round window membrane (RWM) was examined after the round window (RW) administration of different NPs to guinea pigs. First, coumarin-6 was incorporated into PLGA NPs as a fluorescent probe to investigate its ability to cross the RWM. Then, PLGA NPs with salvianolic acid B (Sal B), tanshinone IIA (TS IIA), and total panax notoginsenoside (PNS) including notoginsenoside R1 (R1), ginsenoside Rg1 (Rg1), and ginsenoside Rb1 (Rb1) were developed to evaluate whether NPs loaded with compound drugs would pass through the RWM and improve the local bioavailability of these agents. PLGA NPs loaded with single or compound drugs were prepared by the emulsification solvent evaporation method, and their particle size distribution, particle morphology, and encapsulation efficiency were characterized. In vitro release study showed sustained-release profiles of Sal B, TS IIA, and PNS from the NPs. The pharmacokinetic results showed that NPs applied to the RWM significantly improved drug distribution within the inner ear. The AUC0-t of coumarin-6 in the perilymph (PL) following RW administration of NPs was 4.7-fold higher than that of coumarin-6 solution, and the Cmax was 10.9-fold higher. Furthermore, the AUC(0-t) of R1, Rg1, and Rb1 were 4.0-, 3.1-, and 7.1-fold greater, respectively, after the application of NPs compared to the compound solution, and the Cmax were, respectively, 14.4-, 10.0-, and 16.7-fold higher. These findings suggest that PLGA NPs with unique properties at the nanoscale dimensions have a powerful ability to transport single or compound drugs into the PL through the RWM and remarkably enhance the local bioavailability of the encapsulated drugs in the inner ear. The use of PLGA NPs as nanoscale delivery vehicles to carry drugs across the RWM may be a promising strategy for the treatment of inner ear diseases.

  6. Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

    International Nuclear Information System (INIS)

    Thoma, Clemens; Bachy, Veronique; Seaton, Patricia; Green, Nicola K.; Greaves, David R.; Klavinskis, Linda; Seymour, Leonard W.; Morrison, Joanne

    2013-01-01

    In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer

  7. Adenovirus serotype 11 causes less long-term intraperitoneal inflammation than serotype 5: Implications for ovarian cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Thoma, Clemens, E-mail: c.thoma@oxfordalumni.org [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Bachy, Veronique [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seaton, Patricia [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Green, Nicola K. [Clinical Biomanufacturing Facility, University of Oxford, Old Road, Oxford OX3 7JT (United Kingdom); Greaves, David R. [Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Klavinskis, Linda [Peter Gorer Department of Immunobiology, Kings College London, Guys Hospital, Great Maze Pond, London SE1 9RT (United Kingdom); Seymour, Leonard W. [Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ (United Kingdom); Morrison, Joanne [Nuffield Department of Obstetrics and Gynaecology, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU (United Kingdom); Department of Obstetrics and Gynaecology, Musgrove Park Hospital, Taunton TA1 5DA (United Kingdom)

    2013-12-15

    In a phase II/III clinical trial intraperitoneal (i.p.) administration of a group C adenovirus vector (Ad5) caused bowel adhesion formation, perforation and obstruction. However, we had found that i.p. group B, in contrast to group C adenoviruses, did not cause adhesions in nude BALB/c ovarian cancer models, prompting further investigation. Ex vivo, group B Ad11 caused lower inflammatory responses than Ad5 on BALB/c peritoneal macrophages. In vivo, i.p. Ad11 triggered short-term cytokine and cellular responses equal to Ad5 in both human CD46-positive and -negative mice. In contrast, in a long-term study of repeated i.p. administration, Ad11 caused no/mild, whereas Ad5 induced moderate/severe adhesions and substantial liver toxicity accompanied by elevated levels of IFNγ and VEGF and loss of i.p. macrophages, regardless of CD46 expression. It appears that, although i.p. Ad11 evokes immediate inflammation similar to Ad5, repeated administration of Ad11 is better tolerated and long-term fibrotic tissue remodelling is reduced. - Highlights: • i.p. Ad11 causes less long-term intraperitoneal inflammation than Ad5 in CD46-transgenic mice. • Ex vivo BALB/c peritoneal macrophages express less RANTES after Ad11 than Ad3 or Ad5 treatment. • In vivo, cytokine and cellular responses 6 h after i.p. Ad11 are equal to Ad5. • In contrast, after repeated i.p. application, Ad5, but not Ad11, causes severe i.p. toxicity. • The use of Ad11 instead of Ad5 might increase patient safety in future virotherapy of ovarian cancer.

  8. Feasibility and Safety of Pressurized Intraperitoneal Aerosol Chemotherapy for Peritoneal Carcinomatosis: A Retrospective Cohort Study

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    Martin Hübner

    2017-01-01

    Full Text Available Background. Pressurized intraperitoneal aerosol chemotherapy (PIPAC has been introduced as a novel repeatable treatment for peritoneal carcinomatosis. The available evidence from the pioneer center suggests good tolerance and high response rates, but independent confirmation is needed. A single-center cohort was analyzed one year after implementation for feasibility and safety. Methods. PIPAC was started in January 2015, and every patient was entered into a prospective database. This retrospective analysis included all consecutive patients operated until April 2016 with emphasis on surgical feasibility and early postoperative outcomes. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59–73 years with 91 PIPAC procedures in total (4×: 1,  3×: 17,  2×: 12, and  1×: 12 were analyzed. Abdominal accessibility rate was 95% (42/44; laparoscopic access was not feasible in 2 patients with previous HIPEC. Median initial peritoneal carcinomatosis index (PCI was 10 (IQR 5–17. Median operation time was 94 min (89–108 with no learning curve observed. One PIPAC application was postponed due to intraoperative intestinal lesion. Overall morbidity was 9% with 7 minor complications (Clavien I-II and one PIPAC-unrelated postoperative mortality. Median postoperative hospital stay was 3 days (2-3. Conclusion. Repetitive PIPAC is feasible in most patients with refractory carcinomatosis of various origins. Intraoperative complications and postoperative morbidity rates were low. This encourages prospective studies assessing oncological efficacy.

  9. PHOTODYNAMIC THERAPY OF THE CANINE PERITONEUM - NORMAL TISSUE-RESPONSE TO INTRAPERITONEAL AND INTRAVENOUS PHOTOFRIN FOLLOWED BY 630NM LIGHT

    NARCIS (Netherlands)

    TOCHNER, Z; MITCHELL, JB; HOEKSTRA, HJ; SMITH, P; DELUCA, AM; BARNES, M; HARRINGTON, F; MANYAK, M; RUSSO, D; RUSSO, A

    1991-01-01

    A toxicity study was performed in a canine model to explore the feasibility of using intraperitoneal photodynamic therapy for patients with peritoneal carcinomatosis. Dogs received 1.25 mg/kg Photofrin II both intravenously (48 hours) and intraperitoneally (2 hours) before intraperitoneal light

  10. Experimental intraperitoneal injection of alcohol in rats: Peritoneal findings and histopathology

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    Hyun Sin In

    2014-01-01

    Conclusion: An intraperitoneal injection of alcohol in rats caused peritoneal inflammation or fibrosis during the first 2 weeks. However, these peritoneal abnormalities were short-lived and had completely disappeared after 3 weeks.

  11. Low antigen dose formulated in CAF09 adjuvant Favours a cytotoxic T-cell response following intraperitoneal immunization in Göttingen minipigs

    DEFF Research Database (Denmark)

    Overgaard, Nana Haahr; Frøsig, Thomas Mørch; Jakobsen, Jeanne Toft

    2017-01-01

    in order to generate a certain type of immune response. To investigate this area further, we used Göttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell......-dose immunization. Independent of antigen dose, intraperitoneal administration of antigen increased the amount of TT-specific cytotoxic CD8β+ T cells within the cytokine-producing T-cell pool when compared to the non-cytokine producing T-cell compartment. Taken together, these results demonstrate that a full...... protein formulated in the CAF09 adjuvant and administered to pigs via the intraperitoneal route effectively generates a cytotoxic T-cell response. Moreover, we confirm the inverse relationship between the antigen dose and the induction of polyfunctional T cells in a large animal model. These finding can...

  12. Pathology Report for Intraperitoneal Sodium Dichromate Exposure in Rats, Protocol No. 15-002-3

    Science.gov (United States)

    2015-12-08

    Toxicological Study No. S.0035303-15, March 2016 Toxicology Portfolio Division of Toxicologic Pathology Pathology Report for Intraperitoneal Sodium...distribution unlimited. Specialty: 500C, Toxicity Tests GOOD LABORATORY PRACTICE COMPLIANCE STATEMENT This pathology investigation was conducted in...3 Pathology Report for Intraperitoneal Sodium Dichromate Exposure in Rats 8 December 2015 1 Summary 1.1 Purpose The U.S. Army Center for Environmental

  13. Effect of the route of administration on the biodistribution of radioiodinated OV-TL 3 F(ab')2 in experimental ovarian cancer

    International Nuclear Information System (INIS)

    Tibben, J.G.; Massuger, L.F.A.G.; Boerman, O.C.; Borm, G.F.; Claessens, R.A.M.J.; Corstens, F.H.M.

    1994-01-01

    The effect of the route administration on the distribution of radioiodinated OV-TL 3 F(ab') 2 was studied in Balb/c female mice with intraperitoneal or subcutaneous ovarian carcinoma xenografts. In the intraperitoneal tumour model in which both ascites and solid tumour deposits were present, intraperitoneal administration resulted in a lower estimated radiation dose to blood as compared with intravenous administration. In this model normalization to equal estimated radiation doses to blood for both routes of administration indicated that a twice as high estimated radiation dose can be guided to solid intraperitoneal tumour deposits following intraperitoneal administration. Evacuation of ascitic tumour cells prior to monoclonal antibody injection further increased the estimated radiation dose to solid intraperitoneal tumour deposits following intraperitoneal delivery. Following simultaneous intravenous and intraperitoneal injection of the monoclonal antibody, tissue uptake showed no relevant differences in the subcutaneous tumour model. Overall, the intraperitoneal route of administration was found to be the best choice for therapeutic delivery of iodine-131 labelled monoclonal antibodies. (orig.)

  14. Safety and preliminary results of perioperative chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC for high-risk gastric cancer patients

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    Costa Wilson L

    2012-09-01

    Full Text Available Abstract Background Gastric cancer relapse occurs in about 30% of the patients treated with gastrectomy and D2-lymphadenectomy, mainly as distant or peritoneal metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC has been associated with an improvement in survival and lower peritoneal recurrence, albeit with increased morbidity. The aim of this study is to report the preliminary results of the association of perioperative chemotherapy, radical surgery and HIPEC in high-risk gastric patients in a single institution. Methods Treatment protocol was started in 2007 and included patients younger than 65 years old, with good performance status and gastric adenocarcinoma with serosa involvement and lymph node metastases, located in the body or antrum. Patients should receive three preoperative cycles of DCF (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2 and continuous intravenous infusion of 5-Fluorouracil 750 mg/m2 for 5 days, followed by gastric resection with D2-lymphadenectomy, hyperthermic intraperitoneal chemotherapy with Mytomicin C 34 mg/m2 and three more postoperative cycles of DCF. Results Ten patients were included between 2007 and 2011. Their median age was 47 years old and six were male. Nine were staged with cT4 cN + tumors and one as cT3 cN+. Nine patients completed all three preoperative chemotherapy cycles. Eight individuals were treated with a total gastrectomy and the other two had a distal gastrectomy, all having HIPEC. Postoperative morbidity was 50%, with no deaths. Regarding postoperative chemotherapy, only 5 patients completed three cycles. With a median follow-up of 25 months, three relapses were identified and 7 patients remain disease-free, two with more than 4 years of follow-up. Conclusion The association of perioperative systemic and intraperitoneal chemotherapy plus radical surgery is a feasible multimodality treatment, with acceptable morbidity. With a longer follow-up and a larger group of

  15. Safety and preliminary results of perioperative chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC) for high-risk gastric cancer patients.

    Science.gov (United States)

    Costa, Wilson L; Coimbra, Felipe J F; Ribeiro, Héber S C; Diniz, Alessandro L; de Godoy, André Luís; Begnami, Mariadirleifs; Silva, Milton J B; Fanelli, Marcelo F; Mello, Celso A L

    2012-09-19

    Gastric cancer relapse occurs in about 30% of the patients treated with gastrectomy and D2-lymphadenectomy, mainly as distant or peritoneal metastases. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been associated with an improvement in survival and lower peritoneal recurrence, albeit with increased morbidity. The aim of this study is to report the preliminary results of the association of perioperative chemotherapy, radical surgery and HIPEC in high-risk gastric patients in a single institution. Treatment protocol was started in 2007 and included patients younger than 65 years old, with good performance status and gastric adenocarcinoma with serosa involvement and lymph node metastases, located in the body or antrum. Patients should receive three preoperative cycles of DCF (Docetaxel 75 mg/m2, Cisplatin 75 mg/m2 and continuous intravenous infusion of 5-Fluorouracil 750 mg/m2 for 5 days), followed by gastric resection with D2-lymphadenectomy, hyperthermic intraperitoneal chemotherapy with Mytomicin C 34 mg/m2 and three more postoperative cycles of DCF. Ten patients were included between 2007 and 2011. Their median age was 47 years old and six were male. Nine were staged with cT4 cN + tumors and one as cT3 cN+. Nine patients completed all three preoperative chemotherapy cycles. Eight individuals were treated with a total gastrectomy and the other two had a distal gastrectomy, all having HIPEC. Postoperative morbidity was 50%, with no deaths. Regarding postoperative chemotherapy, only 5 patients completed three cycles. With a median follow-up of 25 months, three relapses were identified and 7 patients remain disease-free, two with more than 4 years of follow-up. The association of perioperative systemic and intraperitoneal chemotherapy plus radical surgery is a feasible multimodality treatment, with acceptable morbidity. With a longer follow-up and a larger group of patients, we hope to be able to determine if it also influences survival

  16. The effect of chronic phenytoin administration on single prolonged stress induced extinction retention deficits and glucocorticoid upregulation in the rat medial prefrontal cortex.

    Science.gov (United States)

    George, Sophie A; Rodriguez-Santiago, Mariana; Riley, John; Rodriguez, Elizabeth; Liberzon, Israel

    2015-01-01

    Post-traumatic stress disorder (PTSD) is a chronic, debilitating disorder. Only two pharmacological agents are approved for PTSD treatment, and they often do not address the full range of symptoms nor are they equally effective in all cases. Animal models of PTSD are critical for understanding the neurobiology involved and for identification of novel therapeutic targets. Using the rodent PTSD model, single prolonged stress (SPS), we have implicated aberrant excitatory neural transmission and glucocorticoid receptor (GR) upregulation in the medial prefrontal cortex (mPFC) and hippocampus (HPC) in fear memory abnormalities associated with PTSD. The objective of this study is to examine the potential protective effect of antiepileptic phenytoin (PHE) administration on SPS-induced extinction retention deficits and GR expression. Forty-eight SPS-treated male Sprague Dawley rats or controls were administered PHE (40, 20 mg/kg, vehicle) for 7 days following SPS stressors; then, fear conditioning, extinction, and extinction retention were tested. Fear conditioning and extinction were unaffected by SPS or PHE, but SPS impaired extinction retention, and both doses of PHE rescued this impairment. Similarly, SPS increased GR expression in the mPFC and dorsal HPC, and PHE prevented SPS-induced GR upregulation in the mPFC. These data demonstrate that PHE administration can prevent the development of extinction retention deficits and upregulation of GR. PHE exerts inhibitory effects on voltage-gated sodium channels and decreases excitatory neural transmission via glutamate antagonism. If glutamate hyperactivity in the days following SPS contributes to SPS-induced deficits, then these data may suggest that the glutamatergic system constitutes a target for secondary prevention.

  17. Intravenous iron administration for post-operative anaemia management after colorectal cancer surgery in clinical practice: a single-centre, retrospective study.

    Science.gov (United States)

    Laso-Morales, María Jesús; Vives, Roser; Gómez-Ramírez, Susana; Pallisera-Lloveras, Anna; Pontes, Caridad

    2018-03-05

    Evidence on the role of intravenous iron (IVI) supplementation after colorectal cancer (CRC) surgery is rather scant. This study was aimed at assessing the benefit of postoperative IVI administration after elective CRC surgery at our institution. This was a single-centre, retrospective observational study including all patients who underwent CRC surgery during 2014. Anaemia was defined as a haemoglobin (Hb) <13 g/dL, regardless of gender. Anaemic patients received 200 mg IVI up to three times a week to cover iron deficiency (IVI group). Those who did not receive IVI were placed on standard care (NIVI group). The primary outcome was the proportion of anaemic patients on post-operative day (POD)1 and POD30. Secondary outcomes included Hb changes from POD1 to POD30, transfusion requirements and complication rates. Of the 159 patients studied, 139 (87%) presented with anaemia: 47 (34%) of these received post-operative IVI and 92 (66%) did not. Patients in the IVI group had lower POD1 Hb levels compared to those in the NIVI group (p=0.001). On POD30, only 103 had their Hb measured (34 IVI, 69 NIVI). Anaemia was more prevalent and more severe among the patients in the IVI group (p=0.027), despite their greater increment in Hb (2.0±1.5 g/dL vs 1.1±1.2 g/dL; p=0.001). Eleven patients needed post-operative transfusions (7 IVI, 4 NIVI; p=0.044). There were no differences in post-operative complication rates between the groups. No IVI-related adverse events were recorded DISCUSSION: Compared with standard care, post-operative IVI administration to anaemic patients improved the recovery of Hb levels at POD30, without increasing post-operative complications.

  18. Pharmacokinetics of Active Components of Yokukansan, a Traditional Japanese Herbal Medicine after a Single Oral Administration to Healthy Japanese Volunteers: A Cross-Over, Randomized Study.

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    Hiroyuki Kitagawa

    Full Text Available Yokukansan (YKS is a traditional Japanese herbal medicine called kampo medicine in Japan. Its extract comprises seven crude drugs: Atractylodis lanceae rhizoma, Poria, Cnidii rhizoma, Uncariae uncis cum ramulus, Angelicae radix, Bupleuri radix, and Glycyrrhizae radix. YKS is used to treat neurosis, insomnia, as well as behavioral and psychological symptoms of dementia.To confirm the exposure and pharmacokinetics of the active components of YKS in healthy volunteers.A randomized, open-label, 3-arm, 3-period, crossover trial was conducted on 21 healthy Japanese volunteers at the Kochi Medical University between May 2012 and November 2012.Single oral administration of YKS (2.5 g, 5.0 g, or 7.5 g/day during each period.Plasma concentrations of three active compounds in YKS, namely 18β-glycyrrhetinic acid (GA, geissoschizine methyl ether (GM, and hirsuteine (HTE.The mean maximum plasma concentrations (Cmax of GM and HTE increased dose-dependently (ranges: 0.650-1.98 ng/mL and 0.138-0.450 ng/mL, respectively. The times to maximum plasma concentration after drug administration (tmax were 0.500 h for GM and 0.975-1.00 h for HTE. The apparent elimination half-lives (t1/2 were 1.72-1.95 h for GM and 2.47-3.03 h for HTE. These data indicate the rapid absorption and elimination of GM and HTE. On the other hand, the Cmax, tmax, and t1/2 of GA were 57.7-108 ng/mL, 8.00-8.01 h, and 9.39-12.3 h, respectively.We demonstrated that pharmacologically active components of YKS are detected in humans. Further, we determined the pharmacokinetics of GM, HTE, and GA. This information will be useful to elucidate the pharmacological effects of YKS.Japan Pharmaceutical Information Center JAPIC CTI-121811.

  19. Delayed effects of thallium in the rat brain: regional changes in lipid peroxidation and behavioral markers, but moderate alterations in antioxidants, after a single administration.

    Science.gov (United States)

    Galván-Arzate, Sonia; Pedraza-Chaverrí, José; Medina-Campos, Omar N; Maldonado, Perla D; Vázquez-Román, Beatriz; Ríos, Camilo; Santamaría, Abel

    2005-07-01

    Thallium (Tl+) toxicity has been related with the generation of reactive oxygen species (ROS) and oxidative stress (OS) in the central nervous system. Since changes in endogenous antioxidant systems might contribute to acute Tl+-induced OS and neurotoxicity, in this study we measured the metal concentration and the levels of lipid peroxidation (LP) in different brain regions (hypothalamus (Ht); cerebellum (Ce); striatum (S); hippocampus (Hc) and frontal cortex (Cx)) in possible correlation with the content of reduced glutathione (GSH), the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD), and the animal performance in behavioral tests, all evaluated after a single administration of thallium acetate (8 or 16 mg/kg, i.p.) to rats. Seven days after Tl+ administration, the metal was homogeneously and dose-dependently accumulated in all regions evaluated. LP was increased in Ht, Ce and S, while GSH was depleted in S. Cu,Zn-SOD activity was also decreased in Ht and S. All these changes occurred with 16 mg/kg dose and at 7 days after treatment, but not at 1 or 3 days. In addition, Tl+-treated animals exhibited general hypokinesis, but no changes were observed in spatial learning. Our findings suggest that a delayed response of the brain to Tl+ may be the result of its residual levels. Also, despite the regional alterations produced by Tl+ in LP and the limited changes in endogenous antioxidants, there is a correlation between the Tl+-induced oxidative damage and the affected behavioral tasks, suggesting that, although still moderate, Tl+ evokes neurotoxic patterns under the experimental conditions tested.

  20. The efficacy of intraperitoneal saline infusion for percutaneous radiofrequency ablation for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Soo Young; Tak, Won Young; Jeon, Seong Woo; Cho, Chang Min; Kweon, Young Oh; Kim, Sung Kook; Choi, Yong Hwan

    2010-01-01

    Objective: To evaluated the efficacy and safety of radiofrequency ablation (RFA) with intraperitoneal saline infusion. Background: Ultrasound-guided RFA is not always feasible due to the tumor location, possible adjacent tissue damage or poor sonographic identification. Patients and methods: Ultrasound-guided RFA with intraperitoneal saline infusion was performed in 116 patients between June 2001 and March 2008. Results: The overall technical feasibility of the intraperitoneal saline infusions was 90.5% (105 patients). The purposes of the intraperitoneal saline infusion were achieved in 100 patients (86.2%) by visualizing the tumor located in hepatic dome (47 patients), prevent adjacent organ damage (42 patients) and withdrawing overlying omentum (10 patients). Complete ablation of tumor was accomplished in 102 patients (87.9%). Complications associated with the treatment occurred in seven patients (6.0%). There was no case of adverse event directly related to intraperitoneal saline infusion. Conclusions: Intraperitoneal saline infusion is an effective and safe procedure that can be used to overcome the current limitations of ultrasound-guided RFA.

  1. Intrauterine pregnancy following low-dose gonadotropin ovulation induction and direct intraperitoneal insemination for severe cervical stenosis

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    Sills E Scott

    2002-11-01

    Full Text Available Abstract Background We present a case of primary infertility related to extreme cervical stenosis, a subset of cervical factor infertility which accounts for approximately 5% of all clinical infertility referrals. Case presentation A 37 year-old nulligravida was successfully treated with ovulation induction via recombinant follicle stimulating hormone (FSH and direct intraperitoneal insemination (IPI. Anticipating controlled ovarian hyperstimulation with in vitro fertilization/embryo transfer (IVF, the patient underwent hysteroscopy and cervical recanalization, but safe intrauterine access was not possible due to severe proximal cervical stricture. Hysterosalpingogram established bilateral tubal patency and confirmed an irregular cervical contour. Since the cervical canal could not be traversed, neither standard intrauterine insemination nor transcervical embryo transfer could be offered. Prepared spermatozoa were therefore placed intraperitoneally at both tubal fimbria under real-time transvaginal sonographic guidance using a 17 gage single-lumen IVF needle. Supplementary progesterone was administered as 200 mg/d lozenge (troche plus 200 mg/d rectal suppository, maintained from the day following IPI to the 8th gestational week. A singleton intrauterine pregnancy was achieved after the second ovulation induction attempt. Conclusions In this report, we outline the relevance of cervical factor infertility to reproductive medicine practice. Additionally, our andrology evaluation, ovulation induction approach, spermatozoa preparation, and insemination technique in such cases are described.

  2. Effect of a Single Administration of Focused Extracorporeal Shock Wave in the Relief of Delayed-Onset Muscle Soreness: Results of a Partially Blinded Randomized Controlled Trial.

    Science.gov (United States)

    Fleckenstein, Johannes; Friton, Mara; Himmelreich, Heiko; Banzer, Winfried

    2017-05-01

    To examine the effects of a single administration of focused extracorporeal shock wave therapy on eccentric exercise-induced delayed-onset muscle soreness (DOMS). Three-arm randomized controlled study. University research center. Participants (N=46; 23 women) had a mean age of 29.0±3.0 years and a mean body mass index of 23.8±2.8kg/m 2 . Participants were randomly allocated to verum- (energy flux density, .06-.09mJ/mm 2 ; pulse ratio per point, 200) or sham-focused extracorporeal shock wave therapy (no energy) at 7 equidistant points along the biceps muscle or no intervention. The primary outcome was the difference in pain intensity. Secondary outcomes included maximum isometric voluntary force (MIVF), pressure pain threshold (PPT), and impairment in daily life. Despite descriptive clinically meaningful differences, mixed-effects analysis (group × time) of changes to baseline did not reveal significant differences in the reduction of pain intensity between groups (F 2,42 =2.5, P=.094). MIVF was not significantly different between groups (F 2,43 =1.9, P=.159). PTT (F 2,43 =0.2, P=.854) and daily life impairment (F 2,42 =1.4, P=.248) were not significantly decreased over time, and there were no differences between groups in the post hoc analysis. DOMS is a common symptom in people participating in exercise, sports, or recreational physical activities. A single treatment with focused extracorporeal shock wave therapy causes clinically relevant effects in the relief of pain, increase in force, and improvement of pain-associated impairments of daily living. Still, results need to be cautiously interpreted because of the pilot character of this study. Focused extracorporeal shock wave therapy might present an option in the midterm recovery from DOMS (72h) and be an approach to enhance the return to play in athletes. Copyright © 2017. Published by Elsevier Inc.

  3. Low minute ventilation episodes during anesthesia recovery following intraperitoneal surgery as detected by a non-invasive respiratory volume monitor.

    Science.gov (United States)

    Cavalcante, Alexandre N; Martin, Yvette N; Sprung, Juraj; Imsirovic, Jasmin; Weingarten, Toby N

    2017-12-20

    An electrical impedance-based noninvasive respiratory volume monitor (RVM) accurately reports minute volume, tidal volume and respiratory rate. Here we used the RVM to quantify the occurrence of and evaluate the ability of clinical factors to predict respiratory depression in the post-anesthesia care unit (PACU). RVM generated respiratory data were collected from spontaneously breathing patients following intraperitoneal surgeries under general anesthesia admitted to the PACU. Respiratory depression was defined as low minute ventilation episode (LMVe, respiratory rate (respiratory rate was a poor predictor of LMVe (sensitivity = 11.8%). Other clinical variables (e.g., obstructive sleep apnea) were not found to be predictors of LMVe. Using RVM we identified that mild, clinically nondetectable, respiratory depression prior to opioid administration in the PACU was associated with the development of substantial subsequent respiratory depression during the PACU stay.

  4. Reduced lung lesions in pigs challenged 25 weeks after the administration of a single dose of Mycoplasma hyopneumoniae vaccine at approximately 1 week of age.

    Science.gov (United States)

    Reynolds, S C; St Aubin, L B; Sabbadini, L G; Kula, J; Vogelaar, J; Runnels, P; Peters, A R

    2009-09-01

    Two independent studies assessed the duration of immunity of an inactivated adjuvanted Mycoplasma hyopneumoniae vaccine against mycoplasmal pneumonia in seronegative (study A, n=52) and seropositive (study B, n=52) pigs. The pigs were allocated randomly to treatment and were then injected with a single dose of either the vaccine or a placebo at approximately 1 week of age. Twenty-five weeks after treatment administration, the pigs were challenged with a virulent strain (LI 36, Strain 232) of M. hyopneumoniae and the extent of lung lesions consistent with mycoplasmal pneumonia was assessed 4 weeks later. In study A, the geometric mean lung lesion score (expressed as least squares mean percentages of lung lesions) was significantly (P=0.0001) lower in vaccinated (0.3%, n=20) than in control pigs (5.9%, n=24) seronegative to M. hyopneumoniae at enrolment; similarly, in study B, the extent of lung lesions was significantly reduced (P=0.0385) in seropositive vaccinated pigs (2.0%, n=22) compared to controls (4.5%, n=26). At the end of the investigation period, 4 weeks after challenge, mean antibody sample-to-positive (S/P) ratios were significantly higher both in seronegative (P=0.0012) and seropositive (P=0.0001) vaccinated pigs (mean values=0.77 and 0.81, respectively) than in controls (mean values=0.51 and 0.38, respectively).

  5. PRIMARY PERITONITIS WITH POCKETED ABSCESS INTRAPERITONEAL CAUSED BY UMBILICAL CATHETER INFECTION IN 22 DAYS OLD BABY

    Directory of Open Access Journals (Sweden)

    Ariputra -

    2015-07-01

    Full Text Available Primary peritonitis defined  as  a microbial  infection  of  the peritoneum  and peritoneal  fluid  in  theabsence of a gastrointestinal or visceral perforation. The source of infection is extra abdominal andmay arise  from  lymphatics  or blood  stream. One  of  the  infection  source  can be  extension  from anomphalitis  or  infected  umbilicus. Omphalitis  can  occur  due  to  complication  of Umbilical VeinCatheterization  (UVC. UVC  are used  to  provide  access  for  resuscitation,  frequent monitoring  ofblood, administration of fluids, blood and parenteral nutrition. We report a case of primary peritonitiswith  pocketed  intraperitoneal  abscess  caused  by umbilical  infection  in  22  days  old  baby. Patientpresent a clinical sign of peritonitis and severe omphalitis with history of using umbilical catheter. X-ray found a free fluid impression in the abdominal cavity. Patient undergo a laparotomy and pocketedintraperitoneal  abscess was  found  around  ligamentum  teres hepatis  area,  suspected  of  infectiouscomplications arising out from the use of umbilical catheter.  [MEDICINA 2014;45:193-198].

  6. Alterations of blood indices associated with low-dose administration ...

    African Journals Online (AJOL)

    The study aimed to investigate haematological and biochemical alterations associated with short-term intraperitoneal sublethal (1/10 LD50, 2 mg/kg body weight) methomyl administration to male albino rats over two and five days, and also the effects of a two-week recovery period. Methomyl administration over five but not ...

  7. Intraperitoneal implantation of life-long telemetry transmitters in three rehabilitated harbor seal pups.

    Science.gov (United States)

    Horning, Markus; Haulena, Martin; Rosenberg, Justin F; Nordstrom, Chad

    2017-05-25

    Pinnipeds, including many phocid species of concern, are inaccessible and difficult to monitor for extended periods using conventional, externally attached telemetry devices that are shed during the annual molt. Archival satellite transmitters were implanted intraperitoneally into three stranded Pacific harbor seal pups (Phoca vitulina richardii) that completed rehabilitation, to evaluate the viability of this surgical technique for the deployment of life long telemetry devices in phocids. The life history transmitters record information throughout the life of the host and transmit data to orbiting satellites after extrusion following death. Surgeries were performed under general anesthesia and a single transmitter was inserted into the ventrocaudal abdominal cavity via a 7-8 cm incision along the ventral midline between the umbilicus and pubic symphysis or preputial opening in each animal. Surgeries lasted from 45 to 51 min, and anesthesic times ranged from 55 to 79 min. All animals recovered well, were released into dry holding pens overnight, and were given access to water the following day. All three animals exhibited an expected inflammatory response, with acute phase responses lasting approximately three to four weeks. All three animals were tracked via externally attached satellite transmitters after release at 58 to 78 days following surgery, and minimum post-release survival was confirmed through continued movement data received over 278 to 289 days. The initial findings of low morbidity and zero mortality encountered during captive observation and post-release tracking periods support the viability of this surgical technique for the implantation of long-term telemetry devices in phocids.

  8. Tumor priming enhances siRNA delivery and transfection in intraperitoneal tumors

    Science.gov (United States)

    Wang, Jie; Lu, Ze; Yeung, Bertrand Z.; Wientjes, M. Guillaume; Cole, David J.; Au, Jessie L.-S.

    2014-01-01

    Cancers originating from digestive system account for 290,000 or ~20% of all new cancer cases annually in the US. We previously developed paclitaxel-loaded tumor-penetrating microparticles (TPM) for intraperitoneal (IP) treatment of peritoneal tumors [1–3]. TPM is undergoing NIH-supported IND-enabling studies for clinical evaluation. The present study evaluated the hypothesis that TPM, via inducing apoptosis and expanding the interstitial space, promotes the delivery and transfection of lipid vectors containing siRNA. The in vivo model was the metastatic human Hs766T pancreatic tumor that, upon IP injection, produced widely distributed solid tumors and ascites in the peritoneal cavity in 100% animals. The target gene was survivin, an anti-apoptotic protein induced by chemotherapy and associated with metastases and poor prognosis of patients with gastric and colorectal cancer. The siRNA carrier was pegylated liposomes comprising cationic and neutral lipids plus a fusogenic lipid (PCat). PCat-loaded with survivin siRNA (PCat-siSurvivin) was active in cultured cells (decreased survivin mRNA and protein levels, reduced cell clonogenicity, enhanced paclitaxel activity), but lost its activity in vivo; this difference is consistent with the well-known problem of inadequate delivery and transfection of siRNA in vivo. In comparison, single agent TPM prolonged animal survival and, as expected, induced survivin expression in tumors. Addition of PCat-siSurvivin reversed the TPM-induced survivin expression and enhanced the antitumor activity of TPM. The finding that in vivo survivin knockdown by PCat-siSurvivin was successful only when it was given in combination with TPM provides the proof-of-concept that tumor priming promotes the delivery and transfection of liposomal siRNA. The data further suggest the TPM/PCat-siSurvivin combination as a potentially useful chemo-gene therapy for peritoneal cancer. PMID:24462901

  9. Optimising intraperitoneal gentamicin dosing in peritoneal dialysis patients with peritonitis (GIPD study

    Directory of Open Access Journals (Sweden)

    Lipman Jeffrey

    2009-12-01

    Full Text Available Abstract Background Antibiotics are preferentially delivered via the peritoneal route to treat peritonitis, a major complication of peritoneal dialysis (PD, so that maximal concentrations are delivered at the site of infection. However, drugs administered intraperitoneally can be absorbed into the systemic circulation. Drugs excreted by the kidneys accumulate in PD patients, increasing the risk of toxicity. The aim of this study is to examine a model of gentamicin pharmacokinetics and to develop an intraperitoneal drug dosing regime that maximises bacterial killing and minimises toxicity. Methods/Design This is an observational pharmacokinetic study of consecutive PD patients presenting to the Royal Brisbane and Women's Hospital with PD peritonitis and who meet the inclusion criteria. Participants will be allocated to either group 1, if anuric as defined by urine output less than 100 ml/day, or group 2: if non-anuric, as defined by urine output more than 100 ml/day. Recruitment will be limited to 15 participants in each group. Gentamicin dosing will be based on the present Royal Brisbane & Women's Hospital guidelines, which reflect the current International Society for Peritoneal Dialysis Peritonitis Treatment Recommendations. The primary endpoint is to describe the pharmacokinetics of gentamicin administered intraperitoneally in PD patients with peritonitis based on serial blood and dialysate drug levels. Discussion The study will develop improved dosing recommendations for intraperitoneally administered gentamicin in PD patients with peritonitis. This will guide clinicians and pharmacists in selecting the most appropriate dosing regime of intraperitoneal gentamicin to treat peritonitis. Trial Registration ACTRN12609000446268

  10. Adjuvant Bidirectional Chemotherapy with Intraperitoneal Pemetrexed Combined with Intravenous Cisplatin for Diffuse Malignant Peritoneal Mesothelioma

    Directory of Open Access Journals (Sweden)

    Lana Bijelic

    2012-01-01

    Full Text Available Cytoreductive surgery (CRS with heated intraoperative intraperitoneal chemotherapy (HIPEC has emerged as optimal treatment for diffuse malignant peritoneal mesothelioma (DMPM showing median survivals of 36–92 months. However, recurrences occur frequently even in patients undergoing optimal cytreduction and are often confined to the abdomen. We initiated a Phase II study of adjuvant intraperitoneal pemetrexed combined with intravenous cisplatin for patients undergoing CRS and HIPEC for DMPM. The treatment consisted of pemetrexed 500 mg/m2 intraperitoneally and cisplatin 50 mg/m2 intravenously given simultaneously on day 1 of every 21 day cycle for 6 cycles. The primary endpoint of the study was treatment related toxicity. From July 2007 until July 2009 ten patients were enrolled. Nine of 10 completed all 6 cycles of adjuvant treatment per protocol. The most common toxicities were fatigue, nausea and abdominal pain grade 1 or 2. There was one grade 3 toxicity consisting of a catheter infection. The median survival for all 10 patients was 33.5 months. Pharmacokinetic analysis of intraperitoneal pemetrexed showed a peritoneal to plasma area under the curve ratio of 70. Our study shows that adjuvant intravenous cisplatin and intraperitoneal pemetrexed can be used following CRS and HIPEC for DMPM with low morbidity.

  11. Specific features of current intraperitoneal therapy in patients with ovarian cancer

    Directory of Open Access Journals (Sweden)

    A. G. Kedrova

    2016-01-01

    Full Text Available Background. Today there are 3 trends in favor of intraperitoneal (IP chemotherapy: maintenance of its potential 5- and 10-year survival benefit in patients with ovarian cancer (OC; advantages of the IP administration of drugs even after nonoptimal surgery; enhancement of the efficiency of chemotherapy irrespective of the number of IP treatment cycles. There is also an expanded list of possible IP medicines and incorporation of novel targeted drugs into treatment regimens. However, the long-expected data of the most recent randomized trial GOG 0252 have proven deplorable and led to the activation of discussions on the role of IP therapy.Objective: to generalize the experience of 4 oncology departments with IP therapy in patients with disseminated OC and to compare the findings with those obtained by the world’s leading medical centers.Materials and methods. The retrospective analysis included 76 patients with Stage IIIC OC who had received IP chemotherapy in accordance with 3 regimens. For standardization of IP treatment procedures, the investigators assessed the following indicators: age; tumor morphological type; surgical radicality; catheter model and port placement procedure; drug administration route; number of treatment cycles; efficiency of therapy from expert ultrasonographic findings and CA-124, HE4, CA-19.9 marker levels, time to disease progression. The analysis also involved adverse manifestations, methods of their correction and the reasons for early treatment discontinuation were separately reported. The obtained data were processed using standard statistical programs.Results. 55 of the 76 patients could complete more than 4 IP therapy cycles. Among them, only 4 patients were observed to have disease progression at follow-ups lasting over 24 months.Conclusion. Current IP therapy is a safe and convenient drug treatment in patients with OC after optimal cytoreductive surgery. The mastery and standardization of the

  12. Intestinal and hepatic contributions to the pharmacokinetic interaction between gamithromycin and rifampicin after single-dose and multiple-dose administration in healthy foals.

    Science.gov (United States)

    Berlin, S; Wallstabe, S; Scheuch, E; Oswald, S; Hasan, M; Wegner, D; Grube, M; Venner, M; Ullrich, A; Siegmund, W

    2017-12-14

    Standard treatment of foals with severe abscessing lung infection caused by Rhodococcus equi using rifampicin and a macrolide antibiotic can be compromised by extensive inhibition and/or induction of drug metabolising enzymes (e.g. CYP3A4) and transport proteins (e.g. P-glycoprotein), as has been shown for rifampicin and clarithromycin. The combination of rifampicin with the new, poorly metabolised gamithromycin, a long-acting analogue of azithromycin and tulathromycin with lower pharmacokinetic interaction potential, might be a suitable alternative. To evaluate the pharmacokinetic interactions and pulmonary distribution of rifampicin and gamithromycin in healthy foals, and to investigate the cellular uptake of gamithromycin in vitro. Controlled, four-period, consecutive, single-dose and multiple-dose study. Pharmacokinetics and lung distribution of rifampicin (10 mg/kg) and gamithromycin (6 mg/kg) were measured in nine healthy foals using LC-MS/MS. Enzyme induction was confirmed using the 4β-OH-cholesterol/cholesterol ratio. Affinity of gamithromycin to drug transport proteins was evaluated in vitro using equine hepatocytes and MDCKII-cells stably transfected with human OATP1B1, OATP1B3 and OATP2B1. Rifampicin significantly (Pgamithromycin (16.2 ± 4.77 vs. 8.57 ± 3.10 μg × h/mL) by decreasing the total body clearance. Otherwise, gamithromycin significantly lowered plasma exposure of single- and multiple-dose rifampicin (83.8 ± 35.3 and 112 ± 43.1 vs. 164 ± 96.7 μg × h/mL) without a change in metabolic ratio and half-life. Gamithromycin was identified as an inhibitor of human OATP1B1, OATP1B3 and OATP2B1 and as a substrate of OATP2B1. In addition, it was extracted by equine hepatocytes via a mechanism which could be inhibited by rifampicin. Influence of gamithromycin on pulmonary distribution of rifampicin was not evaluated. The plasma exposure of gamithromycin is significantly increased by co-administration of rifampicin which is most

  13. Exposure of fatty acids after a single oral administration of sacha inchi (Plukenetia volubilis L.) and sunflower oil in human adult subjects.

    Science.gov (United States)

    Gonzales, Gustavo F; Gonzales, Carla; Villegas, Leon

    2014-01-01

    Sacha inchi (Plukenetia volubilis L.) is a potential oilseed crop because it is rich in α-linolenic acid (ALA) (omega-3 fatty acid). To evaluate the exposure of fatty acids after a single oral administration of sacha inchi or sunflower oil in healthy volunteers. Plasma fatty acids concentrations were assayed by Gas Chromatography with Flame Ionization Detector in 18 adult subjects. After fasting, blood samples were obtained at 0, 0.5, 1, 2, 4, 8 and 24 h after ingestion of 10 or 15 ml of sacha inchi oil or sunflower oil. The proportion ALA/linoleic acid was 1.37 in sacha inchi oil and 0.01 in sunflower oil. ALA, lauric acid, palmitic acid, linolelaidic acid, cis-8,11,14-eicosatrienoic acid, cis-13,16-docosadienoic acid and cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) levels changed over time after sacha inchi oil ingestion but not with sunflower oil. The time at maximal concentration (tmax) for ALA was 2 h after sacha inchi oil ingestion. No ALA in plasma was observed after sunflower oil consumption. The maximal concentration of ALA was 2.84 ± 0.36 mg/ml in women and 0.94 ± 0.57 mg/ml in men, p  0.05). There is a trend for higher plasma ALA levels with 15 ml sacha inchi oil. After 2 h of consumption, plasma delta triacylglycerol were reduced with sunflower oil but slightly increased with sacha inchi oil. A reduction in plasma delta triacylglycerol-rich lipoprotein cholesterol was observed with both oils. Consumption of sacha inchi oil increased ALA and DHA in plasma.

  14. The administration of a single dose of a multivalent (DHPPiL4R vaccine prevents clinical signs and mortality following virulent challenge with canine distemper virus, canine adenovirus or canine parvovirus

    Directory of Open Access Journals (Sweden)

    Stephen Wilson

    2014-01-01

    In conclusion, we demonstrated that a single administration of a minimum titre, multivalent vaccine to dogs of six weeks of age is efficacious and prevents clinical signs and mortality caused by CAV-1 and CDV; prevents clinical signs and significantly reduces virus shedding caused by CAV-2; and prevents clinical signs, leucopoenia and viral excretion caused by CPV.

  15. Evaluation of the curative and preventive efficacy of a single oral administration of afoxolaner against cat flea Ctenocephalides felis infestations on dogs.

    Science.gov (United States)

    Hunter, James S; Dumont, Pascal; Chester, Theodore S; Young, David R; Fourie, Josephus J; Larsen, Diane L

    2014-04-02

    The efficacy of orally administered afoxolaner for treatment and prevention of repeated infestations with adult Ctenocephalides felis on dogs was evaluated in two studies after administration of a beef-flavored soft chew. In each study, 32 dogs were divided randomly into four equal groups. Dogs in Groups 1 and 3 were not treated and served as controls. Dogs in Groups 2 and 4 were treated on Day 0 with a combination of chewable tablets to be as close as possible to the minimum therapeutic dose of 2.5mg/kg. All animals were infested experimentally with unfed C. felis (100 ± 5) on Days -1, 7, 14, 21, 28 and 35. Flea killing efficacy was evaluated in both studies while, efficacy against flea egg production was assessed in Study 1. Live fleas were counted at 12 (Groups 1 and 2) and 24h (Groups 3 and 4), after treatment or after weekly infestations. In Study 1, flea eggs were collected and counted at either 12 or 24h after each flea infestation on Days 7, 14, 21, 28 and 35. The results of both studies demonstrate the long lasting and rapid efficacy of afoxolaner against C. felis, when administered as a single oral dose to dogs. For flea counts conducted 24h after treatment or infestation, efficacy was 100% for all time points up to Day 36 in both studies, except for one time point (99.9% on Day 22) for Study 2. For flea counts performed 12h after treatment or infestation, efficacy was ≥ 95.2% until Day 21 in both studies. Efficacy at 12h was ≥ 93.0% on Day 35 in Study 1 and ≥ 89.7% on Day 35 in Study 2. The treated groups had significantly fewer fleas than untreated control dogs in both studies for all flea counts (p=0.003 Study 1, p=0.0006 Study 2). In Study 1, for all egg counts performed at or beyond Day 7, efficacy in egg reduction was >99% for all time points between Days 7 and 35. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

  16. Automated anesthesia carts reduce drug recording errors in medication administrations - A single center study in the largest tertiary referral hospital in China.

    Science.gov (United States)

    Wang, Ying; Du, Yingying; Zhao, Yingying; Ren, Yang; Zhang, Wei

    2017-08-01

    To clinically evaluate a type of patented automated anesthesia cart in medication administrations in anesthesia. This was a prospectively randomized open label clinical trial. In 10 designated operating suits in the First Affiliated Hospital of Zhengzhou University, in China. 1066 cases originated from 10,812 medication administrations in anesthesia were randomized. 78 registered anesthesiologists managed the medication. The patients received medication administrations in anesthesia with either an automated or a conventional manual cart. American Society of Anesthesiologists (ASA) score, sex, duration of anesthesia and surgical specialty, errors in administration of medications (incorrect medication given (substitution), medication not given (omission) and drug recordings errors"), compliance and satisfaction were recorded. The total error rate was 7.3% with the automated anesthesia carts (1 in 14 administrations) and 11.9% with conventional manual carts (1 in 8 administrations). Automated anesthesia carts significantly reduced the drug recording error rate compared to conventional manual carts (Perrors omission errors was found between groups of automated anesthesia carts and conventional manual carts. The anesthesiologists' compliance with the automated anesthesia carts was unsatisfactory, and all the errors in medication recordings with the automated anesthesia carts were due to the incorrect use of the carts. Most of the participating anesthesiologists preferred the automated anesthesia carts (Perrors in medication administrations of anesthesia. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Intraperitoneal And Incisional Bupivacaine Analgesia For Major Abdominal/Gynecologic Surgery: A Placebocontrolled

    Directory of Open Access Journals (Sweden)

    R. Azarfarin

    2006-05-01

    Full Text Available Background:Postoperative pain is an important surgical problem. Recent studies in pain pathophysiology have led to the hypothesis that with perioperative administration of analgesics (pre-emptive analgesia it may be possible to prevent or reduce postoperative pain. This study was planned to investigate the efficacy of pre-emptive analgesia on postoperative pain after major gynecologic abdominal surgeries. Methods: In this prospective, double-blinded, randomized, and placebocontrolled trial, 60 ASA physical status I and II patients undergoing major abdominal gynecologic surgeries were randomized to receive 45 mL of bupivacaine 0.375% or 45mL of normal saline; 30 mL and 15 mL of the treatment solution was administered into the peritoneal cavity and incision, respectively, before wound closure. The pain score of the patients was evaluated by the visual analogue scale (VAS on awakening, and at 6, 12, and 24h after surgery. Time to first analgesia request and total analgesic requirements in the first 24h were recorded. Results: Pain scores were significantly higher in the placebo group than in the bupivacaine group on awakening (5.98±1.01 v.s 1.05±1.05; p<0.001, and at 6h after surgery (5.37±0.85 vs. 2.51±1.02; p<0.001. First request to analgesia was significantly longer in the bupivacaine patients than in the placebo group (5.87±3.04 h vs.1.35±0.36; p<0.001.Meperidine consumption over 24h was 96.00 ±17.53 mg in the placebo group compared with 23.28 ±14.89 mg in the bupivacaine patients (p<0.001.Conclusion:A combination of intraperitoneal and incisional bupivacaine infiltration at the end of abdominal gynecologic surgeries reduces postoperative pain on awakening and for 6 hours after surgery, and provides significant opioidsparing analgesia for 24 h after gynecologic abdominal surgeries.

  18. Intraperitoneal chemotherapy in the management of ovarian cancer: focus on carboplatin

    Directory of Open Access Journals (Sweden)

    Maurie Markman

    2009-02-01

    Full Text Available Maurie MarkmanUniversity of Texas MD Anderson Cancer Center, Houston, Texas, USAAbstract: Both pre-clinical studies and phase 1–2 clinical trials have provided strong support for the potential role of regional drug delivery in the management of epithelial ovarian cancer, a disease process whose major manifestations remain largely localized to the peritoneal cavity in the majority of individuals with this malignancy. The results of 3 phase 3 randomized trials have revealed the favorable impact of primary cisplatin-based intraperitoneal chemotherapy in women who initiate drug treatment with small-volume residual ovarian cancer following an attempt at optimal surgical cytoreduction. Concerns have been raised regarding the toxicity of regional treatment, particularly the side-effect profile associated with cisplatin. One rational approach to improving the tolerability of intraperitoneal chemotherapy is to substitute carboplatin for cisplatin. This review discusses the rationale for and data supporting regional treatment of epithelial ovarian cancer, and highlights the potential role for intraperitoneal carboplatin in this clinical setting.Keywords: ovarian cancer, intraperitoneal chemotherapy, cisplatin, carboplatin

  19. Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection.

    Directory of Open Access Journals (Sweden)

    Anne-Laure Zilber

    2016-03-01

    Full Text Available Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus. Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics.

  20. Surgical aspects and complications of continuous intraperitoneal insulin infusion with an implantable pump

    NARCIS (Netherlands)

    Haveman, Jan Willem; Logtenberg, Susan J. J.; Kleefstra, Nanne; Groenier, Klaas H.; Bilo, Henk J. G.; Blomme, Adri M.

    Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is safe and effective in selected subjects with diabetes. Our aim was to assess surgical experience and complications with CIPII. We performed a retrospective longitudinal observational cohort study of patients that started

  1. Improved Glycemic Control With Intraperitoneal Versus Subcutaneous Insulin in Type 1 Diabetes A randomized controlled trial

    NARCIS (Netherlands)

    Logtenberg, Susan J.; Kleefstra, Nanne; Houweling, Sebastiaan T.; Groenier, Klaas H.; Gans, Reinold O.; van Ballegooie, Evert; Bilo, Henk J.

    OBJECTIVE - Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump has been available for the past 25 years. CIPII, with its specific pharmacodynamic properties, may be a viable treatment alternative to improve glycemic control in patients with type I diabetes for whom other

  2. Systematic review: continuous intraperitoneal insulin infusion with implantable insulin pumps for diabetes mellitus

    NARCIS (Netherlands)

    Spaan, Nienke; Teplova, Alina; Stam, Gerrit; Spaan, Jos; Lucas, Cees

    2014-01-01

    Continuous intraperitoneal insulin infusion (CIPII) with implantable insulin pumps (IIPs) is a treatment option for diabetes, which is not widely utilized nor freely accessible in clinical practice. The aim of this study was to summarize available evidence on use of IIPs for CIPII for diabetes

  3. Intraperitoneal tenoxicam to prevent abdominal adhesion formation in a rat peritonitis model.

    Science.gov (United States)

    Ezberci, Fikret; Bulbuloglu, Ertan; Ciragil, Pinar; Gul, Mustafa; Kurutas, Ergul Belge; Bozkurt, Serdar; Kale, I Taner

    2006-01-01

    We investigated the effects of intraperitoneal tenoxicam on the development of postoperative intra-abdominal adhesions and oxidative stress in a model of bacterial peritonitis. Bacterial peritonitis was induced in 24 rats by cecal ligation and puncture. The rats were randomly assigned to one of three groups. Group 1 (n = 8) received 2 ml saline intraperitoneally, group 2 (n = 8) received 2 ml (0.5 mg/kg) tenoxicam (Oksamen) intraperitoneally, and group 3 (n = 8) was a control, which did not receive any injection. All animals were killed 14 days later so we could assess the adhesion score and measure anastomotic bursting pressures. Tissue antioxidant levels were measured in 1-g tissue samples taken from the abdominal wall. The adhesion score was significantly lower in the tenoxicam group than in the saline and control groups. The anastomotic bursting pressures were higher in the saline and tenoxicam groups than in the control group. The catalase (CAT) levels were higher in the saline and tenoxicam groups than in the control group. The malondialdehyde (MDH) levels were higher in the saline group than in the tenoxicam and control groups. Intraperitoneal tenoxicam inhibited the formation of postoperative intra-abdominal adhesions without compromising wound healing in this bacterial peritonitis rat model. Tenoxicam also decreased the oxidative stress during peritonitis.

  4. Methylene blue 1% solution on the prevention of intraperitoneal adhesion formation in a dog model

    Directory of Open Access Journals (Sweden)

    Marco Augusto Machado Silva

    Full Text Available Intraperitoneal adhesions usually are formed after abdominal surgeries and may cause technical difficulties during surgical intervention, chronic abdominal pain and severe obstructions of the gastrointestinal tract. The current study aimed to evaluate the efficacy of methylene blue (MB 1% solution on the prevention of intraperitoneal postsurgical adhesion formation in a canine surgical trauma model. Twenty bitches were submitted to falciform ligament resection, omentectomy, ovariohysterectomy and scarification of a colonic segment. Prior to abdominal closure, 10 bitches received 1mg kg-1 MB intraperitoneally (MB group and 10 bitches received no treatment (control group, CT. On the 15th postoperative day the bitches were submitted to laparoscopy to assess adhesions. The mean adhesion scores were 13.9 (±5.6 for MB group and 20.5 (±6.4 for the CT group (P=0,043. In conclusion, the 1% MB solution was efficient on the prevention of intraperitoneal postoperative adhesion formation in bitches, especially those involving the colonic serosa.

  5. Intraperitoneal microdialysis in the postoperative surveillance after surgery for necrotizing enterocolitis

    DEFF Research Database (Denmark)

    Pedersen, Mark E; Dahl, Marianne; Qvist, Niels

    2011-01-01

    BACKGROUND/PURPOSE: The aim of the present pilot study was to evaluate the safety and clinical application of intraperitoneal microdialysis (MD) in preterm infants operated on for necrotizing enterocolitis (NEC). METHODS: Fourteen infants underwent MD. Two were excluded from analysis: 1 because...

  6. Comparison of Mucosal, Subcutaneous and Intraperitoneal Routes of Rat Leptospira Infection

    Science.gov (United States)

    Zilber, Anne-Laure; Belli, Patrick; Grezel, Delphine; Artois, Marc; Kodjo, Angeli; Djelouadji, Zoheira

    2016-01-01

    Leptospirosis is a zoonosis found worldwide that is caused by a spirochete. The main reservoirs of Leptospira, which presents an asymptomatic infection, are wild rodents, including the brown rat (Rattus norvegicus). Experimental studies of the mechanisms of its renal colonization in rats have previously used an intraperitoneal inoculation route. However, knowledge of rat-rat transmission requires the use of a natural route of inoculation, such as a mucosal or subcutaneous route. We investigated for the first time the effects of subcutaneous and mucosal inoculation routes compared to the reference intraperitoneal route during Leptospira infection in adult rats. Infection characteristics were studied using Leptospira renal isolation, serology, and molecular and histological analyses. Leptospira infection was asymptomatic using each inoculation route, and caused similar antibody production regardless of renal colonization. The observed renal colonization rates were 8 out of 8 rats, 5 out of 8 rats and 1 out of 8 rats for the intraperitoneal, mucosal and subcutaneous inoculation routes, respectively. Thus, among the natural infection routes studied, mucosal inoculation was more efficient for renal colonization associated with urinary excretion than the subcutaneous route and induced a slower-progressing infection than the intraperitoneal route. These results can facilitate understanding of the infection modalities in rats, unlike the epidemiological studies conducted in wild rats. Future studies of other natural inoculation routes in rat models will increase our knowledge of rat-rat disease transmission and allow the investigation of infection kinetics. PMID:27031867

  7. A single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin that produces reduced food and water intake induces long-lasting expression of corticotropin-releasing factor, arginine vasopressin, and proopiomelanocortin in rat brain

    International Nuclear Information System (INIS)

    Moon, Bo-Hyun; Hong, Chang Gwun; Kim, Soo-Young; Kim, Hyun-Ju; Shin, Seung Keon; Kang, Seungwoo; Lee, Kuem-Ju; Kim, Yong-Ku; Lee, Min-Soo; Shin, Kyung-Ho

    2008-01-01

    The mechanism by which a single administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) reduces food and water intake is unclear. We examined whether such a food and water intake-reducing single administration of TCDD induced changes in corticotropin-releasing factor (CRF), arginine vasopressin (AVP), and proopiomelanocortin (POMC) expression in rat brain. To observe time-dependent changes in these neuropeptides, male Sprague-Dawley rats were given TCDD (50 μg/kg) and terminated 1, 2, 4, or 7 days later. In addition, to observe dose-dependent changes in feeding and neuropeptides, rats were also given a range of TCDD doses (12.5, 25, or 50 μg/kg) and terminated 14 days later. TCDD suppressed food and water intake over 14 days in a dose-dependent manner. TCDD treatment also increased CRF and POMC mRNA levels in the hypothalamic paraventricular nucleus (PVN) and arcuate nucleus, respectively, in a dose- and time-dependent manner. These increases were related to decreased food intake following TCDD administration. TCDD treatment increased AVP and CRF mRNA levels in the PVN, and these increases were related to decreased water intake. Interestingly, the increases in CRF, AVP and POMC expression were observed 7 to 14 days after TCDD administration. These results suggest that a single administration of TCDD induced long-lasting increases in CRF, AVP, and POMC mRNA levels in the hypothalamus and that these changes are related to reduced food and water intake 7 to 14 days after TCDD administration

  8. Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Surface Malignancy: Experience with 1,000 Patients

    Science.gov (United States)

    Levine, Edward A.; Stewart, John H.; Shen, Perry; Russell, Gregory B.; Loggie, Brian L.; Votanopoulos, Konstantinos I

    2014-01-01

    Background Peritoneal dissemination of abdominal malignancy (carcinomatosis) has a clinical course marked by bowel obstruction and death; it traditionally does not respond well to systemic therapy and has been approached with nihilism. To treat carcinomatosis, we utilize cytoreductive surgery (CS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods A prospective database of patients has been maintained since 1992. Patients with biopsy proven peritoneal surface disease (PSD) were uniformly evaluated for, and treated with, CS and HIPEC. Patient demographics, performance status (ECOG), resection status (R), PSD was classified according to primary site. Univariate and multivariate analysis were performed. The experience was divided into quintiles and compared with outcomes. Results Between 1991 and 2013, 1,000 patients underwent 1,097 HIPEC procedures. Average age was 52.9 years and 53.1% were female. Primary tumor sites were: appendix 472(47.2%), colorectal 248(24.8%), mesothelioma 72(7.2%), ovary 69(6.9%), gastric 46(4.6%), others 97(9.7%). Thirty day mortality rate was 3.8% and median hospital stay was 8 days. Median overall survival (OS) was 29.4 months, with a 5 year survival of 32.5%. Factors correlating with improved survival on univariate and multivariate analysis (p≤.0001 for each) were preoperative performance status, primary tumor type, resection status, and experience quintile (p=.04). Over the 5 quintiles, the 1 and 5 year survival, as well as the complete cytoreduction score (R0,R1,R2a) have increased, while transfusions, stoma creations, and complications have all significantly decreased (p<.001 for all). Conclusions This largest reported single center experience with CS and HIPEC demonstrates that prognostic factors include primary site, performance status, completeness of resection, and institutional experience. The data shows that outcomes have improved over time with more complete cytoreduction and fewer serious complications

  9. Comparison of the glucose-lowering properties of vanadyl sulfate and bis(maltolato)oxovanadium(IV) following acute and chronic administration.

    Science.gov (United States)

    Yuen, V G; Orvig, C; McNeill, J H

    1995-01-01

    Numerous studies, both in vitro and in vivo, have demonstrated the insulin-mimetic properties of vanadium. Chronic oral administration of inorganic and organic compounds of both vanadium(IV) and vanadium(V) reduced plasma glucose levels and restored plasma lipid levels in streptozotocin-diabetic rats. We investigated the acute effects of both vanadyl sulfate and bis(maltolato)oxovanadium(IV) (BMOV), an organic vanadium compound, on plasma glucose levels by several routes of administration. Previous studies have shown that chronic administration of vanadyl sulfate has resulted in a sustained euglycemia following withdrawal of the drug. This effect was not observed following the chronic administration of BMOV; therefore, we investigated the effect of increasing the concentration of BMOV on the production of a sustained euglycemic response. An acute plasma glucose lowering effect was obtained with both vanadyl sulfate and BMOV when administered as a single dose by either oral gavage or intraperitoneal injection. In those animals that responded to vanadium treatment, plasma glucose levels were within the normal range within 2 to 6 h when given by i.p. injection or within 4 to 8 h when given by oral gavage. BMOV-treated rats that responded to treatment maintained the euglycemic effect for extended periods, ranging from 1 to 14 weeks following administration. However, vanadyl sulfate treated rats reverted to hyperglycemia within 12 to 24 h, depending on the route of administration. Intravenous administration of BMOV was effective in lowering plasma glucose levels only when administered by continuous infusion. An oral dose-response curve showed that BMOV was 2 to 3 times as potent as vanadyl sulfate. This difference in potency was observed with both oral and intraperitoneal administration, which suggests that the increase in potency with BMOV cannot be totally attributed to increased gastrointestinal absorption. Organic chelation of vanadium may facilitate uptake into

  10. A High-Fat Meal, or Intraperitoneal Administration of a Fat Emulsion, Increases Extracellular Dopamine in the Nucleus Accumbens

    Directory of Open Access Journals (Sweden)

    Bartley G. Hoebel

    2012-06-01

    Full Text Available Evidence links dopamine (DA in the nucleus accumbens (NAc shell to the ingestion of palatable diets. Less is known, however, about the specific relation of DA to dietary fat and circulating triglycerides (TG, which are stimulated by fat intake and promote overeating. The present experiments tested in Sprague-Dawley rats whether extracellular levels of NAc DA increase in response to acute access to fat-rich food or peripheral injection of a fat emulsion and, if so, whether this is related to caloric intake or elevated circulating lipids. When rats consumed more calories of a high-fat meal compared with a low-fat meal, there was a significant increase in extracellular accumbens DA (155% vs. 119%. Systemic injection of a fat emulsion, which like a high-fat diet raises circulating TG but eliminates the factor of taste and allows for the control of caloric intake, also significantly increased extracellular levels of DA (127% compared to an equicaloric glucose solution (70% and saline (85%. Together, this suggests that a rise in circulating TG may contribute to the stimulatory effect of a high-fat diet on NAc DA.

  11. Single-dose local administration of parathyroid hormone (1-34, PTH) with β-tricalcium phosphate/collagen (β-TCP/COL) enhances bone defect healing in ovariectomized rats.

    Science.gov (United States)

    Tao, Zhou-Shan; Zhou, Wan-Shu; Wu, Xin-Jing; Wang, Lin; Yang, Min; Xie, Jia-Bing; Xu, Zhu-Jun; Ding, Guo-Zheng

    2018-02-01

    Parathyroid hormone (1-34, PTH) combined β-tricalcium phosphate (β-TCP) achieves stable bone regeneration without cell transplantation in previous studies. Recently, with the development of tissue engineering slow release technology, PTH used locally to promote bone defect healing become possible. This study by virtue of collagen with a combination of drugs and has a slow release properties, and investigated bone regeneration by β-TCP/collagen (β-TCP/COL) with the single local administration of PTH. After the creation of a rodent critical-sized femoral metaphyseal bone defect, β-TCP/COL was prepared by mixing sieved granules of β-TCP and atelocollagen for medical use, then β-TCP/COL with dripped PTH solution (1.0 µg) was implanted into the defect of OVX rats until death at 4 and 8 weeks. The defected area in distal femurs of rats was harvested for evaluation by histology, micro-CT, and biomechanics. The results of our study show that single-dose local administration of PTH combined local usage of β-TCP/COL can increase the healing of defects in OVX rats. Furthermore, treatments with single-dose local administration of PTH and β-TCP/COL showed a stronger effect on accelerating the local bone formation than β-TCP/COL used alone. The results from our study demonstrate that combination of single-dose local administration of PTH and β-TCP/COL had an additive effect on local bone formation in osteoporosis rats.

  12. Efficacy of Single-dose and 2-dose Intravenous Administration of Ramosetron in Preventing Postoperative Nausea and Vomiting After Laparoscopic Gynecologic Operation: A Randomized, Double-blind, Placebo-controlled, Phase 2 Trial.

    Science.gov (United States)

    Lee, Banghyun; Kim, Kidong; Suh, Dong Hoon; Shin, Hyun-Jung; No, Jae Hong; Lee, Jung Ryeol; Jee, Byung Chul; Hwang, Jung Won; Do, Sang Hwan; Kim, Yong Beom

    2017-06-01

    This randomized trial investigated whether a 2-dose administration of intravenous ramosetron (5-hydroxytryptamine type 3 receptor antagonist) is more effective than a single-dose administration in preventing postoperative nausea and vomiting (PONV) in 89 patients who were scheduled to undergo laparoscopic operation for benign gynecologic diseases and to receive intravenous patient-controlled analgesia for relief of postoperative pain. After assignment at a ratio of 1:1, intravenous ramosetron (0.3 mg) was initially administered at the end of skin closure in all patients. Thereafter, ramosetron (0.3 mg) and placebo were administered to the study and control groups, respectively, at 4 hours after the operation. The baseline and operative characteristics were similar between the groups. The incidence of PONV during the 24-hour period after operation which was assessed as the primary endpoint did not differ between the groups. No serious adverse events occurred in either group. A 2-dose administration of intravenous ramosetron may not be superior to a single-dose administration in preventing PONV in patients undergoing laparoscopic operation for benign gynecologic diseases.

  13. Administration of nitrite after chlorine gas exposure prevents lung injury: effect of administration modality.

    Science.gov (United States)

    Samal, Andrey A; Honavar, Jaideep; Brandon, Angela; Bradley, Kelley M; Doran, Stephen; Liu, Yanping; Dunaway, Chad; Steele, Chad; Postlethwait, Edward M; Squadrito, Giuseppe L; Fanucchi, Michelle V; Matalon, Sadis; Patel, Rakesh P

    2012-10-01

    Cl(2) gas toxicity is complex and occurs during and after exposure, leading to acute lung injury (ALI) and reactive airway syndrome (RAS). Moreover, Cl(2) exposure can occur in diverse situations encompassing mass casualty scenarios, highlighting the need for postexposure therapies that are efficacious and amenable to rapid and easy administration. In this study, we assessed the efficacy of a single dose of nitrite (1 mg/kg) to decrease ALI when administered to rats via intraperitoneal (ip) or intramuscular (im) injection 30 min after Cl(2) exposure. Exposure of rats to Cl(2) gas (400 ppm, 30 min) significantly increased ALI and caused RAS 6-24h postexposure as indexed by BAL sampling of lung surface protein and polymorphonucleocytes (PMNs) and increased airway resistance and elastance before and after methacholine challenge. Intraperitoneal nitrite decreased Cl(2)-dependent increases in BAL protein but not PMNs. In contrast im nitrite decreased BAL PMN levels without decreasing BAL protein in a xanthine oxidoreductase-dependent manner. Histological evaluation of airways 6h postexposure showed significant bronchial epithelium exfoliation and inflammatory injury in Cl(2)-exposed rats. Both ip and im nitrite improved airway histology compared to Cl(2) gas alone, but more coverage of the airway by cuboidal or columnar epithelium was observed with im compared to ip nitrite. Airways were rendered more sensitive to methacholine-induced resistance and elastance after Cl(2) gas exposure. Interestingly, im nitrite, but not ip nitrite, significantly decreased airway sensitivity to methacholine challenge. Further evaluation and comparison of im and ip therapy showed a twofold increase in circulating nitrite levels with the former, which was associated with reversal of post-Cl(2) exposure-dependent increases in circulating leukocytes. Halving the im nitrite dose resulted in no effect in PMN accumulation but significant reduction of BAL protein levels, indicating a distinct

  14. Sonographic evidence of intraperitoneal fluid: An experimental study and its clinical implications

    International Nuclear Information System (INIS)

    Dinkel, E.; Lehnart, R.; Troeger, J.; Peters, H.; Dittrich, M.

    1984-01-01

    In order to evaluate the sensitivity of ultrasound to intraperitoneal fluid, such as ascites or blood, an experimental study was performed in the pig. Various amounts of fluid were injected into the peritoneal cavity to investigate distribution and diagnostic criteria in different positions. As little as 10 ml of fluid was visualized around the urinary bladder in an upright position. In the supine position, 20 ml could be detected around the bladder and below the diaphragm. The injection of 60 ml resulted in a pattern of free-floating bowel loops. The sonographic findings of fluid distribution were correlated to radiological and contrast studies. A different amounts of fluid produce characteristic sonographic patterns, an approximate estimation of the intraperitoneal fluid volume can be made. (orig.)

  15. An overview of cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion for the anesthesiologist.

    Science.gov (United States)

    Webb, Christopher Allen-John; Weyker, Paul David; Moitra, Vivek K; Raker, Richard K

    2013-04-01

    Anesthesiologists face several perioperative challenges when patients need cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion. To adequately care for these patients, anesthesiologists must understand the goals and objectives of the operation in addition to having a basic knowledge of the chemotherapeutic drugs that are frequently used. Optimal anesthetic management of patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion requires control of a complex interplay of physiologic mechanisms, including hyperthermia, abdominal hypertension, electrolyte abnormalities, coagulopathies, increased cardiac index, oxygen consumption, and decreased systemic vascular resistance. As this surgery continues to gain popularity among oncologic surgeons, further studies that clearly define the chemistry, pharmacokinetics, pharmacodynamics, and end points of efficacy need to be performed to elucidate optimal perioperative management.

  16. Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation in the rat model

    Energy Technology Data Exchange (ETDEWEB)

    Urman, B.; Gomel, V.; Jetha, N. (Department of Obstetrics and Gynecology, University of British Columbia, Vancouver (Canada))

    1991-09-01

    The aim of this study was to determine the effectiveness of hyaluronic acid solution in preventing intraperitoneal (IP) adhesions. The study design was prospective, randomized and blinded and involved 83 rats. Measured serosal injury was inflicted using a CO2 laser on the right uterine horn of the rat. Animals randomized to groups 1 and 2 received either 0.4% hyaluronic acid or its diluent phosphate-buffered saline (PBS) intraperitoneally before and after the injury. In groups 3 and 4, the same solutions were used only after the injury. Postoperative adhesions were assessed at second-look laparotomy. Histologic assessment of the fresh laser injury was carried out on uteri pretreated with hyaluronic acid, PBS, or nothing. Pretreatment with hyaluronic acid was associated with a significant reduction in postoperative adhesions and a significantly decreased crater depth. Hyaluronic acid appears to reduce postoperative IP adhesion formation by coating the serosal surfaces and decreasing the extent of initial tissue injury.

  17. Laparoscopic appendectomy for perforated appendicitis in children: Is intraperitoneal drainage necessary?

    Directory of Open Access Journals (Sweden)

    Mithat Günaydın

    2015-09-01

    Full Text Available Objective: In this study, our aim is to evaluate the necessity of intraperitoneal drainage in perforated appendicitis. Methods: 510 pediatric patients [246 laparoscopic (LA and 264 open (OA] underwent appendectomy between 2007 and 2014. 275 of them were perforated appendicitis (106 LA, 169 OA. The patients were retrospectively evaluated in terms of age, sex, symptoms, length of hospital stay (LOHS, antibiotherapy, postoperative nasogastric tube placement and intraperitoneal drainage, follow-up period, intraoperative and postoperative complications. Results: Statistically significant differences were observed between laparoscopic perforated appendicitis (71 male, 35 female; median 9.5 years and open perforated appendicitis (108 male, 61 female; median 9 years groups in terms of placement of nasogastric tube (102/106 vs.169/169 (p=0.021, length of hospital stay (1.67± 0.11 days vs. 2.34± 0.09 days (p<0.001, intraperitoneal drainage (32/106 vs. 138/169, (p<0.001, duration of intraperitoneal drainage (1.66± 0.28 vs. 4.21± 0.2 days and LOHS (5.82± 0.3 vs. 4.23± 0.6 days respectively (p <0.001. There was no significant difference between the two groups in terms of development of intra-abdominal abscess (10/106 vs. 9/169, (p=0.144, surgical site infection (2/106 vs. 8/169, (p=0.187 and development of adhesive intestinal obstruction (1/106 vs. 9/169 (p=0.053. Conclusion: Laparoscopic access reduces the necessity for drainage and shortens duration of nasogastric tube and length of hospital stay. J Clin Exp Invest 2015; 6 (3: 224-227

  18. Intraperitoneal injection of technetium-99m sulfur colloid in visualization of a peritoneo-vaginalis connection

    International Nuclear Information System (INIS)

    Ducassou, D.; Vuillemin, L.; Wone, C.; Ragnaud, J.M.; Brendel, A.J.

    1984-01-01

    Ten minutes after an intraperitoneal infusion of Tc-99m sulfur colloid, a gamma camera was used to obtain anterior abdominal views. This visualized a peritoneo-scrotal communication in an 80-yr-old patient. He had developed extensive edema of the genitals and lower limbs after about 6 wk of continuous ambulatory peritoneal dialysis. At operation the communication was confirmed and closed. A repeat test verified the success of operation

  19. Intraperitoneal injection of technetium-99m sulfur colloid in visualization of a peritoneo-vaginalis connection

    Energy Technology Data Exchange (ETDEWEB)

    Ducassou, D.; Vuillemin, L.; Wone, C.; Ragnaud, J.M.; Brendel, A.J.

    1984-01-01

    Ten minutes after an intraperitoneal infusion of Tc-99m sulfur colloid, a gamma camera was used to obtain anterior abdominal views. This visualized a peritoneo-scrotal communication in an 80-yr-old patient. He had developed extensive edema of the genitals and lower limbs after about 6 wk of continuous ambulatory peritoneal dialysis. At operation the communication was confirmed and closed. A repeat test verified the success of operation.

  20. A meta-analysis of the efficacy of intraperitoneal cisplatin for the front-line treatment of ovarian cancer.

    Science.gov (United States)

    Hess, L M; Benham-Hutchins, M; Herzog, T J; Hsu, C-H; Malone, D C; Skrepnek, G H; Slack, M K; Alberts, D S

    2007-01-01

    Ovarian cancer is the fourth leading cause of cancer death among women in the United States. First-line chemotherapy offered to patients with ovarian cancer generally consists of an intravenous (IV) platinum plus taxane regimen and has remained virtually unchanged for the past 10 years. A number of recently completed phase III randomized trials in the United States have reported improved progression-free survival (PFS) and/or overall survival (OS) with the intraperitoneal (IP) administration of cisplatin. The purpose of this study was to pool the published data to perform a meta-analysis of randomized trials of IP cisplatin in the initial chemotherapy treatment of ovarian cancer patients. This study was initiated to obtain a more valid estimate of the therapeutic impact of IP treatment for these patients. A search strategy was initiated that searched published findings of randomized trials of IP cisplatin therapy from multiple sources from January 1990 through January 2006. Six randomized trials of 1716 ovarian cancer patients were identified and included in this analysis. The pooled hazard ratio (HR) for PFS of IP cisplatin as compared to IV treatment regimens is 0.792 (95% CI: 0.688-0.912, P= 0.001), and the pooled HR for OS is 0.799 (95% CI: 0.702-0.910, P= 0.0007). These findings strongly support the incorporation of an IP cisplatin regimen to improve survival in the front-line treatment of stage III, optimally debulked ovarian cancer.

  1. Percutaneous Drainage of 300 Intraperitoneal Abscesses with Long-Term Follow-Up

    International Nuclear Information System (INIS)

    Akinci, Devrim; Akhan, Okan; Ozmen, Mustafa N.; Karabulut, Nevzat; Ozkan, Orhan; Cil, Barbaros E.; Karcaaltincaba, Musturay

    2005-01-01

    The purpose of the study was to evaluate the efficacy of percutaneous drainage of intraperitoneal abscesses with attention to recurrence and failure rates. A retrospective analysis of percutaneous treatment of 300 intraperitoneal abscesses in 255 patients (147 male, 108 female; average age: 38 years; range: 40 days to 90 years) for whom at least 1-year follow-up data were available was performed. Abscesses were drained with fluoroscopic, sonographic, or computed tomographic guidance. Nine abscesses were drained by simple aspiration; catheter drainage either by Seldinger or trocar technique was used in the remaining 291 abscesses with 6F to 14 F catheters. Initial cure and failure rates were 68% (203/300) and 12% (36/300), respectively. Sixty-one abscesses (20%) were either palliated or temporized. The recurrence rate was 4% (12/300) and nine of them were cured by recatheterization, whereas three of them were treated by medication or surgery. The overall success and failure rates were 91% (273/300) and 9% (27/300), respectively, with temporized, palliated, and recatheterized recurred abscesses. The 30-day mortality rate was 3.1% (8/255). The mean duration of catheterization was 13 days. Intraperitoneal abscesses with safe access routes should be drained percutaneously because of high success and low morbidity, mortality, and recurrence rates

  2. The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia

    International Nuclear Information System (INIS)

    Gharagozloo, F.; Bulkley, G.B.; Zuidema, G.D.; O'Mara, C.S.; Alderson, P.O.

    1984-01-01

    We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. 133 Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. ''Blinded'' readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of 133 Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia

  3. The use of intraperitoneal xenon for early diagnosis of acute mesenteric ischemia

    Energy Technology Data Exchange (ETDEWEB)

    Gharagozloo, F.; Bulkley, G.B.; Zuidema, G.D.; O' Mara, C.S.; Alderson, P.O.

    1984-04-01

    We evaluated the technique of intraperitoneal use of xenon Xe 133, previously described for the diagnosis of early intestinal strangulation obstruction in rats and dogs, for the recognition of acute mesenteric vascular occlusion in these animals. /sup 133/Xe was injected intraperitoneally into five groups of six rats: control, sham operation, superior mesenteric artery (SMA) ligation, superior mesenteric vein ligation, and portal vein ligation. Residual gamma-activity was monitored by external counting and camera imaging. At 30 minutes after injection, the activity was significantly higher in the rats from the three groups with vascular ligation than in the control and sham operation animals (P less than 0.001). gamma-Camera images reflected these findings, with positive images only in the rats that underwent vascular ligation. ''Blinded'' readings of the 30 sets of scans confirmed the diagnostic accuracy of the images. Results were essentially the same in a second series of experiments in eight control dogs and six dogs with balloon occlusion of the SMA. Concentrations of isotope in ischemic intestine ranged from 10(3) to 10(5) times the levels in adjacent normal bowel. These levels and the positive images appeared early, prior to the development of tissue necrosis. The intraperitoneal use of /sup 133/Xe therefore continues to show promise for the recognition of patients with early intestinal ischemia.

  4. Assessment of the specificity of a new folate-targeted photosensitizer for peritoneal metastasis of epithelial ovarian cancer to enable intraperitoneal photodynamic therapy. A preclinical study.

    Science.gov (United States)

    Azaïs, Henri; Schmitt, Caroline; Tardivel, Meryem; Kerdraon, Olivier; Stallivieri, Aurélie; Frochot, Céline; Betrouni, Nacim; Collinet, Pierre; Mordon, Serge

    2016-03-01

    Ovarian cancer's prognosis remains dire after primary therapy. Recurrence rate is disappointingly high as 60% of women with epithelial ovarian cancer considered in remission will develop recurrent disease within 5 years. Special attention to undetected peritoneal metastasis during surgery is necessary as they are the main predictive factors of recurrences. Folate Receptor α (FRα) shows promising prospects in targeting ovarian cancerous cells and intraperitoneal photodynamic therapy (PDT) could be a solution in addition to macroscopic cytoreductive surgery to treat peritoneal micrometastasis. The aim of this preclinical study is to assess the specificity of a folate-targeted photosensitizer for ovarian peritoneal micrometastasis. We used the NuTu-19 epithelial ovarian cancer cell line to induce peritoneal carcinomatosis in female Fischer 344 rats. Three groups of 6 rats were studied (Control (no photosensitizer)/Non-conjugated photosensitizer (Porph)/Folate-conjugated photosensitizer (Porph-s-FA)). Four hours after the administration of the photosensitizer, animals were sacrificed and intraperitoneal organs tissues were sampled. FRα tissue expression was evaluated by immunohistochemistry. Tissue incorporation of photosensitizers was assessed by confocal microscopy and tissue quantification. FRα is overexpressed in tumor, ovary, and liver whereas, peritoneum, colon, small intestine, and kidney do not express it. Cytoplasmic red endocytosis vesicles observed by confocal microscopy are well correlated to FRα tissue expression. Photosensitizer tissue quantification shows a mean tumor-to-normal tissue ratio of 9.6. We demonstrated that this new generation folate-targeted photosensitizer is specific of epithelial ovarian peritoneal metastasis and may allow the development of efficient and safe intraperitoneal PDT procedure. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Comparison of waterborne and intraperitoneal exposure to fipronil in the Caspian white fish (Rutilus frisii on acute toxicity and histopathology

    Directory of Open Access Journals (Sweden)

    Rashid Alijani Ardeshir

    Full Text Available Fipronil is an effective insecticide widely used in agriculture with potential ecotoxicological consequences. The median lethal dose (LD50 and concentration (LC50 of fipronil in 16.3 g Caspian white fish, Rutilus frisii kutum fingerlings were determined. To determine the LD50, a total of 133 fish were assigned to 19 tanks (7 fish/tank including one control and 6 treatment groups (300, 450, 550, 650, 750, 850 mg/kg. Fish were injected intraperitoneally and monitored at 96 h. The LD50 of fipronil was 632 mg/kg suggesting it was slightly toxic to the Caspian white fish. To determine LC50, 114 fish were assigned to 19 tanks (6 fish/tank including one control and 6 treatment groups (300, 400, 500, 600, 700, 800 μg/L. The LC50 of fipronil was 572 μg/L, which was highly toxic to the fish. The degree of tissue change (DTC in vital organs from moribund fish exposed via waterborne exposure showed severe damage (DTC: 71 ± 52 for 700 μg/L in the gill, including aneurisms, extensive fusion and necrosis. The fish exposed through the intraperitoneal route seemed to have severe lesions (DTC: 66 ± 50 for 750 mg/kg in the kidney, involving hemorrhage, tubular degeneration and necrosis. The liver had no significant differences in DTC values between the two routes and showed pyknosis and sinusoid dilation. Hematoxylin and eosin staining did not show any histological alterations in the brain but nissl staining showed some alterations in distribution of purkinje cells. Generally, this study showed that the route of exposure to fipronil not only affects its acute toxicity but also determines the main target organs of toxicity and histopathological alterations in Caspian white fish. Keywords: Fipronil, Caspian white fish, Acute toxicity, Administration route

  6. Challenging diagnosis — Icterus associated with a single perforating duodenal ulcer after long-term nonsteroidal antiinflammatory drug administration in a dog

    Science.gov (United States)

    2004-01-01

    Abstract A dog developed icterus, vomiting, and anorexia 2 wk after orthopedic surgery and treatment with meloxicam for approximately 1 y. Exploratory laparotomy revealed a single perforated duodenal ulcer. The most likely cause of the hyperbilirubinemia was intrahepatic cholestasis resulting from peritonitis associated with the perforation. PMID:15283521

  7. Impact of intra-operative intraperitoneal chemotherapy on organ/space surgical site infection in patients with gastric cancer.

    Science.gov (United States)

    Liu, X; Duan, X; Xu, J; Jin, Q; Chen, F; Wang, P; Yang, Y; Tang, X

    2015-11-01

    Various risk factors for surgical site infection (SSI) have been identified such as age, overweight, duration of surgery, blood loss, etc. Intraperitoneal chemotherapy during surgery is a common procedure in patients with gastric cancer, yet its impact on SSI has not been evaluated. To evaluate whether intra-operative intraperitoneal chemotherapy is a key risk factor for organ/space SSI in patients with gastric cancer. All patients with gastric cancer who underwent surgery at the Department of Gastrointestinal Surgery between January 2008 and December 2013 were studied. The organ/space SSI rates were compared between patients who received intra-operative intraperitoneal chemotherapy and patients who did not receive intra-operative intraperitoneal chemotherapy, and the risk factors for organ/space SSI were analysed by univariate and multi-variate regression analyses. The microbial causes of organ/space SSI were also identified. Of the eligible 845 patients, 356 received intra-operative intraperitoneal chemotherapy, and the organ/space SSI rate was higher in these patients compared with patients who did not receive intra-operative intraperitoneal chemotherapy (9.01% vs 3.88%; P = 0.002). Univariate analysis confirmed the significance of this finding (odds ratio 2.443; P = 0.003). As a result, hospital stay was increased in patients who received intra-operative intraperitoneal chemotherapy {mean 20.91 days [95% confidence interval (CI) 19.76-22.06] vs 29.72 days (95% CI 25.46-33.99); P = 0.000}. The results also suggested that intra-operative intraperitoneal chemotherapy may be associated with more Gram-negative bacterial infections. Intra-operative intraperitoneal chemotherapy is a significant risk factor for organ/space SSI in patients with gastric cancer. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  8. Intraperitoneal injection of Bupivacaine and Lidocaine in reducing postoperative pain in gynecologic laparoscopic surgeries: a comparative study

    Directory of Open Access Journals (Sweden)

    Alleyassin A

    2007-08-01

    Full Text Available Background: As less invasive surgical procedures, such as laparoscopy, become more common, patients can go home soon after the surgery. However, some pain is accompanied by such procedures due to peritoneal stretching, diaphragmatic irritation, or, to a lesser extent, abdominal puncture. It is important to reduce the level of pain to the point that narcotics are not necessary. The administration of opioids for pain after abdominal surgeries is common. The receptors involved seem to be susceptible to blockade with low-dose local anesthesia, although this is subject to some controversy. In this study, we assess and compare the effectiveness of intraperitoneal Bupivacaine and Lidocaine in pain reduction after diagnostic gynecologic laparoscopy in infertility patients. Methods: In this randomized clinical trial, 150 patients admitted to Dr. Shariati Hospital for diagnostic gynecologic laparoscopy were entered into three randomized groups. Group B received Bupivacaine after the diagnostic laparoscopic procedure, group L received Lidocaine and group C, the control group, received a placebo after the surgery, all administered intraperi- toneally. Postsurgerical pain was assessed using the numeric visual analogue scale at 6 and 24 hours after surgery. Results: In group B, the pain scores at 6 and 24 hours after surgery were significantly less than those of group L. Conclusions: Administration of Bupivacaine after diagnostic gynecologic laparoscopic procedures is more effective in pain control than Lidocaine. The effect of this drug is temporary, yet it significantly decreases early postoperative pain, reducing the need for additional postoperative analgesics. Furthermore, the time at which patients can be discharged from the hospital is significantly reduced.

  9. Prophylactic administration of an extract from Plantaginis Semen and its major component aucubin inhibits mechanical allodynia caused by paclitaxel in mice.

    Science.gov (United States)

    Andoh, Tsugunobu; Kato, Mitsuru; Kitamura, Ryo; Mizoguchi, Shizuka; Uta, Daisuke; Toume, Kazufumi; Komatsu, Katsuko; Kuraishi, Yasushi

    2016-07-01

    The chemotherapeutic agent paclitaxel (PTX) causes peripheral neuropathy as a major dose-limiting side effect, and this peripheral neuropathy is difficult to control. Our previous report showed that prophylactic repetitive administration of goshajinkigan ( niú chē shèn qì wán), but not hachimijiogan ( bā wèi dì huáng wán), which lacks two of the constituents of goshajinkigan, inhibited PTX-induced mechanical allodynia in mice. Thus, the herbal medicines Plantaginis Semen ( chē qián zǐ) or Achyranthis Radix ( niú xī) may contribute to the inhibitory action of goshajinkigan on the exacerbation of PTX-induced mechanical allodynia [Andoh et al, J. Tradit. Complement. Med. 2014; 4: 293-297]. Therefore, in this study, we examined whether an extract of Plantaginis Semen (EPS) or Achyranthis Radix (EAR) would relieve PTX-induced mechanical allodynia in mice. A single intraperitoneal injection of PTX caused mechanical allodynia, which peaked on day 14 after injection. Repetitive oral administration of EPS, but not EAR, starting from the day after PTX injection significantly inhibited the exacerbation of PTX-induced mechanical allodynia. Repetitive intraperitoneal injection of aucubin, one of the main components of EPS, starting from the day after PTX injection also significantly reduced PTX-induced mechanical allodynia. However, repetitive intraperitoneal injection of geniposide acid (a precursor of aucubin) or catalpol (a metabolite of aucubin) did not prevent the exacerbation of mechanical allodynia. These results suggest that prophylactic administration of EPS is effective for preventing the exacerbation of PTX-induced allodynia. Aucubin may contribute to the inhibitory action of EPS on the exacerbation of PTX-induced allodynia.

  10. Establishment of disseminated intravascular coagulation (DIC) model by a single iv administration of Escherichia coli-derived lipopolysaccharide (LPS) to cynomolgus monkeys and evaluation of its pathophysiological status.

    Science.gov (United States)

    Minomo, Hirofumi; Inoue, Kengo; Sakaki, Shuko; Okazaki, Takanobu; Kobayashi, Kinji; Inoue, Kazuhiko; Miyata, Atsuro

    2017-02-01

    We prepared a DIC model by administrating LPS to cynomolgus monkeys, and investigated its potential for evaluations of new medicines for DIC therapy. Peripheral blood mononuclear cells (PBMC) collected from cynomolgus monkeys were incubated with LPS (8 types), and TNF-α levels in the media were measured. LPS from Escherichia coli (K-235) was most appropriate in terms of larger increases and smaller variation in TNF-α levels. PBMC from rats, cynomolgus monkeys or humans were incubated with LPS (K-235), and the TNF-α response to LPS was investigated. The response was comparable between cynomolgus monkeys and humans but small in rats. In an in vivo experiment, LPS (K-235) was administered once intravenously to cynomolgus monkeys with or without recombinant human thrombomodulin (rhTM) to investigate any changes in coagulation and fibrinolysis biomarkers and the suppressive effect of rhTM. The liver, kidney, and lung were examined histopathologically. Almost all of the changes resembled the pathophysiological status of human DIC and were suppressed by co-administration of rhTM. The DIC model resembling human DIC was established by LPS (K-235) treatment in cynomolgus monkeys, and therapeutic effect of rhTM was noted, suggesting that this model is useful in evaluations of the efficacy of new medicines for DIC therapy. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  11. Administrating Solr

    CERN Document Server

    Mohan, Surendra

    2013-01-01

    A fast-paced, example-based guide to learning how to administrate, monitor, and optimize Apache Solr.""Administrating Solr"" is for developers and Solr administrators who have a basic knowledge of Solr and who are looking for ways to keep their Solr server healthy and well maintained. A basic working knowledge of Apache Lucene is recommended, but this is not mandatory.

  12. Administrative Synergy

    Science.gov (United States)

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2012-01-01

    One of the biggest obstacles to overcome in creating and sustaining an administrative professional learning community (PLC) is time. Administrators are constantly deluged by the tyranny of the urgent. It is a Herculean task to carve out time for PLCs, but it is imperative to do so. In this article, the authors describe how an administrative PLC…

  13. Space administration

    OpenAIRE

    Worthington, Scott; Worthington, Scott

    2015-01-01

    My dissertation consists of two parts. The larger portion is an hour-long piece for double bass, electronics, and projected text called Space Administration. The second portion, this essay, discusses my musical background leading up to Space Administration, details of the composition itself, and what new directions I see in my work that in part stem from creating the piece Space Administration

  14. Pharmacokinetics (PK), pharmacodynamics (PD), and PK-PD integration of ceftiofur after a single intravenous, subcutaneous and subcutaneous-LA administration in lactating goats.

    Science.gov (United States)

    Fernández-Varón, Emilio; Cárceles-García, Carlos; Serrano-Rodríguez, Juan Manuel; Cárceles-Rodríguez, Carlos M

    2016-10-13

    Bacterial pneumonia in goats is usually caused by Mannheimia haemolytica and Pasteurella multocida. Another important infection disease in lactating goats is intramammary infection producing mastitis, usually associated with coagulase-negative Staphylococcus spp. However, treatment of bacterial pneumonia in goats not affected by mastitis problems should be restricted to antimicrobials with scant penetration to milk in order to avoid long withdrawal times. Ceftiofur is a third-generation cephalosporin antimicrobial with activity against various gram-positive and gram-negative, aerobic and anaerobic bacteria encountered by domestic animals. The objectives of the present study were to establish the serum concentration-time profile for ceftiofur in lactating goats after intravenous, subcutaneous and a SC-long-acting ceftiofur formulation; to determine ceftiofur penetration into milk; to determine in vitro and ex vivo activity of ceftiofur establishing MIC, MBC, MPC and time-kill profiles against field strains of M. haemolytica and finally to calculate the main surrogate markers of efficacy. The pharmacokinetics studies revealed an optimal PK properties for the SC-LA formulation tested. Ceftiofur was well absorbed following SC and SC-LA administration, with absolute bioavailabilities (F) of 85.16 and 84.43 %, respectively. After ceftiofur analysis from milk samples, no concentrations were found at any sampling time. The MIC, MBC and MPC data of ceftiofur against five M. haemolytica strains isolated from goats affected by pneumonia were tested showing excelent sensitivity of ceftiofur against this pathogen. For PK-PD analysis, ratios were calculated suggesting a high level of bacterial kill against the five strains of M. haemolytica tested. The systemic ceftiofur exposure achieved in lactating goats following IV, SC and especially with the SC-LA administration is consistent with the predicted PK-PD ratios needed for a positive therapeutic outcome for M. haemolytica

  15. Reduced glutathione concentration and glutathione reductase activity in various rat tissues after the administration of some radioprotective agents

    International Nuclear Information System (INIS)

    Pulpanova, J.; Kovarova, H.; Ledvina, M.

    1982-01-01

    The concentrations of reduced glutathione (GSH) and activity of glutathione reductase were investigated in rat liver, kidney and spleen after intraperitoneal administration of cystamine (50 mg/kg), mexamine (10 mg/kg), or a mixture of cystamine with mexamine (20 + 10 mg/kg). The GSH concentration increased after the administration of cystamine in the liver (maximum between the 20th and 30th min), in the kidney and spleen (maximum after 60 min). The cystamine + mexamine mixture also caused a significant increase of the GSH concentration in all the organs investigated; however, the values increased at earlier intervals as after the cystamine administration. No substantial effect was shown in the case of the mexamine administration, only 30 min after the administration the values were higher. The activity of glutathione reductase was significantly lower over the entire period examined. This was found in the liver and kidney as after the administration of cystamine, as after the radioprotective mixture. There was also a less pronounced inhibition of the enzyme activity in the spleen. Mexamine as a single radioprotector had practically no influence on the activity. (author)

  16. Effect of intraperitoneal and incisional port site lidocaine on pain relief after gynecological laparoscopic surgery: A randomized controlled study

    Directory of Open Access Journals (Sweden)

    Nahla W. Shady

    2018-03-01

    Conclusions: This study clearly depicts that incisional and intraperitoneal infiltration of lidocaine is an easy, safe, inexpensive, and noninvasive method that provides good analgesia during the early post-operative period and also provides early recovery from laparoscopic surgery.

  17. Single administration of recombinant IL-6 restores the gene expression of lipogenic enzymes in liver of fasting IL-6-deficient mice

    DEFF Research Database (Denmark)

    Gavito, A L; Cabello, R; Suarez, J

    2016-01-01

    lipogenic enzymes. EXPERIMENTAL APPROACH: Gene and protein expression of lipogenic enzymes were examined in livers of wild-type (WT) and IL-6-deficient (IL-6(-/-) ) mice during fasting and re-feeding conditions. Effects of exogenous IL-6 administration on gene expression of these enzymes were evaluated...... in vivo. The involvement of STAT3 in mediating these IL-6 responses was investigated by using siRNA in human HepG2 cells. KEY RESULTS: During feeding, the up-regulation in the hepatic expression of lipogenic genes presented similar time kinetics in WT and IL-6(-/-) mice. During fasting, expression...... of lipogenic genes decreased gradually over time in both strains, although the initial drop was more marked in IL-6(-/-) mice. Protein levels of hepatic lipogenic enzymes were lower in IL-6(-/-) than in WT mice at the end of the fasting period. In WT, circulating IL-6 levels paralleled gene expression...

  18. Growth responses following a single intra-muscular hGH plasmid administration compared to daily injections of hGH in dwarf mice.

    Science.gov (United States)

    Higuti, Eliza; Cecchi, Claudia R; Oliveira, Nelio A J; Vieira, Daniel P; Jensen, Thomas G; Jorge, Alexander A L; Bartolini, Paolo; Peroni, Cibele N

    2012-12-01

    In previous work, sustained levels of circulating human growth hormone (hGH) and a highly significant weight increase were observed after electrotransfer of naked plasmid DNA (hGH-DNA) into the muscle of immunodeficient dwarf mice (lit/scid). In the present study, the efficacy of this in vivo gene therapy strategy is compared to daily injections (5 μg/twice a day) of recombinant hGH (r-hGH) protein, as assessed on the basis of several growth parameters. The slopes of the two growth curves were found to be similar (P > 0.05): 0.095 g/mouse/d for protein and 0.094 g/mouse/d for DNA injection. In contrast, the weight increases averaged 35.5% (P hGH-DNA administration thus appears to be comparable to repeated hormone injections for promoting growth and may represent a feasible alternative for the treatment of growth hormone deficiency.

  19. Pharmacokinetics and Tolerance of the Phage Endolysin-Based Candidate Drug SAL200 after a Single Intravenous Administration among Healthy Volunteers.

    Science.gov (United States)

    Jun, Soo Youn; Jang, In Jin; Yoon, Seonghae; Jang, Kyungho; Yu, Kyung-Sang; Cho, Joo Youn; Seong, Moon-Woo; Jung, Gi Mo; Yoon, Seong Jun; Kang, Sang Hyeon

    2017-06-01

    This study was a phase 1, single-center, randomized, double-blind, placebo-controlled, single-dosing, and dose-escalating study of intravenous SAL200. It is a new candidate drug for the treatment of antibiotic-resistant staphylococcal infections based on a recombinant form of the phage endolysin SAL-1. The study evaluated the pharmacokinetics, pharmacodynamics, and tolerance among healthy male volunteers after the intravenous infusion of single ascending doses of SAL200 (0.1, 0.3, 1, 3, and 10 mg/kg of body weight). SAL200 was well tolerated, and no serious adverse events (AEs) were observed in this clinical study. Most AEs were mild, self-limiting, and transient. The AEs reported in more than three participants were fatigue, rigors, headache, and myalgia. No clinically significant values with respect to the findings of clinical chemistry, hematology, and coagulation analyses, urinalysis, vital signs, and physical examinations were observed, and no notable trends in our electrocardiogram (ECG) results for any tested dose were noticed. A greater-than-dose-proportional increase with regard to systemic exposure and the maximum serum concentration was observed when the SAL200 dose was increased from 0.1 mg/kg to 10 mg/kg. This investigation constitutes the first-in-human phase 1 study of an intravenously administered, phage endolysin-based drug. (This study has been registered at ClinicalTrials.gov under identifier NCT01855048 and at the Clinical Research Information Service [https://cris.nih.go.kr/cris/] under identifier KCT0000968.). Copyright © 2017 Jun et al.

  20. Administrative Circulars

    CERN Multimedia

    Département des Ressources humaines

    2004-01-01

    Administrative Circular N° 2 (Rev. 2) - May 2004 Guidelines and procedures concerning recruitment and probation period of staff members This circular has been revised. It cancels and replaces Administrative Circular N° 2 (Rev. 1) - March 2000. Administrative Circular N° 9 (Rev. 3) - May 2004 Staff members contracts This circular has been revised. It cancels and replaces Administrative Circular N° 9 (Rev. 2) - March 2000. Administrative Circular N° 26 (Rev. 4) - May 2004 Procedure governing the career evolution of staff members This circular has also been revised. It Administrative Circulars Administrative Circular N° 26 (Rev. 3) - December 2001 and brings up to date the French version (Rev. 4) published on the HR Department Web site in January 2004. Operational Circular N° 7 - May 2004 Work from home This circular has been drawn up. Operational Circular N° 8 - May 2004 Dealing with alcohol-related problems...

  1. Complete intraperitoneal displacement of a double J stent: a first case

    Directory of Open Access Journals (Sweden)

    Filippo Maria Turri

    2015-03-01

    Full Text Available Objectives: Ureteral double-J stents are known to migrate proximally and distally within the urinary tract, while perforation and stent displacement are uncommon. Possible mechanisms of displacement are either original malpositioning with ureteral perforation or subsequent fistula and erosion of the excretory system, due to infection or long permanence of the device. We present the unique case of complete intraperitoneal stent migration in a 59-year-old caucasian male without evidence of urinary fistula at the moment of diagnosis, so far an unreported complication. Materials and Methods: Eight months after the placement of a double-J stent for lower right ureteral stricture at a district hospital, the patient came at our observation for urosepsis and hydro-uretero-nephrosis. A CT scan demonstrated intraperitoneal migration of the stent outside the urinary tract. Cystoscopy failed to visualize the lower extremity of the stent, a percutaneous nephrostomy was placed to drain the urinary system and the stent was removed through a small abdominal incision on the right lower quadrant. Results: In our case we presume that during the positioning manoeuvre the guide wire perforated simultaneously the lower ureteral wall and the pelvic peritoneum, and that once the upper end of the stent was coiled, the lower extremity was also attracted intraperitoneally. The lack of pain due to the spinal lesion concurred to this unusual complication. Conclusions: We must be aware that ureteral double J stents may be found displaced even inside the peritoneal cavity, and that the use of retrograde pyelography during placement is of paramount importance to exclude misplacement of an apparently normally coiled upper extremity of the stent.

  2. intraperitoneal infiltration of ropivacaine for post-operative analgesia in open cholecystectomy

    International Nuclear Information System (INIS)

    Ahmed, A.; Ahmed, M.

    2017-01-01

    Objective: To assess the role of Intraperitoneal infiltration of Ropivacaine for post-op analgesia in open cholecystectomy in a low resource setting. Study Design: Randomized controlled trial. Place and Duration of Study: Study was conducted at department of Anesthesia, Scouts Hospital Chitral, from Jul 2014 to Jun 2016. Material and Methods: After taking approval from hospital ethical committee, total 126 patients were divided randomly in two groups. Group I (study group) was given intraperitoneal ropivacaine and group II (control group) was given routine standard analgesia. After complete recovery, pain was measure on VAS score (1-10) at 1 hour, 6 hour and 24 hour in all patients. Patients having pain score of 4 or more were managed with nalbuphine 5 mg IV bolus. Data was analyzed by SPSS version 16. Results: The comparison of pain score (after 1, 6and 24 hours of surgery), showed that study group had significantly (p-value<0.05) less mean pain score as compared with placebo group. Significant rate of nausea/vomiting was observed (p-value<0.05) higher (62%) in placebo group as compared with (38%) in study group. Statistically there was no significant difference (p-value>0.05) between groups on the basis of mean age (47.89 ± 8.56 vs. 48.75 ± 9.36), gender (Females 70% vs. 68%), duration of the surgery (88.54 ± 12.34 minutes vs. 91.70 ± 13.50 minutes) and American society of anesthesiologist (ASA) grades in study and placebo group patients respectively. Conclusion: Intraperitoneal ropivacaine infiltration helped in reducing the post op pain significantly in open cholecystectomy. (author)

  3. Safety, tolerability, and pharmacokinetics of PTC124, a nonaminoglycoside nonsense mutation suppressor, following single- and multiple-dose administration to healthy male and female adult volunteers.

    Science.gov (United States)

    Hirawat, Samit; Welch, Ellen M; Elfring, Gary L; Northcutt, Valerie J; Paushkin, Sergey; Hwang, Seongwoo; Leonard, Eileen M; Almstead, Neil G; Ju, William; Peltz, Stuart W; Miller, Langdon L

    2007-04-01

    Nonsense (premature stop codon) mutations are causative in 5% to 15% of patients with monogenetic inherited disorders. PTC124, a 284-Dalton 1,2,4-oxadiazole, promotes ribosomal readthrough of premature stop codons in mRNA and offers therapeutic potential for multiple genetic diseases. The authors conducted 2 phase I studies of PTC124 in 62 healthy adult volunteers. The initial, single-dose study evaluated doses of 3 to 200 mg/kg and assessed fed-fasting status on pharmacokinetics following a dose of 50 mg/kg. The subsequent multiple-dose study evaluated doses from 10 to 50 mg/kg/dose twice per day (bid) for up to 14 days. PTC124 administered orally as a liquid suspension was palatable and well tolerated through single doses of 100 mg/kg. At 150 and 200 mg/kg, PTC124 induced mild headache, dizziness, and gastrointestinal events. With repeated doses through 50 mg/kg/dose bid, reversible transaminase elevations Duchenne muscular dystrophy.

  4. Ny behandling af peritoneal karcinose fra kolorektal cancer. Cytoreduktiv kirurgi og hyperterm intraperitoneal kemoterapi

    DEFF Research Database (Denmark)

    Iversen, Lene Hjerrild; Rasmussen, Peter C; Laurberg, Søren

    2007-01-01

    Peritoneal carcinomatosis (PC) is commonly seen in colorectal cancer and is uniformly fatal. Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIIC) is a new treatment in strictly selected patients with PC. CS includes peritonectomy procedures and resection...... of infiltrated viscera leaving no macroscopic tumor thicker than 2.5 mm behind. Peritoneal perfusion with mitomycin C at a temperature of 40 degrees -41 degrees C is performed at the end of surgery. The postoperative morbidity and mortality rates are 20%-30% and 4%-8% respectively. Median survival is 1-2 years...

  5. Evaluation of effects on the peritoneum after intraperitoneal α-radioimmunotherapy with (211)At

    DEFF Research Database (Denmark)

    Cederkrantz, Elin; Angenete, Eva; Bäck, Tom

    2012-01-01

    The introduction of the short-lived α-emitter (211)At to intraperitoneal radioimmunotherapy has raised the issue of the tolerance dose of the peritoneum. The short range of the α-particles (70 μm) and the short half-life (7.21 h) of the nuclide yield a dose distribution in which the peritoneum......-ethylenediamine tetraacetic acid, was measured for evaluation of the small solute transport capacity of the peritoneal membrane. The macroscopic status of the peritoneum and the mesenteric windows was documented when the mice were sacrificed. Biopsies of the peritoneum were taken for morphology and immunohistochemical...

  6. Separation of input function for rapid measurement of quantitative CMRO{sub 2} and CBF in a single PET scan with a dual tracer administration method

    Energy Technology Data Exchange (ETDEWEB)

    Kudomi, Nobuyuki; Watabe, Hiroshi; Hayashi, Takuya; Iida, Hidehiro [Department of Investigative Radiology, Advanced Medical-Engineering Center, National Cardiovascular Center-Research Institute, 5-7-1, Fujishirodai, Suita, Osaka 565-8565 (Japan)

    2007-04-07

    Cerebral metabolic rate of oxygen (CMRO{sub 2}), oxygen extraction fraction (OEF) and cerebral blood flow (CBF) images can be quantified using positron emission tomography (PET) by administrating {sup 15}O-labelled water (H{sup 15}{sub 2}O) and oxygen ({sup 15}O{sub 2}). Conventionally, those images are measured with separate scans for three tracers C{sup 15}O for CBV, H{sup 15}{sub 2}O for CBF and {sup 15}O{sub 2} for CMRO{sub 2}, and there are additional waiting times between the scans in order to minimize the influence of the radioactivity from the previous tracers, which results in a relatively long study period. We have proposed a dual tracer autoradiographic (DARG) approach (Kudomi et al 2005), which enabled us to measure CBF, OEF and CMRO{sub 2} rapidly by sequentially administrating H{sup 15}{sub 2}O and {sup 15}O{sub 2} within a short time. Because quantitative CBF and CMRO{sub 2} values are sensitive to arterial input function, it is necessary to obtain accurate input function and a drawback of this approach is to require separation of the measured arterial blood time-activity curve (TAC) into pure water and oxygen input functions under the existence of residual radioactivity from the first injected tracer. For this separation, frequent manual sampling was required. The present paper describes two calculation methods: namely a linear and a model-based method, to separate the measured arterial TAC into its water and oxygen components. In order to validate these methods, we first generated a blood TAC for the DARG approach by combining the water and oxygen input functions obtained in a series of PET studies on normal human subjects. The combined data were then separated into water and oxygen components by the present methods. CBF and CMRO{sub 2} were calculated using those separated input functions and tissue TAC. The quantitative accuracy in the CBF and CMRO{sub 2} values by the DARG approach did not exceed the acceptable range, i.e., errors in those

  7. A single center, open label study of intradermal administration of an inactivated purified chick embryo cell culture rabies virus vaccine in adults.

    Science.gov (United States)

    Recuenco, Sergio; Warnock, Eli; Osinubi, Modupe O V; Rupprecht, Charles E

    2017-08-03

    In the USA, rabies vaccines (RVs) are licensed for intramuscular (IM) use only, although RVs are licensed for use by the intradermal (ID) route in many other countries. Recent limitations in supplies of RV in the USA reopened discussions on the more efficient use of available biologics, including utilization of more stringent risk assessments, and potential ID RV administration. A clinical trial was designed to compare the immunogenic and adverse effects of a purified chicken embryo cell (PCEC) RV administered ID or IM. Enrollment was designed in four arms, ID Pre-Exposure Prophylaxis (Pre-EP), IM Pre-EP, ID Booster, and IM Booster vaccination. Enrollment included 130 adult volunteers. The arms with IM administration received vaccine according to the current ACIP recommendations: Pre-EP, three 1mL (2.5 I.U.) RV doses, each on day 0, 7, and 21; or a routine Booster, one 1ml dose. The ID groups received the same schedule, but doses administered were in a volume of 0.1mL (0.25 I.U.). The rate of increase in rabies virus neutralizing antibody titers 14-21days after vaccination were similar in the ID and correspondent IM groups. The GMT values for ID vaccination were slightly lower than those for IM vaccination, for both naïve and booster groups, and these differences were statistically significant by t-test. Fourteen days after completing vaccination, all individuals developed RV neutralizing antibody titers over the minimum arbitrary value obtained with the rapid fluorescent focus inhibition test (RFFIT). Antibodies were over the set threshold until the end of the trial, 160days after completed vaccination. No serious adverse reactions were reported. Most frequent adverse reactions were erythema, induration and tenderness, localized at the site of injection. Multi use of 1mL rabies vaccine vials for ID doses of 0.1 was demonstrated to be both safe and inmunogenic. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. A precise evaluation of glomerular filtration rate (GFR) in two plasma samples following a single administration of 57Co-B12 vitamin

    International Nuclear Information System (INIS)

    Camargo, E.E.; Rockmann, R.L.; Barreto, T.M.; Eston, T.E.; Papaleo Netto, M.; Carvalho, N.

    1974-01-01

    Through a logarithmic regression performed with the contings of 4 plasma samples withdrawn at 20,40,60 and 80 minutes after a venous injection of vitamin B 12 - 57 Co, the glomerular filtration-rate(GFR) in 11 patients, performing simultaneously the same study with EDTA- 51 Cr in 3 of them, is evaluated. The values obtained through the regression straight line are compared with those given by only 2 points, in the 6 possible combinations: 20 and 40 minutes, 20 and 60 minutes, 20 and 80 minutes, 40 and 60 minutes, 40 and 80 minutes, 60 and 80 minutes. The pair of points obtained at 20 and 80 minutes determined the straight line most similar to the logarithmic regression and as a simplification of the method, the withdraw of only 2 plasma samples, at and 80 minutes after a single injection of vitamin B 12 -57 Co is proposed [pt

  9. Radioprotective effects in mice by a single dose of subcutaneous administration of cobaltous chloride post γ-rays irradiation with a sublethal dose

    International Nuclear Information System (INIS)

    Izumo, Yoshiro; Ogata, Hiromitsu

    1993-01-01

    Radioprotective effects were investigated in mice which received subcutaneously a single dose of each inorganic metal: Co, Cu, Rb, Sr, Mo and W 24 hours post irradiation of 60 Co γ-rays with a sublethal dose. The effects were observed in mice injected with Co at an optimum dosage of 20 mg/kg·body weight. Then to elucidate mechanisms of the effects, mice were injected with Co containing the radioactive tracer ( 60 Co) following the radiation exposure, measured elimination of the radioactivity for 7 days, then sacrificed and divided to some tissues and organs. The radioactivity in whole body during this period resulted in a markedly higher retention than that for mice injected with [ 60 Co] alone, as well as liver in the organs. These higher retentions appeared to be related to the radioprotective effects. (author)

  10. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy.

    Directory of Open Access Journals (Sweden)

    Valeria Ricotti

    Full Text Available SMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD. This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage.This multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A-C. Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10. A safety review was performed on all patients following the single dose and there was at least 2 weeks between each dose escalation, for safety and PK review. Adverse events (AEs were monitored throughout the study.Most patients experienced mild AEs and there were no serious AEs. Two patients required analgesia for pain (headache, ear pain and toothache. One patient experienced moderate psychiatric AEs (abnormal behaviour and mood swings. Plasma concentrations of SMT C1100 at Days 1 and 11 indicated a high degree of patient variability regardless of dose. Unexpectedly the SMT C1100 levels were significantly lower than similar doses administered to healthy volunteers in an earlier clinical study. In general, individual baseline changes of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase levels fell with SMT C1100 dosing.SMT C1100 was well tolerated in pediatric DMD patients.ClinicalTrials.gov NCT02383511.

  11. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy.

    Science.gov (United States)

    Ricotti, Valeria; Spinty, Stefan; Roper, Helen; Hughes, Imelda; Tejura, Bina; Robinson, Neil; Layton, Gary; Davies, Kay; Muntoni, Francesco; Tinsley, Jonathon

    2016-01-01

    SMT C1100 is a utrophin modulator being evaluated as a treatment for Duchenne muscular dystrophy (DMD). This study, the first in pediatric DMD patients, reports the safety, tolerability and PK parameters of single and multiple doses of SMT C1100, as well as analyze potential biomarkers of muscle damage. This multicenter, Phase 1 study enrolled 12 patients, divided equally into three groups (A-C). Group A were given 50 mg/kg on Days 1 and 11, and 50 mg/kg bid on Days 2 to 10. Group B and C received 100 mg/kg on Days 1 and 11; Group B and Group C were given 100 mg/kg bid and 100 mg/kg tid, respectively, on Days 2 to 10. A safety review was performed on all patients following the single dose and there was at least 2 weeks between each dose escalation, for safety and PK review. Adverse events (AEs) were monitored throughout the study. Most patients experienced mild AEs and there were no serious AEs. Two patients required analgesia for pain (headache, ear pain and toothache). One patient experienced moderate psychiatric AEs (abnormal behaviour and mood swings). Plasma concentrations of SMT C1100 at Days 1 and 11 indicated a high degree of patient variability regardless of dose. Unexpectedly the SMT C1100 levels were significantly lower than similar doses administered to healthy volunteers in an earlier clinical study. In general, individual baseline changes of creatine phosphokinase, alanine aminotransferase, aspartate aminotransferase levels fell with SMT C1100 dosing. SMT C1100 was well tolerated in pediatric DMD patients. ClinicalTrials.gov NCT02383511.

  12. Comparative pharmacokinetics of tylosin or florfenicol after a single intramuscular administration at two different doses of tylosin-florfenicol combination in pigs.

    Science.gov (United States)

    Kim, Mi-Hee; Gebru, Elias; Chang, Zhi-Qiang; Choi, Jae-Young; Hwang, Mi-Hyun; Kang, Eun-Hee; Lim, Jong-Hwan; Yun, Hyo-In; Park, Seung-Chun

    2008-01-01

    Clinical pharmacokinetic profiles were investigated following intramuscular (i.m.) administration to pigs with a commercial tylosin-florfenicol combination product at a dose of 2.5 mg/kg tylosin and 5 mg/kg florfenicol or 10 mg/kg tylosin and 20 mg/kg florfenicol. The quantitation limit (QL) of florfenicol was 0.1 microg/ml, the inter-day and intra-day precision (CV%) were both beow 10%. The quantitation limit (QL) of tylosin was 0.05 microg/mL. The pharmacokinetic characteristics after i.m. doses were fitted by a one compartment open model. A fourfold decrease in the normal dose of each drug (20 mg/kg to 5 mg/kg for florfenicol, and 10 mg/kg to 2.5 mg/kg for tylosin) resulted in a corresponding two fold decrease in each drug of the maximum plasma concentration (C(max)) and the area under curve (AUC) values.

  13. An usual approach to treatment of a case of multidrug resistance Pseudomonas aeruginosa peritonitis: parenteral and intraperitoneal aminoglycosides and parenteral colistin

    Directory of Open Access Journals (Sweden)

    Ian May

    2012-09-01

    Full Text Available Infections caused by Pseudomonas aeruginosa are becoming more common and increasingly more difficult to treat due to the continued development of drug resistance. While sensitivity to colistin (polymyxin E is well known, it is frequently avoided due to concerns of nephrotoxicity. Reported here is a case of a multi-drug resistance pseudomonal typhlitis, bacteremia and pleural cavity infection that required significant intensive care, and serial abdominal washouts. Intra-peritoneal tobramycin in combination with broad-spectrum intravenous antibiotics including colistin were used. Several instillations of tobramycin into the abdominal cavity along with concomitant IV administration of colistin, ceftazidime and tobramycin and per os colistin, tobramycin and nystatin resulted in the clearance of the pseudomonal infection without any evidence of toxicity from the treatment. Intra-abdominal tobramycin with parenteral colistin therapy can be used in complicated clinical settings with appropriate nephroprotection.

  14. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting...

  15. An open-label phase 1 dose-escalation clinical trial of a single intravenous administration of gemcitabine in dogs with advanced solid tumors.

    Science.gov (United States)

    Marconato, L; Finotello, R; Bonfanti, U; Dacasto, M; Beatrice, L; Pizzoni, S; Leone, V F; Balestra, G; Furlanello, T; Rohrer Bley, C; Aresu, L

    2015-01-01

    A broad range of gemcitabine dosages have been used in dogs. To determine maximally tolerated dose (MTD), dose-limiting toxicity (DLT), and preliminary antitumor activity of intravenous administration of gemcitabine in dogs with advanced solid tumors. Twenty-two client-owned dogs. Dogs with advanced cancer were prospectively enrolled in an open-label Phase 1 study of gemcitabine. Gemcitabine was administered as a 30-minute intravenous bolus starting at 800 mg/m(2), using escalation of 50 mg/m(2) increments with 3 dogs per dose level. MTD was established based on the number of dogs experiencing DLT assessed after 1 cycle. Treatment continued until disease progression or unacceptable toxicosis. Additional dogs were enrolled at MTD to better characterize tolerability, and to assess the extent and duration of gemcitabine excretion. Twenty-two dogs were treated at 4 dose levels, ranging from 800 to 950 mg/m(2). Neutropenia was identified as DLT. MTD was 900 mg/m(2). DLT consisting of grade 4 febrile neutropenia was observed at 950 mg/m(2) in 2 dogs. There were no nonhematologic DLTs. Twenty dogs received multiple doses, and none had evidence of severe toxicosis from any of their subsequent treatments. At 900 mg/m(2), 2 complete and 5 partial responses were observed in dogs with measurable tumors. The amount of gemcitabine excreted in urine decreased over time, and was undetectable after the first 24 hours. The recommended dose of gemcitabine for future Phase 2 studies is weekly 900 mg/m(2). In chemotherapy-naïve dogs with advanced solid tumor this dose level merits further evaluation. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  16. Intraperitoneal Gemcitabine Chemotherapy Treatment for Patients with Resected Pancreatic Cancer: Rationale and Report of Early Data

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2011-01-01

    Full Text Available Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Despite a potentially curative R0 resection, long-term survival is rare. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a pharmacologic basis in that the exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 200–500 times the exposure that occurs within the plasma. A standardized treatment with intraoperative and long-term chemotherapy that is well tolerated would greatly facilitate further improvements in pancreas cancer treatment and may lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this paper is to present the early data on a protocol in progress in patients with resected pancreatic cancer.

  17. Experimental intraperitoneal infusion of OK-432 in rats: Evaluation of peritoneal complications and pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Dong Wook [Department of Radiology, Busan Paik Hospital, Inje University College of Medicine, Busan (Korea, Republic of); Kim, Hak Jin, E-mail: hakjink@pusan.ac.k [Department of Radiology, Pusan National University Hospital, Pusan National University College of Medicine, Medical Research Institute, Busan (Korea, Republic of); Lee, Jun Woo [Department of Radiology, Pusan National University Hospital, Pusan National University College of Medicine, Medical Research Institute, Busan (Korea, Republic of)

    2010-06-15

    Purpose: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. Materials and methods: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. Results: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. Conclusion: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications.

  18. Experimental intraperitoneal infusion of OK-432 in rats: Evaluation of peritoneal complications and pathology

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Kim, Hak Jin; Lee, Jun Woo

    2010-01-01

    Purpose: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. Materials and methods: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. Results: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. Conclusion: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications.

  19. Current status and future prospects of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) clinical trials in ovarian cancer.

    Science.gov (United States)

    Cowan, Renee A; O'Cearbhaill, Roisin E; Zivanovic, Oliver; Chi, Dennis S

    2017-08-01

    The natural history of advanced-stage epithelial ovarian cancer is one of clinical remission after surgery and platinum/taxane-based intravenous (IV) and/or intraperitoneal (IP) chemotherapy followed by early or late recurrence in the majority of patients. Prevention of progression and recurrence remains a major hurdle in the management of ovarian cancer. Recently, many investigators have evaluated the use of normothermic and hyperthermic intraoperative IP drug delivery as a management strategy. This is a narrative review of the current status of clinical trials of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in ovarian cancer and the future directions for this treatment strategy. The existing studies on HIPEC in patients with epithelial ovarian cancer are mostly retrospective in nature, are heterogeneous with regards to combined inclusion of primary and recurrent disease and lack unbiased data. Until data are available from evidence-based trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is a rational and interesting, though still investigative, approach in the management of epithelial ovarian cancer, whose use should be employed within prospective clinical trials.

  20. Non-specific immune response of bullfrog Rana catesbeiana to intraperitoneal injection of bacterium Aeromonas hydrophila

    Science.gov (United States)

    Zhang, Junjie; Zou, Wenzheng; Yan, Qingpi

    2008-08-01

    Non-specific immune response of bullfrog Rana catesbeiana to pathogenic Aeromonas hydrophila was studied to 60 individuals in two groups. Each bullfrog in bacterium-injected group was injected intraperitoneally (i.p.) with 0.2 ml bacterial suspension at a density of 5.2 × 106 CFU/ml, while each one in control group injected i.p. with 0.2 ml sterile saline solution (0.85%, w/v). Three bullfrogs in both groups were sampled at 0, 1, 3, 7, 11, 15 and 20 days post-injection (dpi) for the evaluation of non-specific immune parameters. It was observed that intraperitoneal injection of A. hydrophila significantly increased the number of leucocytes and that of NBT-positive cells in peripheral blood. Significant increases in serum bactericidal activity and serum acid phosphatase activity were also observed in the bacterium-injected frogs when compared with those in the control group. However, a significant reduction was detected in vitro in phagocytosis activity of peripheral blood phagocytes. No significant difference in changes in the number of peripheral erythrocytes, serum superoxide dismutase (SOD) activity, and lysozyme activity was detected between the two groups. It is suggested that bullfrogs may produce a series of non-specific immune reactions in response to the A. hydrophila infection.

  1. Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

    Science.gov (United States)

    Nazarali, A J; Baker, G B; Coutts, R T; Pasutto, F M

    1983-01-01

    Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

  2. Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography in patients with major cerebral artery steno-occlusive diseases

    International Nuclear Information System (INIS)

    Saito, Hideo; Ogasawara, Kuniaki; Suzuki, Taro; Kuroda, Hiroki; Kobayashi, Masakazu; Yoshida, Kenji; Kubo, Yoshitaka; Ogawa, Akira

    2011-01-01

    Adverse effects of intravenous acetazolamide administration for evaluation of cerebrovascular reactivity using brain perfusion single-photon emission computed tomography (SPECT) were prospectively investigated in 100 patients with major cerebral artery, atherosclerotic, and steno-occlusive diseases. All patients underwent two SPECT studies (with and without acetazolamide challenge) at an interval of 2 or 3 days, received a questionnaire immediately after each SPECT study, and returned the answered questionnaire within 7 days after the study. None of the 100 patients studied experienced any symptoms during the SPECT study without acetazolamide challenge. Sixty-three patients (63%) developed symptoms during the SPECT study with acetazolamide challenge, such as headache, nausea, dizziness, tinnitus, numbness of the extremities, motor weakness of the extremities, and general malaise 1-3 hours (mean 1.6 hours) after administration of acetazolamide, and these symptoms lasted for 0.5-72 hours (mean 7.9 hours). Multivariate statistical analysis revealed that younger age (95% confidence interval [CI] 0.896-0.980, p=0.0047) and female sex (95% CI 1.178-16.129, p=0.0274) were significantly associated with development of symptoms with acetazolamide challenge. The incidences of the development of symptoms with acetazolamide challenge were 91% (21/23) and 41% (12/29) in subgroups of women <70 years and men ≥70 years, respectively. Patients should be informed of such adverse effects of intravenous acetazolamide administration prior to the acetazolamide challenge test for evaluation of cerebrovascular reactivity. (author)

  3. Comparable pharmacokinetics and pharmacodynamics of two epoetin alfa formulations Eporon® and Eprex® following a single subcutaneous administration in healthy male volunteers

    Directory of Open Access Journals (Sweden)

    Yoon S

    2017-10-01

    Full Text Available Sumin Yoon,1 Su-jin Rhee,1 Sun Ju Heo,2 Tae Young Oh,2 Seo Hyun Yoon,1 Joo-Youn Cho,1 SeungHwan Lee,1,3 Kyung-Sang Yu1,3 1Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, 2Dong-A ST Co. Ltd., Seoul, 3Clinical Trials Center, Seoul National University Hospital, Seoul, Republic of Korea Purpose: This study aimed to assess and compare the pharmacokinetic (PK and pharmacodynamic (PD properties following a single subcutaneous injection of epoetin alfa (Eporon® with those of the comparator (Eprex® in healthy male subjects. Subjects and methods: A randomized, double-blind, two-sequence, crossover study was conducted. Subjects were randomly assigned to receive a single dose, that is, 4,000 IU, of the test or comparator epoetin alfa. After 4 weeks, all subjects received the alternative formulation. The primary PK parameters, maximum observed concentration (Cmax and area under the curve extrapolated to infinity (AUCinf, were calculated with the serum erythropoietin (EPO concentrations from blood samples collected for 144 h after dosing. The reticulocyte, hematocrit, hemoglobin and red blood cell counts were measured up to 312 h as PD markers. The primary PD parameters, maximum observed effect (Emax and area under the effect curve (AUEC, were obtained from the baseline-corrected reticulocyte count. The serum EPO concentration and the reticulocyte count were used to assess the concentration–response relationship. The tolerability and immunogenicity profiles were assessed together. Results: Forty-two subjects completed the study. The mean EPO concentration–time profiles were comparable between the two formulations. The geometric mean ratios (90% CI of the Cmax and AUCinf were 0.908 (0.843–0.978 and 1.049 (0.999–1.101, respectively, both of which were within the regulatory range of 0.80–1.25. Additionally, the PD and tolerability profiles were similar between the two

  4. Effect of intraperitoneal injection of sulodexide on peritoneal function and albumin leakage in continuous ambulatory peritoneal dialysis patients.

    Science.gov (United States)

    Guedri, Yosra; Damma, K Najla; Toumi, Melek; Sahtout, Wissal; Azzabi, Awatef; Mrabet, Sinda; Nouira, Safa; Saidane, Dalila; Amor, Samira; Belarbia, Anis; Zellama, Dorsaf; Achour, Abdellatif

    2016-01-01

    Peritoneal protein loss is one of the inevitable consequences during continuous ambulatory peritoneal dialysis (CAPD). Our objective was to study the effect of sulodexide on the protein loss and efficiency of dialysis. This study included six patients receiving CAPD treated with sulodexide at the dose of 600 IU/day given by intraperitoneal injection for 10 days. Clinical and biologic parameters were assessed before starting the treatment (D0 and after 10 days of treatment (D10. We also evaluated the benefit of therapy persisting 20 days after the end of treatment (D30. The sulodexide administration produced a significant improvement of the peritoneal function as determined by a significant increase in the following ratios measured at the 4 th h of dwell time on D0 and D30: dialysate-to plasma (D/P) creatinine from 0.63 ± 1.45 to 0.85 ± 0.073 (P = 0.028) and D/P urea from 0.63 ± 0.15 to 79 ± 0.2 (P = 0.048). A significant decrease of albumin leakage was observed, which was 0.90 ± 0.40 g/L at baseline, 0.67 ± 0.36 g/L on the 10 th day, and 0.43 ± 0.22g/L 20 days after the end of treatment. Within 10-day treatment period, use of sulodexide resulted in a reduction in the peritoneal loss of albumin, in addition to improvement of the quality of dialysis and the residual renal function among these patients.

  5. Comparison of postoperative analgesic efficacy of intraoperative single-dose intravenous administration of dexketoprofen trometamol and diclofenac sodium in laparoscopic cholecystectomy.

    Science.gov (United States)

    Anıl, Ali; Kaya, Fatma Nur; Yavaşcaoğlu, Belgin; Mercanoğlu Efe, Esra; Türker, Gürkan; Demirci, Abdurrahman

    2016-08-01

    The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy. A randomized fashion. Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery. Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded. Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The dataset from administration of single or combined immunomodulation agents to modulate anti-FVIII antibody responses in FVIII plasmid or protein primed hemophilia A mice

    Directory of Open Access Journals (Sweden)

    Chao Lien Liu

    2016-06-01

    Full Text Available Hemophilia A mice with pre-existing inhibitory antibodies against factor VIII (FVIII were treated with single agents, AMD3100 and GCS-F, respectively. Inhibitor titers in treated mice and control HemA inhibitors mice were followed over time. Total B cells and plasma cells (PCs were characterized by flow cytometry. HemA inhibitor mice were then treated with a combination regimen of IL-2/IL-2mAb complexes plus rapamycin and AMD3100. Finally, HemA inhibitor mice were treated with a new combination therapy using include IL-2/IL-2mAb complexes + Anti-CD20+AMD3100+G-CSF. The timeline of combination therapy was illustrated. Inhibitor titers following treatment in FVIII plasmid or protein induced inhibitor mice were evaluated overtime. A representative figure and gating strategies to characterize the subsets of Treg cells and B cells are presented. Please see http://dx.doi.org/10.1016/j.cellimm.2016.01.005 [1] for interpretation and discussion of these data and results.

  7. Investigation of the bioequivalence of montelukast chewable tablets after a single oral administration using a validated LC-MS/MS method

    Directory of Open Access Journals (Sweden)

    Zaid AN

    2015-09-01

    geometric means were 101.2%, 101.6%, and 98.11% for area under the curve (AUC0→last, AUC0→inf, and Cmax, respectively. The 90% confidence intervals were within the predefined limits of 80.00%–125.00% as specified by the US Food and Drug Administration and European Medicines Agency for BE studies.Conclusion: Broncast® pediatric chewable tablets (5 mg/tablet are bioequivalent to Singulair® pediatric chewable tablets (5 mg/tablet, with a similar safety profile. This suggests that these two formulations can be considered interchangeable in clinical practice. Keywords: montelukast, bioequivalence, chewable, safety, efficacy

  8. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    Science.gov (United States)

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Effect of Administration of Ramelteon, a Melatonin Receptor Agonist, on the Duration of Stay in the ICU: A Single-Center Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Nishikimi, Mitsuaki; Numaguchi, Atsushi; Takahashi, Kunihiko; Miyagawa, Yasuhiro; Matsui, Kota; Higashi, Michiko; Makishi, Go; Matsui, Shigeyuki; Matsuda, Naoyuki

    2018-03-27

    Occurrence of delirium in the ICU is associated with a longer stay in the ICU. To examine whether the use of ramelteon, a melatonin agonist, can prevent delirium and shorten the duration of ICU stay of critically ill patients. A single-center, triple-blinded, randomized placebo-controlled trial. ICU of an academic hospital. Eligible patients were ICU patients who could take medicines orally or through a nasogastric tube during the first 48 hours of admission. The intervention group received ramelteon (8 mg/d), and the control group received placebo (1 g/d of lactose powder) at 20:00 hours every day until discharge from the ICU. A total of 88 subjects were randomized to the ramelteon group (45 subjects) or the placebo group (43 subjects). As the primary endpoint, there was a trend toward decrease in the duration of ICU stay (4.56 d) in the ramelteon group compared with the placebo group (5.86 d) (p = 0.082 and p = 0.028 before and after adjustments). As the secondary endpoints, statistically significant decreases in the occurrence rate (24.4% vs 46.5%; p = 0.044) and duration (0.78 vs 1.40 d; p = 0.048) of delirium were observed in the ramelteon group. The nonintubated patients of the ramelteon group showed statistically significantly fewer awakenings per night and a higher proportion of nights without awakenings. Ramelteon tended to decrease the duration of ICU stay as well as decreased the occurrence rate and duration of delirium statistically significantly.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  10. Long-term outcomes of {sup 131}Iodine mIBG therapy in metastatic gastrointestinal pancreatic neuroendocrine tumours: single administration predicts non-responders

    Energy Technology Data Exchange (ETDEWEB)

    Mulholland, Nicola; Chakravartty, Riddhika; Devlin, Lindsey; Kalogianni, Eleni; Corcoran, Ben; Vivian, Gillian [King' s College Hospital, Department of Nuclear Medicine, London (United Kingdom)

    2015-12-15

    {sup 131}Iodine (I131)-metaiodobenzylguanidine (mIBG) is a radionuclide-based treatment option for metastatic gastrointestinal-pancreatic neuroendocrine tumours (GEP NET). This study aimed at identifying prognostic indicators of long-term outcome based on initial evaluation following a first mIBG treatment (7400 MBq) in a patient cohort with such tumours, with a secondary aim of evaluating progression-free survival (PFS) and overall survival (OS) following mIBG therapy. Retrospective review of the hospital records was performed to identify a cohort of 38 adult patients who underwent {sup 131}Iodine-mIBG therapy over a 9-year period for metastatic GEP NETs and neuroendocrine tumours with an unknown primary. Treatment response was evaluated based on radiological criteria (RECIST1.1), biochemical markers [serum Chromogranin A (CgA)/urinary 5HIAA] and symptomatic response at clinical follow-up, all evaluated at 3-6 months from first mIBG treatment. Progression-free survival (PFS) and overall survival (OS) from the first mIBG treatment were recorded. At 3-6 months following a single mIBG therapy, 75 %, 67 %, and 63 % of patients showed either a partial response (PR) or stable disease (SD) on radiological, biochemical, and symptomatic criteria, respectively. Complete response (CR) was not seen in any patient. OS from the date of diagnosis and from the first therapy was 8 years +/-1.1 (95 % CI 5.7 to 10.2 years) and 4 years+/-0.69 (95 % CI 2.6-5.3 years), respectively. Twenty-nine percent of patients were alive at 10 years. Significant survival advantage was seen in patients with SD/PR as compared to those who had progressive disease (PD) for each of these three criteria. Biochemical, radiological (RECIST 1.1) and symptomatic assessment of disease status at 3 to 6 months after first I131-mIBG therapy stratifies patients with a poor prognosis. This can be used to identify patients who may benefit from alternative strategies of treatment. (orig.)

  11. Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

    Science.gov (United States)

    Renard, Eric; Place, Jerome; Cantwell, Martin; Chevassus, Hugues; Palerm, Cesar C.

    2010-01-01

    OBJECTIVE Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS Two-day closed-loop therapy (except for a 15-min premeal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean ± SEM percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was significantly higher (39.1 ± 4.5 vs. 27.7 ± 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4–6.6 mmol/l range (46.3 ± 5.3 vs. 28.6 ± 7.4, P = 0.025) and lower mean blood glucose levels (6.9 ± 0.3 vs. 7.9 ± 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. CONCLUSIONS Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the premeal bolus in terms of timing and amount warrant further research. PMID:19846796

  12. Dexamethasone loaded nanoparticles exert protective effects against Cisplatin-induced hearing loss by systemic administration.

    Science.gov (United States)

    Sun, Changling; Wang, Xueling; Chen, Dongye; Lin, Xin; Yu, Dehong; Wu, Hao

    2016-04-21

    Ototoxicity is one of the most important adverse effects of cisplatin chemotherapy. As a common treatment of acute sensorineural hearing loss, systemic administration of steroids was demonstrated ineffective against cisplatin-induced hearing loss (CIHL) in published studies. The current study aimed to evaluate the potential protective effect of dexamethasone (DEX) encapsulated in polyethyleneglycol-coated polylactic acid (PEG-PLA) nanoparticles (DEX-NPs) against cisplatin-induced hearing loss following systemic administration. DEX was fabricated into PEG-PLA nanoparticles using emulsion and evaporation technique as previously reported. DEX or DEX-NPs was administered intraperitoneally to guinea pigs 1h before cisplatin administration. Auditory brainstem response (ABR) threshold shifts were measured at four frequencies (4, 8, 16, and 24kHz) 1 day before and three days after cisplatin injection. Cochlear morphology was examined to evaluate inner ear injury induced by cisplatin exposure. A single dose of DEX-NPs 1h before cisplatin treatment resulted in a significant preservation of the functional and structural properties of the cochlea, which was equivalent to the effect of multidose (3 days) DEX injection. In contrast, no significant protective effect was observed by single dose injection of DEX. The results of histological examination of the cochleae were consistent with the functional measurements. In conclusion, a single dose DEX-NPs significantly attenuated cisplatin ototoxicity in guinea pigs after systemic administration at both histological and functional levels indicating the potential therapeutic benefits of these nanoparticles for enhancing the delivery of DEX in acute sensorineural hearing loss. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. A protocol for management of blood loss in surgical treatment of peritoneal malignancy by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Sargant, N; Roy, A; Simpson, S; Chandrakumaran, K; Alves, S; Coakes, J; Bell, J; Knight, J; Wilson, P; Mohamed, F; Cecil, T; Moran, B

    2016-04-01

    The treatment of peritoneal malignancies with cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) has been shown to be associated with massive surgical blood loss. Maintaining high fibrinogen levels throughout surgery may reduce blood loss in these patients. The primary aim of the study was to see if Tranexamic Acid (TXA) and cryoprecipitate reduced surgical blood loss and hence red cell transfusions. A comparison was made with a cohort of patients treated with fresh frozen plasma (FFP) alone. The secondary aim was to measure the effect of both protocols on coagulation parameters and the incidence of arterial or venous thrombosis. We used prospectively collected data from 201 patients who had complete CRS with HIPEC for peritoneal malignancy using different protocols during two discrete 12-month time periods. The new transfusion protocol led to a higher average fibrinogen level intra-operatively and post-operatively, with a significant reduction in average RBC, FFP and platelet transfusion intra-operatively per patient from 4·2 to 1·8 units, 6·2 to 0·2 units and 0·1 to 0 units, respectively. No significant difference in PT or APTT was seen between patients treated with the standard and new protocols. Venous thrombosis occurred in seven patients treated with the standard protocol and five with the new protocol. A single case of arterial thrombosis was seen in both groups. Patients treated with upfront TXA and cryoprecipitate during CRS required less RBC transfusion than those treated with the standard protocol of early FFP. © 2016 British Blood Transfusion Society.

  14. Effect of intraperitoneal electronic identification on productive performance of Sardinian suckling lambs

    Directory of Open Access Journals (Sweden)

    I.L. Solinas

    2010-01-01

    Full Text Available The electronic identification could represent a further step to improve the traceability of meat, considering that, starting from the 1st of January 2008, this method will be compulsory in the whole EU (Reg. CE n. 21/2004. The “Agnello di Sardegna” is a Protected Geographic Identification product (Provv. 13/03/2001 and it has to match up a series of requirements, such as the identification of animals in 20 days time from birth. In a previous work, Pinna et al. (2004 showed the results of a survey carried out for the development of the intraperitoneal identification systems in lambs. In the present work, the effects on the main productive in vivo and post mortem performance are taken into account.

  15. Presumptive intraperitoneal envenomation resulting in hemoperitoneum and acute abdominal pain in a dog.

    Science.gov (United States)

    Istvan, Stephanie A; Walker, Julie M; Hansen, Bernard D; Hanel, Rita M; Marks, Steven L

    2015-01-01

    To describe the clinical features, diagnostic findings, treatment, and outcome of a dog with acute abdominal pain and hemoperitoneum secondary to a presumptive intraperitoneal (IP) snakebite. A 10-month-old castrated male mixed-breed dog was evaluated for suspected snake envenomation. The dog presented recumbent and tachycardic with signs of severe abdominal pain. Two cutaneous puncture wounds and hemoperitoneum were discovered during evaluation. Ultrasonographic examination revealed communication of the wounds with the peritoneal cavity. The dog was treated with supportive care, parenteral analgesia, packed red blood cell and fresh frozen plasma transfusions, crotalid antivenom, and placement of an IP catheter to provide local analgesia. The dog recovered fully and was discharged 5 days after initial presentation. To our knowledge, this is the first report of IP envenomation accompanied by hemorrhage treated with continuous IP analgesia in the veterinary literature. © Veterinary Emergency and Critical Care Society 2015.

  16. Insulin delivery route for the artificial pancreas: subcutaneous, intraperitoneal, or intravenous? Pros and cons.

    Science.gov (United States)

    Renard, Eric

    2008-07-01

    Insulin delivery is a crucial component of a closed-loop system aiming at the development of an artificial pancreas. The intravenous route, which has been used in the bedside artificial pancreas model for 30 years, has clear advantages in terms of pharmacokinetics and pharmacodynamics, but cannot be used in any ambulatory system so far. Subcutaneous (SC) insulin infusion benefits from the broad expansion of insulin pump therapy that promoted the availability of constantly improving technology and fast-acting insulin analog use. However, persistent delays of insulin absorption and action, variability and shortterm stability of insulin infusion from SC-inserted catheters generate effectiveness and safety issues in view of an ambulatory, automated, glucose-controlled, artificial beta cell. Intraperitoneal insulin delivery, although still marginally used in diabetes care, may offer an interesting alternative because of its more-physiological plasma insulin profiles and sustained stability and reliability of insulin delivery.

  17. Is Palliative Laparoscopic Hyperthermic Intraperitoneal Chemotherapy Effective in Patients with Malignant Hemorrhagic Ascites?

    Science.gov (United States)

    de Mestier, Louis; Volet, Julien; Scaglia, Elodie; Msika, Simon; Kianmanesh, Reza; Bouché, Olivier

    2012-01-01

    Malignant hemorrhagic ascites may complicate the terminal evolution of digestive cancers with peritoneal carcinomatosis. It has a bad influence on prognosis and may severely impair patients’ quality of life. Palliative laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to treat debilitating malignant ascites. Two cases of peritoneal carcinomatosis causing hemorrhagic ascites and severe anemia that needed iterative blood transfusions are reported. These patients were treated by laparoscopic HIPEC (mitomycin C and cisplatin with an inflow temperature of 43°C), resulting in cessation of peritoneal bleeding. No postoperative complication or relapse of ascites occurred during the following months. No more blood transfusion was needed. Laparoscopic HIPEC might be an effective and safe therapeutic option to consider in patients with malignant hemorrhagic ascites. PMID:22679405

  18. Intraperitoneal Calcitriol for Treatment of Severe Hyperparathyroidism in Children with Chronic Kidney Disease: A Therapy Forgotten.

    Science.gov (United States)

    Chanchlani, Rahul; Ackerman, Susan; Piva, Elizabeth; Harvey, Elizabeth

    Active Vitamin D sterols such as calcitriol and alfacalcidol are quite effective in the treatment of mineral bone disease secondary to chronic kidney disease. However, some children on peritoneal dialysis (PD) are resistant to oral formulations of active Vitamin D, and use of an intravenous formulation in such patients is inconvenient. In these children, intraperitoneal (IP) calcitriol has been shown to be effective in the treatment of secondary hyperparathyroidism. However, its use has declined. We report 2 children, aged 1 and 9.5 years, on chronic cycler PD with severe secondary hyperparathyroidism refractory to oral active Vitamin D who were successfully treated with IP calcitriol for a period of 12 and 4 months, respectively. We also discuss the published literature on the efficacy of IP calcitriol for treatment of secondary hyperparathyroidism and specific considerations for its use in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  19. Use of intraperitoneal xenon-133 for imaging of intestinal strangulation in small bowel obstruction. [Rats; Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Bulkley, G.B.; Gharagozloo, F.; Alderson, P.O.; Horn, S.D.; Zuidema, G.D.

    1981-01-01

    Intraperitoneal xenon-133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay inexternally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponsed to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction.

  20. Use of intraperitoneal xenon-133 for imaging of intestinal strangulation in small bowel obstruction

    International Nuclear Information System (INIS)

    Bulkley, G.B.; Gharagozloo, F.; Alderson, P.O.; Horn, S.D.; Zuidema, G.D.

    1981-01-01

    Intraperitoneal xenon-133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay inexternally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponsed to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction

  1. Polyethylene Glycol (PEG-3350, Colyte Poisoning due to Intra-Peritoneal Leakage in an Elderly Patient

    Directory of Open Access Journals (Sweden)

    Jae Hee Chung

    Full Text Available Polyethylene glycol (PEG-3350 is the most frequently used lavage solution for bowel cleansing prior to colonoscopy or elective surgery because its large molecular weight means that it is poorly absorbed. However, if it leaks into the peritoneal cavity, complications may arise. Few published studies have assessed the absorption, distribution, metabolism and excretion of PEG. Moreover, no published clinical data regarding complications due to the intra-peritoneal leakage of PEG-3350 could be found. We report on an elderly patient who developed the poisoning caused by leaking of PEG-3350 during bowel preparation. It resulted in severe metabolic acidosis, hypernatremia, hyperosmolality and a high anion gap, but it was effectively treated with early continuous renal replacement therapy after surgery.

  2. SAT administrator

    International Nuclear Information System (INIS)

    Havas, A.

    1998-01-01

    SAT Administrator is the Information System for Nuclear Power Plant Personnel Training Program Design. It supports the design of training programs in the following phases: job analysis; task analysis; competency analysis; task competency association; definition of learning objectives to competencies; training program design; definition of test items. The general structure of the database and management software supports application of the SAT Administrator in any nuclear power installation

  3. Offentlig administration

    DEFF Research Database (Denmark)

    Nielsen, Elof Nellemann; Rehr, Preben René

    En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer.......En undervisningsbog der henvender sig til administrationsbacheloruddannelsen. Kapitlerne er inddelt efter modulerne på uddannelsen og indeholder derfor elementer af administration, forvaltning, økonomistyring, innovation, samfundsvidenskabelige metoder og politisk styrede organisationer....

  4. Pharmacokinetic study of five ginsenosides using a sensitive and rapid liquid chromatography-tandem mass spectrometry method following single and multiple oral administration of Shexiang Baoxin pills to rats.

    Science.gov (United States)

    Peng, Chengcheng; Yang, Yongge; Lv, Chao; Jin, Huizi; Tao, Jianfei; Yuan, Xing; Huang, Huimei; Han, Lin; Chang, Wanlin; Liu, Runhui; Zhang, Weidong

    2015-03-01

    Shexiang Baoxin pills (SBP) are a traditional Chinese medicine that are used for treating coronary heart disease. Ginsenosides are the main effective components of SBP, but a comprehensive and deep pharmacokinetic study of ginsenosides in SBP, including multiple dosing and linear or nonlinear properties, is lacking. This study was designed to investigate and compare the pharmacokinetic characteristics of ginsenosides in SBP at a single dose and in multiple doses. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous determination of the ginsenosides Rg1, Re, Rb3, Rc and Rb1 in rat plasma. Rats were randomly assigned to receive a single dose of 4, 8 or 12 g/kg and multiple doses (4 g/kg) of SBP for 8, 15 or 22 consecutive days. The results revealed that ginsenosides, following a single oral dose of 4 or 8 g/kg, were absorbed rapidly, with a Tmax ranging from 0.250 to 1.08 h. The AUC0-t and Cmax of the ppd-type ginsenosides Rb3, Rc and Rb1 were greater than those of the ppt-type ginsenosides Rg1 and Re. Nondose-dependent exposure was observed at doses of 4-12 g/kg for all of the ginsenosides. After multiple dosing, the plasma levels of the ppt-type ginsenosides decreased, whereas those of the ppd-type ginsenosides did not change significantly. In conclusion, the LC-MS/MS method was successfully applied to investigate the pharmacokinetics of ginsenosides after single and multiple oral administrations of SBP. The ginsenosides did not accumulate after multiple dosing. The ppd-type ginsenosides displayed more favorable pharmacokinetic properties compared with the ppt-type ginsenosides. Copyright © 2014 John Wiley & Sons, Ltd.

  5. EXPERIMENTAL CONFIRMATION FOR SELECTION OF IRRADIATION REGIMENS FOR INTRAPERITONEAL PHOTODYNAMIC THERAPY WITH PORPHYRIN AND PHTHALOCYANINE PHOTOSENSITIZERS

    Directory of Open Access Journals (Sweden)

    A. A. Pankratov

    2017-01-01

    Full Text Available Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental  study on НЕр2 cell line showed that reduce of power density for constant  light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death for half as much concentration of the photosensitizer.The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2  and power density of 25 mW/cm2 none of animals in the experimental  group had total resorption of the tumor. For the same light dose and decrease  of power density to 12 mW/cm2  total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic  shock. For twofold decrease  of light dose – to 45 J/cm2  with the same low-intensity power density (12 mW/cm2 we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2  with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

  6. Intraperitoneal Hydrocortisone plus Bupivacaine versus Bupivacaine alone for Pain Relief after Laparoscopic Cholecystectomy

    Directory of Open Access Journals (Sweden)

    Mahesh Sharma

    2016-11-01

    Full Text Available Introduction: Laparoscopic cholecystectomy has been the gold standard in the treatment of gallstones since last decades. Beside several benefits of laparoscopic cholecystectomy compared with open surgery, postoperative pain is still a frequent melancholy.  Hence, pain management is utmost regarding patients' comfort. The main objective of the study was to compare the effect of intraperitoneal hydrocortisone plus bupivacaine with bupivacaine alone on pain relief following laparoscopic cholecystectomy.   Methods: A randomized study was conducted from December 2015 to August 2015 that included 100 patients aged 20 to 60 years of both genders who were found to have symptomatic gallstones and were scheduled for elective laparoscopic cholecystectomy at Lumbini Medical College. Patients randomly received 100 mg hydrocortisone plus 100 mg bupivacaine in 200 ml normal saline (group A or 100 mg bupivacaine in 200 ml normal saline (group B into the peritoneum. Post-operative abdominal and shoulder pain were evaluated using Visual Analog Score (VAS. The patients were also followed up for postoperative analgesic requirements, and recovery variables. Data were collected, tabulated and analyzed statistically using SPSS version 19.   Results: Total number of patients in this study were 100. Age and gender among both groups were comparable. VAS scores for pain was significantly lower for group A as compared to group B at 0, 2, 4, 6, 12, and 24 hours. Time of oral intake in hrs for liquids and solids was statistically significant in Group A compared to Group B. Rescue analgesic requirement was also significantly low in Group A compared to Group B. Hospital stay in both group were comparable.   Conclusion: Combination of hydrocortisone plus bupivacaine can relieve pain after laparoscopic cholecystectomy better compared to bupivacaine alone when administered intraperitoneally.

  7. Formation of adhesion after intraperitoneal application of TiMesh: experimental study on a rodent model.

    Science.gov (United States)

    Delibegovic, Samir; Koluh, Anhel; Cickusic, Elmir; Katica, Muhamed; Mustedanagic, Jasminka; Krupic, Ferid

    2016-10-01

    After laparoscopic repair of an incisive hernia, intraperitoneal prosthetic mesh, as a foreign material, is a strong stimulus for the development of adhesion, which may be the cause of serious complications. This experimental study compared three different meshes and their ability to prevent the formation of adhesion and shrinkage. Ninety rats were divided randomly into three groups: in Group 1 Proceed mesh was implanted, in Group 2 Ultrapro mesh was implanted, and in Group 3 TiMesh was implanted. Mesh samples were fixed as an intraabdominal mesh in the upper part of the abdomen. Ten animals from each group were sacrificed on days 7, 28 and 60 post-surgery. After opening the abdomen, the formation of adhesion was assessed according to the Surgical Membrane Study Group (SMSG) score, the percentage of shrinkage of the mesh was established and inflammatory reaction scored. The SMSG score for adhesion was statistically significantly higher on all the postoperative days in the Proceed and Ultrapro mesh groups than in the TiMesh group which caused milder inflammatory reaction on 60th day than others meshes. The size of the mesh after 7 days was statistically significantly smaller in the Proceed and Ultrapro groups than in the TiMesh group, but after 60 days it was statistically significantly larger than in the TiMesh group. The least formation of adhesion was noted in the TiMesh group, in which the highest level of shrinkage was noticed after 28 and 60 days. TiMesh has advantages over the other meshes studied, but a larger size mesh may be recommended for intraperitoneal application.

  8. Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

    International Nuclear Information System (INIS)

    Syme, A M; McQuarrie, S A; Middleton, J W; Fallone, B G

    2003-01-01

    A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

  9. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for refractory malignant ascites in patients unsuitable for cytoreductive surgery.

    Science.gov (United States)

    Valle, S J; Alzahrani, N A; Alzahrani, S E; Liauw, W; Morris, D L

    2015-11-01

    Malignant ascites (MA) is the abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal dissemination of their disease and is associated with a short life expectancy. The most common clinical feature is a progressive increase of abdominal distention resulting in pain, discomfort, anorexia and dyspnoea. Currently, no treatment is established standard of care due to limited efficacy or considerable toxicity. The objective was to examine the efficacy of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliation of refractory MA in patients who were unsuitable for cytoreductive surgery. From May 2009 to June 2015, 12 patients with MA due to their peritoneal malignancy were treated with laparoscopic HIPEC. The time between operation and repeat paracentesis, in-hospital data, and the proportion of patients that did not require repeat paracentesis was analyzed. One patient (8%) was admitted to ICU for 1 day. The mean operating time and hospital stay was 149.3 min (range 79-185) and 4.6 days (range 2-11) respectively. Neither high-grade morbidity nor mortality was observed. The median OS was 57 days. In our experience, a complete and definitive disappearance of MA was observed in 83% of patients. Two patients (17%) developed recurrent MA 124 days and 283 days post-HIPEC. Laparoscopic HIPEC is a beneficial treatment for the management and palliation of refractory MA and results in an excellent clinical and radiological resolution in patients with a complete resolution observed in selected patients. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  10. Intraperitoneal mesh devices for small midline hernias: mesh behavior in a porcine model.

    Science.gov (United States)

    Reynvoet, E; Chiers, K; Van Overbeke, I; Troisi, R; Berrevoet, F

    2015-12-01

    Although clinical data on long-term efficacy are lacking, the use of self-expanding devices for intraperitoneal placement in the management of small midline hernias has been popularized. In the present experimental study, two different devices were investigated regarding tissue ingrowth, adhesion formation and solid mesh placement. Two devices of 4.3 cm diameter, one ePTFE-containing small pore polypropylene mesh (PP/ePTFE) and a multi-layered large-pore polypropylene patch with an oxidized cellulose anti-adhesive barrier (PP/ORC), both containing a self-deployment system, were placed intraperitoneally at the linea alba of 24 female pigs. A first laparoscopy was performed to evaluate mesh positioning against the abdominal wall. 1 (n = 6), 2 (n = 6), 4 (n = 6) and 12 weeks (n = 6) later, mesh appearance was inspected and adhesion formation was assessed. All meshes were excised for histological evaluation. Folding of the patch was more frequently observed at PP/ePTFE, yet no excessive cupping was noticed. Adhesions predominantly presented at short-term evaluation. Overall adhesion formation at all samples was significantly more extensive for PP/ORC (p = 0.048). Massive shrinkage was observed for PP/ORC: after a 12-week period 22% residual surface was preserved, compared to 83% for PP/ePTFE (p < 0.001). While at short-term inflammatory reaction was comparable, at long-term PP/ORC induced a significant more pronounced inflammatory and foreign body reaction. Although a strong deployment system provides adequate initial placement, shrinkage and excessive adhesion formation are much more prominent in the large-pore multi-layered restorbable devices compared to the ePTFE patch. This might influence long-term clinical outcome and caution seems warranted.

  11. Intraperitoneal xenon for the detection of early intestinal ischemia: effect of ascites, adhesions, and misdirected injections

    International Nuclear Information System (INIS)

    Gharagozloo, F.; Bulkley, G.B.; LaFrance, N.; Zuidema, G.D.

    1983-01-01

    Significant delay in the washout of intraperitoneal xenon ( 133 Xe) in rats and dogs with decreased splanchnic blood flow (bowel strangulation, superior mesenteric artery and vein occlusion) has been previously demonstrated as the basis for radionuclide imaging to detect early (prenecrotic) intestinal ischemia. In this study, the effect of ascites, adhesions, and misdirected injections on the validity of this technique is evaluated. Xenon-133 (0.6 mCi) in 3 ml saline was injected into the peritoneal cavity of anesthetized rats and the washout of gamma activity monitored externally for 90 min. Gamma camera images were obtained at 30-min intervals. After 60 min, only 12 +/- 2% of injected activity remained in the controls. Sham option (13 +/- 1%) and simple obstruction (12 +/- 2) had been previously shown not to significantly slow washout, but segmental strangulation had done so dramatically (32 +/- 2%, P less than 0.0001). In these experiments, ascitic fluid (Ringer's lactate) in volumes of 10 ml (13 +/- 1%), 20 ml (13 +/- 1%), and 40 ml (13 +/- 1%), did not significantly slow washout in nonischemic rats. Sixty and eighty milliliters produced very tense ascites and slight but significant delay in washout (14 +/- 1%, 17 +/- 1%, respectively, P less than 0.05). Moderate (11 +/- 1%) and severe (11 +/- 1%) adhesions produced by serosal scarification did not delay washout nor affect imaging. Injections of isotope intentionally misdirected into the abdominal wall (32 +/- 2%), bowel wall (18 +/- 1%), and bowel lumen (19 +/- 2%), each significantly (P less than 0.001) slowed washout. However, such misdirected injections were easily recognizable as such on the 1-min gamma camera images and could thereby be excluded as artifactual. It is concluded that the intraperitoneal xenon technique is not invalidated by mild to moderate ascites nor by moderate to severe adhesions

  12. Intraperitoneal xenon for the detection of early intestinal ischemia: effect of ascites, adhesions, and misdirected injections

    Energy Technology Data Exchange (ETDEWEB)

    Gharagozloo, F.; Bulkley, G.B.; LaFrance, N.; Zuidema, G.D.

    1983-06-01

    Significant delay in the washout of intraperitoneal xenon (/sup 133/Xe) in rats and dogs with decreased splanchnic blood flow (bowel strangulation, superior mesenteric artery and vein occlusion) has been previously demonstrated as the basis for radionuclide imaging to detect early (prenecrotic) intestinal ischemia. In this study, the effect of ascites, adhesions, and misdirected injections on the validity of this technique is evaluated. Xenon-133 (0.6 mCi) in 3 ml saline was injected into the peritoneal cavity of anesthetized rats and the washout of gamma activity monitored externally for 90 min. Gamma camera images were obtained at 30-min intervals. After 60 min, only 12 +/- 2% of injected activity remained in the controls. Sham option (13 +/- 1%) and simple obstruction (12 +/- 2) had been previously shown not to significantly slow washout, but segmental strangulation had done so dramatically (32 +/- 2%, P less than 0.0001). In these experiments, ascitic fluid (Ringer's lactate) in volumes of 10 ml (13 +/- 1%), 20 ml (13 +/- 1%), and 40 ml (13 +/- 1%), did not significantly slow washout in nonischemic rats. Sixty and eighty milliliters produced very tense ascites and slight but significant delay in washout (14 +/- 1%, 17 +/- 1%, respectively, P less than 0.05). Moderate (11 +/- 1%) and severe (11 +/- 1%) adhesions produced by serosal scarification did not delay washout nor affect imaging. Injections of isotope intentionally misdirected into the abdominal wall (32 +/- 2%), bowel wall (18 +/- 1%), and bowel lumen (19 +/- 2%), each significantly (P less than 0.001) slowed washout. However, such misdirected injections were easily recognizable as such on the 1-min gamma camera images and could thereby be excluded as artifactual. It is concluded that the intraperitoneal xenon technique is not invalidated by mild to moderate ascites nor by moderate to severe adhesions.

  13. EXPERIENCE WITH INTRAPERITONEAL CHEMOTHERAPY USING ASCITIC FLUID AS A SOLVENT OF CHEMICALS IN THE TREATMENT OF OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2009-01-01

    Full Text Available Thirty two with the ascitic form of Stages IIIC—IV ovarian cancer underwent 1 to 3 courses of intraperitoneal multidrug therapy using a protein ascitic fluid concentrate (PAFC as a solvent of drugs (cisplatin, cyclophosphan, doxorubicin according to the CAP regimen. The induction chemotherapy allowed remission to be achieved in 78.1% of cases (against 40% with standard intraperitoneal therapy, the stan- dard volume of surgical treatment was performed in 28 (87.5% patients (21 (70% receiving the control regime; with the use of PAFC, the size of minimum residual tumour (less than 1 cm was achieved in 81.3% versus 63.3% with standard intraperitoneal chemotherapy. This treatment enables the use large-dose chemotherapy regimens that cause no severe systemic toxic reactions. The method is highly-effective, low-toxic and may be recommended for the treatment of patients with the ascitic form of Stages III—IV ovarian cancer.

  14. Oral administration of choline does not affect metabolic characteristics of gliomas and normal-appearing white matter, as detected with single-voxel 1H-MRS at 1.5 T

    International Nuclear Information System (INIS)

    Chernov, Mikhail F.; Iseki, Hiroshi; Takakura, Kintomo; Muragaki, Yoshihiro; Maruyama, Takashi; Ono, Yuko; Usukura, Masao; Yoshida, Shigetoshi; Nakamura, Ryoichi; Kubo, Osami; Hori, Tomokatsu

    2009-01-01

    The present study was done for evaluation of the possible influence of the oral administration of choline on metabolic characteristics of gliomas detected with proton magnetic resonance spectroscopy ( 1 H-MRS). Thirty patients (22 men and eight women; mean age 38±15 years) with suspicious intracranial gliomas underwent single-voxel long-echo (TR 2,000 ms, TE 136 ms, 128-256 acquisitions) 1 H-MRS of the tumor, peritumoral brain tissue, and distant normal-appearing white matter before and several hours (median, 3 h; range, 1.2-3.7 h) after ingestion of choline with prescribed dose of 50 mg/kg (median actual dose, 52 mg/kg; range, 48-78 mg/kg). Investigations were done using 1.5 T clinical magnetic resonance imager. The volume of the rectangular 1 H-MRS voxel was either 3.4 or 8 cm 3 . At the time of both spectroscopic examinations, similar voxels' positioning and size and technical parameters of 1 H-MRS were used. Surgery was done in 27 patients within 1 to 68 days thereafter. In all cases, more than 80% resection of the neoplasm was attained. There were 12 low-grade gliomas and 15 high-grade gliomas. MIB-1 index varied from 0% to 51.7% (median, 13.8%). Statistical analysis did not disclose significant differences of any investigated metabolic parameter of the tumor, peritumoral brain tissue and distant normal-appearing white matter between two spectroscopic examinations. Single-voxel 1 H-MRS at 1.5 T could not detect significant changes of the metabolic characteristics of gliomas, peritumoral brain tissue, and distant normal-appearing white matter after oral administration of choline. (orig.)

  15. Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previous History of IVF/ICSI Failure: A Randomized Controlled Trial

    Science.gov (United States)

    Zafardoust, Simin; Jeddi-Tehrani, Mahmood; Akhondi, Mohammad Mehdi; Sadeghi, Mohammad Reza; Kamali, Koroush; Mokhtar, Sara; Badehnoosh, Bita; Arjmand-Teymouri, Fatemeh; Fatemi, Farnaz; Mohammadzadeh, Afsaneh

    2015-01-01

    Background GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This blind randomized controlled study evaluates the effect of GnRH (Gonadotropine Releasing Hormone) agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. Methods One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention (received a single dose injection of GnRH agonist (0.1 mg of Decapeptil) subcutaneously 6 days after oocyte retrieval) and control (did not receive GnRH agonist) groups. Implantation and clinical pregnancy rates were the primary outcome measures. Results Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation (Mann Whitney test, p = 0.041) and pregnancy (32.6% vs. 12.5%, p = 0.030, OR = 3.3, 95%CI, 1.08 to 10.4) in the intervention group. Conclusion Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte retrieval in women with previous history of 2 or more IVF/ICSI failures led to a significant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol. PMID:25927026

  16. Pharmacokinetics of marbofloxacin in pigs after intravenous and intramuscular administration of a single dose of 8 mg/kg: dose proportionality, influence of the age of the animals and urinary elimination.

    Science.gov (United States)

    Schneider, M; Paulin, A; Dron, F; Woehrlé, F

    2014-12-01

    The pharmacokinetics of marbofloxacin in pigs were evaluated as a function of dose and animal age following intravenous and intramuscular administration of a 16% solution (Forcyl(®) ). The absolute bioavailability of marbofloxacin as well as the dose proportionality was evaluated in 27-week-old fattening pigs. Blood PK and urinary excretion of marbofloxacin were evaluated after a single intramuscular dose of 8 mg/kg in 16-week-old male pigs. An additional group of 12-week-old weaned piglets was used for the evaluation of age-related kinetics. The plasma and urine concentration of marbofloxacin was determined using a HPLC method. Pharmacokinetic parameters were calculated using noncompartmental methods. After intravenous administration in 27-week-old fattening pigs, the total body clearance was 0.065 L/h·kg. After intramuscular administration to the same animals, the mean observed Cmax was 6.30 μg/mL, and the AUCINF was 115 μg·h/mL. The absolute bioavailability was 91.5%, and dose proportionality was shown within the dose range of 4-16 mg/kg. The renal clearance was about half of the value of the total clearance. The total systemic clearance values significantly decreased as a function of age, being 0.092 L/h·kg and 0.079 L/h·kg in pigs aged 12 and 16 weeks, respectively. © 2014 The Authors. Journal of Veterinary Pharmacology and Therapeutics Published by John Wiley & Sons Ltd.

  17. Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Ring-Larsen, H; Lassen, N A

    1983-01-01

    Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between...... the plasma-to-peritoneal transport rate of albumin (index of 'lymph-imbalance') and the mass of intraperitoneal albumin (rlog = 0.82, P less than 0.001), indicating a significant role of 'lymph-imbalance' to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration...

  18. Presión intraperitoneal y ultrafiltración conseguida con diferentes volúmenes intraperitoneales

    Directory of Open Access Journals (Sweden)

    Lucila Fernández Arroyo

    Full Text Available En condiciones fisiológicas el abdomen actúa como una cavidad cerrada cuya presión aumenta de forma proporcional al volumen que contiene. El valor normal de la presión hidrostática intraperitoneal está alrededor de 0 y en pacientes en diálisis peritoneal con volúmenes intraperitoneales de 2 litros puede estar en torno a 12±2 cmH2O. Realizamos un estudio multicéntrico cuantitativo, descriptivo, longitudinal y prospectivo, que incluía a 42 pacientes en programa de diálisis peritoneal con el fin de examinar la presión intraperitoneal y la ultrafiltración conseguida al infundir diferentes volúmenes de líquido de diálisis. Se hicieron dos intercambios consecutivos el primero con 2500 ml y el segundo con 1500 ml con líquido de diálisis con glucosa 2,3% y permanencia de 120 minutos en cada intercambio. De los 42 pacientes el 71,5% eran hombres, con una edad de 59.31±12.23 años y con un índice de masa corporal de 27.01±4.46. La presión intraperitoneal con volumen intraperitoneal 0 fue de 8.2±4.1; con volumen intraperitoneal 2500 ml la presión fue de 13.8±4.4 y la ultrafiltración de 131±206; con volumen intraperitoneal de 1500 ml la presión fue de 11.2±4.2 y la ultrafiltración de 192±145. La ultrafiltración con respecto a la infusión fue del 5,2%±8,2% con volumen de 2500 ml y del 12,8%±9,6% con volumen de 1500 ml. Podemos describir un aumento de la presión intraperitoneal al aumentar el volumen intraperitoneal, al mismo tiempo hemos observado una mayor ultrafiltración con volúmenes más bajos que implicaban a su vez cifras menores de presión.

  19. Administrative Reform

    DEFF Research Database (Denmark)

    Plum, Maja

    Through the example of a Danish reform of educational plans in early childhood education, the paper critically addresses administrative educational reforms promoting accountability, visibility and documentation. Drawing on Foucaultian perspectives, the relation between knowledge and governing......, implied in the reform, is analysed as a technology of accounting. A technology producing ‘the professional nursery teacher' as a reflective daily researcher, who outlives her pedagogical desire as an analytical care of the optimisation of ‘the learning child'. Thus, the paper analyses the micro physics...... of administrative technology, tracing how the humanistic values of education embed and are embedded within ‘the professional nursery teacher' as an object and subject of administrative practice. Rather than undermining the humanistic potential of education, it is argued that the technology of accounting...

  20. Post Chlorine gas exposure administration of nitrite prevents lung injury: effect of administration modality

    Science.gov (United States)

    Samal, Andrey A.; Honavar, Jaideep; Brandon, Angela; Bradley, Kelley M.; Doran, Stephen; Liu, Yanping; Dunaway, Chad; Steele, Chad; Postlethwait, Edward M.; Squadrito, Giuseppe L.; Fanucchi, Michelle V.; Matalon, Sadis; Patel, Rakesh P.

    2012-01-01

    Cl2 gas toxicity is complex and occurs during, and post exposure leading to acute lung injury (ALI) and reactive airway syndrome (RAS). Moreover, Cl2 exposure can occur in diverse situations encompassing mass casualty scenarios underscoring the need for post-exposure therapies that are efficacious and amenable to rapid and easy administration. In this study, we compared the efficacy of a single dose, post (30min) Cl2 exposure administration of nitrite (1mg/kg) via intraperitoneal (IP) or intramuscular (IM) injection in rats, to decrease ALI. Exposure of rats to Cl2 gas (400ppm, 30min) significantly increased ALI and caused RAS 6–24h post exposure as indexed by BAL sampling of lung surface protein, PMN and increased airway resistance and elastance prior to and post methacholine challenge. IP nitrite decreased Cl2 - dependent increases in BAL protein but not PMN. In contrast IM nitrite decreased BAL PMN levels without decreasing BAL protein in a xanthine oxidoreductase independent manner. Histological evaluation of airways 6h post exposure showed significant bronchial epithelium exfoliation and inflammatory injury in Cl2 exposed rats. Both IP and IM nitrite improved airway histology compared to Cl2 gas alone, but more coverage of the airway by cuboidal or columnar epithelium was observed with IM compared to IP nitrite. Airways were rendered more sensitive to methacholine induced resistance and elastance after Cl2 gas exposure. Interestingly, IM nitrite, but not IP nitrite, significantly decreased airway sensitivity to methacholine challenge. Further evaluation and comparison of IM and IP therapy showed a two-fold increase in circulating nitrite levels with the former, which was associated with reversal of post-Cl2 exposure dependent increases in circulating leukocytes. Halving the IM nitrite dose resulted in no effect in PMN accumulation but significant reduction of of BAL protein levels indicating distinct nitrite dose dependence for inhibition of Cl2 dependent

  1. Webb Administration

    OpenAIRE

    Prahl, Hampus

    2005-01-01

    I’ve built an Internet based administration front-end for the company Allt I Brand in Jamjö. Allt I Brand’s main goals are maintenance and sale of fire preventive equipment. This front-end is programmed mostly in PHP, connected to a MySQL database. Because both Allt I Brand’s main page and my administration front-end use the same database and the database is designed to virtually fit any type of company, the result is both dynamic and powerful. The front-end design is made to make it easy to ...

  2. Database Administrator

    Science.gov (United States)

    Moore, Pam

    2010-01-01

    The Internet and electronic commerce (e-commerce) generate lots of data. Data must be stored, organized, and managed. Database administrators, or DBAs, work with database software to find ways to do this. They identify user needs, set up computer databases, and test systems. They ensure that systems perform as they should and add people to the…

  3. La presión intraperitoneal en diálisis peritoneal

    Directory of Open Access Journals (Sweden)

    Vicente Pérez Díaz

    2017-11-01

    Full Text Available La medida de la presión intraperitoneal en diálisis peritoneal es muy sencilla y aporta claros beneficios terapéuticos. Sin embargo, su monitorización todavía no se ha generalizado en las unidades de diálisis peritoneal de adultos. Esta revisión pretende divulgar su conocimiento y la utilidad de su medida. Se realiza en decúbito antes de iniciar el drenaje de un intercambio manual con bolsa en Y, elevando la bolsa de drenaje y midiendo la altura que alcanza la columna de líquido desde la línea medio-axilar. Los valores habituales son 10 a 16 cmH2O y nunca debe superar los 18 cmH2O. Aumenta de 1 a 3 cmH2O por litro de volumen intraperitoneal sobre valores basales que dependen del índice de masa corporal y varía con la postura y la actividad física. Su aumento provoca malestar, alteraciones del sueño y de la respiración, y se ha relacionado con la aparición de fugas de líquido, hernias, hidrotórax, reflujo gastroesofágico y peritonitis por gérmenes intestinales. Menos conocida y valorada es su capacidad para disminuir la eficacia de la diálisis contrarrestando, sobre todo, la ultrafiltración y, en menor grado, el aclaramiento de solutos. Por su facilidad de medida y potencial utilidad, debería ser uno de los factores que investigar en los fallos de ultrafiltración, pues su elevación podría contribuir a ellos en algunos pacientes. Aunque todavía no se menciona en las guías de actuación en diálisis peritoneal, sus claros beneficios justifican su inclusión entre las mediciones periódicas que considerar para la prescripción y seguimiento de la diálisis peritoneal.

  4. Quality of life after cytoreductive surgery plus early intraperitoneal postoperative chemotherapy for pseudomyxoma peritonei: A prospective study

    DEFF Research Database (Denmark)

    Jess, Per; Iversen, Lene Hjerrild; Nielsen, Mette B

    2008-01-01

    PURPOSE: The modern treatment of pseudomyxoma peritonei is cytoreductive surgery plus intraperitoneal chemotherapy resulting in a survival of up to 70 percent after 20 years. The goal of this study was to investigate the impact on quality of life of this very aggressive treatment, which has not b...

  5. Continuous intraperitoneal insulin infusion in type 1 diabetes : a 6-year post-trial follow-up

    NARCIS (Netherlands)

    van Dijk, Peter R.; Logtenberg, Susan J. J.; Groenier, Klaas H.; Gans, Rijk. O.B.; Kleefstra, Nanne; Bilo, Henk J. G.

    2014-01-01

    Background: Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL)

  6. Work Environment in the Operating Room during Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy : Factors Influencing Choice of Protective Equipment

    OpenAIRE

    Näslund Andréasson, Sara

    2011-01-01

    Peritoneal carcinomatosis (PC) is a common metastatic manifestation of both gastrointestinal and gynecological malignancies. Curative modes of treatment are cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). Surgeons and operating room (OR) staff attending these procedures are exposed to chemotherapy and electrocautery smoke. Heated chemotherapy (HIPEC) may vaporize and become inhaled by those administering it and, moreover, large quant...

  7. Influence of intraperitoneal therapy with mitomycin C adsorbed on activated carbon on anastomotic and wound healing in rats

    NARCIS (Netherlands)

    Jansen, M; Jansen, PL; Fass, J; Langejurgen, E; Forsch, S; Tietze, L; Schumpelick, [No Value

    In an effort to prevent intraperitoneal dissemination of gastric carcinoma, local chemotherapy with mitomycin C adsorbed to activated carbon (MMC-CH) has been implemented. Results of clinical studies showed improved survival and a reduced systemic toxicity after the use of prophylactic treatment

  8. Oral administration of caffeic acid ameliorates the effect of cisplatin on brush border membrane enzymes and antioxidant system in rat intestine.

    Science.gov (United States)

    Arivarasu, N A; Priyamvada, Shubha; Mahmood, Riaz

    2013-01-01

    Cisplatin (CP) is a widely used antineoplastic drug that exhibits gastrointestinal toxicity. We have previously shown that administration of a single dose of CP results in a decrease in the activities of several brush border membrane (BBM) enzymes, induces oxidative stress and alters the activities of several antioxidant enzymes in the small intestine of rats. In the present study we have investigated the effect of treatment with the dietary antioxidant caffeic acid (CA) on CP induced biochemical changes in the intestine. Administration of a single intraperitoneal dose of CP alone (6 mg/kg body weight) led to a decrease in the activities of the BBM enzymes, increase in lipid peroxidation, decrease in sulfhydryl groups and changes in the activities of catalase, superoxide dismutase, glutathione peroxidase, glucose 6-phosphate dehydrogenase, glutathione reductase, glutathione S-transferase and thioredoxin reductase. Administration of two doses of CA (each of 250 mg/kg body weight), at 15 and 120 min after treatment with CP, significantly attenuated the CP-induced changes in all these parameters but the administration of CA alone had no effect. These results suggest that CA is an effective agent in reducing the effects of CP on the intestine and could prove to be useful in alleviating the gastrointestinal toxicity of this drug. Copyright © 2011 Elsevier GmbH. All rights reserved.

  9. Oral thymoquinone administration ameliorates: the effect of cisplatin on brush border membrane enzymes, energy metabolism, and redox status in rat kidney.

    Science.gov (United States)

    Farooqui, Zeba; Shahid, Faaiza; Abidi, Subuhi; Parwez, Iqbal; Khan, Farah

    2017-12-01

    Therapeutic use of cisplatin (CP), an effective anticancer drug, is limited by dose dependent nephrotoxicity. Thymoquinone (TQ), the major Nigella sativa seed oil constituent has been shown to prevent progression of various renal disorders. The present study investigates the protective effect of TQ on CP-induced nephrotoxicity. Rats were divided into six groups viz. control, CP, CPTQ 1 , CPTQ 2 , CPTQ 3 , and TQ alone group. Animals in CP and TQ combination groups were administered TQ (0.5, 1.5, and 3 mg/kg bwt, orally) with single intraperitoneal dose of CP (6 mg/kg bwt). The effect of TQ administration was determined on CP-induced alterations in various serum/urine parameters and on the enzymes of brush border membrane enzyme (BBM), carbohydrate metabolism, and antioxidant defense system in renal cortex and medulla. Oral administration of TQ in all the three doses prior to and following a single dose CP treatment caused significant recovery of serum creatinine and blood urea nitrogen levels; however, maximum recovery was seen in CPTQ 2 group. TQ administration averted CP-induced decline in BBM activities, both in the cortical and medullary homogenates and in isolated BBM vesicles. TQ administration also ameliorated CP-induced impairments in renal metabolic and antioxidant status. Histopathological studies supported these biochemical findings. TQ ameliorates CP-induced oxidative damage owing to its intrinsic antioxidant properties.

  10. Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion.

    Directory of Open Access Journals (Sweden)

    Xinhe Wang

    2015-07-01

    Full Text Available The prion hypothesis postulates that the infectious agent in transmissible spongiform encephalopathies (TSEs is an unorthodox protein conformation based agent. Recent successes in generating mammalian prions in vitro with bacterially expressed recombinant prion protein provide strong support for the hypothesis. However, whether the pathogenic properties of synthetically generated prion (rec-Prion recapitulate those of naturally occurring prions remains unresolved. Using end-point titration assay, we showed that the in vitro prepared rec-Prions have infectious titers of around 104 LD50/μg. In addition, intraperitoneal (i.p. inoculation of wild-type mice with rec-Prion caused prion disease with an average survival time of 210-220 days post inoculation. Detailed pathological analyses revealed that the nature of rec-Prion induced lesions, including spongiform change, disease specific prion protein accumulation (PrP-d and the PrP-d dissemination amongst lymphoid and peripheral nervous system tissues, the route and mechanisms of neuroinvasion were all typical of classical rodent prions. Our results revealed that, similar to naturally occurring prions, the rec-Prion has a titratable infectivity and is capable of causing prion disease via routes other than direct intra-cerebral challenge. More importantly, our results established that the rec-Prion caused disease is pathogenically and pathologically identical to naturally occurring contagious TSEs, supporting the concept that a conformationally altered protein agent is responsible for the infectivity in TSEs.

  11. Indications for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in elderly patients with peritoneal malignancy.

    Science.gov (United States)

    Kitai, Toshiyuki; Yamanaka, Kenya; Miyauchi, Yuya; Kawashima, Masahiro

    2017-06-01

    A combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is effective for some peritoneal malignancies. However, the indications for elderly patients remain unclear, with substantial postoperative morbidity and mortality being problematic. Clinical data were analyzed in 42 patients undergoing CRS + HIPEC for peritoneal malignancy. The primary tumor was located in the appendix in 32 cases and elsewhere in 10 cases. Operative results and survival data were compared between patients aged ≥70 and Elderly patients had a higher peritoneal cancer index (32.0 vs. 21.5), higher CA19-9 level (189.0 vs. 28.1), and higher frequency of grade 4-5 complications (5/9 vs. 2/26) than the younger patients. Grade 4-5 respiratory failure occurred in three elderly patients. There was a significant difference of postoperative survival between the elderly patients and younger patients, with 5-year survival rates being 41.3 and 74.2%, respectively (p = 0.0166). The poor prognosis of elderly patients was related to the higher frequency of grade 4-5 complications. Elderly patients were referred for treatment with more advanced disease than younger patients. An age ≥70 years was associated with more frequent grade 4-5 complications and worse survival. Performing CRS + HIPEC in elderly patients should be considered carefully due to the risk of severe complications, especially respiratory failure.

  12. Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, J.S.; Hird, V.; Snook, D.; Sullivan, M.; Hooker, G.; Courtenay-Luck, N.; Sivolapenko, G.; Griffiths, M.; Myers, M.J.; Lambert, H.E.

    1989-02-01

    Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.

  13. Intraperitoneal microdialysis in the postoperative surveillance after surgery for necrotizing enterocolitis: a preliminary report.

    Science.gov (United States)

    Pedersen, Mark E; Dahl, Marianne; Qvist, Niels

    2011-02-01

    The aim of the present pilot study was to evaluate the safety and clinical application of intraperitoneal microdialysis (MD) in preterm infants operated on for necrotizing enterocolitis (NEC). Fourteen infants underwent MD. Two were excluded from analysis: 1 because of catheter malfunction and 1 because of fatal outcome immediately after surgery. The median MD time was 122 hours. Samples were collected every 4 hours, and the concentration of glucose, lactate, pyruvate, and glycerol was measured. Three infants were reoperated on: 2 because of recurrent NEC and 1 because of ileal stenosis. In the 2 cases with recurrent NEC, changes in MD variables were found. Another had a prolonged postoperative period owing to diffuse fecal peritonitis. The values of MD normalized along with the return of bowel function. In 8 infants, the postoperative course was uncomplicated. The results of peritoneal MD in patients with complications were significantly different from those with an uncomplicated course (lactate/pyruvate ratio and glucose concentration). Peritoneal MD is a safe procedure and an applicable method in surveillance of the metabolic and inflammatory changes in the peritoneal cavity after surgery for NEC. Larger series are needed to evaluate the clinical significance and use of this method. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. Transcriptome of intraperitoneal organs of starry flounder Platichthys stellatus challenged by Edwardsiella ictaluri JCM1680

    Science.gov (United States)

    Tong, Yanli; Sun, Xiuqin; Wang, Bo; Wang, Ling; Li, Yan; Tian, Jinhu; Zheng, Fengrong; Zheng, Minggang

    2015-01-01

    Platichthys stellatus is an economically important marine bony fish species that is cultured in China on a large scale. However, very little is known about its immune-related genes. In this study, the transcriptome of the immune organs of P. stellatus that were intraperitoneally challenged with the pathogen E dwardsiella ictaluri JCM1680 is analyzed. Total RNA from four tissues (spleen, kidney, liver, and intestine) was mixed equally and then sequenced on an Illumina HiSeq 2000 platform. Overall, 28 465 813 quality reads were generated and assembled into 43 061 unigenes. Similarity searches against public protein sequence databases were used to annotate 28 291 unigenes (65.7% of the total), 368 of which were associated with immunoregulation, including 188 related to immunity response. Additionally, the transcript levels of immunity response unigenes annotated as related to tumor necrosis factor (TNF), TNF receptor, chemokine, major histocompatibility complex, and interleukin-6 were investigated in the different tissues of normal and infected P. stellatus by real-time quantitative PCR. The results confirmed that the unigenes identified in the transcriptome database were indeed expressed and up-regulated in infected P. stellatus. To our knowledge, this is the first report of the sequencing and analysis of the transcriptome of P. stellatus. These findings provide insights into the transcriptomics and immunogenetics of bony fish.

  15. Subcutaneous versus subcutaneous and intraperitoneal local anaesthetic in the management of post appendicectomy pain

    International Nuclear Information System (INIS)

    Qureshi, K.Z.; Gondal, Z.I.; Raza, A.

    2014-01-01

    To compare the efficacy of subcutaneous only and combined subcutaneous and peritoneal infiltration of 0.5% bupivacaine during appendicectomy for the management of early post operative pain. Study Design: Randomized controlled study. Place and Duration of Study: Department of Surgery, CMH Kohat from 13th December 2007 to 20th December 2008. Patients and Methods: Sixty patients of a cute appendicitis, divided into two groups of 30 each, were included in the study. Group A was given 0.5% bupivacaine subcutaneously, whereas group B was given the anaesthetic subcutaneously as well as intraperitoneally during appendectomy. Results: In group A, 24 (80%) were VAS (visual analoguescoring) 3 (uncomfortable) and 6 (20%) were VAS 2 (mild pain) whereas in study group B, 11 (36.6%) were VAS 3, 19 (63.3%) were VAS 2 and 19 (63.3%) were VAS 2 during 1st 12 hrs postoperatively (p=0.001). In 12-24 hrs post operatively, 15 (50%) patients were VAS 3 in group A and same number was VAS 2 and in group B, only 3 (10%) were in VAS 3 and 27 (90%) were VAS 2 (p=0.001). Conclusion: A combination of subcutaneous and peritoneal infiltration with bupivacaine is superior in relieving post appendectomy pain so patients require less dosage of analgesics in early post operative period along with early mobilization. (author)

  16. Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Plas, Matthijs; Hemmer, Patrick H J; Been, Lukas B; van Ginkel, Robert J; de Bock, Geertruida H; van Leeuwen, Barbara L

    2018-02-01

    Incidence of, and baseline characteristics associated with delirium in patients after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), were subject of investigation. The study was conducted among a consecutive series of prospectively included patients who underwent CRS-HIPEC at the University Medical Center Groningen, Groningen, the Netherlands, between February 2006 and January 2015. A chart-based instrument for delirium during hospitalization was used to identify patients with symptoms of delirium who were not diagnosed by a psychiatrist during admission. Uni- and multivariate logistic regression analyses were performed. Data of 136 patients were included in the analysis. Median age was 60 years (range: 18-76) and 50 (37%) patients were male. During hospitalization, 38 (28%) patients were diagnosed with delirium. Factors that differed significantly between the patients with and without delirium by univariate analysis were included in multivariate analysis. Multivariate analysis showed that after adjustment for age and complications other than delirium, having three or more organs resected and the CRP serum levels were independent predictors for delirium (OR: 3.97; 95% 1.24-12.76; OR: 1.01; 95% 1-1.01, respectively). This report shows an incidence of 28% of delirium, occurring after CRS-HIPEC and suggests a role for systemic inflammation in the development of postoperative delirium. © 2017 Wiley Periodicals, Inc.

  17. Administrative contracts

    Directory of Open Access Journals (Sweden)

    Vukićević-Petković Milica

    2015-01-01

    Full Text Available Administrative contracts are a special type of contract where usually one of the contracting parties is a public law body and which is concluded for the performance of public service and the realization of a public interest. They go a long way since its inception to its eventual final acceptance of all the legal systems. One of the enduring characteristics of this type of contract is their disquised or unnoticed existence. This is why only monitoring their development may lead to a complete understanding of the importance and essence of this institution as well as the need for its complete legal regulation.

  18. Administrative contracts

    OpenAIRE

    Vukićević-Petković Milica

    2015-01-01

    Administrative contracts are a special type of contract where usually one of the contracting parties is a public law body and which is concluded for the performance of public service and the realization of a public interest. They go a long way since its inception to its eventual final acceptance of all the legal systems. One of the enduring characteristics of this type of contract is their disquised or unnoticed existence. This is why only monitoring their development may lead to a complete u...

  19. Effect of administration route on FES uptake into MCF-7 tumors

    International Nuclear Information System (INIS)

    Downer, Joanna B.; Jones, Lynne A.; Katzenellenbogen, John A.; Welch, Michael J.

    2001-01-01

    We have observed that intraperitoneal administration of [ 18 F]fluoroestradiol (FES), a radiolabeled estrogen receptor ligand, results in higher abdominal organ uptake and slower blood clearance than intravenous administration in female mice. In SCID mice bearing MCF-7 human tumors SC, IP administration resulted in tumor uptake that was only about one third that obtained with IV administration. Thus, the route of administration of a radiopharmaceutical for imaging or radiotherapy of a tumor in the abdomen, an ovarian tumor, for example, could have a profound effect on the efficiency and selectivity of delivery of the agent to the tumor

  20. Intraperitoneal bupivacaine with or without incisional bupivacaine for postoperative analgesia in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Kalchofner Guerrero, Karin S; Campagna, Ivo; Bruhl-Day, Rodolfo; Hegamin-Younger, Cecilia; Guerrero, Tomas G

    2016-09-01

    Intraperitoneal (IP) bupivacaine provides postoperative analgesia in dogs undergoing ovariohysterectomy (OHE) alone or in combination with incisional (INC) bupivacaine. This study investigated whether the combination of INC and IP bupivacaine is superior to IP bupivacaine alone. Prospective, randomized, blinded clinical study. Thirty-nine privately owned dogs undergoing OHE, aged 25 ± 23 months and weighing 11.8 ± 5.7 kg. Dogs were premedicated with acepromazine (0.05 mg kg(-1) ) and morphine (0.5 mg kg(-1) ) intramuscularly (IM); anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Carprofen (4 mg kg(-1) ) was administered subcutaneously (SC) after intubation. Bupivacaine (3 mg kg(-1) ) IP was administered before complete closure of the linea alba to all dogs. Dogs were randomly assigned into two groups: group B received bupivacaine (n = 20; 1 mg kg(-1) ) and group S received saline (n = 19; 0.2 mL kg(-1) ) INC as a subcutaneous 'splash' before skin closure. Postoperative analgesia was assessed with a dynamic interactive visual analogue scale, the short form of the Glasgow Composite Pain Scale, and mechanical nociceptive threshold (MNT) measurement at 0.5, 1, 2, 4, 6, 8, 12 and 20 hours after surgery by one blinded observer. Parametric data were tested using t-test; nonparametric data were analysed using the two-sample Wilcoxon test (p Bupivacaine IP and carprofen SC after morphine IM did provide satisfactory postoperative analgesia in dogs undergoing OHE with the anaesthetic protocol used. There appears to be no clinical advantage to adding bupivacaine INC. Neither protocol could prevent the development of primary hyperalgesia. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

  1. Unresectability during open surgical exploration in planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Yong, Zachary Zihui; Tan, Grace Hwei Ching; Wong, Joelle Fui Sze; Lim, Cindy; Soo, Khee Chee; Teo, Melissa Ching Ching

    2016-12-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are the treatment of choice for selected patients with peritoneal metastasis. Despite a stringent selection process, some patients were found to be unresectable only at surgery, which leads to disappointment and poor utilisation of limited infrastructural resources. This study aims to determine the pre-operative factors associated with unresectability in planned CRS and HIPEC. Retrospective analysis of 172 consecutive patients eligible for CRS and HIPEC at the National Cancer Centre Singapore from April 2004 to May 2014 was performed. Pre-operative factors (clinical presentation, disease factors, and investigation findings) between the unresectable (13%) and the successful groups (87%) were compared. Patient demographics between the two cohorts were comparable. In terms of clinical presentation, the unresectable group was more likely to present with bloating (p = .00), altered bowel habits (p = .04), abdominal distension (p = .00), palpable abdominal masses (p = .00) and palpable pouch of Douglas nodules (p = .00). Differences were also noted in disease factors with the unresectable group having more high-grade tumours (p = .01), inadequate initial resections (p = .01), progression through chemotherapy (p = .00) and shorter median disease-free intervals (p = .03). In addition, investigations in the unresectable group revealed more patients with elevated tumour markers (p = .01), thrombocytosis (p = .00) and computed tomography findings of ascites (p = .00), omental thickening (p = .00), lymphadenopathy (p = .02) and small bowel disease (p = .00). Significant factors associated with unresectability that were identified in our study could potentially create a new treatment algorithm and refine current selection process to exclude patients at risk of unresectability in planned CRS and HIPEC.

  2. Intraperitoneal ectopic infestation of parasites invading through gastrointestinal tract : CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jeong Kon; Rha, Sung Eun; Ha, Hyun Kwon; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Ulsan Univ., Ulsan (Korea, Republic of); Choi, Byung Ihn [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of); Shim, Jae Chul [Inje Univ. College of Medicine, Kimhae (Korea, Republic of); Kim, Hyun [St. Mary' s Hospital, The Catholic Univ. of Korea, Seoul (Korea, Republic of); Lee, Jong Hwa; Ham, Soo Youn [Ulsan Univ. Hospital, Ulsan (Korea, Republic of)

    1999-03-01

    The purpose of this study was to evaluate the CT findings of parasitic ectopic infestation in the peritoneal cavity, a transitional route for parasites invading the gastrointestinal tract, to migrate to various target organs. CT scans of nine patients with pathologically(n=8) or serologically(n=1) proven intraperitoneal involvement of parasitic infestation were retrospectively reviewed. The primary causes of parasitic infestation in nine patients were Paragonimus westermani(n=5), Sparganosis(n=2), and hepatic fascioliasis(n=2). We analyzed the CT findings with regard to the sites and patterns of lesions in the peritoneal cavity and gastrointestinal track, as well as in other solid organs. The clinical features of these patients were also evaluated. The clinical symptoms and signs were chronic abdominal pain and general weakness in seven patients, while peripheral blood eosinophilia was observed in four. The CT features of these nine patients included multiseptated cystic masses of 2-6cm, diameter (mean 4.1{+-}1.7cm) in the omentum or mesentery in six(67%), omental or mesenteric infiltration in seven(78%), focal peritoneal thickening in seven(78%), 1ymphadenopathy in five(56%), and ascites in four(44%). In six of the nine patients, the gastrointestinal tract(stomach in four, colon in one, both stomach and colon in one) was concomitantly involved with focal wall thickening. Branching patterns of hypoattenuating lesions were noted in the liver of three patients; two of these had hepatic fascioliasis and one had paragonimiasis. Ectopic parasitic infestation in the peritoneal cavity manifests as mass formation, adjacent gastrointestinal wall thickening, and focal peritonitis. An understanding of these image features is important for both early diagnosis and adequate treatment.

  3. Base Excess as a Predictor of Complications in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Eng, Oliver S; Dumitra, Sinziana; O'Leary, Michael; Wakabayashi, Mark; Dellinger, Thanh H; Han, Ernest S; Lee, Stephen J; Benjamin Paz, I; Singh, Gagandeep; Lee, Byrne

    2017-09-01

    Base excess is important in assessing metabolic status. Postoperative management in patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies can be a challenge, and we therefore sought to investigate perioperative predictors of overall morbidity in CRS/HIPEC patients at our institution. Patients who underwent CRS/HIPEC from 2012 to 2016 were identified retrospectively from a prospectively collected institutional database. Patient demographics and perioperative variables were obtained and the comprehensive complication index (CCI) was calculated for each patient in order to assess perioperative morbidity. Stepwise linear regression analyses were performed, with CCI as the outcome variable. A total of 72 CRS/HIPEC patients had recorded base excesses in the first 48 h postoperatively. Mean immediate postoperative base excess was -6.0 mmol/L (interquartile range [IQR] -8 to -4.1), mean delta base excess at 48 h was +4.3 mmol/L (IQR +2.1 to +6.2), and mean CCI was 25.2 (IQR 8.7-36.7). On multivariate analysis, delta base excess was the only significant predictor of CCI, demonstrating a protective effect (p = 0.001). In patients who experienced less than the mean delta base excess of +4.3 mmol/L, lower delta base excess was an independent predictor of complications (p < 0.001). Delta base excess is an independent predictor of morbidity in patients undergoing CRS/HIPEC. A delta base excess of greater than +4.3 mmol/L at 48 h may be an appropriate goal for resuscitation of CRS/HIPEC patients in the immediate postoperative period. Standardized protocols to correct the base deficit in CRS/HIPEC patients during the early postoperative period can potentially help mitigate perioperative morbidity.

  4. The Comprehensive Complication Index: a New Measure of the Burden of Complications After Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Dumitra, Sinziana; O'Leary, Michael; Raoof, Mustafa; Wakabayashi, Mark; Dellinger, Thanh H; Han, Ernest S; Lee, Stephen J; Lee, Byrne

    2018-03-01

    Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) are complex surgeries with multiple comorbidities. The Clavien-Dindo classification (CDC) is the most commonly used method to report surgical morbidity, but limits it to the highest-grade complication. The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all 30-day complications and their treatment after abdominal surgery. The aim of this study is to assess the CCI's validity in the HIPEC patient population. A review of our institutional cytoreduction database from 2009 to 2015 was undertaken. Patient demographics, pathology, Peritoneal Carcinomatosis Index (PCI), complications and their treatments, and length of stay (LOS) were reviewed. The CCI was calculated for each patient. Linear regression was used to assess whether the CCI and CDC were predictors of LOS. Of 157 patients reviewed, 110 (70.1%) underwent HIPEC. The majority were female (77, 66.9%), and the mean age was 53.7 years. Mean PCI was 13.2 [interquartile range (IQR) 7-18]. Median CDC was grade 2 (IQR 0-2), and only 9.8% had CDC of grade 4 or higher. Mean CCI was 21.4, while the median was 20.9 (IQR 0-30.8). Mean LOS was 16.2 days, while the median was 11 days (IQR 8-15 days). The CCI strongly correlated with LOS with coefficient of 0.46 [95% confidence interval (CI) 0.38-0.54, p = 0.000]. The CCI is an adequate tool to capture all complications and their overall burden in patients having undergone HIPEC. This study shows that the CCI can predict LOS and could be used to quantify and compare the burden of multiple complications.

  5. Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites.

    Science.gov (United States)

    Randle, Reese W; Swett, Katrina R; Swords, Douglas S; Shen, Perry; Stewart, John H; Levine, Edward A; Votanopoulos, Konstantinos I

    2014-05-01

    In peritoneal surface disease, accumulation of malignant ascites represents a difficult problem to treat, with adverse impact on quality of life. The role of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites is not well defined. A retrospective analysis of a prospectively maintained database of 1,000 procedures was performed. Type of malignancy, resolution of ascites, duration and agent of chemoperfusion, performance status, resection status, morbidity, mortality, and survival were reviewed. Ascites was found in 299 patients (310 procedures) either before or during exploration. A total of 142 (46 %) procedures were performed for appendiceal primary disease, 53 (17 %) colorectal, 20 (6 %) gastric, 45 (15 %) mesothelioma, and 26 (8 %) ovarian. A total of 288 (93 %) patients had resolution of ascites by 3 months' follow-up. In patients with ascites, complete cytoreduction was obtained in 15 versus 59 % when ascites was not present (p < 0.001). In the group of patients who had their ascites controlled, 243 of 288 (84 %) had resection with residual macroscopic disease (R2 status). Twenty-two patients (7 %) had persistent ascites at 3 months' follow-up, 19 (86 %) of whom had an R2 resection. Univariate analysis revealed that type of primary disease, resection status, duration or agent of chemoperfusion, and performance status did not predict failure. CRS-HIPEC is effective in controlling ascites in 93 % of patients with malignant ascites, even when a complete cytoreduction is not feasible. Ascites is predictive of incomplete cytoreduction and worse overall survival. Although complete cytoreduction remains the goal of this procedure, HIPEC can provide palliative value in selected patients with malignant ascites.

  6. Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study.

    Science.gov (United States)

    Coccolini, Federico; Campanati, Luca; Catena, Fausto; Ceni, Valentina; Ceresoli, Marco; Jimenez Cruz, Jorge; Lotti, Marco; Magnone, Stefano; Napoli, Josephine; Rossetti, Diego; De Iaco, Pierandrea; Frigerio, Luigi; Pinna, Antonio; Runnebaum, Ingo; Ansaloni, Luca

    2015-01-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

  7. Hybrid NOTES transvaginal intraperitoneal onlay mesh in abdominal wall hernias: an alternative to traditional laparoscopic procedures.

    Science.gov (United States)

    Descloux, Alexandre; Pohle, Sebastian; Nocito, Antonio; Keerl, Andreas

    2015-12-01

    Abdominal wall hernias are increasingly treated by laparoscopic placement of an intraperitoneal onlay mesh (IPOM). We present an alternative technique for women: the laparoscopic-assisted transvaginal IPOM. Before surgery, all patients underwent a gynecological examination. The patients agreed to IPOM repair via a transvaginal approach, and written informed consent for surgery was obtained. Pneumoperitoneum was established with a Veress needle at the umbilicus. This access was subsequently dilated to 5 mm (VersaStep), and a 5-mm laparoscope was inserted. Under laparoscopic view, the transvaginal trocars (12-mm VersaStep and 5-mm flexible accesses) were safely inserted after lifting the uterus with a uterus manipulator. After preparation of the falciform ligament, the ligamentum teres and the preperitoneal fat, a lightweight composite mesh was introduced through the transvaginal access and fixed with absorbable tacks using the double-crown technique. From September 2011 to December 2012, we performed six laparoscopic-assisted transvaginal IPOM procedures (one epigastric, three umbilical, two combined epigastric and umbilical hernias; all were primary hernias). In the initial phase, only patients with small or medium primary abdominal wall hernia were selected (max. 3 cm diameter). Median hospital stay was 3 days (range 2-6 days). One minor complication occurred perioperatively (second-degree skin burn to the labia majora). At 1-year follow-up, we identified one recurrence in a high-risk patient with a body mass index higher than 35 kg/m(2). No infection and no mortality were observed. Although no final conclusion can be made regarding the presumed non-inferiority of this technique in terms of recurrence and mesh infection compared with traditional laparoscopic IPOM, laparoscopic-assisted transvaginal IPOM is a feasible alternative to treat abdominal wall hernias.

  8. Splenectomy Increases Postoperative Complications Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Dagbert, Francois; Thievenaz, Remy; Decullier, Evelyne; Bakrin, Naoual; Cotte, Eddy; Rousset, Pascal; Vaudoyer, Delphine; Passot, Guillaume; Glehen, Olivier

    2016-06-01

    Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is increasingly performed on patients with peritoneal carcinomatosis of various origins. Splenectomy often is required in these patients to achieve complete tumor removal. Although splenectomy has been associated with increased morbidity in many major abdominal surgeries, its effect in patients undergoing CRS + HIPEC is unknown. The purpose of this study was to evaluate the impact of splenectomy during CRS + HIPEC on postoperative outcomes. We retrospectively identified 39 patients who underwent CRS + HIPEC with splenectomy during a 3-year study period from a prospective database. We compared them to case controls (CRS + HIPEC without splenectomy) that were matched for the complexity of the procedure. We evaluated the complication rate and outcomes of patients in each group. During the study period, splenectomy was performed in 32 % of patients undergoing CRS + HIPEC procedure. Patients in the splenectomy group experienced more grade 3-4 complications than patients in the control group (59 vs. 35.9 %, p = 0.041) as well as more pulmonary complications (41 vs. 7.7 %, p = 0.0006). Multivariate analysis identified splenectomy as the only predictor of overall major complications (odds ratio = 2.57, 95 % confidence interval = 1.03-6.40). Mortality was similar in both groups. Splenectomy increases major complication rate in patients undergoing CRS + HIPEC and efforts should be made to preserve the spleen during the surgery.

  9. Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

    Directory of Open Access Journals (Sweden)

    Schlitt Hans J

    2009-01-01

    Full Text Available Abstract Background Peritoneal tumor dissemination arising from colorectal cancer, appendiceal cancer, gastric cancer, gynecologic malignancies or peritoneal mesothelioma is a common sign of advanced tumor stage or disease recurrence and mostly associated with poor prognosis. Methods and results In the present review article preoperative workup, surgical technique, postoperative morbidity and mortality rates, oncological outcome and quality of life after CRS and HIPEC are reported regarding the different tumor entities. Conclusion Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC provide a promising combined treatment strategy for selected patients with peritoneal carcinomatosis that can improve patient survival and quality of life. The extent of intraperitoneal tumor dissemination and the completeness of cytoreduction are the leading predictors of postoperative patient outcome. Thus, consistent preoperative diagnostics and patient selection are crucial to obtain a complete macroscopic cytoreduction (CCR-0/1.

  10. Laparoscopic intraperitoneal mesh fixation with fibrin sealant (Tisseel((R))) vs. titanium tacks: a randomised controlled experimental study in pigs

    DEFF Research Database (Denmark)

    Eriksen, J.R.; Bech, J.I.; Linnemann, D.

    2008-01-01

    ) test). There was no significant difference in the formation of fibrosis or inflammation between the different meshes or fixation methods. All samples showed significant foreign-body reaction with giant cells. CONCLUSION: Our results suggest that the laparoscopic fixation of an intraperitoneal mesh...... chronic) pain after LVHR. Therefore, non-invasive and patient-friendly mesh fixation methods must be considered. The present study was designed to investigate the technical applicability, safety and effect of Tisseel((R)) for intraperitoneal mesh fixation. METHODS: Nine 40-kg Danish Landrace female pigs...... and the mesh-tissue samples were tested for strength of ingrowth (peel test), adhesion formation, mesh shrinkage and examined for histological alterations. RESULTS: No meshes were displaced from their initial position at autopsy, but we observed two cases of mesh folding that could have resulted in hernia...

  11. Long-term intravenous administration of carboxylated single-walled carbon nanotubes induces persistent accumulation in the lungs and pulmonary fibrosis via the nuclear factor-kappa B pathway

    Directory of Open Access Journals (Sweden)

    Qin Y

    2016-12-01

    Full Text Available Yue Qin,1,* Suning Li,2,* Gan Zhao,2,* Xuanhao Fu,1 Xueping Xie,1 Yiyi Huang,1 Xiaojing Cheng,3 Jinbin Wei,1 Huagang Liu,1 Zefeng Lai1 1Pharmaceutical College, Guangxi Medical University, 2Department of Pharmacy, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, 3Life Sciences Institute, Guangxi Medical University, Nanning, Guangxi, People’s Republic of China *These authors contributed equally to this work Abstract: Numerous studies have demonstrated promising application of single-walled carbon nanotubes (SWNTs in drug delivery, diagnosis, and targeted therapy. However, the adverse health effects resulting from intravenous injection of SWNTs are not completely understood. Studies have shown that levels of “pristine” or carboxylated carbon nanotubes are very high in mouse lungs after intravenous injection. We hypothesized that long-term and repeated intravenous administration of carboxylated SWNTs (c-SWNTs can result in persistent accumulation and induce histopathologic changes in rat lungs. Here, c-SWNTs were administered repeatedly to rats via tail-vein injection for 90 days. Long-term intravenous injection of c-SWNTs caused sustained embolization in lung capillaries and granuloma formation. It also induced a persistent inflammatory response that was regulated by the nuclear factor-kappa B signaling pathway, and which resulted in pulmonary fibrogenesis. c-SWNTs trapped within lung capillaries traversed capillary walls and injured alveolar epithelial cells, thereby stimulating production of pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta and pro-fibrotic growth factors (transforming growth factor-beta 1. Protein levels of type-I and type-III collagens, matrix metalloproteinase-2, and the tissue inhibitor of metalloproteinase-2 were upregulated after intravenous exposure to c-SWNTs as determined by immunohistochemical assays and Western blotting, which suggested collagen deposition

  12. The Impact of 0.9% NaCl on Mesothelial Cells After Intraperitoneal Lavage During Surgical Procedures.

    Science.gov (United States)

    Cwaliński, Jarosław; Bręborowicz, Andrzej; Połubińska, Alicja

    2016-01-01

    Normal saline gained wide popularity in abdominal surgery as a basic compound used in intraoperative drainage of the peritoneal cavity. However, recent studies have revealed that saline solution is not quite biocompatible with the intraperitoneal enviroment and may promote peritoneal adhesions. The aim of the study was to evaluate the function and viability of human mesothelial cells cultured in vitro in 0.9% NaCl solution from intraperitoneal lavage carried out during laparoscopic cholecytectomies. The study included 40 consecutive patients suffering from gallstones who underwent laparoscopic cholecystectomy. Fluid was collected after intraperitoneal lavage during the surgical procedures. The samples obtained were used as a medium for in vitro incubation of primary human mesothelial cells. After 24 h the synthesis of interleukin 6 (IL-6), plasminogen activator inhibitor (PAI) and tissue plasminogen activator (tPA), as well as the index of cell proliferation were assessed in all the experimental groups. All the mesothelium cell cultures treated with fluid samples obtained ex vivo were characterized by elevated levels of IL-6. The highest concentrations of PAI-1 were found in groups of cells exposed to fluid with bile; similarly, tPA synthesis was extremely elevated in groups treaded with fluid containing bile and small amounts of hemolyzed blood. In contrast, cell proliferation was exceedingly high in 2 groups of cells placed in a standard culture medium and in 0.9% NaCl solution. Normal saline introduced into the abdominal cavity modifies the biological and physicochemical conditions of the intraperitoneal environment. The impact of 0.9% NaCl on mesothelial cells is manifested in destabilized tissue regeneration, which supposedly initiates adhesion formation.

  13. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis.

    Science.gov (United States)

    Esquis, Philippe; Consolo, David; Magnin, Guy; Pointaire, Philippe; Moretto, Philippe; Ynsa, Maria Dolores; Beltramo, Jean-Luc; Drogoul, Carole; Simonet, Michel; Benoit, Laurent; Rat, Patrick; Chauffert, Bruno

    2006-07-01

    To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs. The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical

  14. Diffusion of intraperitoneal (IP chemotherapy in women with advanced ovarian cancer in community settings 2003-2008: the effect of the NCI clinical recommendation

    Directory of Open Access Journals (Sweden)

    Erin J A Bowles

    2014-03-01

    Full Text Available Purpose: A 2006 National Cancer Institute (NCI clinical announcement recommended the use of combined intravenous (IV and intraperitoneal (IP chemotherapy over IV chemotherapy alone for women with International Federation of Gynecology and Obstetrics (FIGO stage 3 optimally debulked ovarian cancer due to significant survival benefit demonstrated in multiple randomized clinical trials. We examined uptake of IP chemotherapy in community practice before and after this recommendation. Methods: We identified 288 women with FIGO stage 2 or greater incident ovarian cancer diagnosed from 2003 to 2008 at three integrated delivery systems in the US. Administrative health plan data were used to determine patient characteristics and receipt of IV and IP chemotherapy within 12 months of diagnosis. We compared characteristics of women receiving IV chemotherapy alone versus IP chemotherapy (with or without IV chemotherapy and assessed temporal trends in IP chemotherapy use. Results: Overall 12.5% (n=36 of women received IP chemotherapy during the study period. IP chemotherapy use was nonexistent between 2003 and 2005. Use of IP chemotherapy occurred among 26.9% of women diagnosed in 2006 and plateaued at 20.4% of women diagnosed in 2008. IP recipients were younger (mean age 55.9 vs 63.5 years, p= Conclusions: Use of IP chemotherapy for newly diagnosed advanced stage ovarian cancer patients was uncommon in this community setting. Future research should identify potential patient, physician, and system barriers and facilitators to using IP chemotherapy in this setting.

  15. Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

    Science.gov (United States)

    Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

    2017-08-01

    To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Efficacy of port-site and intraperitoneal application of bupivacaine in reducing early post-laparoscopic cholecystectomy pain

    International Nuclear Information System (INIS)

    Ahmad, J.; Khan, Z.A.; Khan, A.

    2015-01-01

    The aim of this study was to assess the analgesic efficacy of Bupivacaine application at port-site and intraperitoneal infiltration in patients with laparoscopic cholecystectomy. Study Design: Randomized Controlled Clinical Trial. Place and Duration: The study was conducted at Rehman Medical Institute (RMI) Peshawar, Pakistan from June 2009 to June 2012. Materials and Methods: Patients who underwent elective laparoscopic cholecystectomy during the study period were included in the study. Eighty patients were randomized into two groups, study group and control group. The study group received 40 ml of 0.25% bupivacaine intraoperatively as intraperitoneal infiltration and local infiltration at the port sites. Pain assessment was done using visual analogue pain score (VAS) of 0-10 at fixed intervals during the first 24 hours post surgery. Results: The mean VAS score in the study group was less as compared to the control group throughout the 24 hours assessment period, however this difference was statistically significant (p<0.001) only during the first three assessments at 1 hour, 4 hours and 8 hours post surgery. The analgesia requirement was also significantly (p<0.001) decreased in the study group. Conclusion: Port site and intraperitoneal application of local anesthetic bupivacaine significantly reduced pain during the first 8 hours post surgery and total analgesia requirement was also significantly reduced. It is a simple and easily applicable technique which increases patient comfort and can be safely used to decrease post operative pain in patients undergoing laparoscopic cholecystectomy. (author)

  17. A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

    International Nuclear Information System (INIS)

    Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

    2005-01-01

    Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

  18. Intraperitoneal fipronil effects on liver histopathological, biochemistry and morphology in Caspian kutum, Rutilus frisii kutum (Kamenskii, 1901

    Directory of Open Access Journals (Sweden)

    R. Alijani Ardeshir

    2017-12-01

    Full Text Available Fipronil is a relatively new insecticide in agriculture with health and environmental effects. This is the first report studying effect of fipronil on fish administered via intraperitoneal route. Intraperitoneal LD50  of fipronil in 16.3 g Caspian kutum, Rutilus frisii kutum, fingerlings was determined using a total of 133 fish in 19 tanks (7 fish/tank including one control and 6 treatment groups (300, 450, 550, 650, 750, 850 mg/kg. Fish were injected intraperitoneally and monitored at 96 h. The LD50 of fipronil was 632 mg/kg in Caspian kutum. Sub-lethal test doses of 10, 20, and 30% of the LD50 at 96 h were used to assess the effect of fipronil on the fish’s liver.  The blood plasma of 90 fish were used (18 at each test dose and in controls on days 7 and 14 for biochemistry. The hepatosomatic index (HSI of the livers were obtained and histopathology done on the same days. Pyknosis, sinusoid dilation and vacuolization were common histological changes, and these changes became more severe in a time and dose dependent manner. This dependence was also observed for HSI and the liver biochemical test (alanine and aspartate transaminase. Liver histological alterations showed that fipronil can be a potential factor in liver carcinoma.

  19. Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial

    International Nuclear Information System (INIS)

    Gandhi, Mihir; Choo, Su Pin; Thng, Choon Hua; Tan, Say Beng; Low, Albert Su Chong; Cheow, Peng Chung; Goh, Anthony Soon Whatt; Tay, Kiang Hiong; Lo, Richard Hoau Gong; Goh, Brian Kim Poh; Wong, Jen San; Ng, David Chee Eng; Soo, Khee Chee; Liew, Wei Ming; Chow, Pierce K. H.

    2016-01-01

    Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. Definitive data comparing these two therapies will help to determine clinical practice in the large group of

  20. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

  1. Is extended antibiotic prophylaxis necessary after penetrating trauma to the thoracolumbar spine with concomitant intraperitoneal injuries?

    Science.gov (United States)

    Pasupuleti, Latha V; Sifri, Ziad C; Mohr, Alicia M

    2014-02-01

    Prolonged courses of broad-spectrum antibiotics are often cited as standard care for the prevention of infectious complications in thoracolumbar or sacral (TLS) fractures following penetrating abdominal trauma. Perforation of a hollow viscus in addition to a TLS fracture is believed to be associated with a high incidence of spine infection. Because over use of antibiotics is associated with an increasing prevalence of multi-drug-resistant organisms, this study seeks to define the actual risk of infection of the spine and need for antibiotics in patients with TLS fractures and intraperitoneal injuries following penetrating trauma. A retrospective review of 67 patients with penetrating abdominal trauma and concomitant TLS fracture was performed. Demographics, level of TLS fracture, associated spinal cord injury (SCI), need for operative intervention, presence of concomitant hollow viscus injury, and type and duration of antibiotic coverage were collected. In addition, associated infectious complications were reviewed. Spine infections were defined as spinal or paraspinal abscess, osteomyelitis of the spine, or meningitis. Intraabdominal infections were defined with imaging studies or positive peritoneal cultures. Sixty-seven patients (mean age of 27 ± 9 years) had an exploratory laparotomy and one or more TLS fractures. Four patients died within 24 h and were excluded from further study. Thirty-eight patients (60%) had one or more hollow viscus injuries, 13 (21%) had solid organ injuries alone and 12 (19%) had a non-therapeutic laparotomy. All patients received perioperative antibiotics; 92% received 48 h or less of antibiotic prophylaxis and 62% received only 24 h of antibiotics. In one patient with an isolated solid organ injury there was a spine infection (1%). In this study, 92% of patients received antibiotics for 48 h or less with no increased incidence of spine infections. Bacterial colonization of the vertebrae was not higher in patients with penetrating

  2. Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus).

    Science.gov (United States)

    Zatroch, Katie K; Knight, Cameron G; Reimer, Julie N; Pang, Daniel S J

    2017-02-21

    The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia. In a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability in CHB was assessed by calculating the coefficient of variation (CV). The fastest euthanasia method (CHB) was HH (283.7 ± 38.0 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 17.0% (7/41) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (4/11, LL) to 46% (5/11, HH). These data illustrate refinement of the IP pentobarbital euthanasia technique. Both dose and volume contribute to speed of death, with a dose of 800 mg/kg (HH) being the most effective method. An increase in volume alone does not significantly reduce variability. The

  3. Effects of intraperitoneal nitroglycerin on the strength and healing attitude of anastomosis of rat intestines with ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Ahmet Oktay Cihan

    2011-01-01

    Full Text Available Background: Ischemic conditions in the intestine result in deterioration of anastomosis healing process. In this study, our aim was to evaluate the possible effects of intraperitoneal nitroglycerin on the intestinal anastomosis healing and anastomosis burst pressures in rats with ischemia and reperfusion injury (I/R. Materials and Methods: Fifty four Wistar albino rats were divided into six groups. In the first two groups, the rats underwent I/R. In the Group 1, the rats had normal saline (S and in Group 2, the rats had nitroglycerin (N injection. In the 3 rd and 4 th groups, an intestinal anastomosis was made at the 10 cm proximally to the ileocecal valve. In Group 3, S and in Group 4, N were injected. In Group 5, the rats received I/R, intestinal anastomosis and intraperitoneal S injection. I/R, intestinal anastomosis and intraperitoneal N injection were made in Group 6 rats. All nitroglycerin (50 ΅g/kg injections were made at postoperative days of 0, 1, 2, 3, 4, 5 consecutively. On the sixth day, all rats were killed. In all rats with anastomosis, anastomotic burst pressure (ABP was measured. Histopathological specimens were collected from all rats and evaluated under light microscopy. Results: Serious tissue damage was only detected in the Group 1 histopathologically (8 rats had grade 4 damage. In Group 2, there was a decrease in tissue damage according to histopathologic examination (5 rats had grade 1 damage. The effect onto the healing was similar in S and N groups. Nitroglycerin was noted to have a positive effect on collagen production. Nitroglycerin increased the ABP levels in rats both with and without I/R (the means are 17.93, 21.10, 14.67, and 17.63 in Groups 3, 4, 5, and 6, respectively. Conclusion: I/R may weaken the strength of intestinal anastomosis. Intraperitoneal application of nitroglycerin may prevent the histopathologic changes within a limited degree. Intraperitoneal nitroglycerin has also positive effects on the healing

  4. In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.

    Science.gov (United States)

    Marshell, R; Kearney-Ramos, T; Brents, L K; Hyatt, W S; Tai, S; Prather, P L; Fantegrossi, W E

    2014-09-01

    Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick latency in response to radiant heat, horizontal bar catalepsy, and suppression of locomotor activity were assessed in each animal. In separate studies, mice were trained to discriminate Δ(9)-THC (IP) from saline, and tests were performed with inhaled or injected doses of the SCBs. Both SCBs elicited Δ(9)-THC-like effects across both routes of administration, and effects following inhalation were attenuated by pretreatment with the CB1 antagonist/inverse agonist rimonabant. No cataleptic effects were observed following inhalation, but all compounds induced catalepsy following injection. Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. The effects of intraperitoneal clenbuterol injection on protein degradation and myostatin expression differ between the sartorius and pectoral muscles of neonatal chicks.

    Science.gov (United States)

    Ijiri, Daichi; Ishitani, Kanae; Shimamoto, Saki; Ishimaru, Yoshitaka; Ohtsuka, Akira

    2014-09-15

    The purpose of this study was to investigate the effects of injection of the β2-adrenergic receptor agonist clenbuterol on the skeletal muscles of neonatal chicks (Gallus gallus domesticus). One-day-old chicks were randomly divided into four groups and given a single intraperitoneal injection of clenbuterol (0.01, 0.1, or 1mg/kg) or phosphate-buffered saline. Twenty-four hours after the injection, the sartorius muscles (which consist of both slow- and fast-twitch fibers) of chicks that received 0.01 or 0.1mg/kg clenbuterol were significantly heavier than those of controls, while there were no between-group differences in the weight of the pectoral muscles, which consist of only fast-twitch fibers. Muscle free N(t)-methylhistidine, regarded as an index of myofibrillar proteolysis, was decreased in the sartorius muscle of the clenbuterol-injected chicks, while it was not affected in the pectoral muscles. In the sartorius muscle of the clenbuterol-injected chicks, myostatin and atrogin-1/MAFbx mRNA expressions were decreased, while insulin-like growth factor-I was unaffected. These observations suggested, in 1-day-old chicks, clenbuterol might increase mass of the sartorius muscle by decreasing myostatin gene expression and protein degradation. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Regional perfusion and oxygenation of tumors upon methylxanthine derivative administration

    International Nuclear Information System (INIS)

    Kelleher, Debra K.; Thews, Oliver; Vaupel, Peter

    1998-01-01

    Purpose: The use of methylxanthine derivatives has been postulated as a means of increasing tumor perfusion and thus ameliorating tumor hypoxia. The aim of this study was to quantify and compare the effects of three methylxanthine derivatives: pentoxifylline (PX), torbafylline (TB), and HWA 138 (HW) on tumor perfusion and oxygenation. Methods and Materials: Anesthetized Sprague Dawley rats with DS-sarcomas implanted subcutaneously onto the hind foot dorsum were used in this study. Mean arterial blood pressure (MABP) was measured throughout experiments. Regional red blood cell (RBC) flux was monitored using a multichannel laser Doppler device and tumor oxygenation on a more global level was assessed polarographically using an O 2 -sensitive catheter electrode. The methylxanthine derivatives were administered as a single dose intraperitoneally (for PX 50 mg/kg; for TB and HW 75 mg/kg). Results: Following drug administration, initial decreases in MABP down to 75% of baseline values were observed for all three substances. PX, HW, and TB caused initial transient reductions in mean RBC flux followed by gradual increases to values of 137 ± 27 %, 139 ± 14 %, and 122 ± 14 % respectively at t = 60 min. Following a small initial decrease upon drug administration, O 2 partial pressure (pO 2 ) rose to 160 ± 31 %, 153 ± 34 %, and 121 ± 11 % for PX, HW, and TB, respectively at t = 60 min. At the end of the observation period (t = 90 min), increases in RBC flux and pO 2 were still evident. When individual tumors were considered, a variety of patterns (including opposing effects) for changes in RBC flux were seen, not necessarily reflected in the mean values. Thus, while the methylxanthine derivatives caused an increased average tumor perfusion, there is evidence suggesting that a redistribution of tumor blood flow occurs which may amplify preexisting heterogeneity. Conclusions: Substantial improvements in tumor oxygenation and perfusion were observed after administration of

  7. On the effects of the Fusarium toxin deoxynivalenol (DON) administered per os or intraperitoneal infusion to sows during days 63 to 70 of gestation.

    Science.gov (United States)

    Goyarts, Tanja; Brüssow, Klaus-Peter; Valenta, Hana; Tiemann, Ute; Jäger, Kathrin; Dänicke, Sven

    2010-05-01

    Six pregnant sows of 180.6 ± 5.6 kg were fed either a Fusarium-contaminated (4.42 mg DON and 48.3 µg ZON per kg, DON per os, n = 3) or a control diet (0.15 mg DON and 5 µg ZON/kg) in the period of days 63 and 70 of gestation. On day 63 of gestation, sows fed the control diet were implanted with an intraperitoneal osmotic minipump (delivery rate of 10 µL/h, for 7 days) containing 50 mg pure (98%) DON in 2 ml 50% DMSO (DON ip, n = 3). Frequent plasma samples were taken to estimate the kinetics after oral and ip DON exposure. The intended continuous delivery of DON by the intraperitoneal minipump could not be shown, as there was a plasma peak (Cmax) of 4.2-6.4 ng DON/mL either immediately (sow IP-2+3) or 2.5 h (sow IP-1) after implantation of the pump followed by a one-exponential decline with a mean half-time (t1/2) of 1.75-4.0 h and only negligible DON plasma concentrations after 12 h. Therefore, the DON ip exposure has to be regarded as one single dose 1 week before termination of experiment. The DON per os sows showed a mean basis level (after achieving a steady state) of DON plasma concentration of about 6-8 ng/mL, as also indicated by the plasma DON concentration at the termination of the experiment. On day 70, caesarean section was carried out, the fetuses were killed immediately after birth, and samples of plasma, urine, and bile were taken to analyze the concentration of DON and its metabolite de-epoxy-DON. At necropsy there were no macroscopic lesions observed in any organ of either sows or piglets. Histopathological evaluation of sows liver and spleen revealed no alterations. The proliferation rate of peripheral blood mononuclear cells (PBMC) with or without stimulation was not affected by the kind of DON treatment. The exposure of pregnant sows at mid-gestation (days 63-70, period of organogenesis) to a Fusarium toxin-contaminated diet (4.42 mg DON and 0.048 mg ZON per kg) or pure DON via intraperitoneal osmotic minipump

  8. Single administration of Selective Internal Radiation Therapy versus continuous treatment with sorafeNIB in locally advanced hepatocellular carcinoma (SIRveNIB): study protocol for a phase iii randomized controlled trial.

    Science.gov (United States)

    Gandhi, Mihir; Choo, Su Pin; Thng, Choon Hua; Tan, Say Beng; Low, Albert Su Chong; Cheow, Peng Chung; Goh, Anthony Soon Whatt; Tay, Kiang Hiong; Lo, Richard Hoau Gong; Goh, Brian Kim Poh; Wong, Jen San; Ng, David Chee Eng; Soo, Khee Chee; Liew, Wei Ming; Chow, Pierce K H

    2016-11-07

    Approximately 20 % of hepatocellular carcinoma (HCC) patients diagnosed in the early stages may benefit from potentially curative ablative therapies such as surgical resection, transplantation or radiofrequency ablation. For patients not eligible for such options, prognosis is poor. Sorafenib and Selective Internal Radiation Therapy (SIRT) are clinically proven treatment options in patients with unresectable HCC, and this study aims to assess overall survival following either SIRT or Sorafenib therapy for locally advanced HCC patients. This investigator-initiated, multi-centre, open-label, randomized, controlled trial will enrol 360 patients with locally advanced HCC, as defined by Barcelona Clinic Liver Cancer stage B or stage C, without distant metastases, and which is not amenable to immediate curative treatment. Exclusion criteria include previous systemic therapy, metastatic disease, complete occlusion of the main portal vein, or a Child-Pugh score of >7. Eligible patients will be randomised 1:1 and stratified by centre and presence or absence of portal vein thrombosis to receive either a single administration of SIRT using yttrium-90 resin microspheres (SIR-Spheres®, Sirtex Medical Limited, Sydney, Australia) targeted at HCC in the liver by the trans-arterial route or continuous oral Sorafenib (Nexavar®, Bayer Pharma AG, Berlin, Germany) at a dose of 400 mg twice daily until disease progression, no further response, complete regression or unacceptable toxicity. Patients for both the Sorafenib and SIRT arms will be followed-up every 4 weeks for the first 3 months and 12 weekly thereafter. Overall survival is the primary endpoint, assessed for the intention-to-treat population. Secondary endpoints are tumour response rate, time-to-tumour progression, progression free survival, quality of life and down-staging to receive potentially curative therapy. Definitive data comparing these two therapies will help to determine clinical practice in the large group

  9. Intrathecal Administration of Tempol Reduces Chronic Constriction Injury-Induced Neuropathic Pain in Rats by Increasing SOD Activity and Inhibiting NGF Expression.

    Science.gov (United States)

    Zhao, Baisong; Pan, Yongying; Wang, Zixin; Tan, Yonghong; Song, Xingrong

    2016-08-01

    We investigate the antinociceptive effect of intrathecal and intraperitoneal tempol administration in a rat model of chronic constriction injury (CCI)-induced neuropathic pain and explore the underlying antinociceptive mechanisms of tempol. Rats were randomly assigned to four groups (n = 8 per group): sham group, CCI group, Tem1 group (intrathecal injection of tempol), and Tem2 group (intraperitoneal injection of tempol). Neuropathic pain was induced by CCI of the sciatic nerve. Tempol was intrathecally or intraperitoneally administered daily for 7 days beginning on postoperative day one. The mechanical withdrawal threshold and thermal withdrawal latency were tested on preoperative day 3 and postoperative days 1, 3, 5, 7, 10, 14, and 21. Structural changes were examined by hematoxylin and eosin staining, toluidine blue staining, and electron microscopy. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were determined using the thiobarbituric acid and nitroblue tetrazolium methods, respectively. Nerve growth factor (NGF) expression levels were determined by immunohistochemistry and Western blot. Intrathecal, but not intraperitoneal, injection of tempol produced a persistent antinociceptive effect. Intraperitoneal injection of tempol did not result in high enough concentration of tempol in the cerebrospinal fluid. Intrathecal, but not intraperitoneal, injection of tempol inhibited CCI-induced structural damage in the spinal cord reduced MDA levels, and increased SOD activities in the spinal cord. Furthermore, intrathecal, but not intraperitoneal, injection of tempol further downregulated the expression of NGF in the spinal cord following CCI, and this effect was blocked by p38MAPK inhibitor. Intrathecal injection of tempol produces antinociceptive effects and reduces CCI-induced structural damage in the spinal cord by increasing SOD activities and downregulating the expression of NGF via the p38MAPK pathway. Intraperitoneal administration of tempol does

  10. Oral and intraperitoneal LD/sub 50/ of thymoquinone, an active principle of nigella sativa, in mice and rats

    International Nuclear Information System (INIS)

    Ali, A.A.; Aziz, A.

    2008-01-01

    Thymoquinone is the major active principle of Nigella sativa (N. sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone. The present study was carried out to determine LD/sub 50/ of thymoquinone both in mice and rats, orally as well as intraperitoneall, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined. The LD/sub 50/ in mice after intraperitoneal injection was determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD/sub 50/ in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6-69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8- 1118.8, 95% confidence intervals). The LD/sub 50/ values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals. (author)

  11. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

    Energy Technology Data Exchange (ETDEWEB)

    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

  12. Acute intraperitoneal injection of caffeine improves endurance exercise performance in association with increasing brain dopamine release during exercise.

    Science.gov (United States)

    Zheng, Xinyan; Takatsu, Satomi; Wang, Hongli; Hasegawa, Hiroshi

    2014-07-01

    The purpose of this study was to examine changes of thermoregulation, neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH), which is the thermoregulatory center, and endurance exercise performance after the intraperitoneal injection of caffeine in rats. Core body temperature (Tcore), oxygen consumption (VO₂) and tail skin temperature (Ttail) were measured. A microdialysis probe was inserted in the PO/AH, and samples for the measurements of extracellular dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels were collected. During the rest experiment, 1 h after baseline collections in the chamber (23 °C), the rats were intraperitoneally injected with saline, or 3 mg kg(-1) or 10 mg kg(-1) caffeine. The duration of the test was 4 h. During the exercise experiment, baseline collections on the treadmill were obtained for 1 h. One hour before the start of exercise, rats were intraperitoneally injected with either 10 mg kg(-1) caffeine (CAF) or saline (SAL). Animals ran until fatigue at a speed of 18 m min(-1), at a 5% grade, on the treadmill in a normal environment (23 °C). At rest, 3 mg kg(-1) caffeine did not influence Tcore, Ttail, VO₂, extracellular DA, NA and 5-HT. 10 mg kg(-1) caffeine caused significant increases in Tcore, VO₂, Ttail and extracellular DA in the PO/AH. In addition, 10 mg kg(-1) caffeine increased the run time to fatigue (SAL: 104.4 ± 30.9 min, CAF: 134.0 ± 31.1 min, pcaffeine and exercise increased Tcore, VO₂, Ttail and extracellular DA in the PO/AH. NA increased during exercise, while neither caffeine nor exercise changed 5-HT. These results indicate that caffeine has ergogenic and hyperthermic effects, and these effects may be related to changes of DA release in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Repeated intraperitoneal injections of interleukin 1 beta induce glucose intolerance in normal rats

    DEFF Research Database (Denmark)

    Wogensen, L; Reimers, J; Mandrup-Poulsen, T

    1991-01-01

    Previous in vitro findings suggest the involvement of interleukin 1 (IL-1) in the pathogenesis of insulin-dependent diabetes mellitus. The aims of the present study were to investigate the effects of single or repeated ip injections of recombinant IL-1 beta on blood glucose and glucose tolerance ...

  14. Diagnostic value of contrast-enhanced CT combined with 18-FDG PET in patients selected for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC).

    Science.gov (United States)

    Sommariva, Antonio; Evangelista, Laura; Pintacuda, Giovanna; Cervino, Anna Rita; Ramondo, Gaetano; Rossi, Carlo Riccardo

    2018-05-01

    Aim of the study is to assess the reliability and correlation with surgical peritoneal cancer index (PCI) of combined PET/CT and ceCT scans (PET/ceCT) performed in a session in patients with peritoneal carcinomatosis candidates for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We retrospectively analyzed data collected from 27 patients with different types of peritoneal carcinomatosis candidates to CS + HIPEC who underwent FDG PET/ceCT in a single session. Two nuclear medicine physicians and two radiologists independently and blindly evaluated PET/CT and ceCT imaging, respectively. In the case of discordance, the consensus was reached by a discussion between the specialists. Moreover, the combined images were evaluated by all the specialists in consensus. The PCIs obtained from surgical look, PET/CT, ceCT, and PET/ceCT were compared with each other. The coefficients of correlation (r) were calculated. The study was conducted after approval of local ethics committee. Surgical PCI was available in 21 patients. The coefficient of correlation between PCI of PET/CT and surgery was 0.528, while it resulted higher between PET/ceCT and surgery (r = 0.878), very similar to ceCT and surgery (r = 0.876). The r coefficient between surgical PCI and PET/CT was higher in patients with a non-mucinous cancer (n = 12) than the counterpart (0.601 vs. 0.303) and the addition of ceCT significantly increases the correlation (r = 0.863), which is anyway similar to ceCT alone (r = 0.856). PET/ceCT as single examination is more accurate than PET/CT but not than ceCT alone for the definition of PCI in a selected group of patients candidates to CS + HIPEC.

  15. The Effect of Chronic Administration of Buspirone on 6-Hydroxydopamine-Induced Catalepsy in Rats

    Directory of Open Access Journals (Sweden)

    Hamdolah Sharifi

    2012-06-01

    Full Text Available Purpose: Several evidences show that serotonergic neurons play a role in the regulation of movements executed by the basal ganglia. Recently we have reported that single dose of buspirone improved 6-hydroxydopamine (6-OHDA and haloperidol-induced catalepsy. This study is aimed to investigate effect of chronic intraperitoneal (i.p. administration of buspirone on 6-OHDA-induced catalepsy in male Wistar rats. Methods: Catalepsy was induced by unilateral infusion of 6-OHDA (8 μg/2 μl/rat into the central region of the SNc and was assayed by the bar-test method 5, 60, 120 and 180 min after drugs administration in 10th day. The effect of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days was assessed in 6-OHDA-lesioned rats. Results: The results showed that chronic injection of buspirone (0.5, 1 and 2 mg/kg, i.p. for 10 days decreased catalepsy when compared with the control group. The best anticataleptic effect was observed at the dose of 1 mg/kg. The catalepsy-improving effect of buspirone was reversed by 1-(2-methoxyphenyl- 4-[4-(2-phthalimido butyl]piperazine hydrobromide (NAN-190, 0.5 mg/kg, i.p.,as a 5-HT1A receptor antagonist. Conclusion: Our study indicates that chronic administration of buspirone improves catalepsy in a 6-OHDA-induced animal model of parkinson's disease (PD. We also suggest that buspirone may be used as an adjuvant therapy to increase effectiveness of antiparkinsonian drugs. In order to prove this hypothesis, further clinical studies should be done.

  16. Comparison of lymphatic uptake, metabolism, excretion, and biodistribution of free and liposome-entrapped [14C]cytosine beta-D-arabinofuranoside following intraperitoneal administration to rats

    International Nuclear Information System (INIS)

    Parker, R.J.; Priester, E.R.; Sieber, S.M.

    1982-01-01

    Free [ 14 C]cytosine beta-D-arabinofuranoside ([ 14 C]ara-C) was completely absorbed from the peritoneal cavity of thoracic duct-cannulated rats by 6 hr after ip dosing. 14 C levels in most tissues were higher at 4 hr than at 12 hr after dosing and were generally undetectable at 24 hr. By 6 hr after treatment only 2% of the dose was recovered in lymph, whereas 90% had been excreted in urine. Liposome entrapment of ara-C reduced the rates at which the drug was absorbed from the peritoneal cavity and excreted in urine while enhancing lymphatic uptake of the drug by more than 10-fold. Radioactivity in plasma and most tissues achieved higher concentrations and persisted for longer periods in rats given liposome-entrapped ara-C than in rats receiving the free drug. Most striking was the localization of 14 C-activity in renal and thoracic lymph nodes of rats give liposome-entrapped ara-C, with 300 to 1000-fold higher levels present at 4, 12, and 24 hr after dosing than in corresponding lymph nodes of rats receiving the free drug. The metabolic conversion of ara-C to uracil beta-D-arabinofuranoside (ara-U) was reduced by approximately 3-fold following liposome entrapment of the drug. The enhanced lymphatic uptake and the localization and persistence of ara-C in lymph nodes resulting from liposome entrapment of the drug may be of benefit in treating tumors that metastasize via lymphatic pathways

  17. Intraintestinal administration of ulinastatin protects against sepsis by relieving intestinal damage.

    Science.gov (United States)

    Yang, Bingchang; Gao, Min; Wang, Kangkai; Jiang, Yu; Peng, Yue; Zhang, Huali; Yang, Mingshi; Xiao, Xianzhong

    2017-05-01

    Intravenous administration of ulinastatin (UTI), a broad spectral protease inhibitor, has been used on an experimental basis with severe sepsis patients in Asia. However, the effects of intraintestinal administration of UTI on intestinal and multiple organ damage in sepsis have not been reported. In this study, we established a sepsis model in rats using cecal ligation and puncture and compared the effects of intraintestinal administration of UTI through an artificial fistula of duodenum and intraperitoneal administration of UTI on the pathophysiological changes of sepsis. It was found that intraintestinal administration of UTI (1) significantly improved the survival of septic rats, (2) significantly reduced the serum levels of tumor necrosis factor-α, interleukin-1β, interleukin-6 as well as intestinal injury biomarkers diamine oxidase, D-lactic acid, and fluorescein isothiocyanate-dextran 4, and (3) significantly reduced intestinal microscopic and ultrastructural damage of septic rats. In addition, the protective effects of intraintestinal administration of UTI were significantly better than those of intraperitoneal administration of UTI. Overall, the present study for the first time revealed that intraintestinal administration of protease inhibitor UTI could reduce systemic inflammatory responses and multiple organ dysfunction in rats with sepsis by inhibiting autodigestion of intestinal wall due to proteases and provided new research ideas and experimental evidences for treatment of sepsis by intraintestinal administration of UTI. Copyright © 2016. Published by Elsevier Inc.

  18. [Intraperitoneal irrigation for pseudomyxoma peritonei-a case of critical metabolic alkalosis precipitated by irrigation with 101 of sodium bicarbonate--].

    Science.gov (United States)

    Shirasaki, Reimi; Yamasaki, Saeko; Wakamatsu, Masaki; Mori, Yasuichiro; Hirano, Hiroko; Kaida, Takeshi; Machino, Asami

    2013-05-01

    Pseudomyxoma peritonei causes marked accumulation of jelly-like ascites in the peritoneal cavity. Removal of much mucinous ascites by irrigating the cavity appears to be an effective treatment. We describe a patient who underwent the irrigation with sodium bicarbonate solution and developed critical alkalemia. A 68-year-old woman with normal renal function was operated on for recurrent pseudomyxoma peritonei. Fol- lowing the excision of primary lesion, her intraperitoneal cavity was irrigated with 10 1 of 7% sodium bicarbonate in about 45 minutes. Thirty minutes after irrigation, blood gas analysis revealed severe metabolic alkalosis (pH 7.714, BE 25.6 mmol x l-1 ) with electrolyte disorder (Na 157.8 mmol x l-1 K 2.31mmol x l-1, Ca 0.73 mmol x l-1). Hypotension (130 beats x min -1) supervened 75 minutes later. Transferring to the ICU, she was given KC1 solution intravenously based on serial blood analysis while on mechanical ventilation. The next day acid-base disturbance returned spontaneously to normal (pH 7.45, BE 8.0mmol x l-1), leading to endotracheal extubation. Electrolyte imbalance was gradually resolved on 2nd POD and she was discharged from the ICU. Intraperitoneal irrigation with sodium bicarbonate requires special perioperative considerations for lifethreatening alkalemia, especially in a patient with renal impairment.

  19. Rare cause of acute surgical abdomen with free intraperitoneal air: Spontaneous perforated pyometra. A report of 2 cases.

    Science.gov (United States)

    Lim, Siew Fung; Lee, Song Liang; Chiow, Adrian Kah Heng; Foo, Chek Siang; Wong, Andrew Siang Yih; Tan, Su-Ming

    2012-01-01

    The acute abdomen accounts for up to 40% of all emergency surgical hospital admissions and a large proportion are secondary to gastrointestinal perforation. Studies have shown the superiority of the abdominal CT over upright chest radiographs in demonstrating free intraperitoneal air. Spontaneous perforated pyometra is a rare cause of the surgical acute abdomen with free intraperitoneal air. Only 38 cases have been reported worldwide. We report 2 cases of spontaneously perforated pyometra in our hospital's general surgery department. Both underwent exploratory laparotomy: one had a total hysterectomy and bilateral salpingo-oophorectomy, while the other had an evacuation of the uterine cavity, primary repair of uterine perforation and a peritoneal washout. A literature search was conducted and all reported cases reviewed in order to describe the clinical presentations and management of the condition. Of the 40 cases to date, including 2 of our cases, the most common presenting symptoms were abdominal pain (97.5%), fever (37.5%) and vomiting (25.0%). The main indication for exploratory laparotomy was pneumoperitoneum (97.5%). Pyometra is an unusual but serious condition in elderly women presenting with an acute abdomen. A high index of suspicion is needed to make the appropriate diagnosis.

  20. Establishment and characterization of intraperitoneal xenograft models by co-injection of human tumor cells and extracellular matrix gel

    Science.gov (United States)

    YAO, YUQIN; ZHOU, YONGJUN; SU, XIAOLAN; DAI, LEI; YU, LIN; DENG, HONGXIN; GOU, LANTU; YANG, JINLIANG

    2015-01-01

    Establishing a feasible intraperitoneal (i.p.) xenograft model in nude mice is a good strategy to evaluate the antitumor effect of drugs in vivo. However, the manipulation of human cancer cells in establishing a stable peritoneal carcinomatosis model in nude mice is problematic. In the present study, the ovarian and colorectal peritoneal tumor models were successfully established in nude mice by co-injection of human tumor cells and extracellular matrix gel. In ovarian tumor models, the mean number tumor nodes was significantly higher in the experimental group (intraperitoneal tumor cell co-injection with ECM gel) compared with the PBS control group on the 30th day (21.0±3.0 vs. 3.6±2.5; P<0.05). The same results were observed in the colorectal peritoneal tumor models on the 28th day. The colorectal peritoneal tumor model was further used to evaluate the chemotherapy effect of irinotecan (CPT-11). The mean weight of peritoneal tumor nodes in CPT-11 treatment group was significantly less than that of the control group (0.81±0.16 vs. 2.18±0.21 g; P<0.05). The results confirmed the value of these i.p. xenograft models in nude mice as efficient and feasible tools for preclinical evaluation. PMID:26788149

  1. Individual monitoring of immune responses in rainbow trout after cohabitation and intraperitoneal injection challenge with Yersinia ruckeri.

    Science.gov (United States)

    M Monte, Milena; Urquhart, Katy; Secombes, Christopher J; Collet, Bertrand

    2016-08-01

    Yersinia ruckeri, the causative agent of enteric red mouth disease (ERM), is a widely studied pathogen in disease models using rainbow trout. This infection model, mostly based on intraperitoneally injection or bath immersion challenges, has an impact on both components (innate and adaptive) of the fish immune system. Although there has been much attention in studying its host-pathogen interactions, there is still a lack of knowledge regarding the impact of a cohabitation challenge. To tackle this we used a newly established non-lethal sampling method (by withdrawing a small amount of blood) in rainbow trout which allowed the individual immune monitoring before (non-infected) and after infection with Yersinia ruckeri either by intraperitoneal (i.p.) injection or by cohabitation (cohab). A range of key immune genes were monitored during the infection by real-time PCR, and results were compared between the two infection routes. Results indicated that inflammatory (IL-1β1 and IL-8) cytokines and certain antimicrobial peptides (cathelicidins) revealed a different pattern of expression between the two infected groups (i.p. vs cohab), in comparison to adaptive immune cytokines (IL-22, IFN-γ and IL-4/13A) and β-defensins. This suggests a different involvement of distinct immune markers according to the infection model, and the importance of using a cohabitation challenge as a more natural disease model that likely simulates what would occur in the environment. Copyright © 2016. Published by Elsevier Ltd.

  2. Radiographic, Hematologic and Biochemical Alterations in Peritoneal Fluid after Intraperitoneal Injection of Barium Sulfate and Gastrografin in Rabbit

    Directory of Open Access Journals (Sweden)

    Sardar Jafari-Shoorijeh

    2012-07-01

    Full Text Available Background: Evaluation of contrast-induced changes in the peritoneal area may reveal the effects of their permeation followed by gastrointestinal perforation. This study aims to compare the radiographic changes and hematological and biochemical parameters of peritoneal fluid and blood after intraperitoneal injection of barium sulfate and gastrografin to the rabbit.Materials and Methods: In this clinical trial, 15 healthy male rabbits were randomly divided into 3 groups. Respectively to each group 10 ml/kg barium sulfate 30%, 10 ml/kg gastrografin, and 10 ml/kg saline was intraperitoneally injected. Before injection and 24 hours after injection, blood samples and peritoneal fluid were collected to measure glucose, total protein, WBC count and pH. Lateral and dorsal-ventral radiography was provided 20 min and 24 hours after contrast injection.Results: After injection of barium sulfate, serum glucose decreased, cell count and blood neutrophil percentage increased, glucose and the percentage of peritoneal fluid lymphocytes decreased (p<0.05. The amount of total protein, cell count and peritoneal fluid neutrophil percentage increased (p<0.05. Gastrografin injection only increased peritoneal fluid total protein (p=0.04. Other blood factors and peritoneal fluid showed no significant changes. In radiographies, barium sulfate remained in abdominal area and rapid absorption of gastrografin was observed.Conclusion: The use of gastrografin has fewer side effects than barium sulfate and is recommended in patients suspected with gastrointestinal perforation.

  3. Biodistribution of a High Dose of Diamond, Graphite, and Graphene Oxide Nanoparticles After Multiple Intraperitoneal Injections in Rats.

    Science.gov (United States)

    Kurantowicz, Natalia; Strojny, Barbara; Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Grodzik, Marta; Wierzbicki, Mateusz; Lipińska, Ludwika; Mitura, Katarzyna; Chwalibog, André

    2015-12-01

    Carbon nanoparticles have recently drawn intense attention in biomedical applications. Hence, there is a need for further in vivo investigations of their biocompatibility and biodistribution via various exposure routes. We hypothesized that intraperitoneally injected diamond, graphite, and graphene oxide nanoparticles may have different biodistribution and exert different effects on the intact organism. Forty Wistar rats were divided into four groups: the control and treated with nanoparticles by intraperitoneal injection (4 mg of nanoparticles/kg body weight) eight times during the 4-week period. Blood was collected for evaluation of blood morphology and biochemistry parameters. Photographs of the general appearance of each rat's interior were taken immediately after sacrifice. The organs were excised and their macroscopic structure was visualized using a stereomicroscope. The nanoparticles were retained in the body, mostly as agglomerates. The largest agglomerates (up to 10 mm in diameter) were seen in the proximity of the injection place in the stomach serous membrane, between the connective tissues of the abdominal skin, muscles, and peritoneum. Numerous smaller, spherical-shaped aggregates (diameter around 2 mm) were lodged among the mesentery. Moreover, in the connective and lipid tissue in the proximity of the liver and spleen serosa, small aggregates of graphite and graphene oxide nanoparticles were observed. However, all tested nanoparticles did not affect health and growth of rats. The nanoparticles had no toxic effects on blood parameters and growth of rats, suggesting their potential applicability as remedies or in drug delivery systems.

  4. Biodistribution of a High Dose of Diamond, Graphite, and Graphene Oxide Nanoparticles After Multiple Intraperitoneal Injections in Rats

    Science.gov (United States)

    Kurantowicz, Natalia; Strojny, Barbara; Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Grodzik, Marta; Wierzbicki, Mateusz; Lipińska, Ludwika; Mitura, Katarzyna; Chwalibog, André

    2015-10-01

    Carbon nanoparticles have recently drawn intense attention in biomedical applications. Hence, there is a need for further in vivo investigations of their biocompatibility and biodistribution via various exposure routes. We hypothesized that intraperitoneally injected diamond, graphite, and graphene oxide nanoparticles may have different biodistribution and exert different effects on the intact organism. Forty Wistar rats were divided into four groups: the control and treated with nanoparticles by intraperitoneal injection (4 mg of nanoparticles/kg body weight) eight times during the 4-week period. Blood was collected for evaluation of blood morphology and biochemistry parameters. Photographs of the general appearance of each rat's interior were taken immediately after sacrifice. The organs were excised and their macroscopic structure was visualized using a stereomicroscope. The nanoparticles were retained in the body, mostly as agglomerates. The largest agglomerates (up to 10 mm in diameter) were seen in the proximity of the injection place in the stomach serous membrane, between the connective tissues of the abdominal skin, muscles, and peritoneum. Numerous smaller, spherical-shaped aggregates (diameter around 2 mm) were lodged among the mesentery. Moreover, in the connective and lipid tissue in the proximity of the liver and spleen serosa, small aggregates of graphite and graphene oxide nanoparticles were observed. However, all tested nanoparticles did not affect health and growth of rats. The nanoparticles had no toxic effects on blood parameters and growth of rats, suggesting their potential applicability as remedies or in drug delivery systems.

  5. Assessment of Ovarian Cancer Tumors Treated with Intraperitoneal Cisplatin Therapy by Nanoscopic X-ray Fluorescence Imaging

    Science.gov (United States)

    Laforce, Brecht; Carlier, Charlotte; Vekemans, Bart; Villanova, Julie; Tucoulou, Rémi; Ceelen, Wim; Vincze, Laszlo

    2016-07-01

    Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions.

  6. Administrative Appeals and ADR in Danish Administrative Law

    DEFF Research Database (Denmark)

    Conradsen, Inger Marie; Gøtze, Michael

    2014-01-01

    Administrative Appeals, review, administrative tribunals, ombudsman, alternative dispute resolution......Administrative Appeals, review, administrative tribunals, ombudsman, alternative dispute resolution...

  7. Effect of single and three months treatment with Ukrain on aminotransferases (ALT and AST) and on the serum protein level in rodents.

    Science.gov (United States)

    Jagiełło-Wójtowicz, E; Kleinrok, Z; Surmaczyńska, B; Baran, E; Feldo, M; Nowicky, J W

    1992-01-01

    The influence of Ukrain on the activity of aminotransferases (ALT and AST) and on the serum total protein content was estimated in mice and rats of both sexes receiving single or repeated doses of the drug. It was found that one hour after intraperitoneal (i.p.) administration of Ukrain no characteristic changes were recorded in the activity of the investigated enzymes, or in the serum protein content of animals of either sex. Similar effects were observed after three months treatment with Ukrain in rats of either sex. Only in mice receiving Ukrain for three months was a rise in ALT and AST activity found. No particular changes were observed in the total serum protein level, except for a small decreases in the sera of male mice.

  8. Senior Administrators Should Have Administrative Contracts.

    Science.gov (United States)

    Posner, Gary J.

    1987-01-01

    Recognizing that termination is viewed by the employee as the equivalent to capital punishment of a career, an administrative contract can reduce the emotional and financial entanglements that often result. Administrative contracts are described. (MLW)

  9. Indium-111 autologous tagged leukocytes in the diagnosis of intraperitoneal sepsis

    Energy Technology Data Exchange (ETDEWEB)

    Ascher, N.L.; Ahrenholz, D.H.; Simmons, R.L.; Weiblen, B.; Gomez, L.; Forstrom, L.A.; Frick, M.P.; Henke, C.; McCullough, J.

    1979-04-01

    The results of a new test using indium oxine in the diagnosis of postoperative infection are reported. Indium-111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection and inflammation. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection.

  10. Indium-111 autologous tagged leukocytes in the diagnosis of intraperitoneal sepsis

    International Nuclear Information System (INIS)

    Ascher, N.L.; Ahrenholz, D.H.; Simmons, R.L.; Weiblen, B.; Gomez, L.; Forstrom, L.A.; Frick, M.P.; Henke, C.; McCullough, J.

    1979-01-01

    The results of a new test using indium oxine in the diagnosis of postoperative infection are reported. Indium-111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection and inflammation. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection

  11. Indium 111 autologous tagged leukocytes in the diagnosis of intraperitoneal sepsis.

    Science.gov (United States)

    Ascher, N L; Ahrenholz, D H; Simmons, R L; Weiblen, B; Gomez, L; Forstrom, L A; Frick, M P; Henke, C; McCullough, J

    1979-04-01

    We report the results of a new test, indium oxine in 111 scanning, in the diagnosis of postoperative infection. Indium 111 was used to label autologous polymorphonuclear leukocytes, which when reinjected migrate to sites of infection, inflammation, or both. Standard scintigraphy localizes the labeled inflammatory cells at these sites. Sixty-six scans were performed in 43 surgical patients. Thirty-seven scans were categorized as true-positive; 19 scans were categorized as true-negative. Therefore, the accuracy rate was 85%. Two scans (3%) in one patient represented false-positive results. Two scans (3%) were positive for inflammation but there was no infection present; this group was denoted as equivocal. Six scans (9%) were false-negative; false-negative scans are more likely in old lesions with poor blood supply and in areas that overlap regions of normal uptake. The noninvasive nature of the test, high accuracy rate, and ease of administration make it a potentially useful tool in the diagnosis of postoperative infection.

  12. Parastomal Hernia Repair with a 3D Funnel Intraperitoneal Mesh Device and Same-Sided Stoma Relocation: Results of 56 Cases.

    Science.gov (United States)

    Fischer, Ines; Wundsam, Helwig; Mitteregger, Martin; Köhler, Gernot

    2017-12-01

    Parastomal hernias (PSHs) are a common and challenging issue. In previous studies, three-dimensional (3D) funnel mesh devices have been used successfully for the repair of PSHs. We performed an analysis of prospectively collected data of patients who underwent a same-sided stoma reposition with 3D funnel-shaped mesh augmentation in intraperitoneal (IPOM) position at our department between the years of 2012 and 2015. Primary outcome parameters were intra- and postoperative surgical complications and recurrence rate during the follow-up period. Fifty-six patients could be included in this analysis. PSH repair was performed in 89.3% as elective surgery and in 73% in laparoscopic technique. A concomitant incisional hernia (EHS type 2 and 4) was found in 50% and repaired in a single-step procedure with PSH. Major postoperative complications requiring redo surgery (Clavien-Dindo ≥3b) were identified in 8.9% (5/56). Overall recurrence rate was 12.5% (7/56). Median follow-up time was 38 months, and a 1-year follow-up rate of 96.4% was reached. PSH repair with 3D funnel mesh in IPOM technique is safe, efficient and easy to perform in laparoscopic and open surgical approaches providing advantageous results compared to other techniques. Furthermore, simultaneous detection and treatment of concomitant incisional hernias has shown favorable. However, the mesh funnel distends and becomes shortened encasing a bulky bowel mesentery and further shrinkage happens eccentric. Changing mesh construction according to lengthening the funnel could possibly lead to reduction in recurrence.

  13. Effect of early luteal phase administration of a single dose mifepristone on immunohistochemical distribution of interleukin 1 alpha (IL-1 alpha) and transforming growth factor beta 1 (TGF-beta 1) in mid-luteal phase ovary of the rhesus monkey.

    Science.gov (United States)

    Sengupta, Shaon; Ghosh, D

    2003-04-01

    A single low dose administration of a high affinity anti-progestin agent like mifepristone during the early luteal phase inhibits blastocyst implantation in human and non-human primates. Though it has been observed that luteal phase serum concentrations of estradiol and progesterone were not affected by the application of anti-nidatory dose of early luteal phase mifepristone suggesting that ovarian steroidogenic function is not compromised, it is nevertheless possible that ovarian physiology at the local tissue level is affected in this treatment schedule. In the present study, healthy, mature, proven fertile female rhesus monkeys were divided into two groups. Group 2 animals were treated with a single dose of mifepristone (2 mg/kg body weight), while group 1 animals were injected with vehicle (1:4 benzoyl benzoate: olive oil, v/v, s.c.) on day 2 post-ovulation. The morphological examination including that of vascularity, as well as, histometric determination of profiles of immunopositivity for IL-1alpha and TGF-beta1 in stromal, follicular and luteal compartments of mid-luteal phase ovaries from animals with or without a single, anti-nidatory dose of mifepristone applied on day 2 after ovulation failed to reveal any significant change between the two groups. Thus, it appears that early luteal phase administration of a single antinidatory dose of mifepristone does not affect the ovarian physiology in the treatment cycle.

  14. Intraperitoneal pressure: ascitic fluid and splanchnic vascular pressures, and their role in prevention and formation of ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Stage, J G; Schlichting, P

    1980-01-01

    Seventeen patients with ascites due to cirrhosis underwent hepatic venous catheterization and pressure measurement in the ascitic fluid. Intraperitoneal fluid hydrostatic pressure (IFP) ranged 3.5-22, mean 11.2 mm Hg, and correlated closely to the pressure in the inferior vena cava (r = 0.97, P ....001), which was on average 1.8 mmHg above that of ascitic fluid (P ascites (range 12-27, mean 20 mmHg, P ....005). After diuretic therapy WHVP decreased to an average of 20 mmHg. Mean plasma colloid osmotic pressures were 20 mmHg (range 18-24 mmHg)( and 23 mmHg (range 19-29 mmHg) in patients with and without ascites, the values being significantly different (P ascitic fluid...

  15. Optimization of Drug Delivery Systems for Intraperitoneal Therapy to Extend the Residence Time of the Chemotherapeutic Agent

    Directory of Open Access Journals (Sweden)

    L. De Smet

    2013-01-01

    Full Text Available Intraperitoneal (IP chemotherapy is an effective way of treating peritoneal carcinomatosis of colorectal origin after complete cytoreduction. Although IP therapy has been already performed for many years, no standardized treatment design has been developed in terms of schedule, residence time, drug, or carrier solution. Because of the fast clearance of the conventional intravenous (IV drug delivery systems used for IP therapy, a lot of research is performed to optimize IP drug delivery and extend the residence time of the cytotoxic agent in the peritoneal cavity. This paper reviews the recent advances made in drug delivery systems for IP chemotherapy, discussing the use of microparticles, nanoparticles, liposomes, micelles, implants, and injectable depots for IP delivery.

  16. Acute intraperitoneal mercury chloride contamination and distribution in liver, muscle and gill of a neotropical fish Hoplias malabaricus (BLOCK, 1794

    Directory of Open Access Journals (Sweden)

    Taise Bomfim de Jesus

    2011-04-01

    Full Text Available The present study investigated with the distribution of mercury chloride in muscle, liver and gills of Hoplias malabaricus contaminated through intraperitoneal injection (6 µg in 0.1mL of PBS for a period of 24, 48, 72 and 96h. The liver, gill and muscle were analyzed for mercury content in an ICP/AES (Varian Liberty II with vapor generating accessory (VGA 77. The muscle and liver tissues presented the same contamination pattern increasing concentrations in 24 h of exposure with a decrease in Hg concentration with 72 h and a new increase in Hg concentrations with 96 h of exposure. The Hg concentrations in contaminated organisms were always higher than the control although only for liver samples the difference was statistically significant. Liver samples always presented higher Hg contents when compared with gill and muscle samples.

  17. Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

    Directory of Open Access Journals (Sweden)

    Jingjing Mao

    Full Text Available Rabbit hepatitis E virus (HEV is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

  18. [An experiment control study on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model].

    Science.gov (United States)

    Fan, B Z; Xia, H; Chu, L; Tong, X W

    2017-04-25

    Objective: To compare the impact on the ovarian reserve function after cisplatin intraperitoneal or intravenous chemotherapy in rats model. Methods: Thirty 8-weeks old female Sprague Dawley rats were randomly assigned to control group (group A, n= 10), intraperitoneal chemotherapy group (group B, n= 10) and intravenous chemotherapy group (group C, n= 10). Cisplatin was diluted by normal saline (NS) into 4 mg/ml. On the first day of chemotherapy, 0.2 ml cisplatin dilution was injected into the abdomen of rats in group B, isodose cisplatin was injected into vein and 1.8 ml NS was injected into abdomen of rats in group C, 2.0 ml NS was injected into abdomen of rats in group A for control. Feed the three groups rats and test the anti-Mullerian hormone (AMH) in serum on day 0 (just before injection), day 10 and day 20 by ELISA, count the numble of follicle in bilateral ovaries on day 20. Results: (1) The levels of serum AMH in the three groups before and after chemotherapy were compared: ① comparison between groups: On day 10 and day 20, the AMH level in group B [(64.5±2.9), (68.6±3.4) ng/L] and group C [(76.1±4.9), (91.3±3.9) ng/L] was significantly lower than that in group A [(120.1±5.3), (121.7±4.6) ng/L; P< 0.01], AMH level in group B was significantly also lower than that in group C ( P= 0.000). ② Comparison within groups: the AMH level on day 0 was significantly lower than that on day 10 and day 20 in group A ( P< 0.01), but there was no significant difference between day 10 and day 20 ( P= 0.427). The AMH level on day 0 was significantly higher than those on day 10 and day 20 in group B ( P< 0.01) and group C ( P< 0.01). There was no difference in AMH level between day 10 and day 20 ( P= 0.124) in group B, but the level was significant lower on day 10 than that on day 20 in group C ( P= 0.011). (2)Comparison of the number of follicles in ovaries of three groups 20 days after chemotherapy: the follicles number in group A (35±13) was greater than that in

  19. Intraperitoneal pressure: ascitic fluid and splanchnic vascular pressures, and their role in prevention and formation of ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Stage, J G; Schlichting, P

    1980-01-01

    .005). After diuretic therapy WHVP decreased to an average of 20 mmHg. Mean plasma colloid osmotic pressures were 20 mmHg (range 18-24 mmHg)( and 23 mmHg (range 19-29 mmHg) in patients with and without ascites, the values being significantly different (P osmotic pressure of ascitic fluid...... pressure, (b) decreased interstitial fluid colloid osmotic pressure, (c) increased lymph flow, and it is concluded that the peritoneal space can be considered as a special part of the interstitium in which IFP is considered to play an important role in regulation of ascitic fluid.......Seventeen patients with ascites due to cirrhosis underwent hepatic venous catheterization and pressure measurement in the ascitic fluid. Intraperitoneal fluid hydrostatic pressure (IFP) ranged 3.5-22, mean 11.2 mm Hg, and correlated closely to the pressure in the inferior vena cava (r = 0.97, P

  20. Evaluating the effects of pentoxifylline administration on experimental pressure sores in rats by biomechanical examinations

    OpenAIRE

    Velaei, Kobra; Bayat, Mohammad; Torkman, Giti; Rezaie, Fatemealsadat; Amini, Abdollah; Noruzian, Mohsen; Tavassol, Azaedh; Bayat, Mehernoush

    2012-01-01

    This study used a biomechanical test to evaluate the effects of pentoxifylline administration on the wound healing process of an experimental pressure sore induced in rats. Under general anesthesia and sterile conditions, experimental pressure sores generated by no. 25 Halsted mosquito forceps were inflicted on 12 adult male rats. Pentoxifylline was injected intraperitoneally at a dose of 50 mg/kg daily from the day the pressure sore was generated, for a period of 20 days. At the end of 20 da...

  1. Prognostic significance of peritoneal cytology in patients with endometrial cancer and preliminary data concerning therapy with intraperitoneal radiopharmaceuticals

    International Nuclear Information System (INIS)

    Creasman, W.T.; Disaia, P.J.; Blessing, J.; Wilkinson, R.H. Jr.; Johnston, W.; Weed, J.C. Jr.

    1981-01-01

    One hundred sixty-seven patients with clinical State I carcinoma of the endometrium were treated primarily by operation consisting of total abdominal hysterectomy, bilateral salpingo-oophorectomy, selective pelvic and para-aortic lymphadenectomy, and cytologic testing of peritoneal washings. Twenty-six (15.5%) of the 167 patients had malignant cells identified on cytologic examinations of peritoneal washings. Recurrence developed in 10 of these 26 (34.0%) compared to 14/141 (9.9%) patients with negative cytologic testing. Of the 26 patients, 13 (50%) had disease outside of the uterus at operation and seven have died of disease (54%). Thirteen patients had malignant cells in the peritoneal washings but no disease outside of the uterus and six (46%) of these have died of disseminated intra-abdominal carcinomatosis. On the basis of the poor outcome of those patients who had malignant cells in the peritoneal washings in the 167 patients studied, a plan of treating such patients with intraperitoneal radioactive chromic phosphate suspension (P-32) was instituted. Twenty-three subsequent patients with clinical Stage I carcinoma of the endometrium were found to have malignant cells in the peritoneal fluid. All 23 received intra-abdominal P-32 suspension instillation after operation. There have been three recurrences with two patients dying of disease. All of the three recurrences appeared at sites distant from the abdominal cavity. Peritoneal cytologic examination appears to be an important factor in the prognosis of endometrial cancer and, when the washings are positive for malignant cells, intraperitoneal chronic phosphate therapy appears to be efficacious

  2. Warning against co-administration of 3,4-methylenedioxymethamphetamine (MDMA) with methamphetamine from the perspective of pharmacokinetic and pharmacodynamic evaluations in rat brain.

    Science.gov (United States)

    Yuki, Fuchigami; Rie, Ikeda; Miki, Kuzushima; Mitsuhiro, Wada; Naotaka, Kuroda; Kenichiro, Nakashima

    2013-04-11

    3,4-Methylenedioxymethamphetamine (MDMA) and methamphetamine often cause serious adverse effects (e.g., rhabdomyolysis, and cardiac disease) following hyperthermia triggered by release of brain monoamines such as dopamine and serotonin. Therefore, evaluation of brain monoamine concentrations is useful to predict these drugs' risks in human. This study aimed to evaluate risks of co-administration of MDMA and methamphetamine, both of which are abused frequently in Japan, based on drug distribution and monoamine level in the rat brain. Rats were allocated to three groups: (1) sole MDMA administration (12 or 25 mg/kg, intraperitoneally), (2) sole methamphetamine administration (10 mg/kg, intraperitoneally) and (3) co-administration of MDMA (12 mg/kg, intraperitoneally) and methamphetamine (10 mg/kg, intraperitoneally). We monitored pharmacokinetic and pharmacodynamic variables for drugs and monoamines in the rat brain. Area under the curve for concentration vs. time until 600 min from drug administration (AUC₀₋₆₀₀) increased from 348.0 to 689.8 μgmin/L for MDMA and from 29.9 to 243.4 μMmin for dopamine in response to co-administration of methamphetamine and MDMA compared to sole MDMA (12 mg/kg) administration. After sole methamphetamine or that with MDMA administration, AUC₀₋₆₀₀ of methamphetamine were 401.8 and 671.1 μgmin/L, and AUC₀₋₆₀₀ of dopamine were 159.9 and 243.4 μMmin. In conclusion, the brain had greater exposure to MDMA, methamphetamine and dopamine after co-administration of MDMA and methamphetamine than when these two drugs were given alone. This suggests co-administration of MDMA with methamphetamine confers greater risk than sole administration, and that adverse events of MDMA ingestion may increase when methamphetamine is co-administered. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Administrative Data Repository (ADR)

    Data.gov (United States)

    Department of Veterans Affairs — The Administrative Data Repository (ADR) was established to provide support for the administrative data elements relative to multiple categories of a person entity...

  4. Philippines - Revenue Administration Reform

    Data.gov (United States)

    Millennium Challenge Corporation — The Millennium Challenge Account-Philippines' (MCA-P) implementation of the Revenue Administration Reform Project (RARP) is expected to improve tax administration,...

  5. Acute intraperitoneal lipopolysaccharide influences the immune system in the absence of gut dysbiosis.

    Science.gov (United States)

    Sylvia, Kristyn E; Demas, Gregory E

    2018-03-01

    There is bidirectional communication between the immune system and the gut microbiome, however the precise mechanisms regulating this crosstalk are not well understood. Microbial-associated molecular patterns (MAMPs) within the gut, including lipopolysaccharide (LPS) that produces a quick and robust activation of the immune system, may be one way by which these interactions occur. Endogenous levels of LPS in the gut are low enough that they do not usually cause disease, although, in times of increased LPS loads, they may be capable of increasing vulnerability of the gut to pathogenic bacteria. Furthermore, chronic, low-grade inflammation can have lasting effects on the gut, but the effects of acute inflammation on gut communities have not been thoroughly assessed. In this study, we first investigated whether a single modest dose of LPS administered to adult male and female Siberian hamsters (Phodopus sungorus) activated the immune system by measuring levels of circulating cortisol and the proinflammatory cytokine TNF-α in the liver compared with saline-treated animals. We then investigated whether this same acute dose of LPS altered the microbiome 48 h after treatment. We found that, although LPS increased cortisol and liver cytokine levels, and produced changes in food intake and body mass in both sexes, immunological changes were independent of gut dysbiosis 48 h after LPS injection. These data suggest that an acute immune activation may not be capable of altering the gut microbiome in healthy individuals. It is likely, however, that this type of immune challenge may have other physiological impacts on the gut's vulnerability, and future studies will investigate these relationships further. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

  6. Biological effects of fractionated administration of radioactive phosphorus in rats

    International Nuclear Information System (INIS)

    Takizawa, Shoichi; Ohtsuka, Shoichiro; Morii, Kazuyo; Hirose, Fumio

    1978-01-01

    Female rats were given 1 μCi per g body weight of 32 P intraperitoneally four or eight times at intervals of two weeks, and half the rats received ovariectomy after two weeks. Various damages in the rats which received ovariectomy were compared with those in rats which did not receive ovariectomy. As to a change of body weight, an increase of body weight observed through the whole observation term after desexualization (for 11 months after the administration) was inhibited, and there was not any difference between ovariectomized and not-ovariectomized rats. The number of leukocytes decreased just after the administration. It took one month and a half in 4 times administration and three months and a half in 8 times administration to recover the number of leukocytes to normal values. There was no effect of desexualization. On the group administered 32 P 8 times the number of erythrocytes tended to decrease markely, but it recovered to a normal condition rapidly after the finish of the administration. As to onset of tumors, osteosarcoma occurred with high incidence (63%) regardless of presence of desexualization and frequency of the administration. The incidence of leukemia was about 15%. One case of breast tumor was recognized in nonovariectomized rats. Malignant tumors were not recognized in cases with normal sexual cycle for 8 to 10 months after the beginning of the administration. (Kanao, N.)

  7. The effect of oral 5-HTP administration on 5-HTP and 5-HT immunoreactivity in monoaminergic brain regions of rats.