WorldWideScience

Sample records for model intraperitoneal administration

  1. 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.

  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. 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

  4. 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 .

  5. 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.

  6. 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.

  7. 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.

  8. [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.

  9. 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.

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. 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

  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. 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

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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...

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  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. [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

  8. 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.

  9. Intraperitoneal curcumin decreased lung, renal and heart injury in abdominal aorta ischemia/reperfusion model in rat.

    Science.gov (United States)

    Aydin, Mehmet Salih; Caliskan, Ahmet; Kocarslan, Aydemir; Kocarslan, Sezen; Yildiz, Ali; Günay, Samil; Savik, Emin; Hazar, Abdussemet; Yalcin, Funda

    2014-01-01

    Previous studies have demonstrated that curcumin (CUR) has protective effects against ischemia reperfusion injury to various organs. We aimed to determine whether CUR has favorable effects on tissues and oxidative stress in abdominal aorta ischemia-reperfusion injury. Thirty rats were divided into three groups as sham, control and treatment (CUR) group. Control and CUR groups underwent abdominal aorta ischemia for 60 min followed by a 120 min period of reperfusion. In the CUR group, CUR was given 5 min before reperfusion at a dose of 200 mg/kg via an intraperitoneal route. Total antioxidant capacity (TAC), total oxidative status (TOS), and oxidative stress index (OSI) in blood serum were measured, and lung, renal and heart tissue histopathology were evaluated with light microscopy. TOS and OSI activity in blood samples were statistically decreased in sham and CUR groups compared to the control group (p OSI). Renal, lung, heart injury scores of sham and CUR groups were statistically decreased compared to control group (p model. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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...

  15. Directory of Energy Information Administration models 1996

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-07-01

    This directory revises and updates the Directory of Energy Information Administration Models 1995, DOE/EIA-0293(95), Energy Information Administration (EIA), U.S. Department of Energy, July 1995. Four models have been deleted in this directory as they are no longer being used: (1) Market Penetration Model for Ground-Water Heat Pump Systems (MPGWHP); (2) Market Penetration Model for Residential Rooftop PV Systems (MPRESPV-PC); (3) Market Penetration Model for Active and Passive Solar Technologies (MPSOLARPC); and (4) Revenue Requirements Modeling System (RRMS).

  16. Directory of Energy Information Administration Models 1994

    Energy Technology Data Exchange (ETDEWEB)

    1994-07-01

    This directory revises and updates the 1993 directory and includes 15 models of the National Energy Modeling System (NEMS). Three other new models in use by the Energy Information Administration (EIA) have also been included: the Motor Gasoline Market Model (MGMM), Distillate Market Model (DMM), and the Propane Market Model (PPMM). This directory contains descriptions about each model, including title, acronym, purpose, followed by more detailed information on characteristics, uses and requirements. Sources for additional information are identified. Included in this directory are 37 EIA models active as of February 1, 1994.

  17. Directory of Energy Information Administration Models 1994

    International Nuclear Information System (INIS)

    1994-07-01

    This directory revises and updates the 1993 directory and includes 15 models of the National Energy Modeling System (NEMS). Three other new models in use by the Energy Information Administration (EIA) have also been included: the Motor Gasoline Market Model (MGMM), Distillate Market Model (DMM), and the Propane Market Model (PPMM). This directory contains descriptions about each model, including title, acronym, purpose, followed by more detailed information on characteristics, uses and requirements. Sources for additional information are identified. Included in this directory are 37 EIA models active as of February 1, 1994

  18. Zebrafish (Danio rerio) as a model to visualize infection dynamics of Vibrio anguillarum following intraperitoneal injection and bath exposure.

    Science.gov (United States)

    Schmidt, Jacob Günther; Korbut, Rozalia; Ohtani, Maki; Jørgensen, Louise von Gersdorff

    2017-08-01

    Vaccine development is important for sustainable fish farming and novel vaccines need to be efficacy tested before release to the market. Challenge of fish with the pathogen towards which the vaccine has been produced can be conducted either by external exposure though bathing or cohabitation, or by bypassing the mucosa through injection. The latter approach is often preferred since it is easier to control than the former. However, injection is not a very natural route of infection, and the bypass of the mucosa may result in a different efficacy profile of experimental fish compared to farmed fish, for which the vaccines are targeted. The zebrafish is by now a well established practical vertebrate model species due in part to its size and ease of maintenance and genetic manipulation. Here we use zebrafish as a model to visualize and compare the development of infection of Vibrio anguillarum on and in the fish following injection or bathing. Injection of 10 3 bacteria per fish resulted in approximately 50% mortality by day 4 post-injection. Similar mortality levels were reached in the other group by bathing in 1.25 × 10 9 bacteria for 1 min. The spreading of bacteria was followed for the first 24 h after injection/bathing by immunohistochemistry and optical projection tomography. The tissues and organs where bacteria were detected differed significantly as a result of time as well as treatment. In the bath group, bacteria were initially found on external surfaces including gut. After 24 h V. anguillarum still persisted in gut but had now also spread to the blood. In the injection group bacteria were found in the blood throughout all sampling times, as well as in the hypodermis and body cavity at most sampling times. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. 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

  20. Anticancer activity of the intraperitoneal-delivered DFP-10825, the cationic liposome-conjugated RNAi molecule targeting thymidylate synthase, on peritoneal disseminated ovarian cancer xenograft model

    Directory of Open Access Journals (Sweden)

    Iizuka K

    2018-03-01

    Full Text Available Kenzo Iizuka, Cheng Jin, Kokoro Eshima, Mei Hua Hong, Kiyoshi Eshima, Masakazu Fukushima Division of Research and Development, Delta-Fly Pharma Inc., Tokushima, Japan Introduction: Peritoneal disseminated ovarian cancer is one of the most difficult cancers to treat with conventional anti-cancer drugs and the treatment options are very limited, although an intraperitoneal (ip paclitaxel has shown some clinical benefit. Therefore, treatment of peritoneal disseminated ovarian cancer is a highly unmet medical need and it is urgent to develop a new ip delivered drug regulating the fast DNA synthesis. Methods: We developed a unique RNAi molecule consisting of shRNA against the thymidylate synthase (TS and a cationic liposome (DFP-10825 and tested its antitumor activity and PK profile in peritoneally disseminated human ovarian cancer ascites models by the luciferase gene-transfected SCID mice. DFP-10825 alone, paclitaxel alone or combination with DFP-10825 and paclitaxel were administered in an ip route to the tumor-bearing mice. The TS expression level was measured by conventional RT-PCR. The anti-tumor activity and host survival benefit by DFP-10825 treatment on tumor-bearing mice were observed as resulting from the specific TS mRNA knock-down in tumors. Results: DFP-10825 alone significantly suppressed the growth of SKOV3-luc tumore ascites cells and further extended the survival time of these tumor-bearing mice. Combination with the ip paclitaxel augmented the antitumor efficacy of DFP-10825 and significantly prolonged the survival time in the tumor-bearing mice. Short-hairpin RNA for TS (TS shRNA levels derived from DFP-10825 in the ascetic fluid were maintained at a nM range across 24 hours but not detected in the plasma, suggesting that TS shRNA is relatively stable in the peritoneal cavity, to be able to exert its anti-tumor activity, but not in blood stream, indicating little or no systemic effect. Conclusion: Collectively, the ip delivery of

  1. Intraperitoneal inoculation of Haemophilus influenzae local isolates in BALB/c mice model in the presence and absence of virulence enhancement agents

    Directory of Open Access Journals (Sweden)

    N Mojgani

    2013-01-01

    Full Text Available Purpose:Haemophilus influenzae (Hi, predominantly type b accounts for approximately 4% of cases of community-acquired and nosocomial meningitis, in adults. The objective of this study was to evaluate the pathogenicity of local Hi isolates (type b, f and non-typable in BALB/c mice in the presence of virulence enhancement agents. Materials and Methods: Three different concentrations of the Hi isolates were inoculated intraperitoneally in BALB/c mice in the presence of 2% hemoglobin and 4% mucin as virulence enhancing agents (VEA. The ability of the isolates to produce bacteremia, the percent survival and lethal dose (LD 50 were recorded in different challenge groups. Results: The 3 Haemophilus influenzae type b (Hib isolates used in study were able to show virulence in BALB/c mice model only in the presence of VEA and their LD 50 decreased significantly when 2% hemoglobin and 4% mucin were used. All survived animals showed bacteremia within 4 h of inoculation which was cleared within 18 h. Significant differences ( P < 0.01 in the virulence and survival percentage of Hib challenge groups were observed based on their dose of inoculation and VEA. None of the isolates were able to induce infection in the absence of VEA. Non-type b isolates failed to produce disease in the mice models even at the highest inoculated dose (10 8 cfu and in the presence of VEA. Conclusions: BALB/c mice appeared suitable for evaluating the virulence of Hib strains, and 2% hemoglobin with 4% mucin an appropriate concentration for inducing infection in this animal model.

  2. 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.

  3. 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.

  4. The effect of the administration of human gamma globulins in a model of BCG infection in mice.

    Science.gov (United States)

    Olivares, Nesty; León, Annette; López, Yamilé; Puig, Alina; Cádiz, Armando; Falero, Gustavo; Martínez, Máximo; Sarmiento, Marie E; Fariñas, Mildrey; Infante, Juan F; Sierra, Gustavo; Solís, Rosa L; Acosta, Armando

    2006-01-01

    The effect of the administration of a commercial preparation of human gamma globulins has been evaluated in a mouse model of intranasal infection with BCG. First, we demonstrated the passage of specific antibodies to saliva and lung lavage following the intranasal or intraperitoneal administration to mice of human gamma globulins. This treatment of mice inhibited BCG colonization of the lungs (p < 0.01). A similar inhibitory effect was observed after infection of mice with gamma globulin opsonized BCG organisms (p < 0.01). These results are relevant for the development of new strategies for the control and treatment of tuberculosis.

  5. Russian Model Of The Administrative Justice

    Directory of Open Access Journals (Sweden)

    Natalja I. Jaroshenko

    2014-12-01

    Full Text Available On December 25, 2014 it would be twenty-one year since the Constitution of the Russian Federation was adopted on the national referendum on December 12, 1993. During this time, almost all constitutional provisions are implemented. The key point of course was the judicial reform in Russia, launched simultaneously with the adoption of Constitution of the Russian Federation. Adopted the new Civil Procedural Code, Criminal Procedural Code, Arbitration Procedural Code of the Russian Federation, Federal Constitutional Law "On the Constitutional Court of the Russian Federation", Federal Constitutional Law "On the courts of general jurisdiction in Russia", Federal Constitutional Law "On the Supreme Court of the Russian Federation". However, during twenty-one year of Russian Constitution work, the question on establishment of administrative courts in our country has not been resolved. Merger of the Supreme Court and the Supreme Arbitration Court of the Russian Federation, which happened in the year 2014, also shown the need to resolve the status of administrative courts in Russia. Previously submitted to the State Duma of the Federal Assembly of the Russian Federation the draft of the Federal Constitutional Law "On the Federal Administrative Courts in the Russian Federation" and is on the revision, which does not correspond to changes in the judicial system of the Russian Federation. Despite the failure of the Federal Constitutional Law "On the Federal Administrative Courts in the Russian Federation", in the opinion of the author, and it should be called that way, it Russia has already developed an own model of the Russian administrative justice, which is very specific.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.)

  11. 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.

  12. 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

  13. Semantic Modeling of Administrative Procedures from a Spanish Regional Public Administration

    Directory of Open Access Journals (Sweden)

    Francisco José Hidalgo López

    2018-02-01

    Full Text Available Over the past few years, Public Administrations have been providing systems for procedures and files electronic processing to ensure compliance with regulations and provide public services to citizens. Although each administration provides similar services to their citizens, these systems usually differ from the internal information management point of view since they usually come from different products and manufacturers. The common framework that regulations demand, and that Public Administrations must respect when processing electronic files, provides a unique opportunity for the development of intelligent agents in the field of administrative processes. However, for this development to be truly effective and applicable to the public sector, it is necessary to have a common representation model for these administrative processes. Although a lot of work has already been done in the development of public information reuse initiatives and common vocabularies standardization, this has not been carried out at the processes level. In this paper, we propose a semantic representation model of both processes models and processes for Public Administrations: the procedures and administrative files. The goal is to improve public administration open data initiatives and help to develop their sustainability policies, such as improving decision-making procedures and administrative management sustainability. As a case study, we modelled public administrative processes and files in collaboration with a Regional Public Administration in Spain, the Principality of Asturias, which enabled access to its information systems, helping the evaluation of our approach.

  14. 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.

  15. 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.

  16. Land administration domain model is an ISO standard now

    NARCIS (Netherlands)

    Lemmen, C.H.J.; Van Oosterom, P.J.M.; Uitermark, H.T.; De Zeeuw, K.

    2013-01-01

    A group of land administration professionals initiated the development of a data model that facilitates the quick and efficient set-up of land registrations. Just like social issues benefit from proper land administration, land administration systems themselves benefit from proper data standards. In

  17. A domain model for land administration

    NARCIS (Netherlands)

    Lemmen, C.H.J.

    2012-01-01

    75% or the “people to land relationships” worldwide are not documented. This concerns about 4.5 billion cases. With a growing population this situation results in land disputes, land grabbing and neglecting of rights of local people. Land Administration provides documentation on people to land

  18. Planning Models in Higher Education Administration

    Science.gov (United States)

    Gaunt, Roger N.; Haight, Michael J.

    1977-01-01

    Examines issues related to real-world applications of higher education planning models, describing four different models as representative examples of the model spectrum. Also reviews situations in which qualitative considerations relegate the use of models to a low priority and situations in which information generated by models may be misused.…

  19. [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.

  20. 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

  1. 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.

  2. Directory of energy information administration models 1995

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-07-13

    This updated directory has been published annually; after this issue, it will be published only biennially. The Disruption Impact Simulator Model in use by EIA is included. Model descriptions have been updated according to revised documentation approved during the past year. This directory contains descriptions about each model, including title, acronym, purpose, followed by more detailed information on characteristics, uses, and requirements. Sources for additional information are identified. Included are 37 EIA models active as of February 1, 1995. The first group is the National Energy Modeling System (NEMS) models. The second group is all other EIA models that are not part of NEMS. Appendix A identifies major EIA modeling systems and the models within these systems. Appendix B is a summary of the `Annual Energy Outlook` Forecasting System.

  3. Rhode Island Model Evaluation & Support System: Building Administrator. Edition III

    Science.gov (United States)

    Rhode Island Department of Education, 2015

    2015-01-01

    Rhode Island educators believe that implementing a fair, accurate, and meaningful educator evaluation and support system will help improve teaching, learning, and school leadership. The primary purpose of the Rhode Island Model Building Administrator Evaluation and Support System (Rhode Island Model) is to help all building administrators improve.…

  4. 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.

  5. 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...

  6. Modeling veterans healthcare administration disclosure processes :

    Energy Technology Data Exchange (ETDEWEB)

    Beyeler, Walter E; DeMenno, Mercy B.; Finley, Patrick D.

    2013-09-01

    As with other large healthcare organizations, medical adverse events at the Department of Veterans Affairs (VA) facilities can expose patients to unforeseen negative risks. VHA leadership recognizes that properly handled disclosure of adverse events can minimize potential harm to patients and negative consequences for the effective functioning of the organization. The work documented here seeks to help improve the disclosure process by situating it within the broader theoretical framework of issues management, and to identify opportunities for process improvement through modeling disclosure and reactions to disclosure. The computational model will allow a variety of disclosure actions to be tested across a range of incident scenarios. Our conceptual model will be refined in collaboration with domain experts, especially by continuing to draw on insights from VA Study of the Communication of Adverse Large-Scale Events (SCALE) project researchers.

  7. Modelling of web-based virtual university administration for Nigerian ...

    African Journals Online (AJOL)

    This research work focused on development of a model of web based virtual University Administration for Nigerian universities. This is necessary as there is still a noticeable administrative constraint in our Universities, the establishment of many University Web portals notwithstanding. More efforts are therefore needed to ...

  8. Pretreatment with Pancaspase Inhibitor (Z-VAD-FMK Delays but Does Not Prevent Intraperitoneal Heat-Killed Group B Streptococcus-Induced Preterm Delivery in a Pregnant Mouse Model

    Directory of Open Access Journals (Sweden)

    Ozlem Equils

    2009-01-01

    Full Text Available Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS. Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u. or intraperitoneal (i.p. HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p. prior to HK-GBS (i.p. delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

  9. 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...

  10. Public Administration: Modernizing The Current Model Of State Management

    Directory of Open Access Journals (Sweden)

    Evgenii V. Ohotskii

    2014-01-01

    Full Text Available Applying the method of retrospective analysis the article deals with the process of forming the scientific fundamentals and the search by the international community of effective and adequate to the current stage of social development public administration system. The author attempts to analyze, in a number of cases in terms of models, features of public administration systems at different stages of historical development, drawing attention to reasons why the Soviet model of public administration did not manage to meet competition, did not provide the required social effect and as a natural result suffered a defeat in the global confrontation between the two social systems. Current models and theoretical concepts of public administration, especially the "new public administration", which became scientific basis for administrative reforms implemented in many countries, are the particular subject of scientific analysis. The author draws attention to major comprehensive characteristics of modern state public administration: making it impossible to absolutize principles of traditional hierarchy system of forced administration; globalization - gradual destruction of boundaries between national and international levels of administration, the growing role of supranational subjects of administration relations; informatization - increasing importance of information and communication technologies and of political networks: development of civil society, especially political parties and non-governmental organizations, growing public involvement in discussion and adoption of the most important administrative decisions; making the state policy more pluralistic and which will result in the formation of nonlinear - humanistic social consciousness as the intellectual basis of modern social governance. The author's position is that Russia is yet to solve the issue of choosing a public administration model that would be effective for further administrative

  11. PUBLIC ADMINISTRATION: MODERNIZING THE CURRENT MODEL OF STATE MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Evgenii V. Ohotskii

    2014-01-01

    Full Text Available Applying the method of retrospective analysis the article deals with the process of forming the scientific fundamentals and the search by the international community of effective and adequate to the current stage of social development public administration system. The author attempts to analyze, in a number of cases in terms of models, features of public administration systems at different stages of historical development, drawing attention to reasons why the Soviet model of public administration did not manage to meet competition, did not provide the required social effect and as a natural result suffered a defeat in the global confrontation between the two social systems. Current models and theoretical concepts of public administration, especially the "new public administration", which became scientific basis for administrative reforms implemented in many countries, are the particular subject of scientific analysis. The author draws attention to major comprehensive characteristics of modern state public administration: making it impossible to absolutize principles of traditional hierarchy system of forced administration; globalization - gradual destruction of boundaries between national and international levels of administration, the growing role of supranational subjects of administration relations; informatization - increasing importance of information and communication technologies and of political networks: development of civil society, especially political parties and non-governmental organizations, growing public involvement in discussion and adoption of the most important administrative decisions; making the state policy more pluralistic and which will result in the formation of nonlinear - humanistic social consciousness as the intellectual basis of modern social governance. The author's position is that Russia is yet to solve the issue of choosing a public administration model that would be effective for further administrative

  12. Public Administration: Modernizing The Current Model Of State Management

    OpenAIRE

    Evgenii V. Ohotskii

    2014-01-01

    Applying the method of retrospective analysis the article deals with the process of forming the scientific fundamentals and the search by the international community of effective and adequate to the current stage of social development public administration system. The author attempts to analyze, in a number of cases in terms of models, features of public administration systems at different stages of historical development, drawing attention to reasons why the Soviet model of public administra...

  13. 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...

  14. 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 ...

  15. Prenatal administration of retinoic acid upregulates connective tissue growth factor in the nitrofen CDH model.

    Science.gov (United States)

    Ruttenstock, Elke Maria; Doi, Takashi; Dingemann, Jens; Puri, Prem

    2011-06-01

    Recent studies have suggested that retinoids may be involved in the molecular mechanisms of pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). Connective tissue growth factor (CTGF) plays a key role in foetal lung development and remodelling during later gestation. CTGF knockout mice exhibit PH with similar characteristics to the human and nitrofen-induced PH. Prenatal administration of retinoic acid (RA) has been shown to stimulate alveologenesis in nitrofen-induced PH. In vitro studies have revealed that RA can induce CTGF gene expression. We hypothesized that pulmonary gene expression of CTGF is downregulated during the later stages of lung development, and that prenatal administration of RA upregulates CTGF in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Foetuses were harvested on D21 and divided into control, CDH, control + RA and CDH + RA group. Pulmonary CTGF gene and protein expression levels were determined using RT-PCR and immunohistochemistry. On D21, CTGF relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, expression levels of CTGF were significantly upregulated in CDH + RA and control + RA compared to the CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary CTGF gene and protein expression during later stages of lung development may interfere with normal alveologenesis in the nitrofen CDH model. Upregulation of CTGF pulmonary gene expression after prenatal RA treatment may promote lung growth by promoting alveologenesis in the nitrofen-induced CDH model.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. Modeling of corneal and retinal pharmacokinetics after periocular drug administration.

    Science.gov (United States)

    Amrite, Aniruddha C; Edelhauser, Henry F; Kompella, Uday B

    2008-01-01

    To develop pharmacokinetics models to describe the disposition of small lipophilic molecules in the cornea and retina after periocular (subconjunctival or posterior subconjunctival) administration. Compartmental pharmacokinetics analysis was performed on the corneal and retinal data obtained after periocular administration of 3 mg of celecoxib (a selective COX-2 inhibitor) to Brown Norway (BN) rats. Berkeley Madonna, a differential and difference equation-based modeling software, was used for the pharmacokinetics modeling. The data were fit to different compartment models with first-order input and disposition, and the best fit was selected on the basis of coefficient of regression and Akaike information criteria (AIC). The models were validated by using the celecoxib data from a prior study in Sprague-Dawley (SD) rats. The corneal model was also fit to the corneal data for prednisolone at a dose of 2.61 mg in albino rabbits, and the model was validated at two other doses of prednisolone (0.261 and 26.1 mg) in these rabbits. Model simulations were performed with the finalized model to understand the effect of formulation on corneal and retinal pharmacokinetics after periocular administration. Celecoxib kinetics in the BN rat cornea can be described by a two-compartment (periocular space and cornea, with a dissolution step for periocular formulation) model, with parallel elimination from the cornea and the periocular space. The inclusion of a distribution compartment or a dissolution step for celecoxib suspension did not lead to an overall improvement in the corneal data fit compared with the two-compartment model. The more important parameter for enhanced fit and explaining the apparent lack of an increase phase in the corneal levels is the inclusion of the initial leak-back of the dose from the periocular space into the precorneal area. The predicted celecoxib concentrations from this model also showed very good correlation (r = 0.99) with the observed values in

  3. Application of Computer Simulation Modeling to Medication Administration Process Redesign

    Directory of Open Access Journals (Sweden)

    Nathan Huynh

    2012-01-01

    Full Text Available The medication administration process (MAP is one of the most high-risk processes in health care. MAP workflow redesign can precipitate both unanticipated and unintended consequences that can lead to new medication safety risks and workflow inefficiencies. Thus, it is necessary to have a tool to evaluate the impact of redesign approaches in advance of their clinical implementation. This paper discusses the development of an agent-based MAP computer simulation model that can be used to assess the impact of MAP workflow redesign on MAP performance. The agent-based approach is adopted in order to capture Registered Nurse medication administration performance. The process of designing, developing, validating, and testing such a model is explained. Work is underway to collect MAP data in a hospital setting to provide more complex MAP observations to extend development of the model to better represent the complexity of MAP.

  4. Model Predictive Control Algorithms for Pen and Pump Insulin Administration

    DEFF Research Database (Denmark)

    Boiroux, Dimitri

    parameters are personalized using a priori available patient information. We consider an autoregressive integrated moving average with exogenous input (ARIMAX) model. Wesummarize and the results of the overnight clinical studies conducted at Hvidovre Hospital. Based on these results, we propose improvements...... ARMAX model in which we estimate the parameters of the stochastic part using a Recursive Least Square (RLS) method. We test the controller in a virtual clinic of 100 patients. This virtual clinic is based on the Hovorka model. We consider the case where only half of the bolus is administrated...

  5. 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...

  6. Changes on metabolic parameters induced by acute cannabinoid administration (CBD, THC) in a rat experimental model of nutritional vitamin A deficiency.

    Science.gov (United States)

    El Amrani, Loubna; Porres, Jesús M; Merzouki, Abderrahmane; Louktibi, Abdelaziz; Aranda, Pilar; López-Jurado, María; Urbano, Gloria

    2013-01-01

    Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer. Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD) or thetrahydrocannabinol (THC) on the levels of retinol in plasma and in the liver, and biochemical parameters related to lipid and glucose metabolism (cholesterolaemia, triglyceridemia and glycemia) in a rat experimental model of vitamin A deficiency. The experimental animal model of Vitamin A deficiency was developed during a 50-day experimental period in which rats consumed a vitamin A-free diet. Cannabidiol (10 mg/kg body weight) or thetrahydrocannabinol (5 mg/kg body weight) were administered intraperitoneally 2 hours prior to sacrifice of the animals. The nutritional deficiency caused a significant decrease in plasmatic and liver contents of retinol and biochemical parameters of glycemic, lipidic, and mineral metabolism. Acute intraperitoneal administration of Cannabidiol and thetrahydrocannabinol did not improve the indices of vitamin A status in either control or vitamin A-deficient rats. However, it had a significant effect on specific biochemical parameters such as glucose, triglycerides, and cholesterol. Under our experimental conditions, the reported effects of cannabinoid administration on certain signs of nutritional vitamin A deficiency appeared to be mediated through mechanisms other than changes in retinol metabolism or its mobilization after the acute administration of such compounds. Copyright © AULA MEDICA EDICIONES 2013. Published by AULA MEDICA. All rights reserved.

  7. 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

  8. Effect of Pentoxifylline Administration on an Experimental Rat Model of Femur Fracture Healing With Intramedullary Fixation

    Science.gov (United States)

    Vashghani Farahani, Mohammad Mahdi; Masteri Farahani, Reza; Mostafavinia, Ataroalsadat; Abbasian, Mohammad Reza; Pouriran, Ramin; Noruzian, Mohammad; Ghoreishi, Seyed Kamran; Aryan, Arefe; Bayat, Mohammad

    2015-01-01

    Background: Globally, musculoskeletal injuries comprise a major public health problem that contributes to a large burden of disability and suffering. Pentoxifylline (PTX) has been originally used as a hemorheologic drug to treat intermittent claudication. Previous test tube and in vivo studies reported the beneficial effects of PTX on bony tissue. Objectives: This study aims to evaluate the effects of different dosages of PTX on biomechanical properties that occur during the late phase of the fracture healing process following a complete femoral osteotomy in a rat model. We applied intramedullary pin fixation as the treatment of choice. Materials and Methods: This experimental study was conducted at the Shahid Beheshti University of Medical Sciences, Tehran, Iran. We used the simple random technique to divide 35 female rats into five groups. Group 1 received intraperitoneal (i.p.) PTX (50 mg/kg, once daily) injections, starting 15 days before surgery, and group 2, group 3, and group 4 received 50 mg/kg, 100 mg/kg, and 200 mg/kg i.p. PTX injections, respectively, once daily after surgery. All animals across groups received treatment for six weeks (until sacrificed). Complete surgical transverse osteotomy was performed in the right femur of all rats. At six weeks after surgery, the femurs were subjected to a three-point bending test. Results: Daily administration of 50 mg/kg PTX (groups 1 and 2) decreased the high stress load in repairing osteotomized femurs when compared with the control group. The highest dose of PTX (200 mg/kg) significantly increased the high stress load when compared with the control group (P = 0.030), group 1 (P = 0.023), group 2 (P = 0.008), and group 3 (P = 0.010), per the LSD findings. Conclusions: Treatment with 200 mg/kg PTX accelerated fracture healing when compared with the control group. PMID:26756019

  9. Effect of Pentoxifylline Administration on an Experimental Rat Model of Femur Fracture Healing With Intramedullary Fixation.

    Science.gov (United States)

    Vashghani Farahani, Mohammad Mahdi; Masteri Farahani, Reza; Mostafavinia, Ataroalsadat; Abbasian, Mohammad Reza; Pouriran, Ramin; Noruzian, Mohammad; Ghoreishi, Seyed Kamran; Aryan, Arefe; Bayat, Mohammad

    2015-12-01

    Globally, musculoskeletal injuries comprise a major public health problem that contributes to a large burden of disability and suffering. Pentoxifylline (PTX) has been originally used as a hemorheologic drug to treat intermittent claudication. Previous test tube and in vivo studies reported the beneficial effects of PTX on bony tissue. This study aims to evaluate the effects of different dosages of PTX on biomechanical properties that occur during the late phase of the fracture healing process following a complete femoral osteotomy in a rat model. We applied intramedullary pin fixation as the treatment of choice. This experimental study was conducted at the Shahid Beheshti University of Medical Sciences, Tehran, Iran. We used the simple random technique to divide 35 female rats into five groups. Group 1 received intraperitoneal (i.p.) PTX (50 mg/kg, once daily) injections, starting 15 days before surgery, and group 2, group 3, and group 4 received 50 mg/kg, 100 mg/kg, and 200 mg/kg i.p. PTX injections, respectively, once daily after surgery. All animals across groups received treatment for six weeks (until sacrificed). Complete surgical transverse osteotomy was performed in the right femur of all rats. At six weeks after surgery, the femurs were subjected to a three-point bending test. Daily administration of 50 mg/kg PTX (groups 1 and 2) decreased the high stress load in repairing osteotomized femurs when compared with the control group. The highest dose of PTX (200 mg/kg) significantly increased the high stress load when compared with the control group (P = 0.030), group 1 (P = 0.023), group 2 (P = 0.008), and group 3 (P = 0.010), per the LSD findings. Treatment with 200 mg/kg PTX accelerated fracture healing when compared with the control group.

  10. Public sector administration of ecological economics systems using mediated modeling.

    Science.gov (United States)

    van den Belt, Marjan; Kenyan, Jennifer R; Krueger, Elizabeth; Maynard, Alison; Roy, Matthew Galen; Raphael, Ian

    2010-01-01

    In today's climate of government outsourcing and multiple stakeholder involvement in public sector management and service delivery, it is more important than ever to rethink and redesign the structure of how policy decisions are made, implemented, monitored, and adapted to new realities. The traditional command-and-control approach is now less effective because an increasing amount of responsibility to deliver public goods and services falls on networks of nongovernment agencies. Even though public administrators are seeking new decision-making models in an increasingly more complex environment, the public sector currently only sparsely utilizes Mediated Modeling (MM). There is growing evidence, however, that by employing MM and similar tools, public interest networks can be better equipped to deal with their long-term viability while maintaining the short-term needs of their clients. However, it may require a shift in organizational culture within and between organizations to achieve the desired results. This paper explores the successes and barriers to implementing MM and similar tools in the public sector and offers insights into utilizing them through a review of case studies and interdisciplinary literature. We aim to raise a broader interest in MM and similar tools among public sector administrators at various administrative levels. We focus primarily, but not exclusively, on those cases operating at the interface of ecology and socio-economic systems.

  11. Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia.

    Science.gov (United States)

    Ruda-Kucerova, Jana; Babinska, Zuzana; Stark, Tibor; Micale, Vincenzo

    2017-07-01

    Ketamine may prove to be a potential candidate in treating the widespread drug addiction/substance abuse epidemic among patients with schizophrenia. Clinical studies have shown ketamine to reduce cocaine and heroin cravings. However, the use of ketamine remains controversial as it may exacerbate the symptoms of schizophrenia. Therefore, the aim of this study is to characterize the effects of ketamine on drug addiction in schizophrenia using the methylazoxymethanol (MAM) acetate rat model on operant IV methamphetamine (METH) self-administration. MAM was administered intraperitoneally (22 mg/kg) on gestational day 17. Locomotor activity test and later IV self-administration (IVSA) were then performed in the male offspring followed by a period of forced abstinence and relapse of METH taking. After reaching stable intakes in the relapse phase, ketamine (5 mg/kg) was administered intraperitoneally 30 min prior to the self-administration session. As documented previously, the MAM rats showed a lack of habituation in the locomotor activity test but developed stable maintenance of METH self-administration with no difference in operant behaviour to control animals. Results show that ketamine treatment significantly reduced the METH intake in the control animals but not in MAM animals. Ketamine effect on METH self-administration may be explained by increased glutamatergic signalling in the prefrontal cortex caused by the N-methyl-D-aspartate antagonism and disinhibition of GABA interneurons which was shown to be impaired in the MAM rats. This mechanism may at least partly explain the clinically proven anti-craving potential of ketamine and allow development of more specific anti-craving medications with fewer risks.

  12. 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.

  13. 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)

  14. Life course epidemiology: Modeling educational attainment with administrative data.

    Directory of Open Access Journals (Sweden)

    Leslie L Roos

    Full Text Available Understanding the processes across childhood and adolescence that affect later life inequalities depends on many variables for a large number of individuals measured over substantial time periods. Linkable administrative data were used to generate birth cohorts and to study pathways of inequity in childhood and early adolescence leading to differences in educational attainment. Advantages and disadvantages of using large administrative data bases for such research were highlighted.Children born in Manitoba, Canada between 1982 and 1995 were followed until age 19 (N = 89,763, with many time-invariant measures serving as controls. Five time-varying predictors of high school graduation-three social and two health-were modelled using logistic regression and a framework for examining predictors across the life course. For each time-varying predictor, six temporal patterns were tested: full, accumulation of risk, sensitive period, and three critical period models.Predictors measured in early adolescence generated the highest odds ratios, suggesting the importance of adolescence. Full models provided the best fit for the three time-varying social measures. Residence in a low-income neighborhood was a particularly influential predictor of not graduating from high school. The transmission of risk across developmental periods was also highlighted; exposure in one period had significant implications for subsequent life stages.This study advances life course epidemiology, using administrative data to clarify the relationships among several measures of social behavior, cognitive development, and health. Analyses of temporal patterns can be useful in studying such other outcomes as educational achievement, teen pregnancy, and workforce participation.

  15. Life course epidemiology: Modeling educational attainment with administrative data.

    Science.gov (United States)

    Roos, Leslie L; Wall-Wieler, Elizabeth

    2017-01-01

    Understanding the processes across childhood and adolescence that affect later life inequalities depends on many variables for a large number of individuals measured over substantial time periods. Linkable administrative data were used to generate birth cohorts and to study pathways of inequity in childhood and early adolescence leading to differences in educational attainment. Advantages and disadvantages of using large administrative data bases for such research were highlighted. Children born in Manitoba, Canada between 1982 and 1995 were followed until age 19 (N = 89,763), with many time-invariant measures serving as controls. Five time-varying predictors of high school graduation-three social and two health-were modelled using logistic regression and a framework for examining predictors across the life course. For each time-varying predictor, six temporal patterns were tested: full, accumulation of risk, sensitive period, and three critical period models. Predictors measured in early adolescence generated the highest odds ratios, suggesting the importance of adolescence. Full models provided the best fit for the three time-varying social measures. Residence in a low-income neighborhood was a particularly influential predictor of not graduating from high school. The transmission of risk across developmental periods was also highlighted; exposure in one period had significant implications for subsequent life stages. This study advances life course epidemiology, using administrative data to clarify the relationships among several measures of social behavior, cognitive development, and health. Analyses of temporal patterns can be useful in studying such other outcomes as educational achievement, teen pregnancy, and workforce participation.

  16. 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.

  17. The Potential Impact of Humanistic Psychology on Modern Administrative Style. Part II. Administrative Models and Psychological Variants.

    Science.gov (United States)

    Taylor, Raymond G., Jr.

    1984-01-01

    Explains six administrative models from insights gained through the work of modern humanistic psychologists. Suggests a modified person-oriented administrative control system which integrates the importance of the self-concept of the worker with the organization's need to be productive. (BH)

  18. 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.

  19. Semantic Modeling of Administrative Procedures from a Spanish Regional Public Administration

    OpenAIRE

    Francisco José Hidalgo López; Jose Emilio Labra Gayo; Patricia Ordóñez de Pablos

    2018-01-01

    Over the past few years, Public Administrations have been providing systems for procedures and files electronic processing to ensure compliance with regulations and provide public services to citizens. Although each administration provides similar services to their citizens, these systems usually differ from the internal information management point of view since they usually come from different products and manufacturers. The common framework that regulations demand, and that Public Administ...

  20. Model-based administration of inhalation anaesthesia. 1. Developing a system model.

    NARCIS (Netherlands)

    Lerou, J.G.C.; Booij, L.H.D.J.

    2001-01-01

    This paper is the first of a series of reports on a system model for the administration of inhalation anaesthesia. We present the development and basic testing of the model. It is a multiple-gas model; it covers fresh-gas flow rates from basal to more than total ventilation and includes an actual,

  1. Knowledge Transfer and Teaching Public Administration: The Academy Model

    Science.gov (United States)

    Hall, Michael

    2015-01-01

    Since the beginnings of Public Administration in the US and its accompanying education in other parts of the world, government and policy have become more complex. The education in Public Administration created a professional pathway to public service. The addition of education to Public Administration came out of the Progressive Movement in the…

  2. 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.

  3. Project Management in Public Administration. TPM – Total Project Management Maturity Model. The Case of Slovenian Public Administration

    Directory of Open Access Journals (Sweden)

    Gordana ŽURGA

    2018-02-01

    Full Text Available The purpose of the article is to present the importance of project management for the functioning of public administration, and its contribution to the realization of the developmental goals of the government. For this, integration of strategic management and project management is of vital importance. The methodology used is a combination of literature review, a case study of project management in public administration of the Republic of Slovenia, and development of a maturity model of project management in public administration, with its verifi cation on the case of Slovenia. The main contribution of the study is development of TPM – Total Project Management maturity model for public administration. Upon the TPM maturity model, project management in Slovene public administration is assessed and discussed. Out of fi ve maturity levels, the results for project management in Slovene public administration are: management of projects – level 2 (initiated, management of programs of projects – level 2 (initiated, management of portfolios of projects – level 3 (implemented, organizational support for project management – level 3 (implemented, HRM for project management – level 2 (initiated, and integration of project management and strategic management – level 3 (implemented. General fi ndings and recommendations in this respect are drawn, together with indicated areas for possible further research and investigation.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Nicotine administration and withdrawal affect survival in systemic inflammation models

    OpenAIRE

    Steiner, Alexandre A.; Oliveira, Daniela L.; Roberts, Jennifer L.; Petersen, Scott R.; Romanovsky, Andrej A.

    2008-01-01

    How different regimens of nicotine administration and withdrawal affect systemic inflammation is largely unknown. We studied the effects of chronic and acute nicotine administration and of nicotine withdrawal on the outcome of aseptic and septic systemic inflammation. Male C57BL/6 mice were implanted with subcutaneous osmotic pumps (to deliver nicotine) and intrabrain telemetry probes (to measure temperature). Aseptic inflammation was induced by lipopolysaccharide (40 mg/kg ip); sepsis was in...

  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. 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

  13. Model of Effective Management of Bulgarian Public Administration Managing EU Funds“

    OpenAIRE

    Nozharov, Shteryo

    2014-01-01

    Abstract: The paper analyzes the possibilities of constructing a model for the effective management of the Bulgarian public administration responsible for managing the EU funds amid the global financial crisis by using McKinsey’s 7S model. The change of the management model of the public administration in charge of the absorption of EU funds in Bulgaria would increase the absorption rate of the funds while streamlining budgetary costs on the maintenance of the administration. The aim of the s...

  14. Application of models for exchange of electronic documents in complex administrative services

    Science.gov (United States)

    Glavev, Victor

    2015-11-01

    The report presents application of models for exchange of electronic documents between different administrations in government and business sectors. It shows the benefits of implementing electronic exchange of documents between different local offices of one administration in government sector such as a municipality and the way it is useful for implementing complex administrative services.

  15. 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

  16. Carving an administrative model for uniosun: a needed reform ...

    African Journals Online (AJOL)

    ... community, to the pursuit of the aims and objectives of University education and the objective of setting up Osun State University would facilitate the realization of these aims and objective. The study examined the methods of reforming and modifying college administration in Osun State University for improved productivity.

  17. Servant-Leadership as a Model for Library Administration.

    Science.gov (United States)

    Doncevic, John

    2003-01-01

    Discussion of the need for library administration to change from traditional methods based on power and competition focuses on the concept of servant-leadership. Explains characteristics of a servant-leader, including being authentic, being present, being vulnerable and choosing appropriate responses, being accepting, and being useful. (LRW)

  18. [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.

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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

  4. A Mixed Method Research for Finding a Model of Administrative Decentralization

    OpenAIRE

    Tahereh Feizy; Alireza Moghali; Masuod Geramipoor; Reza Zare

    2015-01-01

    One of the critical issues of administrative decentralization in translating theory into practice is understanding its meaning. An important method to identify administrative decentralization is to address how it can be planned and implemented, and what are its implications, and how it would overcome challenges. The purpose of this study is finding a model for analyzing and evaluating administrative decentralization, so a mixed method research was used to explore and confirm the model of Admi...

  5. 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

  6. Extracellular administration of BCL2 protein reduces apoptosis and improves survival in a murine model of sepsis.

    Directory of Open Access Journals (Sweden)

    Akiko Iwata

    2011-02-01

    Full Text Available Severe sepsis and septic shock are major causes of morbidity and mortality worldwide. In experimental sepsis there is prominent apoptosis of various cell types, and genetic manipulation of death and survival pathways has been shown to modulate organ injury and survival.We investigated the effect of extracellular administration of two anti-apoptotic members of the BCL2 (B-cell lymphoma 2 family of intracellular regulators of cell death in a murine model of sepsis induced by cecal ligation and puncture (CLP. We show that intraperitoneal injection of picomole range doses of recombinant human (rh BCL2 or rhBCL2A1 protein markedly improved survival as assessed by surrogate markers of death. Treatment with rhBCL2 or rhBCL2A1 protein significantly reduced the number of apoptotic cells in the intestine and heart following CLP, and this was accompanied by increased expression of endogenous mouse BCL2 protein. Further, mice treated with rhBCL2A1 protein showed an increase in the total number of neutrophils in the peritoneum following CLP with reduced neutrophil apoptosis. Finally, although neither BCL2 nor BCL2A1 are a direct TLR2 ligand, TLR2-null mice were not protected by rhBCL2A1 protein, indicating that TLR2 signaling was required for the protective activity of extracellularly adminsitered BCL2A1 protein in vivo.Treatment with rhBCL2A1 or rhBCL2 protein protects mice from sepsis by reducing apoptosis in multiple target tissues, demonstrating an unexpected, potent activity of extracellularly administered BCL2 BH4-domain proteins.

  7. A generic model for evaluation of the Federal Aviation Administration air traffic control specialist training programs.

    Science.gov (United States)

    1982-03-01

    The Systems Analysis Research Unit at the Civil Aeromedical Institute (CAMI) has developed a generic model for Federal Aviation Administration (FAA) Academy training program evaluation. The model will serve as a basis for integrating the total data b...

  8. [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.

  9. Renal and hepatic histopathology of intraperitoneally administered ...

    African Journals Online (AJOL)

    user

    2016-10-12

    Oct 12, 2016 ... with Coppens fish feed containing 55% crude protein and the water quality was maintained daily with a standard test kit .... Probit value was determined from the probit model developed by Finney (1959). RESULTS ..... interbillary portal vein which have to pass through the sinusoids to get to the central vein.

  10. The Effects of Long-Term Chaetomellic Acid A Administration on Renal Function and Oxidative Stress in a Rat Model of Renal Mass Reduction

    Science.gov (United States)

    Nogueira, António; Oliveira, Maria Manuel; Pires, Carlos André; Colaço, Bruno

    2017-01-01

    Purpose. This study aimed to evaluate the effect of chronic treatment with chaetomellic acid A (CAA) on oxidative stress and renal function in a model of renal mass reduction. Methods. Male Wistar rats were subjected to 5/6 nephrectomy (RMR) or sham-operated (SO). One week after surgery, rats have been divided into four experimental groups: RMR: RMR rats without treatment (n = 14); RMR + CAA: RMR rats treated with CAA (n = 13); SO: SO rats without treatment (n = 13); and SO + CAA: SO rats treated with CAA (n = 13). CAA was intraperitoneally administered in a dose of 0.23 µg/Kg three times a week for six months. Results. RMR was accompanied by a significant reduction in catalase and glutathione reductase (GR) activity (p < 0.05) and a decrease in reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. CAA administration significantly increased catalase and GR activity (p < 0.05) and increased GSH/GSSG ratio, but no significant difference between the treated and nontreated groups was found in this ratio. No significant differences were found between the RMR groups in any of the parameters of renal function. However, CAA administration slightly improves some parameters of renal function. Conclusions. These data suggest that CAA could attenuate 5/6 RMR-induced oxidative stress. PMID:28326323

  11. Training of administrative elite in the formation of a new democratic governance model

    Directory of Open Access Journals (Sweden)

    Віктор Васильович Олійник

    2015-09-01

    Full Text Available A key condition to ensure state and public structures in terms of the systemic crisis of Ukrainian society is the formation of new administrative elite with high levels of administrative culture and spiritual and moral features. Proving the theoretical principles of a democratic model of administrative elite in the context of the transformation processes in Ukraine, the author chooses the philosophical and pedagogical ideas of Academician I. Ziaziun about improvement of Human Resource Management as a basis

  12. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    OpenAIRE

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclo...

  13. The 'British-Imperial' Model of administration: Assembling the South ...

    African Journals Online (AJOL)

    With the end of the South African War believed to be in sight, British policy makers in South Africa created the South African Constabulary (SAC) in late 1900 to provide law and order over the new Transvaal and Orange River colonies. By 1900, policy makers no longer simply exported 'English' or 'Irish' models to the ...

  14. MODELING OF TARGETED DRUG DELIVERY PART II. MULTIPLE DRUG ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    A. V. Zaborovskiy

    2017-01-01

    Full Text Available In oncology practice, despite significant advances in early cancer detection, surgery, radiotherapy, laser therapy, targeted therapy, etc., chemotherapy is unlikely to lose its relevance in the near future. In this context, the development of new antitumor agents is one of the most important problems of cancer research. In spite of the importance of searching for new compounds with antitumor activity, the possibilities of the “old” agents have not been fully exhausted. Targeted delivery of antitumor agents can give them a “second life”. When developing new targeted drugs and their further introduction into clinical practice, the change in their pharmacodynamics and pharmacokinetics plays a special role. The paper describes a pharmacokinetic model of the targeted drug delivery. The conditions under which it is meaningful to search for a delivery vehicle for the active substance were described. Primary screening of antitumor agents was undertaken to modify them for the targeted delivery based on underlying assumptions of the model.

  15. The Residual Value Models: A Framework for Business Administration

    OpenAIRE

    Konstantinos J. Liapis

    2010-01-01

    This article investigates the relationship between a firm’s performance and Residual Value Models (RVM) which serve as decision making tools in corporate management. The main measures are the Economic Value Added (EVA®) and Cash Value Added (CVA®), with key components the Residual Income (RI), Free Cash Flow (FCF) and Weighted Average Cost of Capital (WACC). These measures have attracted considerable interest among scientists, practitioners and organizations in recent years. This work focuses...

  16. Using Modified-ISS Model to Evaluate Medication Administration Safety During Bar Code Medication Administration Implementation in Taiwan Regional Teaching Hospital.

    Science.gov (United States)

    Ma, Pei-Luen; Jheng, Yan-Wun; Jheng, Bi-Wei; Hou, I-Ching

    2017-01-01

    Bar code medication administration (BCMA) could reduce medical errors and promote patient safety. This research uses modified information systems success model (M-ISS model) to evaluate nurses' acceptance to BCMA. The result showed moderate correlation between medication administration safety (MAS) to system quality, information quality, service quality, user satisfaction, and limited satisfaction.

  17. 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

  18. 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...

  19. 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.

  20. 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 ...

  1. 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 ...

  2. 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

  3. Developing a Simulation Model for the Development of Higher Education Administrators.

    Science.gov (United States)

    Cabrales, Eusebio J.; Eddy, John P.

    1992-01-01

    Describes a computer-based simulation model that can be used for the training of higher education administrators. Simulation games as instructional and training models are discussed; weighted alternatives used in the model are explained; validation is discussed; and the architecture of the computer simulation is described. (10 references) (LRW)

  4. 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

  5. 78 FR 68030 - Possible Models for the Administration and Support of Discipline-Specific Guidance Groups for...

    Science.gov (United States)

    2013-11-13

    ...-02] Possible Models for the Administration and Support of Discipline- Specific Guidance Groups for... submitting comments relating to Possible Models for the Administration and Support of Discipline-Specific... possible models for the administration and support of discipline-specific guidance groups for Forensic...

  6. 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...

  7. Effect of eye NGF administration on two animal models of retinal ganglion cells degeneration

    Directory of Open Access Journals (Sweden)

    Valeria Colafrancesco

    2011-01-01

    Full Text Available The aim of this study was to investigate the effect of nerve growth factor (NGF administration on retinal ganglion cells (RGCs in experimentally induced glaucoma (GL and diabetic retinopathy (DR. GL was induced in adult rats by injection of hypertonic saline into the episcleral vein of the eye and diabetes (DT was induced by administration of streptozoticin. Control and experimental rats were treated daily with either ocular application of NGF or vehicle solution. We found that both animal models present a progressive degeneration of RGCs and changing NGF and VEGF levels in the retina and optic nerve. We then proved that NGF eye drop administration exerts a protective effect on these models of retinal degeneration. In brief, our findings indicate that NGF can play a protective role against RGC degeneration occurring in GL and DR and suggest that ocular NGF administration might be an effective pharmacological approach.

  8. Preclinical Studies on Intestinal Administration of Antisense Oligonucleotides as a Model for Oral Delivery for Treatment of Duchenne Muscular Dystrophy

    Directory of Open Access Journals (Sweden)

    Maaike van Putten

    2014-01-01

    Full Text Available Antisense oligonucleotides (AONs used to reframe dystrophin mRNA transcripts for Duchenne muscular dystrophy (DMD patients are tested in clinical trials. Here, AONs are administered subcutaneously and intravenously, while the less invasive oral route would be preferred. Oral delivery of encapsulated AONs supplemented with a permeation enhancer, sodium caprate, has been successfully used to target tumor necrosis factor (TNF-α expression in liver. To test the feasibility of orally delivered AONs for DMD, we applied 2′-O-methyl phosphorothioate AONs (with or without sodium caprate supplementation directly to the intestine of mdx mice and compared pharmacokinetics and -dynamics with intravenous, intraperitoneal, and subcutaneous delivery. Intestinally infused AONs were taken up, but resulted in lower plasma levels compared to other delivery routes, although bioavailability could be largely improved by supplementation of sodium caprate. After intestinal infusion, AON levels in all tissues were lower than for other administration routes, as were the ratios of target versus nontarget organ levels, except for diaphragm and heart where comparable levels and ratios were observed. For each administration route, low levels of exon skipping in triceps was observed 3 hours post-AON administration. These data suggest that oral administration of naked 2′-O-methyl phosphorothioate AONs may be feasible, but only when high AON concentrations are used in combination with sodium caprate.

  9. Validation of a Best-Fit Pharmacokinetic Model for Scopolamine Disposition after Intranasal Administration

    Science.gov (United States)

    Wu, L.; Chow, D. S-L.; Tam, V.; Putcha, L.

    2015-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Motion Sickness. Bioavailability and pharmacokinetics (PK) were determined per Investigative New Drug (IND) evaluation guidance by the Food and Drug Administration. Earlier, we reported the development of a PK model that can predict the relationship between plasma, saliva and urinary scopolamine (SCOP) concentrations using data collected from an IND clinical trial with INSCOP. This data analysis project is designed to validate the reported best fit PK model for SCOP by comparing observed and model predicted SCOP concentration-time profiles after administration of INSCOP.

  10. 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

  11. [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.

  12. Overview of the Gems Model of Volunteer Administration (Generate, Educate, Mobilize and Sustain)

    Science.gov (United States)

    Culp, Ken, III

    2012-01-01

    To organize and coordinate the efforts of many volunteers, a framework for volunteer engagement is needed. The "GEMS" Model of volunteer administration was developed to assist Extension professionals and volunteer coordinators to effectively administer volunteer programs without delivering the program themselves. The GEMS Model is…

  13. Application of the Land Administration Domain Model to the City of ...

    African Journals Online (AJOL)

    The paper explores the adoption of ISO 19152, Geographic information -- Land Administration Domain Model (LADM), in the enhancement of the current City of Johannesburg Land Information System (CoJLIS) data model. The CoJLIS was established to support integration of property data within various departments of the ...

  14. Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund's adjuvant-induced knee arthritis.

    Science.gov (United States)

    Robledo-González, L E; Martínez-Martínez, A; Vargas-Muñoz, V M; Acosta-González, R I; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández Del Valle-Laisequilla, C; Reyes-García, J G; Jiménez-Andrade, J M

    2017-01-01

    The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund's adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15-day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic and nonarthritic knee joints

  15. COMPARISON OF THE EFFECTS OF AGING AND IL-6 ON THE HEPATIC INFLAMMATORY RESPONSE IN TWO MODELS OF SYSTEMIC INJURY: SCALD INJURY VERSUS I.P. LPS ADMINISTRATION

    Science.gov (United States)

    Gomez, Christian R.; Nomellini, Vanessa; Baila, Horea; Oshima, Kiyoko; Kovacs, Elizabeth J.

    2011-01-01

    Regardless of age, a marked elevation in circulating IL-6 levels correlates with increased mortality after injury or an inflammatory challenge. We previously reported that aged IL-6 knockout mice given LPS have improved survival and reduced inflammatory response than LPS-treated aged wild type (WT) mice. Herein, we analyzed the effects of aging and IL-6 on the hepatic inflammatory response in two models of systemic injury: dorsal scald (burn) injury versus intraperitoneal LPS administration. At 24 h after burn injury, circulating alanine aminotransferase and hepatic neutrophil accumulation were comparable regardless of age or IL-6 deficiency. However, at this same time point, these indicators of liver damage, in addition to hepatic levels of KC, a neutrophil chemoattractant, were increased in aged WT mice given LPS relative to young WT mice given LPS. The hepatic injury was drastically reduced in aged IL-6 knockout mice given LPS as compared with LPS-exposed aged WT mice. Our results suggest that the nature of the insult will determine the degree of remote injury in aged animals. In addition, the role of IL-6 as a contributing factor of tissue injury may be insult specific. PMID:18636046

  16. 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

  17. 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

  18. Role of mass drug administration in elimination of Plasmodium falciparum malaria: a consensus modelling study.

    Science.gov (United States)

    Brady, Oliver J; Slater, Hannah C; Pemberton-Ross, Peter; Wenger, Edward; Maude, Richard J; Ghani, Azra C; Penny, Melissa A; Gerardin, Jaline; White, Lisa J; Chitnis, Nakul; Aguas, Ricardo; Hay, Simon I; Smith, David L; Stuckey, Erin M; Okiro, Emelda A; Smith, Thomas A; Okell, Lucy C

    2017-07-01

    Mass drug administration for elimination of Plasmodium falciparum malaria is recommended by WHO in some settings. We used consensus modelling to understand how to optimise the effects of mass drug administration in areas with low malaria transmission. We collaborated with researchers doing field trials to establish a standard intervention scenario and standard transmission setting, and we input these parameters into four previously published models. We then varied the number of rounds of mass drug administration, coverage, duration, timing, importation of infection, and pre-administration transmission levels. The outcome of interest was the percentage reduction in annual mean prevalence of P falciparum parasite rate as measured by PCR in the third year after the final round of mass drug administration. The models predicted differing magnitude of the effects of mass drug administration, but consensus answers were reached for several factors. Mass drug administration was predicted to reduce transmission over a longer timescale than accounted for by the prophylactic effect alone. Percentage reduction in transmission was predicted to be higher and last longer at lower baseline transmission levels. Reduction in transmission resulting from mass drug administration was predicted to be temporary, and in the absence of scale-up of other interventions, such as vector control, transmission would return to pre-administration levels. The proportion of the population treated in a year was a key determinant of simulated effectiveness, irrespective of whether people are treated through high coverage in a single round or new individuals are reached by implementation of several rounds. Mass drug administration was predicted to be more effective if continued over 2 years rather than 1 year, and if done at the time of year when transmission is lowest. Mass drug administration has the potential to reduce transmission for a limited time, but is not an effective replacement for existing

  19. Methodology for geometric modelling. Presentation and administration of site descriptive models; Metodik foer geometrisk modellering. Presentation och administration av platsbeskrivande modeller

    Energy Technology Data Exchange (ETDEWEB)

    Munier, Raymond [Swedish Nuclear Fuel and Waste Management Co., Stockholm (Sweden); Hermanson, Jan [Golder Associates (Sweden)

    2001-03-01

    This report presents a methodology to construct, visualise and present geoscientific descriptive models based on data from the site investigations, which the SKB currently performs, to build an underground nuclear waste disposal facility in Sweden. It is designed for interaction with SICADA (SKB:s site characterisation database) and RVS (SKB:s Rock Visualisation System). However, the concepts of the methodology are general and can be used with other tools capable of handling 3D geometries and parameters. The descriptive model is intended to be an instrument where site investigation data from all disciplines are put together to form a comprehensive visual interpretation of the studied rock mass. The methodology has four main components: 1. Construction of a geometrical model of the interpreted main structures at the site. 2. Description of the geoscientific characteristics of the structures. 3. Description and geometrical implementation of the geometric uncertainties in the interpreted model structures. 4. Quality system for the handling of the geometrical model, its associated database and some aspects of the technical auditing. The geometrical model forms a basis for understanding the main elements and structures of the investigated site. Once the interpreted geometries are in place in the model, the system allows for adding descriptive and quantitative data to each modelled object through a system of intuitive menus. The associated database allows each geometrical object a complete quantitative description of all geoscientific disciplines, variabilities, uncertainties in interpretation and full version history. The complete geometrical model and its associated database of object descriptions are to be recorded in a central quality system. Official, new and old versions of the model are administered centrally in order to have complete quality assurance of each step in the interpretation process. The descriptive model is a cornerstone in the understanding of the

  20. Strategic plan modelling by hospital senior administration to integrate diversity management.

    Science.gov (United States)

    Newhouse, John J

    2010-11-01

    Limited research suggests that some hospital senior administrators and chief executive officers (CEOs) have employed a strategic planning function to achieve diversity management practices. As the hospital industry struggles with how to integrate diversity practices to improve patient satisfaction, increase the quality of care and enhance clinical outcomes for minority populations, understanding the planning process involved in this endeavour becomes significant for senior hospital administrators. What is not well understood is what this strategic planning process represents and how it is applied to integrate diversity management. Scant research exists about the type of strategic models that hospital CEOs employ when they wish to reposition their organizations through diversity management. This study examines the strategic planning models used by senior administrators to integrate diversity management for an institutional-wide agenda. A qualitative survey process was used for CEOs in the states of New York, Pennsylvania, New Jersey and Delaware. The key research questions dealt with what type of strategic plan approach senior administrators used for integrating diversity management and what rationale they used to pursue this. Significant differences were reported between three types of strategic plan modelling used by CEOs. Also, when comparing past and current practices over time, such differences existed. The need to integrate diversity management is underscored by this study. How senior hospital administrators apply strategic plan models and what impact these approaches have represent the major implications that this study offers.

  1. Intraperitoneal inflammation decreases endometriosis in a mouse model

    OpenAIRE

    Nowak, N.M.; Fischer, O.M.; Gust, T.C.; Fuhrmann, U.; Habenicht, U.-F.; Schmidt, A.

    2008-01-01

    BACKGROUND The role of the immune system in the pathogenesis of endometriosis remains elusive. It has been shown that patients have an altered peritoneal environment with increased levels of inflammatory cytokines, activated macrophages and reduced clearance of retrogradely transported endometrial fragments. However, it is not known if this unique inflammatory situation is cause or consequence of endometriosis. This study investigates the impact of a pre-existing peritoneal inflammation on en...

  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. 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...

  4. 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)

  5. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models

    Directory of Open Access Journals (Sweden)

    Minmin Li

    2015-01-01

    Full Text Available The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2 and cyclooxygenase- (COX- 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  6. Oral Administration of Escin Inhibits Acute Inflammation and Reduces Intestinal Mucosal Injury in Animal Models.

    Science.gov (United States)

    Li, Minmin; Lu, Chengwen; Zhang, Leiming; Zhang, Jianqiao; Du, Yuan; Duan, Sijin; Wang, Tian; Fu, Fenghua

    2015-01-01

    The present study aimed to investigate the effects of oral administration of escin on acute inflammation and intestinal mucosal injury in animal models. The effects of escin on carrageenan-induced paw edema in a rat model of acute inflammation, cecal ligation and puncture (CLP) induced intestinal mucosal injury in a mouse model, were observed. It was shown that oral administration of escin inhibits carrageenan-induced paw edema and decreases the production of prostaglandin E2 (PGE2) and cyclooxygenase- (COX-) 2. In CLP model, low dose of escin ameliorates endotoxin induced liver injury and intestinal mucosal injury and increases the expression of tight junction protein claudin-5 in mice. These findings suggest that escin effectively inhibits acute inflammation and reduces intestinal mucosal injury in animal models.

  7. Personalized drug administration for cancer treatment using Model Reference Adaptive Control.

    Science.gov (United States)

    Babaei, Naser; Salamci, Metin U

    2015-04-21

    A new Model Reference Adaptive Control (MRAC) approach is proposed for the nonlinear regulation problem of cancer treatment via chemotherapy. We suggest an approach for determining an optimal anticancer drug delivery scenario for cancer patients without prior knowledge of nonlinear model structure and parameters by compounding State Dependent Riccati Equation (SDRE) and MRAC which will lead to personalized drug administration. Several approaches have been proposed for eradicating cancerous cells in nonlinear tumor growth model. The main difficulty in these approaches is the requirement of nonlinear model parameters, which are unknown to physicians in reality. To cope with this shortage, we first determine the drug delivery scenario for a reference patient with known mathematical model and parameters via SDRE technique, and by using the proposed approach we adapt the drug administration scenario for another cancer patient despite unknown nonlinear model structure and model parameters. We propose an efficient approach to determine drug administration which will help physicians for prescribing a chemotherapy protocol for a cancer patient by regulating the drug delivery scenario of the reference patient. Stabilizing the tumor growth nonlinear model has been achieved via full state feedback techniques and yields a near optimal solution to cancer treatment problem. Numerical simulations show the effectiveness of the proposed algorithm for eradicating tumor lumps with different sizes in different patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Oral administration of methysticin improves cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Athanassios Fragoulis

    2017-08-01

    Conclusion: In summary, these findings show that methysticin administration activates the Nrf2 pathway and reduces neuroinflammation, hippocampal oxidative damage and memory loss in a mouse model of AD. Therefore, kavalactones might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.

  9. The road to a standard land administration domain model, and beyond ...

    NARCIS (Netherlands)

    Lemmen, C.H.J.; Uitermark, H.T.; Van Oosterom, P.J.M.; Zevenbergen, J.A.; Greenway, I.

    2011-01-01

    The Land Administration Domain Model (LADM) is a Draft International Standard (ISO DIS 19152) and in January 2011 was distributed by the ISO central secretariat for a five month voting and commenting time interval. If everything goes as planned, ISO 19152 will be an International Standard (IS) by

  10. Entrepreneurial environmental management model of marketing in a political-administrative system of Ukraine

    Directory of Open Access Journals (Sweden)

    Sadchenko Olena Vasylivna

    2015-02-01

    Full Text Available The article deals with proposals for entrepreneurial model of environmental management, in particular environmental marketing in modern political and administrative systems. In the context of the complexity of the social structure, forming a dense network of communications, globalization, cultural and economic-ecological space offers new mechanisms for the relationship between the state and civil society in environmental management.

  11. 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.

  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. Identifying type 1 and type 2 diabetic cases using administrative data: a tree-structured model.

    Science.gov (United States)

    Lo-Ciganic, Weihsuan; Zgibor, Janice C; Ruppert, Kristine; Arena, Vincent C; Stone, Roslyn A

    2011-05-01

    To date, few administrative diabetes mellitus (DM) registries have distinguished type 1 diabetes mellitus (T1DM) from type 2 diabetes mellitus (T2DM). Using a classification tree model, a prediction rule was developed to distinguish T1DM from T2DM in a large administrative database. The Medical Archival Retrieval System at the University of Pittsburgh Medical Center included administrative and clinical data from January 1, 2000, through September 30, 2009, for 209,647 DM patients aged ≥18 years. Probable cases (8,173 T1DM and 125,111 T2DM) were identified by applying clinical criteria to administrative data. Nonparametric classification tree models were fit using TIBCO Spotfire S+ 8.1 (TIBCO Software), with model size based on 10-fold cross validation. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of T1DM were estimated. The main predictors that distinguished T1DM from T2DM are age <40 years; International Classification of Disease, 9th revision, codes of T1DM or T2DM diagnosis; inpatient oral hypoglycemic agent use; inpatient insulin use; and episode(s) of diabetic ketoacidosis diagnosis. Compared with a complex clinical algorithm, the tree-structured model to predict T1DM had 92.8% sensitivity, 99.3% specificity, 89.5% PPV, and 99.5% NPV. The preliminary predictive rule appears to be promising. Being able to distinguish between DM subtypes in administrative databases will allow large-scale subtype-specific analyses of medical care costs, morbidity, and mortality. © 2011 Diabetes Technology Society.

  16. Interoperability and models for exchange of data between information systems in public administration

    Science.gov (United States)

    Glavev, Victor

    2016-12-01

    The types of software applications used by public administrations can be divided in three main groups: document management systems, record management systems and business process systems. Each one of them generates outputs that can be used as input data to the others. This is the main reason that requires exchange of data between these three groups and well defined models that should be followed. There are also many other reasons that will be discussed in the paper. Interoperability is a key aspect when those models are implemented, especially when there are different manufactures of systems in the area of software applications used by public authorities. The report includes examples of implementation of models for exchange of data between software systems deployed in one of the biggest administration in Bulgaria.

  17. Model-based methods for case definitions from administrative health data: application to rheumatoid arthritis.

    Science.gov (United States)

    Kroeker, Kristine; Widdifield, Jessica; Muthukumarana, Saman; Jiang, Depeng; Lix, Lisa M

    2017-06-23

    This research proposes a model-based method to facilitate the selection of disease case definitions from validation studies for administrative health data. The method is demonstrated for a rheumatoid arthritis (RA) validation study. Data were from 148 definitions to ascertain cases of RA in hospital, physician and prescription medication administrative data. We considered: (A) separate univariate models for sensitivity and specificity, (B) univariate model for Youden's summary index and (C) bivariate (ie, joint) mixed-effects model for sensitivity and specificity. Model covariates included the number of diagnoses in physician, hospital and emergency department records, physician diagnosis observation time, duration of time between physician diagnoses and number of RA-related prescription medication records. The most common case definition attributes were: 1+ hospital diagnosis (65%), 2+ physician diagnoses (43%), 1+ specialist physician diagnosis (51%) and 2+ years of physician diagnosis observation time (27%). Statistically significant improvements in sensitivity and/or specificity for separate univariate models were associated with (all p values model produced similar results. Youden's index was associated with these same case definition criteria, except for the length of the physician diagnosis observation time. A model-based method provides valuable empirical evidence to aid in selecting a definition(s) for ascertaining diagnosed disease cases from administrative health data. The choice between univariate and bivariate models depends on the goals of the validation study and number of case definitions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  18. Interoperable domain models: the ISO land administration domain model LADM and its external classes

    CSIR Research Space (South Africa)

    Lemmen, CHJ

    2011-09-01

    Full Text Available This paper provides a brief overview of one of the first spatial domain standards: a standard for the domain of Land Administration (LA). This standard is in the draft stage of development now (May 2011). The development of domain standards is a...

  19. 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.

  20. 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.

  1. Evaluation of simplified stream-aquifer depletion models for water rights administration

    Science.gov (United States)

    Sophocleous, Marios; Koussis, Antonis; Martin, J.L.; Perkins, S.P.

    1995-01-01

    We assess the predictive accuracy of Glover's (1974) stream-aquifer analytical solutions, which are commonly used in administering water rights, and evaluate the impact of the assumed idealizations on administrative and management decisions. To achieve these objectives, we evaluate the predictive capabilities of the Glover stream-aquifer depletion model against the MODFLOW numerical standard, which, unlike the analytical model, can handle increasing hydrogeologic complexity. We rank-order and quantify the relative importance of the various assumptions on which the analytical model is based, the three most important being: (1) streambed clogging as quantified by streambed-aquifer hydraulic conductivity contrast; (2) degree of stream partial penetration; and (3) aquifer heterogeneity. These three factors relate directly to the multidimensional nature of the aquifer flow conditions. From these considerations, future efforts to reduce the uncertainty in stream depletion-related administrative decisions should primarily address these three factors in characterizing the stream-aquifer process. We also investigate the impact of progressively coarser model grid size on numerically estimating stream leakage and conclude that grid size effects are relatively minor. Therefore, when modeling is required, coarser model grids could be used thus minimizing the input data requirements.

  2. Nicotine self-administration reverses cognitive deficits in a rat model for schizophrenia.

    Science.gov (United States)

    Waterhouse, Uta; Brennan, Katharine A; Ellenbroek, Bart A

    2018-03-01

    High comorbidity between schizophrenia and tobacco addiction has been well established. Explanatory theories include nicotine as a cognitive enhancer ameliorating symptoms of schizophrenia and underlying shared substrates increasing susceptibility to addiction in these individuals. To test these non-mutually exclusive theories, the maternal immune activation (MIA) model was utilized. To this end, pregnant Sprague Dawley rats were subcutaneously injected with a bacterial endotoxin, lipopolysaccharide (0.5 mg/kg), on gestation days 10 and 11. Selective attention and working memory in adult male offspring were subsequently assessed using the latent inhibition and delayed non-matching to sample paradigms both before and after nicotine or saline self-administration. MIA led to deficits in both latent inhibition and delayed non-matching to sample in male offspring. Further, these animals showed a small but significantly increased responding for nicotine during self-administration acquisition, although there was no difference in dose-response effect or in progressive ratio testing. However, nicotine, but not saline self-administration, significantly ameliorated the cognitive deficits induced by MIA. While the male offspring of mothers prenatally exposed to lipopolysaccharide was only slightly more sensitive to the reinforcing effects of nicotine, after self-administration, the MIA-induced cognitive deficits significantly improved. These data lend support for the self-medication hypothesis of schizophrenia. © 2017 Society for the Study of Addiction.

  3. [Comparison of Two Methods of Lidocaine Administrating for Neuroprotection in Rabbit Model of Subarachnoid Hemorrhage].

    Science.gov (United States)

    Shi, Xian-Qing; Fu, Yong-Jian; Zheng, Li-Rong

    2017-01-01

    To compare the neuroprotection effect of two methods of Lidocaine administration in rabbit model of subarachnoid hemorrhage. Forty New Zealand white rabbits were randomly divided into sham group, subarachnoid hemorrhage group (SAH), Lidocaine intravenous injection group (L1), and Lidocaine intracisternal administration group (L2). The rabbits were given general anaesthesia, then 1.5 mL autologous nonheparinized arterial blood was injected into cisterna magna to establish SAH model, while 1.5 mL saline was used in sham group. Thirty minutes later, the rabbits in L1 and L2 group respectively received 0.3 mL 2% Lidocaine administration of intravenously and intracisternally injection. All animals were sacrificed at 72 h after SAH. The samples of basilar artery and hippocampus tissue were processed for morphometric analysis. At pre-operation and 72 h after SAH, the level of interleukin-6 (IL-6) in serum was measured. HE staining and C fos immunohistochemical staining were performed in L1 and L2 groups. Artery area and artery diameter of basal arteries, normal neuron density and C-fos positive cell in hippocampus were measured at 72 h after SAH. The baseline level of IL-6 was not significant different in four groups ( P >0.05). The level of IL-6 at 72 h after SAH was significantly higher than that at pre-operation in SAH, L1 and L2 groups ( P L1 group was higher than that in L2 group ( P L2 group, the cross-section area and diameter of basal artery were smaller in SAH and L1 group, while the normal neuron density of hippocampus was less ( P <0.05). Intracisternal administration of Lidocaine could provide neuroprotection in rabbit model of subarachnoid hemorrhage.

  4. 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.

  5. Rodent Models of Alcoholic Liver Disease: Role of Binge Ethanol Administration

    Directory of Open Access Journals (Sweden)

    Shubha Ghosh Dastidar

    2018-01-01

    Full Text Available Both chronic and acute (binge alcohol drinking are important health and economic concerns worldwide and prominent risk factors for the development of alcoholic liver disease (ALD. There are no FDA-approved medications to prevent or to treat any stage of ALD. Therefore, discovery of novel therapeutic strategies remains a critical need for patients with ALD. Relevant experimental animal models that simulate human drinking patterns and mimic the spectrum and severity of alcohol-induced liver pathology in humans are critical to our ability to identify new mechanisms and therapeutic targets. There are several animal models currently in use, including the most widely utilized chronic ad libitum ethanol (EtOH feeding (Lieber–DeCarli liquid diet model, chronic intragastric EtOH administration (Tsukamoto–French model, and chronic-plus-binge EtOH challenge (Bin Gao—National Institute on Alcohol Abuse and Alcoholism (NIAAA model. This review provides an overview of recent advances in rodent models of binge EtOH administration which help to recapitulate different features and etiologies of progressive ALD. These models include EtOH binge alone, and EtOH binge coupled with chronic EtOH intake, a high fat diet, or endotoxin challenge. We analyze the strengths, limitations, and translational relevance of these models, as well as summarize the liver injury outcomes and mechanistic insights. We further discuss the application(s of binge EtOH models in examining alcohol-induced multi-organ pathology, sex- and age-related differences, as well as circadian rhythm disruption.

  6. Preclinical evaluation of erythropoietin administration in a model of radiation-induced kidney dysfunction

    International Nuclear Information System (INIS)

    Andratschke, Nicolaus; Schnaitera, Andrea; Weber, Wolfgang A.; Caia, Lu; Schill, Sabine; Wiedenmann, Nicole; Schwaiger, Markus; Molls, Michael; Nieder, Carsten

    2006-01-01

    Purpose: To test whether the clinically available growth factor erythropoietin (EPO) influences radiation-induced normal-tissue damage in a model of kidney dysfunction. Methods: Animal experiments were conducted to test the role of EPO administration in a C3H mouse model of unilateral kidney irradiation with 6, 8, and 10 Gy and to assess the effects of 2 different dose levels of EPO. The kidney function was assessed before radiotherapy, as well as 19, 25, 31, and 37 weeks thereafter by means of 99m Tc-dimercaptosuccinat scans (static scintigraphy). Results: Concomitant EPO administration significantly increased the degree of radiation-induced kidney dysfunction. A dose of 2,000 IU/kg body weight per injection tended to cause more damage than the lower dose of 500 IU/kg. Conclusion: Administration of growth factors concomitant to radiotherapy might modify the development of kidney dysfunction. Although insulin-like growth factor-1 has previously been shown to protect the kidney, such an effect could not be demonstrated for EPO. The latter agent even increased the development of nephropathy

  7. Performance measurement of administration services using balance scorecard and Kano model

    Directory of Open Access Journals (Sweden)

    Abolfazl Danaei

    2014-04-01

    Full Text Available This paper performs a survey to measure the performance of an administration unit in Iran based on a popular technique of balance scorecard. The study also uses Kano model to prioritize various factors and to provide necessary recommendation to improve the performance of different units. The survey has indicated that while these offices do well in terms of financial figures as well as customer perspective, they perform poorly in terms of learning and growth. According to our survey, it is essential to use information technology in general service offices, properly. In addition, these administrative agencies need to use hardware and software packages, more efficiently and these two basic items have received much attraction.

  8. Effects of chronic administration of drugs of abuse on impulsive choice (delay discounting) in animal models.

    Science.gov (United States)

    Setlow, Barry; Mendez, Ian A; Mitchell, Marci R; Simon, Nicholas W

    2009-09-01

    Drug-addicted individuals show high levels of impulsive choice, characterized by preference for small immediate over larger but delayed rewards. Although the causal relationship between chronic drug use and elevated impulsive choice in humans has been unclear, a small but growing body of literature over the past decade has shown that chronic drug administration in animal models can cause increases in impulsive choice, suggesting that a similar causal relationship may exist in human drug users. This article reviews this literature, with a particular focus on the effects of chronic cocaine administration, which have been most thoroughly characterized. The potential mechanisms of these effects are described in terms of drug-induced neural alterations in ventral striatal and prefrontal cortical brain systems. Some implications of this research for pharmacological treatment of drug-induced increases in impulsive choice are discussed, along with suggestions for future research in this area.

  9. Oral administration of bepotastine besilate suppressed scratching behavior of atopic dermatitis model NC/Nga mice.

    Science.gov (United States)

    Tanizaki, Hideaki; Kambe, Naotomo; Nakamura, Yuumi; Tanaka, Akane; Matsuda, Hiroshi; Miyachi, Yoshiki

    2008-01-01

    Pruritus is the most severe problem in atopic dermatitis. Even though its mechanism is still not fully understood, antihistamines have been prescribed for atopic dermatitis. To evaluate the effect of antihistamine on atopic dermatitis, we analyzed the scratching behavior in atopic dermatitis model NC/Nga mice. BALB/c mice, in which scratching behavior was induced by intradermal injection of compound 48/80 (100 microg/100 microl/mouse), and NC/Nga mice, housed in a conventional environment and having developed spontaneous eczematous regions, were monitored with a SCLABA system after oral administration of bepotastine besilate. The number of eosinophils in the ear skin and the serum leukotriene B(4) (LTB(4)) levels were also evaluated. Bepotastine at doses of 3 and 10 mg/kg effectively inhibited the compound 48/80-induced scratching behavior of BALB/c mice 1 h after oral administration, comparable with the blood T(max), which was reached within 0.8-1.6 h in humans. Bepotastine also significantly inhibited the scratching behavior of NC/Nga mice 1 h after oral administration. Even though 10 mg/kg bepotastine could not influence the number of tissue eosinophils, it effectively suppressed the serum LTB(4) levels, just comparable with the suppression of scratch behavior of NC/Nga mice. Bepotastin effectively suppressed the scratch behavior of atopic dermatitis model mice, which may not simply be explained by the suppression of histamine but also by the suppression of other mediators like LTB(4). Bepotastine could be useful in the treatment of pruritus, especially early after oral administration. 2007 S. Karger AG, Basel

  10. Hippocampal neuronal cyclooxygenase-2 downstream signaling imbalance in a rat model of chronic aluminium gluconate administration.

    Science.gov (United States)

    Wang, Hong; Ye, Mengliang; Yu, Lijuan; Wang, Jianfeng; Guo, Yuanxin; Lei, Wenjuan; Yang, Junqing

    2015-02-18

    Acute and chronic brain damages including neurodegenerative diseases are a group of neuroinflammation-associated diseases characterized by cognitive function defect and progressive neuron loss. The pathophysiological procession of brain damages involves the overexpression of cyclooxygenase (COX)-2. Owing to the limited benefit to chronic brain damage and the late adverse effect of COX-2 inhibitors, the COX downstream signaling pathway has become a focus in neurological research. In order to explore the mechanism of aluminum neurotoxicity and the importance of COX2 downstream signaling pathways to chronic brain damage, the present study was designed to simultaneously observe the prostaglandin (PG) contents, and the expressions of PG synthases and PG receptors of hippocampus in a rat model induced by chronic administration of aluminium gluconate. A rat model of chronic brain damage was established by chronic intragastric administration of aluminium gluconate (Al3+ 200 mg/kg per day, 5d a week for 20 weeks). PG contents, the expressions of PG synthases, and the expressions of PG receptors in rats were measured by ELISA, RT-PCR and Western blotting, respectively. Chronic aluminium gluconate administration resulted in hippocampal neuron injury and learning and memory disorders in rats. Aluminium gluconate administration also resulted in increased levels of PGE2, PGD2, TXA2, PGI2, and PGF2α in rat hippocampus. The DP1, EP2, IP, mPGES-1, EP4, PGIS and TXAS mRNA expressions, and the DP1, EP2 and IP protein expressions significantly increased in the Al-treated hippocampus, while the EP3 and FP mRNA and protein expressions and the TP mRNA expression decreased. The PGS/PGs/PG receptors signaling pathway in chronic aluminium gluconate-overloaded rat hippocampus is disturbed, which may be involved in the mechanism of aluminium neurotoxicity.

  11. 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.

  12. 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

  13. Information Systems Success In Public Administration: Proposal For An Exploratory Model

    Directory of Open Access Journals (Sweden)

    Deyvison de Lima Oliveira

    2015-12-01

    Full Text Available Investments in Information Systems (IS have been significantly increasing and hence the relevance of the studies on the IS success is persistent. Delone and Mclean (2003 developed an IS successful model which is a benchmark for researches in the area, however, in the perspective of the public sector, studies are still rare. In this research it was sought to propose an exploratory model of successful IS in public administration, from the identification of each construct items of the Delone and McLean (2003 original model, through multiple case studies in three Municipalities and a Town Hall of the Southern Cone of Rondônia state, in Brazil. Based on the empirical research, it was found that the IS success factors in municipal public administration are close to those factors indicated in the reviewed literature, however, showing some particularities of the public sector. A model of successful factors and items of IS, from the confrontation between literature and empirical data, is presented in the end of this work.

  14. RATING MODELS AND INFORMATION TECHNOLOGIES APPLICATION FOR MANAGEMENT OF ADMINISTRATIVE-TERRITORIAL COMPLEXES

    Directory of Open Access Journals (Sweden)

    O. M. Pshinko

    2016-12-01

    Full Text Available Purpose. The paper aims to develop rating models and related information technologies designed to resolve the tasks of strategic planning of the administrative and territorial units’ development, as well as the tasks of multi-criteria control of inhomogeneous multiparameter objects operation. Methodology. When solving problems of strategic planning of administrative and territorial development and heterogeneous classes management of objects under control, a set of agreed methods is used. Namely the multi-criteria properties analysis for objects of planning and management, diagnostics of the state parameters, forecasting and management of complex systems of different classes. Their states are estimated by sets of different quality indicators, as well as represented by the individual models of operation process. A new information technology is proposed and created to implement the strategic planning and management tasks. This technology uses the procedures for solving typical tasks, that are implemented in MS SQL Server. Findings. A new approach to develop models of analyze and management of complex systems classes based on the ratings has been proposed. Rating models development for analysis of multicriteria and multiparameter systems has been obtained. The management of these systems is performed on the base of parameters of the current and predicted state by non-uniform distribution of resources. The procedure of sensitivity analysis of the changes in the rating model of inhomogeneous distribution of resources parameters has been developed. The information technology of strategic planning and management of heterogeneous classes of objects based on the rating model has been created. Originality. This article proposes a new approach of the rating indicators’ using as a general model for strategic planning of the development and management of heterogeneous objects that can be characterized by the sets of parameters measured on different scales

  15. 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

  16. AN ANIMAL MODEL OF SCHIZOPHRENIA BASED ON CHRONIC LSD ADMINISTRATION: OLD IDEA, NEW RESULTS

    Science.gov (United States)

    Marona-Lewicka, Danuta; Nichols, Charles D.; Nichols, David E.

    2011-01-01

    Many people who take LSD experience a second temporal phase of LSD intoxication that is qualitatively different, and was described by Daniel Freedman as “clearly a paranoid state.” We have previously shown that the discriminative stimulus effects of LSD in rats also occur in two temporal phases, with initial effects mediated by activation of 5-HT2A receptors (LSD30), and the later temporal phase mediated by dopamine D2-like receptors (LSD90). Surprisingly, we have now found that non-competitive NMDA antagonists produced full substitution in LSD90 rats, but only in older animals, whereas in LSD30, or in younger animals, these drugs did not mimic LSD. Chronic administration of low doses of LSD (>3 months, 0.16 mg/kg every other day) induces a behavioral state characterized by hyperactivity and hyperirritability, increased locomotor activity, anhedonia, and impairment in social interaction that persists at the same magnitude for at least three months after cessation of LSD treatment. These behaviors, which closely resemble those associated with psychosis in humans, are not induced by withdrawal from LSD; rather, they are the result of neuroadaptive changes occurring in the brain during the chronic administration of LSD. These persistent behaviors are transiently reversed by haloperidol and olanzapine, but are insensitive to MDL-100907. Gene expression analysis data show that chronic LSD treatment produced significant changes in multiple neurotransmitter system-related genes, including those for serotonin and dopamine. Thus, we propose that chronic treatment of rats with low doses of LSD can serve as a new animal model of psychosis that may mimic the development and progression of schizophrenia, as well as model the established disease better than current acute drug administration models utilizing amphetamine or NMDA antagonists such as PCP. PMID:21352832

  17. Prophylactic Chronic Zinc Administration Increases Neuroinflammation in a Hypoxia-Ischemia Model

    Directory of Open Access Journals (Sweden)

    Constantino Tomas-Sanchez

    2016-01-01

    Full Text Available Acute and subacute administration of zinc exert neuroprotective effects in hypoxia-ischemia animal models; yet the effect of chronic administration of zinc still remains unknown. We addressed this issue by injecting zinc at a tolerable dose (0.5 mg/kg weight, i.p. for 14 days before common carotid artery occlusion (CCAO in a rat. After CCAO, the level of zinc was measured by atomic absorption spectrophotometry, nitrites were determined by Griess method, lipoperoxidation was measured by Gerard-Monnier assay, and mRNA expression of 84 genes coding for cytokines, chemokines, and their receptors was measured by qRT-PCR, whereas nitrotyrosine, chemokines, and their receptors were assessed by ELISA and histopathological changes in the temporoparietal cortex-hippocampus at different time points. Long-term memory was evaluated using Morris water maze. Following CCAO, a significant increase in nitrosative stress, inflammatory chemokines/receptors, and cell death was observed after 8 h, and a 2.5-fold increase in zinc levels was detected after 7 days. Although CXCL12 and FGF2 protein levels were significantly increased, the long-term memory was impaired 12 days after reperfusion in the Zn+CCAO group. Our data suggest that the chronic administration of zinc at tolerable doses causes nitrosative stress, toxic zinc accumulation, and neuroinflammation, which might account for the neuronal death and cerebral dysfunction after CCAO.

  18. Comparison of MSC-Neurogenin1 administration modality in MCAO rat model

    Directory of Open Access Journals (Sweden)

    Shin Dong Hoon

    2016-12-01

    Full Text Available Intracerebral (IC grafting of mesenchymal stem cells (MSCs is not currently used in humans due to its potential complications. On the other hand, intra-arterial (IA administration can be facilitated for engrafting of intensifed MSCs in the injured human brain. The study is designed to compare the two methods of MSC administration using IA and IC routes through the parameters of behavior, infarct volume, cell distribution, and MSC identification. An ischemic stroke model was generated in Sprague Dawley male rats. This experiment used MSCs/Ngn1 that express Neurogenin1 (Ngn1 to ensure grafted MSC maintenance. MSCs/Ngn1 or normal saline was administrated via the IC or IA route on day 3. All animals were randomly assigned into four groups (five rats in each group: IC-control, IA-control, IC-MSCs/Ngn1, or IA-MSCs/Ngn1. Motor behaviors, infarct volume, and distribution of superparamagnetic iron oxide (SPIO-labeled cells on magnetic resonance imaging (MRI were compared from each group. There were no baseline differencess in motor behaviors or infarct volume between IC-MSCs/Ngn1 and IA-MSCs/Ngn1. Hovever, the IA-MSCs/Ngn1 group showed the greatest recovery on Rotarod testing and adhesive removal tests (p = 0.003 and p = 0.009 vs. IC-MSCs/Ngn1, respectively. The IA-MSCs/Ngn1 group also had more evenly distributed SPIO-labeled cells on MRI. The results suggest that IA administration is likely to be benefcial for humans based on its ability to improve behavioral outcomes and ensure even MSC engrafting.

  19. 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.

  20. 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...

  1. 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.

  2. 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.

  3. 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)

  4. 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.

  5. Combination of dehydroepiandrosterone and orthovanadate administration reduces intestinal leukocyte recruitment in models of experimental sepsis.

    Science.gov (United States)

    Al-Banna, Nadia; Pavlovic, Dragan; Sharawi, Nivin; Bac, Vo Hoai; Jaskulski, Mathis; Balzer, Claudius; Weber, Stefan; Nedeljkov, Vladimir; Lehmann, Christian

    2014-09-01

    Dehydroepiandrosterone (DHEA) was shown to improve the immune function and survival in experimental sepsis. This study examined the effect of DHEA on intestinal leukocyte recruitment during experimental sepsis, considering factors of gender (male, female and ovariectomized female animals) and combined treatment using orthovanadate (OV) in two models of sepsis. Male rats underwent colon ascendens stent peritonitis (CASP) or endotoxemia. DHEA was administered after induction of experimental sepsis. Changes in leukocyte adherence and capillary perfusion (measured as intestinal functional capillary density - FCD) were assessed using intravital microscopy. While DHEA increased baseline leukocyte adherence in control animals, DHEA reduced leukocyte adherence and increased FCD in male animals with CASP. These effects were also observed in DHEA-treated ovariectomized female rats with CASP. Similarly, the administration of DHEA reduced the number of adherent leukocytes to intestinal venules by 30% in the endotoxemia model. The combined treatment of DHEA and OV significantly reduced adherence of leukocytes to intestinal venules and improved FCD. Our results indicate that DHEA is able to reduce intestinal leukocyte recruitment induced by experimental sepsis. Combination of DHEA with OV inhibits leukocyte adherence to intestinal endothelium, similar to what is achieved by the single administration of DHEA but with significantly improved FCD. These findings suggest a potential role for DHEA and OV in clinical sepsis. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. 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

  7. Bootstrap imputation with a disease probability model minimized bias from misclassification due to administrative database codes.

    Science.gov (United States)

    van Walraven, Carl

    2017-04-01

    Diagnostic codes used in administrative databases cause bias due to misclassification of patient disease status. It is unclear which methods minimize this bias. Serum creatinine measures were used to determine severe renal failure status in 50,074 hospitalized patients. The true prevalence of severe renal failure and its association with covariates were measured. These were compared to results for which renal failure status was determined using surrogate measures including the following: (1) diagnostic codes; (2) categorization of probability estimates of renal failure determined from a previously validated model; or (3) bootstrap methods imputation of disease status using model-derived probability estimates. Bias in estimates of severe renal failure prevalence and its association with covariates were minimal when bootstrap methods were used to impute renal failure status from model-based probability estimates. In contrast, biases were extensive when renal failure status was determined using codes or methods in which model-based condition probability was categorized. Bias due to misclassification from inaccurate diagnostic codes can be minimized using bootstrap methods to impute condition status using multivariable model-derived probability estimates. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. 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.

  9. Organizational models of public administration: a study of some aspects of the reality derived from Ceara State reform

    Directory of Open Access Journals (Sweden)

    Maria Lucineide Serpa Gomes

    2010-01-01

    Full Text Available The new public management is a much-debated issue in Brazil and in many other countries worldwide. Its origin is historically dated in the 80´s, attributed to State economic and fiscal crises that had reached many countries in that decade and was also a response to State Welfare deterioration. The answer given prescribed a set of policies that proclaimed the application of market principles and private sector logic to the Public Administration. The study has as the objective to analyze the relation between the new public model practices and the modernization and efficiency of the State administration. The specific objectives are concentrated on presenting the models of Public Administration; on identifying reforms carried through in Brazilian Public Administration until the current days; on analyzing managerial practices of the new model applied to state administration. This is an exploratory, qualitative and documentary research. Interviews had been carried out, and then, the study made use of the technique of content analysis. To choose the respondents in the field research, the study considered the criterion of linking the interviewee to the process of modernization of the Public Administration. Thus, managers, former-managers of the main state secretariats involved with modernization of public administration, and researchers who had previously taken part in this process were selected. The contribution of this work results in a better evaluation of the modernization of the state Administration and also of its consequences.

  10. 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 ...

  11. A physiologically based pharmacokinetic modelling approach to predict buprenorphine pharmacokinetics following intravenous and sublingual administration.

    Science.gov (United States)

    Kalluri, Hari V; Zhang, Hongfei; Caritis, Steve N; Venkataramanan, Raman

    2017-11-01

    Opioid dependence is associated with high morbidity and mortality. Buprenorphine (BUP) is approved by the Food and Drug Administration to treat opioid dependence. There is a lack of clear consensus on the appropriate dosing of BUP due to interpatient physiological differences in absorption/disposition, subjective response assessment and other patient comorbidities. The objective of the present study was to build and validate robust physiologically based pharmacokinetic (PBPK) models for intravenous (IV) and sublingual (SL) BUP as a first step to optimizing BUP pharmacotherapy. BUP-PBPK modelling and simulations were performed using SimCyp® by incorporating the physiochemical properties of BUP, establishing intersystem extrapolation factors-based in vitro-in-vivo extrapolation (IVIVE) methods to extrapolate in vitro enzyme activity data, and using tissue-specific plasma partition coefficient estimations. Published data on IV and SL-BUP in opioid-dependent and non-opioid-dependent patients were used to build the models. Fourteen model-naïve BUP-PK datasets were used for inter- and intrastudy validations. The IV and SL-BUP-PBPK models developed were robust in predicting the multicompartment disposition of BUP over a dosing range of 0.3-32 mg. Predicted plasma concentration-time profiles in virtual patients were consistent with reported data across five single-dose IV, five single-dose SL and four multiple dose SL studies. All PK parameter predictions were within 75-137% of the corresponding observed data. The model developed predicted the brain exposure of BUP to be about four times higher than that of BUP in plasma. The validated PBPK models will be used in future studies to predict BUP plasma and brain concentrations based on the varying demographic, physiological and pathological characteristics of patients. © 2017 The British Pharmacological Society.

  12. Forecasting typhoid fever incidence in the Cordillera administrative region in the Philippines using seasonal ARIMA models

    Science.gov (United States)

    Cawiding, Olive R.; Natividad, Gina May R.; Bato, Crisostomo V.; Addawe, Rizavel C.

    2017-11-01

    The prevalence of typhoid fever in developing countries such as the Philippines calls for a need for accurate forecasting of the disease. This will be of great assistance in strategic disease prevention. This paper presents a development of useful models that predict the behavior of typhoid fever incidence based on the monthly incidence in the provinces of the Cordillera Administrative Region from 2010 to 2015 using univariate time series analysis. The data used was obtained from the Cordillera Office of the Department of Health (DOH-CAR). Seasonal autoregressive moving average (SARIMA) models were used to incorporate the seasonality of the data. A comparison of the results of the obtained models revealed that the SARIMA (1,1,7)(0,0,1)12 with a fixed coefficient at the seventh lag produces the smallest root mean square error (RMSE), mean absolute error (MAE), Akaike Information Criterion (AIC), and Bayesian Information Criterion (BIC). The model suggested that for the year 2016, the number of cases would increase from the months of July to September and have a drop in December. This was then validated using the data collected from January 2016 to December 2016.

  13. [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.

  14. 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.

  15. 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...

  16. 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.

  17. Kombucha brewing under the Food and Drug Administration model Food Code: risk analysis and processing guidance.

    Science.gov (United States)

    Nummer, Brian A

    2013-11-01

    Kombucha is a fermented beverage made from brewed tea and sugar. The taste is slightly sweet and acidic and it may have residual carbon dioxide. Kombucha is consumed in many countries as a health beverage and it is gaining in popularity in the U.S. Consequently, many retailers and food service operators are seeking to brew this beverage on site. As a fermented beverage, kombucha would be categorized in the Food and Drug Administration model Food Code as a specialized process and would require a variance with submission of a food safety plan. This special report was created to assist both operators and regulators in preparing or reviewing a kombucha food safety plan.

  18. Social preference and drug self-administration: a preclinical model of social choice within peer groups.

    Science.gov (United States)

    Smith, Mark A; Pitts, Elizabeth G

    2014-02-01

    selection models of substance use propose that individuals choose or self-select into peer groups based on shared substance use histories. Few experimental studies have examined the role of selection in substance use, possibly because few preclinical models allow subjects to choose or select individuals based on a shared self-administration history. In the present study, we used custom-built, three-compartment, operant conditioning chambers that permitted multiple rats to self-administer cocaine simultaneously in the same session. Rats assigned to the center compartment had access to two response levers, each in close physical proximity to one of its partners. In one group, a rat with access to cocaine was assigned to the center compartment and flanked by one rat with access to cocaine and one rat without access. In a second group, a rat without access to cocaine was assigned to the center compartment and flanked by one rat with access to cocaine and one rat without access. In the first group, rats with access to cocaine emitted more responses on the lever in close proximity to the other rat with access to cocaine; in the second group, rats without access to cocaine emitted more responses on the lever in close proximity to the other rat without access. These preferences were not apparent immediately but developed gradually over the course of several days of testing. These data suggest that rats prefer to be in close physical proximity to another rat with a shared behavioral history during periods of drug self-administration. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Operant self-administration of pregabalin in a mouse model of neuropathic pain.

    Science.gov (United States)

    Bura, S A; Cabañero, D; Maldonado, R

    2018-04-01

    Pregabalin is a first-line agent for neuropathic pain treatment whose abuse liability remains controversial. Surprisingly, studies exploring the reinforcing properties of pregabalin in operant mouse models are missing. We evaluated the acquisition of operant pregabalin self-administration in mice exposed to a partial sciatic nerve ligation (PSNL) or a sham operation. After surgery, mice were trained in operant boxes to intravenously self-administer pregabalin at 1.5 or 3 mg/kg/inf or saline during 10 days. Thermal and mechanical sensitivity were assessed before and after self-medication, and depressive-like behaviour was evaluated after discontinuation of the treatment. Partial sciatic nerve ligation and sham-operated mice exposed to pregabalin at 3 mg/kg/inf showed higher active responding compared to mice exposed to saline. The differences in active responding were more robust in nerve-injured than in sham-operated mice. Self-medication at either dose of pregabalin partially inhibited thermal hypersensitivity, whereas only self-medication at 3 mg/kg/inf reduced mechanical sensitivity. Finally, a depressive-like behaviour was revealed after saline treatment in nerve-injured mice, and this emotional manifestation was abolished after pregabalin treatment at the high dose. Pregabalin showed reinforcing effects both in PSNL and sham-operated mice and attenuated the nociceptive and emotional manifestations of neuropathic pain in mice self-administering this drug. Therefore, pregabalin self-administration was related to neuropathic pain relief, but also to reinforcing properties related to psychotropic drug effects. This study reveals the improvement in nociceptive and emotional manifestations of neuropathic pain after operant pregabalin self-medication in mice and suggests the reinforcing effects of this drug in an operant paradigm. This study shows that mice with a nerve injury self-administer pregabalin at doses effective reducing nociceptive hypersensitivity and

  20. 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

  1. Evaluation of a novel dry eye model induced by oral administration of finasteride.

    Science.gov (United States)

    Li, Kai; Zhang, Chuanwei; Yang, Zichao; Wang, Yuliang; Si, Haipeng

    2017-12-01

    Dry eye is a common eye disease, and suitable animal models are indispensable for investigating the pathogenesis and developing treatments for dry eye. The present study was conducted to develop an androgen deficiency dry eye model induced by finasteride, and to evaluate ocular surface status and inflammatory cytokine gene expression in the lacrimal gland using a cytokine antibody array system. The results revealed that the antiandrogenic drug finasteride induced significant tear deficiency, and the histopathology results revealed significant inflammatory cell infiltration in the lacrimal gland. The cytokine antibody array system identified increased B7‑2 (also known as cluster of differentiation 86), interleukin (IL)‑1β, IL‑4, IL‑6, IL‑10, matrix metalloproteinase‑8, Fas ligand, tumor necrosis factor (TNF)‑α and metalloproteinase inhibitor 1 levels in the lacrimal gland of the dry eye model. These cytokines were validated as candidate markers through the use of western blot analysis and reverse transcription‑quantitative polymerase chain reaction. Both analyses confirmed a significant increase in proinflammatory cytokines, including IL‑1β, IL‑6 and TNF‑α, and anti‑inflammatory cytokines, including IL‑4 and IL‑10. The aforementioned data suggested that inflammation in antiandrogenic models resulted from a balance between inflammatory and anti‑inflammatory responses. Thus, direct finasteride administration may produce an applicable model for dry eye mediated by androgen deficiency. In addition, there may be a correlation between sex, steroid deficiency and the inflammatory response. The findings of the present study have provided useful information for the pathogenesis and diagnosis of dry eye mediated by androgen deficiency.

  2. Lethality of patients with rheumatoid arthritis depending on adalimumab administration: imitation modeling

    Directory of Open Access Journals (Sweden)

    D V Goryachev

    2009-01-01

    Full Text Available Lethality of pts with rheumatoid arthritis (RA exceeds mortality values in general population. Possibility of disease modifying anti-rheumatic drugs (DMARD influence on RA pts lethality has been widely discussed lately in scientific works. Objective. To determine possible lethality diminishment in Russian population of RA pts with one of biological drugs TNFα antagonist adalimumab. Material and methods. Model construction is based on the fact of lethality dependence on pt functional state assessed by HAQ. Model simulating progression of functional disability in pts with RA visiting medical institutions of Russia was made (RAISER study. 3 model variants for imitation of consecutive change of DMARDs including adalimumab were done. First consecution assessed DMARD change in the next chain: adalimumab-methotrexate-sulfasalazine-leflunomide-azathioprine-cyclosporine-palliative therapy. Second consecution: adalimumab administration after failure of first 3 DMARDs. Third consecution considered only change of synthetic DMARDs without adalimumab inclusion. Model imitated participation of 3000 pts in every consecution. Prognosis horizon was 12 years. Age of pts and initial HAQ distribution were get from results of epidemiological RAISER study. Calculation was done on the base of elevation of standardized lethality level (SLL in population of RA pts in average from 135% to 300%. SLL values from 80 to 320% were used depending on functional disability degree with converting to Russian values of age-specific lethality coefficient for 1999. Results. Lethality in treatment consecutions including adalimumab was significantly lower. To the end of 12th year in group not using adalimumab, using it at once and using it after 376 DMARDs respectively 65,1%, 71,6% and 71,1% of pts were still alive. Conclusion. Significant decrease of lethality with adalimumab inclusion in consecution of DMARD change during treatment of RA pts was demonstrated with imitation modeling

  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. Oral Administration of Pentoxifylline Reduces Endometriosis-Like Lesions in a Nude Mouse Model.

    Science.gov (United States)

    Perelló, Maria; González-Foruria, Iñaki; Castillo, Paola; Martínez-Florensa, Mario; Lozano, Francisco; Balasch, Juan; Carmona, Francisco

    2017-06-01

    Recent reports consider endometriosis to be an immunological disorder, thus suggesting potential efficacy of immunomodulators for its treatment. The aim of this study was to assess the effects of oral administration of pentoxifylline on endometriosis-like lesions in a heterologous mice model. Human endometrial tissue obtained from women (n = 5) undergoing surgery for benign conditions was implanted in nude female mice (n = 30). The animals were distributed into 3 experimental groups receiving: saline 0.1 mL/d (control, group 1); pentoxifylline 100 mg/kg/d (group 2), and pentoxifylline 200 mg/kg/d (group 3). After 28 days, the number of implants and the total volume of surgically extracted tissue were recorded. Immunohistochemical analysis was performed to assess the area of endometriosis and vascularization of endometriosis-like lesions. Cytokine levels in peritoneal fluid samples were measured. Macroscopic quantification showed a trend to dose-dependent reduction in the number of the endometriosis-like lesions after 28 days. The volume was significantly reduced in group 3 versus group 2 and controls (399.10 ± 120.68 mm 3 vs 276.75 ± 94.30 mm 3 and 145.33 ± 38.20 mm 3 , respectively; P = .04). Similarly, the mean area of endometriosis was significantly lower in group 3 (0.12 ± 0.08 mm 2 ) versus group 2 (1.35 ± 0.43 mm 2 ) and control (2.84 ± 0.60 mm 2 ; P = .001). Vascularization and cytokine levels were also reduced posttreatment. Our results suggest that the oral administration of pentoxifylline may be an alternative to current therapies for endometriosis. Nonetheless, further studies are required.

  5. A mouse dry eye model induced by topical administration of the air pollutant particulate matter 10.

    Science.gov (United States)

    Li, Juan; Tan, Gang; Ding, Xiaoyan; Wang, Yahong; Wu, Anhua; Yang, Qichen; Ye, Lei; Shao, Yi

    2017-12-01

    To introduce a novel dry eye mouse model induced by topical administration of the air pollutant particulate matter 10 (PM 10 ). A total of 60 male BALB/c mice were used in this study and divided into two groups: group A (PBS eye drops, n=30) and group B (PM 10 eye drop group, n=30). Each treatment was dosed four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14 consecutive days in the right eye. The clinical manifestations of dry eye were measured before therapy and 4, 7 and 14days post-treatment respectively, which included the tear volume, tear break-up (BUT) time, corneal fluorescein staining, rose bengal staining, Lissamine Green staining and inflammatory index. Eye samples were collected on D14 and examined by histologic light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-α (TNF-α), NF-κB-p65 and NF-κB Western Blot analysis. At 0d, 7d and 14d, there were no statistical changes in tear volume, BUT after treatment (P>0.05) with PBS in group A. In group B, all items showed statistical differences at each time point (Peye in humans, representing a novel model of DES. Copyright © 2017. Published by Elsevier Masson SAS.

  6. Brain delivery of valproic acid via intranasal administration of nanostructured lipid carriers: in vivo pharmacodynamic studies using rat electroshock model

    Directory of Open Access Journals (Sweden)

    Sharareh Eskandari

    2011-02-01

    Full Text Available Sharareh Eskandari1, Jaleh Varshosaz1, Mohsen Minaiyan2, Majid Tabbakhian11Department of Pharmaceutics, 2Department of Pharmacology, School of Pharmacy and Isfahan Pharmaceutical Sciences Research Center, Isfahan University of Medical Sciences, Isfahan, IranAbstract: The treatment of brain disorders is one of the greatest challenges in drug delivery because of a variety of main barriers in effective drug transport and maintaining therapeutic concentrations in the brain for a prolonged period. The objective of this study was delivery of valproic acid (VPA to the brain by intranasal route. For this purpose, nanostructured lipid carriers (NLCs were prepared by solvent diffusion method followed by ultrasonication and characterized for size, zeta potential, drug-loading percentage, and release. Six groups of rats each containing six animals received drug-loaded NLCs intraperitoneally (IP or intranasally. Brain responses were then examined by using maximal electroshock (MES. The hind limb tonic extension:flexion inhibition ratio was measured at 15-, 30-, 60-, 90-, and 120-minute intervals. The drug concentration was also measured in plasma and brain at the most protective point using gas chromatography method. The particle size of NLCs was 154 ± 16 nm with drug-loading percentage of 47% ± 0.8% and drug release of 75% ± 1.9% after 21 days. In vivo results showed that there was a significant difference between protective effects of NLCs of VPA and control group 15, 30, 60, and 90 minutes after treatment via intranasal route (P < 0.05. Similar protective effect was observed in rats treated with NLCs of VPA in intranasal route and positive control in IP route (P > 0.05. Results of drug determination in brain and plasma showed that brain:plasma concentration ratio was much higher after intranasal administration of NLCs of VPA than the positive control group (IP route. In conclusion, intranasal administration of NLCs of VPA provided a better protection

  7. Comparison and validation of two mathematical models for the impact of mass drug administration on Ascaris lumbricoides and hookworm infection

    NARCIS (Netherlands)

    L.E. Coffeng (Luc); J. Truscott (James); S.H. Farrell (Sam H.); H.C. Turner (Hugo C.); R. Sarkar (Rajiv); G. Kang (Gagandeep); S.J. de Vlas (Sake); R.M. Anderson (Roy)

    2017-01-01

    textabstractThe predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic

  8. Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

    Science.gov (United States)

    Robledo-González, LE; Martínez-Martínez, A; Vargas-Muñoz, VM; Acosta-González, RI; Plancarte-Sánchez, R; Anaya-Reyes, M; Fernández del Valle-Laisequilla, C; Reyes-García, JG; Jiménez-Andrade, JM

    2017-01-01

    Background The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the anti-nociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA)-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined. Methods Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding) and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p.) administered dose of mazindol was given (1, 3 and 10 mg/kg). Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26) was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro-computed tomography. Results Acute administration of mazindol decreased the spontaneous pain-like behaviors in a dose-dependent manner without reducing the knee edema. However, mazindol at 10 mg/kg significantly increased the locomotor activity; therefore, 3 mg/kg mazindol was used for further studies. Repeated administration of 3 mg/kg mazindol significantly decreased the pain-like behaviors without modifying locomotor activity. The antinociceptive effect of mazindol was blocked by administration of a D2-like receptor antagonist (haloperidol), but not by administration of D1-like receptor antagonist (SCH 23390) or an opioid receptor antagonist (naloxone). Repeated administration of mazindol did not significantly modify the density and microarchitecture of periarticular bone of the arthritic

  9. Predicting 30-day Hospital Readmission with Publicly Available Administrative Database. A Conditional Logistic Regression Modeling Approach.

    Science.gov (United States)

    Zhu, K; Lou, Z; Zhou, J; Ballester, N; Kong, N; Parikh, P

    2015-01-01

    This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". Hospital readmissions raise healthcare costs and cause significant distress to providers and patients. It is, therefore, of great interest to healthcare organizations to predict what patients are at risk to be readmitted to their hospitals. However, current logistic regression based risk prediction models have limited prediction power when applied to hospital administrative data. Meanwhile, although decision trees and random forests have been applied, they tend to be too complex to understand among the hospital practitioners. Explore the use of conditional logistic regression to increase the prediction accuracy. We analyzed an HCUP statewide inpatient discharge record dataset, which includes patient demographics, clinical and care utilization data from California. We extracted records of heart failure Medicare beneficiaries who had inpatient experience during an 11-month period. We corrected the data imbalance issue with under-sampling. In our study, we first applied standard logistic regression and decision tree to obtain influential variables and derive practically meaning decision rules. We then stratified the original data set accordingly and applied logistic regression on each data stratum. We further explored the effect of interacting variables in the logistic regression modeling. We conducted cross validation to assess the overall prediction performance of conditional logistic regression (CLR) and compared it with standard classification models. The developed CLR models outperformed several standard classification models (e.g., straightforward logistic regression, stepwise logistic regression, random forest, support vector machine). For example, the best CLR model improved the classification accuracy by nearly 20% over the straightforward logistic regression model. Furthermore, the developed CLR models tend to achieve better sensitivity of

  10. Modeling the impact and costs of semiannual mass drug administration for accelerated elimination of lymphatic filariasis.

    Directory of Open Access Journals (Sweden)

    Wilma A Stolk

    Full Text Available The Global Program to Eliminate Lymphatic Filariasis (LF has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020.

  11. Effects of methyl-eugenol administration on behavioral models related to depression and anxiety, in rats.

    Science.gov (United States)

    Norte, M C B; Cosentino, R M; Lazarini, C A

    2005-04-01

    Croton zehntneri (Cz) is a popular plant in Brazilian folk medicine. Recently, the use of its essential oil showed depressive activity response in the central nervous system (CNS). Chemical studies show that the main compound of this oil is the methyl-eugenol (ME). This work seeks to evaluate the ME activity in behavioral models of depression and anxiety, in the rat. Male rats (60 days old) were divided into four groups (n = 10) and treated with doses of 1.0, 3.0 and 10.0 ml/100 g body wt., v.o., of ME (experimental) and saline (control). One hour after treatment, they were observed in the forced swimming test and 15 min later in the open-field test. A decrease was observed in the immobility time during the forced swimming test for all experimental groups, in comparison with control group (C = 168.8 +/- 27.3; 1.0 microl = 139.1 +/- 23.5; 3.0 microl = 137.2 +/- 18.7 and 10.0 microl = 139.8 +/- 23.6). The open-field results showed no differences in comparison to the control group. The same was observed for social interaction, plus-maze and holeboard tests, suggesting no alterations in anxiety behavior. These data suggest that ME administration induced antidepressive CNS alterations, expressed by the smallest immobility in the swimming model, and not of a level able to alter motor and exploratory activity in the open-field. The absence of effects observed in the open-field can be a result of the experimental contingency, taking low anxiety levels. These data are in contradiction to observations with Cz essential oil in these models.

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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

  14. 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.

  15. 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.

  16. Amygdala Hyperactivity in MAM Model of Schizophrenia is Normalized by Peripubertal Diazepam Administration.

    Science.gov (United States)

    Du, Yijuan; Grace, Anthony A

    2016-09-01

    In addition to prefrontal cortex (PFC) and hippocampus, amygdala may have a role in the pathophysiology of schizophrenia, given its pivotal role in emotion and extensive connectivity with the PFC and hippocampus. Moreover, abnormal activities of amygdala may be related to the anxiety observed in schizophrenia patients and at-risk adolescents. These at-risk subjects demonstrated heightened levels of anxiety, which are correlated with the onset of psychosis later in life. Similarly, rats that received methyl azoxymethanol acetate (MAM) gestationally exhibited higher levels of anxiety peripubertally. In the current study, the heightened anxiety was also observed in adult MAM animals, as well as higher firing rates of BLA neurons in both peripubertal and adult MAM rats. In addition, the power of BLA theta oscillations of adult MAM rats showed a larger increase in response to conditioned stimuli (CS). We showed previously that administration of the antianxiety drug diazepam during the peripubertal period prevents the hyperdopaminergic state in adult MAM rats. In this study, we found that peripubertal diazepam treatment reduced heightened anxiety, decreased BLA neuron firing rates and attenuated the CS-induced increase in BLA theta power in adult MAM rats, supporting a persistent normalization by this treatment. This study provides a link between BLA hyperactivity and anxiety in schizophrenia model rats and that circumvention of stress may prevent the emergence of pathology in the adult.

  17. Therapeutic Effectiveness of Anti-RAGE Antibody Administration in a Rat Model of Crush Injury.

    Science.gov (United States)

    Matsumoto, Hisatake; Matsumoto, Naoya; Shimazaki, Junya; Nakagawa, Junichiro; Imamura, Yukio; Yamakawa, Kazuma; Yamada, Tomoki; Ikeda, Mitsunori; Hiraike, Hiroko; Ogura, Hiroshi; Shimazu, Takeshi

    2017-09-25

    Crush injury patients often have systemic inflammatory response syndrome that leads to multiple organ failure. Receptor for advanced glycation endproducts (RAGE) functions as a pattern recognition receptor that regulates inflammation. We evaluated the effects of anti-RAGE antibody in a crush injury model. Pressure was applied to both hindlimbs of rats for 6 h by 3.0-kg blocks and then released. Animals were randomly divided into the sham (RAGE-Sh) group, crush (RAGE-Ctrl) group or anti-RAGE antibody-treated crush (RAGE-Tx) group. Samples were collected at 3, 6 and 24 h after releasing pressure. In the RAGE-Ctrl group, fluorescent immunostaining in the lung showed upregulated RAGE expression at 3 h. The serum soluble RAGE (sRAGE) level, which reflects the amount of RAGE expression in systemic tissue, increased at 6 h. Serum interleukin 6 (IL-6; systemic inflammation marker) increased immediately at 3 h. Histological analysis revealed lung injury at 6 and 24 h. Administration of anti-RAGE antibody before releasing compression inhibited upregulated RAGE expression in the lung alveoli, suppressed RAGE-associated mediators sRAGE and IL6, attenuated the lung damage and improved the 7-day survival rate. Collectively, our results indicated that the use of anti-RAGE antibody before releasing compression is associated with a favourable prognosis following crush injury.

  18. Taurine Administration Recovers Motor and Learning Deficits in an Angelman Syndrome Mouse Model

    Directory of Open Access Journals (Sweden)

    Sara Guzzetti

    2018-04-01

    Full Text Available Angelman syndrome (AS, MIM 105830 is a rare neurodevelopmental disorder affecting 1:10–20,000 children. Patients show moderate to severe intellectual disability, ataxia and absence of speech. Studies on both post-mortem AS human brains and mouse models revealed dysfunctions in the extra synaptic gamma-aminobutyric acid (GABA receptors implicated in the pathogenesis. Taurine is a free intracellular sulfur-containing amino acid, abundant in brain, considered an inhibiting neurotransmitter with neuroprotective properties. As taurine acts as an agonist of GABA-A receptors, we aimed at investigating whether it might ameliorate AS symptoms. Since mice weaning, we orally administered 1 g/kg/day taurine in water to Ube3a-deficient mice. To test the improvement of motor and cognitive skills, Rotarod, Novel Object Recognition and Open Field tests were assayed at 7, 14, 21 and 30 weeks, while biochemical tests and amino acid dosages were carried out, respectively, by Western-blot and high-performance liquid chromatography (HPLC on frozen whole brains. Treatment of Ube3am−/p+ mice with taurine significantly improved motor and learning skills and restored the levels of the post-synaptic PSD-95 and pERK1/2-ERK1/2 ratio to wild type values. No side effects of taurine were observed. Our study indicates taurine administration as a potential therapy to ameliorate motor deficits and learning difficulties in AS.

  19. Multiple model predictive control for optimal drug administration of mixed immunotherapy and chemotherapy of tumours.

    Science.gov (United States)

    Sharifi, N; Ozgoli, S; Ramezani, A

    2017-06-01

    Mixed immunotherapy and chemotherapy of tumours is one of the most efficient ways to improve cancer treatment strategies. However, it is important to 'design' an effective treatment programme which can optimize the ways of combining immunotherapy and chemotherapy to diminish their imminent side effects. Control engineering techniques could be used for this. The method of multiple model predictive controller (MMPC) is applied to the modified Stepanova model to induce the best combination of drugs scheduling under a better health criteria profile. The proposed MMPC is a feedback scheme that can perform global optimization for both tumour volume and immune competent cell density by performing multiple constraints. Although current studies usually assume that immunotherapy has no side effect, this paper presents a new method of mixed drug administration by employing MMPC, which implements several constraints for chemotherapy and immunotherapy by considering both drug toxicity and autoimmune. With designed controller we need maximum 57% and 28% of full dosage of drugs for chemotherapy and immunotherapy in some instances, respectively. Therefore, through the proposed controller less dosage of drugs are needed, which contribute to suitable results with a perceptible reduction in medicine side effects. It is observed that in the presence of MMPC, the amount of required drugs is minimized, while the tumour volume is reduced. The efficiency of the presented method has been illustrated through simulations, as the system from an initial condition in the malignant region of the state space (macroscopic tumour volume) transfers into the benign region (microscopic tumour volume) in which the immune system can control tumour growth. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Chitosan microspheres for intrapulmonary administration of moxifloxacin: interaction with biomembrane models and in vitro permeation studies.

    Science.gov (United States)

    Ventura, Cinzia A; Tommasini, Silvana; Crupi, Emanuela; Giannone, Ignazio; Cardile, Venera; Musumeci, Teresa; Puglisi, Giovanni

    2008-02-01

    Chitosan microspheres loaded moxifloxacin were prepared to obtain sustained release of the drug after intrapulmonary administration. The microspheres were produced by the spray-drying method using glutaraldehyde as the crosslinking agent. The particles were spherical with a smooth but distorted surface morphology and were of small size, ranging from 2.5 to 6.0microm, thus suitable for inhalation. In vitro release studies showed a significant burst effect for all crosslinked systems, followed by a prolonged moxifloxacin release, particularly in the presence of the highest glutaraldehyde concentration. Lipid vesicles made of dipalmitoylphosphatidylcholine (DPPC) were used as an in vitro biomembrane model to evaluate the influence of chitosan microspheres on the interaction of moxifloxacin with biological membranes. Differential scanning calorimetry was used as a simple and non-invasive technique of analysis. Moxifloxacin freely permeates through DPPC liposomes, interacting with the hydrophobic zone of the bilayers (lowering of the DeltaH value and loss of the cooperativity of the main transition peak). Uncrosslinked microspheres rapidly swelled and dissolved releasing free chitosan that was able to interact with liposomes (increase of DeltaH value), probably altering the biomembrane permeability to the drug. Crosslinked microspheres did not show this property. Pulmonary absorption of moxifloxacin-loaded chitosan microspheres was evaluated compared to the free drug. A monolayer of Calu-3 human bronchial epithelial cells mounted on Franz diffusion cells was used as an in vitro bronchial epithelium model. Microspheres retard the absorption of moxifloxacin and within 6h the cumulative amount of permeated drug was about 18%, 11% and 7% (w/w) for free moxifloxacin, moxifloxacin-loaded crosslinked and moxifloxacin-loaded uncrosslinked microspheres, respectively.

  1. 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.

  2. Modeling the effects of repeated systemic administrations of small activity amounts In radionuclide therapy with beta emitters

    International Nuclear Information System (INIS)

    Calderon, Carlos; Gonzalez, Joaquin; Cepero, Janet; Colom, Camila; Rodriguez, Juan C.

    2008-01-01

    Full text: Good results for radionuclide therapy treatments where repeated short time spaced systemic injection of small activity amounts are given have been reported. Bone marrow and kidneys are usually considered as dose-limiting organs in radionuclide therapy. The treatments in radionuclide therapy with repeated administration could be optimized if irradiation effects in those one might be estimated. Xeno-grafted mice is the often biological model used during the evaluation of candidates for radionuclide therapy. A mathematical model of tumor cell kinetics was combined with another one reported for marrow cell kinetics which allows the calculation of marrow cell survival and proliferation in response to different irradiation schemes. Radionuclide therapy treatment with repeated administrations with radiopharmaceuticals labeled with beta emitters were simulated. The effects on fast-growing and slow-growing tumors were evaluated, as well as radiosensitive and radioresistant tumors. For more realistic estimation of absorbed dose in mice organs the cross-irradiation due to high energy beta particles was included into the MIRD's formula. Tumor and kidneys responses to the irradiation were estimated on the linear-quadratic model framework which was adapted for a multi-exponential dose rate function describing radionuclide therapy treatments with repeated administrations. Published values for murine tumors kinetics, marrows cellular turnover rates and radiosensitivities were used during the calculations. Iso-effective schemes were also determined varying the interval between fractions and the number of administration. For a given tolerated level of thrombocytopenia and absorbed dose in kidneys an optimal regime of radionuclide therapy with repeated administration could be found. The mathematical model presented here allows the prediction of the nadir and duration of thrombocytopenia, the effects on kidneys and the tumor cell response to various treatment schemes

  3. 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].

  4. 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 ...

  5. The Gateway Hypothesis, Common Liability to Addictions or the Route of Administration Model A Modelling Process Linking the Three Theories.

    Science.gov (United States)

    Mayet, Aurélie; Legleye, Stéphane; Beck, François; Falissard, Bruno; Chau, Nearkasen

    2016-01-01

    The aim of this study was to describe the transitions between tobacco (T), cannabis (C) and other illicit drugs (OIDs) initiations, to simultaneously explore several substance use theories: gateway theory (GT), common liability model (CLM) and route of administration model (RAM). Data from 2 French nationwide surveys conducted in 2005 and 2010 were used (16,421 subjects aged 18-34). Using reported ages at initiations, we reconstituted a retrospective cohort describing all initiation sequences between T, C and OID. Transition probabilities between the substances were computed using a Markov multi-state model that also tested the effect of 2 latent variables (item response theory scores reflecting propensity for early onset and further substance use) on all transitions. T initiation was associated with increased likelihood of subsequent C initiation, but the reverse relationship was also observed. While the most likely initiation sequence among subjects who initiated the 3 groups of substances was the 'gateway' sequence T x2192; C x2192; OID, this pattern was not associated with substance use propensity more than alternative sequences. Early use propensity was associated with the 'gateway' sequence but also with some alternative ones beginning with T, C or OID. If the gateway sequence appears as the most likely pattern, in line with GT, the effects of early onset and substance use propensities were also observed for some alternative sequences, which is more in line with CLM. RAM could explain reciprocal interactions observed between T and C. This suggests shared influences of individual (personality traits) and environmental (substance availability, peer influence) characteristics. © 2015 S. Karger AG, Basel.

  6. Deposition of a model substance, Tc E-HIDA, in the oral cavity after administration of lozenges, chewing gum and sublingual tablets

    DEFF Research Database (Denmark)

    Christrup, Lona Louring; Davis, S.S.; Melia, C.D.

    1990-01-01

    The deposition and clearance of a model substance, Tc E-HIDA, in the oral cavity/upper oesophagus and in the stomach after administration of lozenges, chewing gum and sublingual tablets has been followed by gamma scintigraphy in a group of healthy male volunteers. Following administration...... of sublingual tablets, the residence time of the model substance in the oral cavity was significantly longer than following administration of chewing gum. The residence time following administration of lozenges was found to be the shortest....

  7. Oral administration of sitagliptin activates CREB and is neuroprotective in murine model of brain trauma

    Directory of Open Access Journals (Sweden)

    Brian Dellavalle

    2016-12-01

    Full Text Available Introduction: Traumatic brain injury is a major cause of mortality and morbidity. We have previously shown that the injectable glucagon-like peptide-1 (GLP-1 analogue, liraglutide, significantly improved the outcome in mice after severe traumatic brain injury (TBI. In this study we are interested in the effects of oral treatment of a different class of GLP-1 based therapy, dipeptidyl peptidase IV (DPP-IV inhibition on mice after TBI. DPP-IV inhibitors reduce the degradation of endogenous GLP-1 and extend circulation of this protective peptide in the bloodstream. This class has yet to be investigated as a potential therapy for TBI. Methods: Mice were administrated once-daily 50 mg/kg of sitagliptin in a Nutella® ball or Nutella® alone throughout the study, beginning two days before severe trauma was induced with a stereotactic cryo-lesion. At two days post trauma, lesion size was determined. Brains were isolated for immunoblotting for assessment of selected biomarkers for pathology and protection.Results: Sitagliptin treatment reduced lesion size at day 2 post-injury by ~28% (p0.05. Conversely, apoptotic tone (alpha-spectrin fragmentation, Bcl-2 levels and the neuroinflammatory markers IL-6, and Iba-1 were not affected by treatment.Conclusions: This study shows, for the first time, that DPP-IV inhibition ameliorates both anatomical and biochemical consequences of TBI and activates CREB in the brain. Moreover, this work supports previous studies suggesting that the effect of GLP-1 analogues in models of brain damage relates to GLP-1 receptor stimulation in a dose-dependent manner.Keywords: GLP-1, Traumatic Brain Injury, TBI, sitagliptin, liraglutide, CREB, Oxidative Stress, GIP, DPP-IV, DPP-4

  8. Idaho Model Watershed Project : Annual Report to the Bonneville Power Administration January 1, 1997 - December 31, 1997.

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Allen; Slavin, Katie

    1998-10-28

    The Model Watershed Project was initiated in the fall of 1992 with a grant from Bonneville Power Administration. The objective of this project is to protect, enhance and restore anadromous and resident fish habitat and achieve and maintain a balance between resource protection and resource use on a holistic watershed basis.

  9. Empowering Staff and Clients: Comparing Preferences for Management Models by the Professional Degrees Held by Organization Administrators

    Science.gov (United States)

    Hardina, Donna; Montana, Salvador

    2011-01-01

    In this article, findings from a national survey of social service managers are described. Respondents were asked to identify theories and models of management that influenced their administrative activities. The results indicate that many of the respondents used an empowerment-oriented approach to management. Respondents were more likely to…

  10. INFORMATION MODELLING OF PROCESS OF ADOPTION OF ADMINISTRATIVE DECISIONS AT THE ORGANIZATION OF PROFESSIONAL DEVELOPMENT OF THE PERSONNEL

    Directory of Open Access Journals (Sweden)

    Yaroslav E. Prokushev

    2015-01-01

    Full Text Available The article is devoted to a problem of theorganization of professional developmentof personnel. The article is consideringtwo interconnected tasks. The fi rst task is: estimation of degree of need of professional development of the specifi c worker. The second task is: choice of the programof professional development. Functionalinformation models of procedures ofadoption of administrative decisions withinthese tasks are developed.

  11. Oral administration of the nitroxide radical TEMPOL exhibits immunomodulatory and therapeutic properties in multiple sclerosis models.

    Science.gov (United States)

    Neil, Sarah; Huh, Jaebong; Baronas, Victoria; Li, Xinhui; McFarland, Henry F; Cherukuri, Murali; Mitchell, James B; Quandt, Jacqueline A

    2017-05-01

    Therapies with both immunomodulatory and neuroprotective properties are thought to have the greatest promise in reducing the severity and progression of multiple sclerosis (MS). Several reactive oxygen (ROS) and reactive nitrogen species (RNS) are implicated in inflammatory-mediated damage to the central nervous system (CNS) in MS and its animal model, experimental autoimmune encephalomyelitis (EAE). TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl) is a stable nitroxide radical with potent antioxidant activity. The goal of our studies was to investigate the immunomodulatory effects and therapeutic potential of orally-delivered TEMPOL in the mouse EAE model. Mice receiving TEMPOL chow ad libitum for 2weeks prior to induction of active EAE showed delayed onset and reduced incidence of disease compared to control-fed animals. Reduced disease severity was associated with limited microglial activation and fewer inflammatory infiltrates. TEMPOL's effects were immunomodulatory, not immunosuppressive: T cells produced less interferon-γ and tumor necrosis factor-α, and TEMPOL-fed mice exhibited a shift towards T H 2-type antibody responses. Both myeloid and myeloid-dendritic cells of TEMPOL-fed EAE animals had significantly lower levels of MHC class II expression than controls; CD40 was also significantly reduced. TEMPOL administration was associated with an enrichment of CD8 + T cell populations and CD4 + FoxP 3 + regulatory populations. TEMPOL reduced the severity of clinical disease when administered after the induction of disease, and also after the onset of clinical symptoms. To exclude effects on T cell priming in vivo, TEMPOL was tested with the passive transfer of encephalitogenic T cells and was found to reduce the incidence and peak severity of disease. Protection was associated with reduced infiltrates and a relative sparing of neurofilaments and axons. The ability of oral TEMPOL to reduce inflammation and axonal damage and loss demonstrate both anti

  12. Preemptive analgesic effects of midazolam and diclofenac in rat model

    Directory of Open Access Journals (Sweden)

    Antigona Hasani

    2011-05-01

    Full Text Available The aim of the present study was to investigate the preemptive analgesic effects of intraperitoneally administrated midazolam and diclofenac, before acute and inflammatory induced pain in rat model.One hundred twenty-eight (n=8 in each group male Sprague Dawley rats were included in the study. Paw movements in response to thermal stimulation or paw flinching in response to formalin injection were compared after midazolam (0.1, 1, 5 and 10 mg/kg and diclofenac (10 mg/kg, intraperitoneal administration. Saline was used as a control.Preemptive analgesic effect was significant in both tests when diclofenac and midazolam was administrated before the pain stimuli (p<0.01 and p<0.001. Intraperitoneal injection of midazolam in doses 5 and 10 mg/kg, increase the response time in hot plate test and decrease the number of flinches in formalin test (p<0.01 vs. p<0.001. ED50 of midazolam (with diclofenac in hot plate test was 2.02 mg/kg (CI95% =-3.47-5.03 mg; and, 0.9 mg/kg (CI95% =-0.87-4.09 mg in phase I and 0.7 mg/kg (CI95% = 0.48-6.63 mg in phase II, in formalin test.Intraperitoneally administered midazolam and diclofenac had preemptive analgesic effects on acute thermal, and inflammatory induced pain in rats.

  13. 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.

  14. The Use of 3d City Models Form Oblique Images on Land Administration

    Science.gov (United States)

    Bakici, S.; Erkek, B.; Ayyildiz, E.; Özmüş, L.

    2017-11-01

    The article 718 of the civil law saying "The ownership on property includes the air above and terrain layers below to an extent providing benefit. The structures, plants and sources are included in the content of this ownership reserving the legal restrictions" and the cadastre law no. 3402 envisage 3D Cadastre. 3D data is required in order to perform 3D cadastre. To meet this requirement, oblique photogrammetry arises as the main data acquisition method. The data obtained by this method is used as base in 3D Cadastre and Land Administration activities. 3D cadastre required in the context of land administration activities in Turkey demands high resolution aerial oblique images to be used in services such as real estate value assessment & marketing in urban areas, urban planning, unlicensed construction monitoring & city administration and making location data (national address data etc.) intelligent.

  15. THE USE OF 3D CITY MODELS FORM OBLIQUE IMAGES ON LAND ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    S. Bakici

    2017-11-01

    Full Text Available The article 718 of the civil law saying “The ownership on property includes the air above and terrain layers below to an extent providing benefit. The structures, plants and sources are included in the content of this ownership reserving the legal restrictions” and the cadastre law no. 3402 envisage 3D Cadastre. 3D data is required in order to perform 3D cadastre. To meet this requirement, oblique photogrammetry arises as the main data acquisition method. The data obtained by this method is used as base in 3D Cadastre and Land Administration activities. 3D cadastre required in the context of land administration activities in Turkey demands high resolution aerial oblique images to be used in services such as real estate value assessment & marketing in urban areas, urban planning, unlicensed construction monitoring & city administration and making location data (national address data etc. intelligent.

  16. PK-PD modelling of norfloxacin after oral administration in rabbits

    Directory of Open Access Journals (Sweden)

    B.H. Pavithra

    Full Text Available Norfloxacin posses a wide spectrum of activity, excellent tissue penetration and is rapidly bactericidal at low concentrations and hence an attempt was made to integrate reported pharmacodynamic data with pharmacokinetic data of norfloxacin after oral administration in rabbits to determine its effectiveness against common bacterial pathogens infecting rabbits. Pharmacokinetic data were obtained after a single per oral administration of norfloxacin @ 100mg per kg. Plasma drug concentrations were determined using high performance liquid chromatography (HPLC. From PK-PD integration, it is observed that norfloxacin is highly effective against gram negative infections caused by Pasteurella multocida (AUC/MIC and Cmax/MIC ratio of 133.5 and 111.5 respectively, its efficacy against Salmonella spp., E. Coli, Shigella spp. and Haemophilus influenza is moderate. However, per-oral administration of norfloxacin is not suitable to contain tested gram positive bacterial pathogens infecting rabbits. [Veterinary World 2010; 3(12.000: 546-548

  17. A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease.

    Science.gov (United States)

    Hori, Yukiko; Takeda, Shuko; Cho, Hansang; Wegmann, Susanne; Shoup, Timothy M; Takahashi, Kazue; Irimia, Daniel; Elmaleh, David R; Hyman, Bradley T; Hudry, Eloise

    2015-01-23

    Interfering with the assembly of Amyloid β (Aβ) peptides from monomer to oligomeric species and fibrils or promoting their clearance from the brain are targets of anti-Aβ-directed therapies in Alzheimer disease. Here we demonstrate that cromolyn sodium (disodium cromoglycate), a Food and Drug Administration-approved drug already in use for the treatment of asthma, efficiently inhibits the aggregation of Aβ monomers into higher-order oligomers and fibrils in vitro without affecting Aβ production. In vivo, the levels of soluble Aβ are decreased by over 50% after only 1 week of daily intraperitoneally administered cromolyn sodium. Additional in vivo microdialysis studies also show that this compound decreases the half-life of soluble Aβ in the brain. These data suggest a clear effect of a peripherally administered, Food and Drug Administration-approved medication on Aβ economy, supporting further investigation of the potential long-term efficacy of cromolyn sodium in Alzheimer disease. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Oral Administration of Sitagliptin Activates CREB and Is Neuroprotective in Murine Model of Brain Trauma

    DEFF Research Database (Denmark)

    DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

    2016-01-01

    as a potential therapy for TBI. Methods: Mice were administrated once-daily 50 mg/kg of sitagliptin in a Nutella® ball or Nutella® alone throughout the study, beginning 2 days before severe trauma was induced with a stereotactic cryo-lesion. At 2 days post trauma, lesion size was determined. Brains were isolated...

  19. The representative model of teamwork adapted administrative management theory where leadership is owned exclusively by physician

    OpenAIRE

    Valentina Zaharia; I. Donciu; M.Dogaru; V.Perianu

    2015-01-01

    H.Fayol the organization as a complex organism that divides it into several parts, each part by executing specific operations, such as: technical (production), trade (supply, sale, exchange), financial records (accounting, statistics), security, insurance (Protection of property and persons) and administrative (foresight, organization, coordination, command and control).

  20. Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

    NARCIS (Netherlands)

    W.A. Stolk (Wilma); Q.A. ten Bosch (Quirine); S.J. de Vlas (Sake); P.U. Fischer (Peter); G.J. Weil (Gary); A.S. Goldman (Ann)

    2013-01-01

    textabstractThe Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is

  1. A comparison of two mathematical models of the impact of mass drug administration on the transmission and control of schistosomiasis.

    Science.gov (United States)

    Truscott, J E; Gurarie, D; Alsallaq, R; Toor, J; Yoon, N; Farrell, S H; Turner, H C; Phillips, A E; Aurelio, H O; Ferro, J; King, C H; Anderson, R M

    2017-03-01

    The predictions of two mathematical models describing the transmission dynamics of schistosome infection and the impact of mass drug administration are compared. The models differ in their description of the dynamics of the parasites within the host population and in their representation of the stages of the parasite lifecycle outside of the host. Key parameters are estimated from data collected in northern Mozambique from 2011 to 2015. This type of data set is valuable for model validation as treatment prior to the study was minimal. Predictions from both models are compared with each other and with epidemiological observations. Both models have difficulty matching both the intensity and prevalence of disease in the datasets and are only partially successful at predicting the impact of treatment. The models also differ from each other in their predictions, both quantitatively and qualitatively, of the long-term impact of 10 years' school-based mass drug administration. We trace the dynamical differences back to basic assumptions about worm aggregation, force of infection and the dynamics of the parasite in the snail population in the two models and suggest data which could discriminate between them. We also discuss limitations with the datasets used and ways in which data collection could be improved. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. The Incorporation of Agencies in Colombia’s National Administrative Structure: An Axiological Comparison between Two Organizational Models of Public Administration

    Directory of Open Access Journals (Sweden)

    Alberto Montaña

    2015-06-01

    Full Text Available The incorporation of agencies into Colombia’s Administrative Structure has generated profound debates about the need to create administrative bodies that differ from traditional ones. Such incorporation is all the more problematic when these North American agencies are introduced without any real analysis of the local tradition and culture. The situation became more complicated as a consequence of the undisputed fact that the values and philosophies of the Public Administration Structure in Colombia are different from the predominant values in the United States. Hence, this paper provides a critical analysis of the institution and of its credulous and impulsive adoption of such instruments into our reality. 

  3. Cognitive mechanisms of diazepam administration: a healthy volunteer model of emotional processing.

    Science.gov (United States)

    Pringle, A; Warren, M; Gottwald, J; Cowen, P J; Harmer, C J

    2016-06-01

    Benzodiazepine drugs continue to be prescribed relatively frequently for anxiety disorders, especially where other treatments have failed or when rapid alleviation of anxiety is imperative. The neuropsychological mechanism by which these drugs act to relieve symptoms, however, remains underspecified. Cognitive accounts of anxiety disorders emphasise hypervigilance for threat in the maintenance of the disorders. The current study examined the effects of 7- or 8-day administration of diazepam in healthy participants (n = 36) on a well-validated battery of tasks measuring emotional processing, including measures of vigilance for threat and physiological responses to threat. Compared to placebo, diazepam reduced vigilant-avoidant patterns of emotional attention (p Diazepam administration had limited effects on emotional processing, enhancing the response to positive vs negative words in the emotional categorisation task (p diazepam modulates emotional attention, an effect which may be involved in its therapeutic actions in anxiety.

  4. Whole tissue AC susceptibility after superparamagnetic iron oxide contrast agent administration in a rat model

    International Nuclear Information System (INIS)

    Lazaro, Francisco Jose; Gutierrez, Lucia; Rosa Abadia, Ana; Soledad Romero, Maria; Lopez, Antonio; Jesus Munoz, Maria

    2007-01-01

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem ( R)), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers

  5. Impact of the Type of Continuous Insulin Administration on Metabolism in a Diabetic Rat Model

    Directory of Open Access Journals (Sweden)

    A. Schaschkow

    2016-01-01

    Full Text Available Exogenous insulin is the only treatment available for type 1 diabetic patients and is mostly administered by subcutaneous (SC injection in a basal and bolus scheme using insulin pens (injection or pumps (preimplanted SC catheter. Some divergence exists between these two modes of administration, since pumps provide better glycaemic control compared to injections in humans. The aim of this study was to compare the impacts of two modes of insulin administration (single injections of long-acting insulin or pump delivery of rapid-acting insulin at the same dosage (4 IU/200 g/day on rat metabolism and tissues. The rat weight and blood glucose levels were measured periodically after treatment. Immunostaining for signs of oxidative stress and for macrophages was performed on the liver and omental tissues. The continuous insulin delivery by pumps restored normoglycaemia, which induced the reduction of both reactive oxygen species and macrophage infiltration into the liver and omentum. Injections controlled the glucose levels for only a short period of time and therefore tissue stress and inflammation were elevated. In conclusion, the insulin administration mode has a crucial impact on rat metabolic parameters, which has to be taken into account when studies are designed.

  6. Translational modelling of prolactin response following administration of D2 antagonists in rats

    NARCIS (Netherlands)

    Taneja, Amit; Vermeulen, An; Huntjens, D.; Danhof, Meindert; de Lange, ECM; Proost, Johannes

    2015-01-01

    Objectives: Treatment with D2 antagonists results in prolactin release, and thus prolactin is a biomarker of dopamine antagonism. We compare the model performance of two semi-mechanistic PKPD models, the pool model and the agonist-antagonist interaction model, to describe prolactin release following

  7. GABAergic modulation of human social interaction in a prisoner’s dilemma model via acute administration of alprazolam

    OpenAIRE

    Lane, Scott D.; Gowin, Joshua L.

    2009-01-01

    Recent work in neuroeconomics has utilized game theory paradigms to examine neural systems that subserve human social interaction and decision making. Attempts to modify social interaction through pharmacological manipulation have been less common. Here we show dose-dependent modification of human social behavior in a prisoner’s dilemma (PD) model following acute administration of the GABA-A modulating benzodiazepine alprazolam. Nine healthy adults received doses of placebo, 0.5, 1.0, and 2.0...

  8. Effects of Systemic Administration of Oxytocin on Contextual Fear Extinction in a Rat Model of Post-Traumatic Stress Disorder

    OpenAIRE

    Eskandarian, Sharaf; Vafaei, Abbas Ali; Vaezi, Gholam Hassan; Taherian, Fatemeh; Kashefi, Adel; Rashidy-Pour, Ali

    2013-01-01

    Introduction One of the hallmark symptoms of posttraumatic stress disorder (PTSD) is the impaired extinction of traumatic memory. Single prolonged stress (SPS) has been suggested as an animal model of PTSD, since SPS rats exhibited the impaired fear extinction. Oxytocin (OXT) has been recently suggested as a potential pharmacotherapy for treatment of PTSD. In this study, using SPS rats we investigated the effects of multiple systemic administration of OXT on contextual fear extinction. Method...

  9. 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.

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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...

  16. Measuring the Effects of Customs and Administrative Procedures on Trade: Gravity Model for South-Eastern Europe

    Directory of Open Access Journals (Sweden)

    Katerina Toševska-Trpčevska

    2014-04-01

    Full Text Available This paper measures the effects of certain customs and administrative procedures on trade between the countries of South-Eastern Europe in the period 2008-2012. Following OECD methodology, we employ the augmented gravity model. The empirical results suggest that the number of days spent at the border and costs paid in both importer and exporter countries had significant negative influence on the volume of trade in the period 2008-2012. In addition, the model underlines that sharing the same border and being part of the former Yugoslav market are important determinants of trade in the region.

  17. Orexin-1 and orexin-2 receptor antagonists reduce ethanol self-administration in high-drinking rodent models

    Directory of Open Access Journals (Sweden)

    Rachel Ivy Anderson

    2014-02-01

    Full Text Available To examine the role of orexin-1 and orexin-2 receptor activity on ethanol self-administration, compounds that differentially target orexin (OX receptor subtypes were assessed in various self-administration paradigms using high-drinking rodent models. Effects of the OX1 antagonist SB334867, the OX2 antagonist LSN2424100, and the mixed OX1/2 antagonist almorexant (ACT-078573 on home cage ethanol consumption were tested in ethanol-preferring (P rats using a 2-bottle choice procedure. In separate experiments, effects of SB334867, LSN2424100, and almorexant on operant ethanol self-administration were assessed in P rats maintained on a progressive ratio operant schedule of reinforcement. In a third series of experiments, SB334867, LSN2424100, and almorexant were administered to ethanol-preferring C57BL/6J mice to examine effects of OX receptor blockade on ethanol intake in a binge-like drinking (drinking-in-the-dark model. In P rats with chronic home cage free-choice ethanol access, SB334867 and almorexant significantly reduced ethanol intake, but almorexant also reduced water intake, suggesting nonspecific effects on consummatory behavior. In the progressive ratio operant experiments, LSN2424100 and almorexant reduced breakpoints and ethanol consumption in P rats, whereas the almorexant inactive enantiomer and SB334867 did not significantly affect the motivation to consume ethanol. As expected, vehicle-injected mice exhibited binge-like drinking patterns in the drinking-in-the-dark model. All three OX antagonists reduced both ethanol intake and resulting blood ethanol concentrations relative to vehicle-injected controls, but SB334867 and LSN2424100 also reduced sucrose consumption in a different cohort of mice, suggesting nonspecific effects. Collectively, these results contribute to a growing body of evidence indicating that OX1 and OX2 receptor activity influences ethanol self-administration, although the effects may not be selective for ethanol

  18. Whole tissue AC susceptibility after superparamagnetic iron oxide contrast agent administration in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Lazaro, Francisco Jose [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, 50018 Zaragoza (Spain) and Instituto de Nanociencia de Aragon, Universidad de Zaragoza, 50009 Zaragoza (Spain)]. E-mail: osoro@unizar.es; Gutierrez, Lucia [Departamento de Ciencia y Tecnologia de Materiales y Fluidos, Universidad de Zaragoza, 50018 Zaragoza (Spain); Rosa Abadia, Ana [Dept. Farmacologia y Fisiologia, Universidad de Zaragoza, 50013 Zaragoza (Spain); Soledad Romero, Maria [Dept. Medicina y Psiquiatria, Universidad de Zaragoza, 50009 Zaragoza (Spain); Lopez, Antonio [CNAM - Zaragoza, 50009 Zaragoza (Spain); Jesus Munoz, Maria [Dept. Farmacologia y Fisiologia, Universidad de Zaragoza, 50013 Zaragoza (Spain)

    2007-04-15

    A magnetic AC susceptibility characterisation of rat tissues after intravenous administration of superparamagnetic iron oxide (Endorem{sup (R)}), at the same dose as established for Magnetic Resonance Imaging (MRI) contrast enhancement in humans, has been carried out. The measurements reveal the presence of the contrast agent as well as that of physiological ferritin in liver and spleen while no traces have been magnetically detected in heart and kidney. This preliminary work opens suggestive possibilities for future biodistribution studies of any type of magnetic carriers.

  19. Examination of the low frequency limit for helicopter noise data in the Federal Aviation Administration's Aviation Environmental Design Tool and Integrated Noise Model

    Science.gov (United States)

    2010-04-19

    The Federal Aviation Administration (FAA) aircraft noise modeling tools Aviation Environmental Design Tool (AEDTc) and Integrated Noise Model (INM) do not currently consider noise below 50 Hz in their computations. This paper describes a preliminary ...

  20. Off-Highway Gasoline Consuption Estimation Models Used in the Federal Highway Administration Attribution Process: 2008 Updates

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, Ho-Ling [ORNL; Davis, Stacy Cagle [ORNL

    2009-12-01

    This report is designed to document the analysis process and estimation models currently used by the Federal Highway Administration (FHWA) to estimate the off-highway gasoline consumption and public sector fuel consumption. An overview of the entire FHWA attribution process is provided along with specifics related to the latest update (2008) on the Off-Highway Gasoline Use Model and the Public Use of Gasoline Model. The Off-Highway Gasoline Use Model is made up of five individual modules, one for each of the off-highway categories: agricultural, industrial and commercial, construction, aviation, and marine. This 2008 update of the off-highway models was the second major update (the first model update was conducted during 2002-2003) after they were originally developed in mid-1990. The agricultural model methodology, specifically, underwent a significant revision because of changes in data availability since 2003. Some revision to the model was necessary due to removal of certain data elements used in the original estimation method. The revised agricultural model also made use of some newly available information, published by the data source agency in recent years. The other model methodologies were not drastically changed, though many data elements were updated to improve the accuracy of these models. Note that components in the Public Use of Gasoline Model were not updated in 2008. A major challenge in updating estimation methods applied by the public-use model is that they would have to rely on significant new data collection efforts. In addition, due to resource limitation, several components of the models (both off-highway and public-us models) that utilized regression modeling approaches were not recalibrated under the 2008 study. An investigation of the Environmental Protection Agency's NONROAD2005 model was also carried out under the 2008 model update. Results generated from the NONROAD2005 model were analyzed, examined, and compared, to the extent that

  1. Neutrophil dynamics during concurrent chemotherapy and G-CSF administration: Mathematical modelling guides dose optimisation to minimise neutropenia.

    Science.gov (United States)

    Craig, Morgan; Humphries, Antony R; Nekka, Fahima; Bélair, Jacques; Li, Jun; Mackey, Michael C

    2015-11-21

    The choice of chemotherapy regimens is often constrained by the patient's tolerance to the side effects of chemotherapeutic agents. This dose-limiting issue is a major concern in dose regimen design, which is typically focused on maximising drug benefits. Chemotherapy-induced neutropenia is one of the most prevalent toxic effects patients experience and frequently threatens the efficient use of chemotherapy. In response, granulocyte colony-stimulating factor (G-CSF) is co-administered during chemotherapy to stimulate neutrophil production, increase neutrophil counts, and hopefully avoid neutropenia. Its clinical use is, however, largely dictated by trial and error processes. Based on up-to-date knowledge and rational considerations, we develop a physiologically realistic model to mathematically characterise the neutrophil production in the bone marrow which we then integrate with pharmacokinetic and pharmacodynamic (PKPD) models of a chemotherapeutic agent and an exogenous form of G-CSF (recombinant human G-CSF, or rhG-CSF). In this work, model parameters represent the average values for a general patient and are extracted from the literature or estimated from available data. The dose effect predicted by the model is confirmed through previously published data. Using our model, we were able to determine clinically relevant dosing regimens that advantageously reduce the number of rhG-CSF administrations compared to original studies while significantly improving the neutropenia status. More particularly, we determine that it could be beneficial to delay the first administration of rhG-CSF to day seven post-chemotherapy and reduce the number of administrations from ten to three or four for a patient undergoing 14-day periodic chemotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Biodistribution of indium-111-labeled OC 125 monoclonal antibody after intraperitoneal injection in nude mice intraperitoneally grafted with ovarian carcinoma

    International Nuclear Information System (INIS)

    Thedrez, P.; Saccavini, J.C.; Nolibe, D.; Simoen, J.P.; Guerreau, D.; Gestin, J.F.; Kremer, M.; Chatal, J.F.

    1989-01-01

    The purpose of this work was to study the biodistribution of 111In-labeled OC 125 monoclonal antibody (MAb) with known affinity for ovarian carcinomas in a nude mouse model grafted i.p. with a human ovarian cancer (NIH:OVCAR-3). Tumor uptake 24 h after i.p. injection was higher with intact 111In-labeled OC 125 MAb than with 111In-nonspecific immunoglobulin. The kinetics of tumor uptake also differed, showing a plateau followed by a drop at Day 7 with 111In-OC 125 MAb and a decrease beginning at 24 h with 111In-nonspecific immunoglobulin. Tumor-to-normal tissue ratios ranged between 29.91 +/- 11.85 and 0.68 +/- 0.15 with 111In-OC 125 MAb and between 4.50 +/- 1.06 and 0.53 +/- 0.04 with 111In-nonspecific immunoglobulin according to the normal tissues and the time points considered. Tumor uptake 2 h after injection was the same for F(ab')2 fragments as for intact MAb, whereas maximum uptake at 24 h was lower and was followed by a decrease at Day 4. Tumor-to-normal tissue ratios were in the same range, except for the tumor to blood ratio which was higher and the tumor to kidney ratio which was lower at 24 and 96 h. Maximum tumor uptake was higher after i.p. than i.v. injection. Instead of attaining the plateau noted after i.p. injection, tumor uptake after i.v. injection remained low at 2 h, reaching its peak only after 96 h. 131I-OC 125 injected i.p., which reached maximum tumor uptake at 2 h, showed tumor-to-tissue ratios ranging between 15.98 +/- 2.63 and 0.96 +/- 0.86, i.e., not very different from those with 111In. After i.p. injection of a radiolabeled colloid solution, maximum tumor uptake was reached at 96 h, but with very high nonspecific uptake in liver and spleen. These results indicate high, selective tumor uptake of 111In-OC 125 after i.p

  3. Antinociceptive and Anti-Inflammatory Effects of Orally Administrated Denatured Naja Naja Atra Venom on Murine Rheumatoid Arthritis Models

    Directory of Open Access Journals (Sweden)

    Kou-Zhu Zhu

    2013-01-01

    Full Text Available To investigate the antinociceptive and anti-inflammatory activities of the denatured Naja Naja atra venom (NNAV in rheumatoid arthritis-associated models, the denatured NNAV (heat treated; 30, 90, 270 μg/kg, the native NNAV (untreated with heat; 90 μg/kg, and Tripterygium wilfordii polyglycoside (TWP, 15 mg/kg were administrated orally either prophylactically or therapeutically. We measured time of licking the affected paw in formaldehyde-induced inflammatory model, paw volume in egg-white-induced inflammation, and granuloma weight in formalin-soaked filter paper-induced granuloma. For adjuvant-induced arthritis (AIA rats, paw edema, mechanical withdrawal threshold, serum levels of TNF-α and IL-10, and histopathological changes of the affected paw were assessed. We found that the denatured NNAV (90, 270 μg/kg significantly reduced time of licking paw, paw volume, and granuloma weight in above inflammatory models and also attenuated paw edema, mechanical hyperalgesia, and histopathology changes in AIA rats. Additionally, the increase in serum TNF-α and the decrease in serum IL-10 in AIA rats were reversed by the denatured NNAV. Although the native NNAV and TWP rendered the similar pharmacological actions on the above four models with less potency than that of the denatured NNAV, these findings demonstrate that oral administration of the denatured NNAV produces antinociceptive and anti-inflammatory activities on rheumatoid arthritis.

  4. London Model of Multicultural Development: Urban Administrative Initiatives and Cultural Integration of Ethnic Minorities

    Directory of Open Access Journals (Sweden)

    A B Berson

    2011-09-01

    Full Text Available London is among most culturally diverse cities in Europe and in the world. This paper will investigate ethnic cultural integration of immigrants within the city's social space. Firstly the paper explores multi-cultural political inclusion strategies of London administration, municipal service provision and policy and cultural integration programs both on the city level and locally in London boroughs. Secondly this paper raises the question of the initiatives of ethnic minorities, the issue of ghettoisation and linguistic segregation of the city and analyzes the impact of such integration on social city space. The paper also analyses the preparation to Olympic Games 2012 in London as they are presented as cultural cohesion element.

  5. Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study

    Directory of Open Access Journals (Sweden)

    Marcin Ozarowski

    2015-01-01

    Full Text Available Eryngium planum L. (EP is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o. on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE, butyrylcholinesterase (BuChE, and beta-secretase (BACE-1 mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU, scopolamine (SC was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins in the extract of EP roots.

  6. TRANSDERMAL ADMINISTRATION OF THE DOPAMINE AGONIST N-0437 AND 7 ESTER PRODRUGS - COMPARISON WITH ORAL-ADMINISTRATION IN THE 6-OHDA TURNING MODEL

    NARCIS (Netherlands)

    DENDAAS, [No Value; TEPPER, PG; ROLLEMA, H; HORN, AS

    1990-01-01

    The potent and selective D2-agonist N-0437 [2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin] undergoes considerable first-pass metabolism after oral administration due to glucuronidation of the phenolic group. In an attempt to improve its bioavailability, seven ester prodrugs of N-0437 were

  7. 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.

  8. A Model of Interdisciplinary Ambulatory Geriatric Care in a Veterans Administration Medical Center.

    Science.gov (United States)

    Millman, Andrea; And Others

    1986-01-01

    Presents a model of outpatient interdisciplinary geriatric care provided at a veteran's hospital. Compares characteristics of patients served in this program with those in community-based geriatrics outpatient clinics described in the literature. (Author/ABB)

  9. Co-administration of morphine and gabapentin leads to dose dependent synergistic effects in a rat model of postoperative pain

    DEFF Research Database (Denmark)

    Papathanasiou, Theodoros; Juul, Rasmus Vestergaard; Heegaard, Anne-Marie

    2016-01-01

    dose combinations and investigate whether co-administration leads to synergistic effects in a preclinical model of postoperative pain. The pharmacodynamic effects of morphine (1, 3 and 7 mg/kg), gabapentin (10, 30 and 100 mg/kg) or their combination (9 combinations in total) were evaluated in the rat...... plantar incision model using an electronic von Frey device. The percentage of maximum possible effect (%MPE) and the area under the response curve (AUC) were used for evaluation of the antihyperalgesic effects of the drugs. Identification of synergistic interactions was based on Loewe additivity response...... surface analyses. The combination of morphine and gabapentin resulted in synergistic antihyperalgesic effects in a preclinical model of postoperative pain. The synergistic interactions were found to be dose dependent and the increase in observed response compared to the theoretical additive response...

  10. The effect of systemic administration of ibuprofen in the experimental gingivitis model.

    Science.gov (United States)

    Sekino, Satoshi; Ramberg, Per; Lindhe, Jan

    2005-02-01

    Studies in humans have indicated that systemically administered flurbiprofen and ibuprofen may reduce gingivitis. De novo plaque formation is enhanced at tooth surfaces adjacent to inflamed gingivae. The aim of the present clinical trial was to evaluate the effect of systemic administration of ibuprofen on gingivitis and plaque build-up. Eleven subjects were recruited for the study and were given oral hygiene instruction, scaling and professional mechanical tooth cleaning (PTC). At the end of a preparatory period (Day 0), the participants were told to abstain from all mechanical plaque control measures during a 2-week experimental period but to rinse with an assigned mouth rinse (positive control: 0.1% chlorhexidine digluconate; negative control: saline) or administer ibuprofen (tablets of 200 mg twice daily). Mouth rinsing was performed twice a day (after breakfast and in the evening), for 60 s with 10 ml. Re-examination was performed after 14 days of experiment. After a 2-week "wash-out" period, the participants received a new PTC and a second 14-day experimental period was initiated. The experimental and "wash-out" periods were repeated until all volunteers had been involved in all three regimens. Dental plaque was scored using the Quigley & Hein Plaque Index system and gingivitis according to the Gingival Index (GI) system. Supragingival plaque was collected and prepared for dark-field microscopy. One hundred bacterial cells were counted and classified into six different groups: coccoid cells, straight rods, filaments, fusiforms, spirochetes and motile rods. Gingival crevicular fluid (GCF) was collected from the same sites that were sampled for plaque. The volume of GCF collected in each strip was measured and analysed regarding content of lactoferrin and albumin. During the period when the panelists rinsed with saline they accumulated large amounts of plaque and developed marked signs of gingivitis. When they rinsed with chlorhexidine digluconate, small

  11. Peripubertal diazepam administration prevents the emergence of dopamine system hyperresponsivity in the MAM developmental disruption model of schizophrenia.

    Science.gov (United States)

    Du, Yijuan; Grace, Anthony A

    2013-09-01

    Schizophrenia is believed to arise from an interaction of genetic predisposition and adverse environmental factors, with stress being a primary variable. We propose that alleviating anxiety produced in response to stress during a sensitive developmental period may circumvent the dopamine (DA) system alterations that may correspond to psychosis in adults. This was tested in a developmental rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM). MAM administration leads to a hyperdopaminergic state consisting of an increase in the number of DA neurons firing spontaneously, which correlates with an increased behavioral response to amphetamine. MAM-treated rats exhibited a heightened level of anxiety during adolescence. Peripubertal administration of the antianxiety agent diazepam was found to prevent the increase in DA neuron activity and blunt the behavioral hyperresponsivity to amphetamine in these rats. These data suggest that the pathophysiological factors leading to the onset of psychosis in early adulthood may be circumvented by controlling the response to stress during the peripubertal period.

  12. Peripubertal Diazepam Administration Prevents the Emergence of Dopamine System Hyperresponsivity in the MAM Developmental Disruption Model of Schizophrenia

    Science.gov (United States)

    Du, Yijuan; Grace, Anthony A

    2013-01-01

    Schizophrenia is believed to arise from an interaction of genetic predisposition and adverse environmental factors, with stress being a primary variable. We propose that alleviating anxiety produced in response to stress during a sensitive developmental period may circumvent the dopamine (DA) system alterations that may correspond to psychosis in adults. This was tested in a developmental rat model of schizophrenia based on prenatal administration of the mitotoxin methyl azoxymethanol acetate (MAM). MAM administration leads to a hyperdopaminergic state consisting of an increase in the number of DA neurons firing spontaneously, which correlates with an increased behavioral response to amphetamine. MAM-treated rats exhibited a heightened level of anxiety during adolescence. Peripubertal administration of the antianxiety agent diazepam was found to prevent the increase in DA neuron activity and blunt the behavioral hyperresponsivity to amphetamine in these rats. These data suggest that the pathophysiological factors leading to the onset of psychosis in early adulthood may be circumvented by controlling the response to stress during the peripubertal period. PMID:23612434

  13. Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts

    OpenAIRE

    Kenjiro Shima; Toshiyuki Koya; Keisuke Tsukioka; Takuro Sakagami; Takashi Hasegawa; Chiharu Fukano; Katsuyo Ohashi-Doi; Satoshi Watanabe; Eiichi Suzuki; Toshiaki Kikuchi

    2017-01-01

    Background: Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. Methods: Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or hig...

  14. Repeated administration of mazindol reduces spontaneous pain-related behaviors without modifying bone density and microarchitecture in a mouse model of complete Freund’s adjuvant-induced knee arthritis

    Directory of Open Access Journals (Sweden)

    Robledo-González LE

    2017-07-01

    Full Text Available LE Robledo-González,1 A Martínez-Martínez,1 VM Vargas-Muñoz,1 RI Acosta-González,2 R Plancarte-Sánchez,3 M Anaya-Reyes,4 C Fernández del Valle-Laisequilla,5 JG Reyes-García,6 JM Jiménez-Andrade1 1Laboratorio de Farmacología, 2Departamento de Análisis Clínicos, Unidad Académica Multidisciplinaria Reynosa-Aztlán, UAT, Reynosa, Tamaulipas, Mexico; 3Departamento de Anestesiología, Terapia Intensiva y Clínica del Dolor, Instituto Nacional de Cancerología, Mexico City, Mexico; 4Investigación Clínica y Farmacovigilancia, 5Investigación Clínica y Farmacovigilancia, Productos Medix, S.A. de C.V., Mexico City, Mexico; 6Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Background: The role of dopaminergic system in the development of rheumatoid arthritis-related pain, a major symptom in this disease, has not been explored. Therefore, the antinociceptive effect of mazindol, a dopamine uptake inhibitor, was evaluated in a model of complete Freund’s adjuvant (CFA-induced arthritis. Furthermore, as studies have shown that the dopaminergic system regulates bone metabolism, the effect of mazindol on bone mass and microarchitecture was determined.Methods: Adult ICR male mice received intra-articular injections of either CFA or saline into the right knee joint every week. Spontaneous pain-like behaviors (flinching and guarding and locomotor activity were assessed at day 26 post-first CFA, following which, a single intraperitoneally (i.p. administered dose of mazindol was given (1, 3 and 10 mg/kg. Then, the antinociceptive effect of a repeated administration of 3 mg/kg mazindol (daily, i.p.; day 15–day 26 was evaluated. Additionally, at day 26, the participation of D1-like, D2-like or opioid receptors in the antinociceptive effect of mazindol was evaluated. The effect of mazindol on bone density and microarchitecture was evaluated by micro

  15. Pharmacokinetic model of florfenicol in turbot (Scophthalmus maximus): establishment of optimal dosage and administration in medicated feed.

    Science.gov (United States)

    de Ocenda, V-R; Almeida-Prieto, S; Luzardo-Álvarez, A; Barja, J L; Otero-Espinar, F J; Blanco-Méndez, J

    2017-03-01

    The pharmacokinetics of florfenicol (FF) in turbot (Scophthalmus maximus) was studied after single intravenous (10 mg kg -1 ) and oral (100 mg kg -1 ) administration. The plasma concentration-time data of florfenicol were described by an open one-compartment model. The elimination half-life (t 1/2 ) was estimated to be 21.0 h, and the total body clearance, Cl, was determined as 0.028 L kg h -1 . The apparent volume distribution (V d ) was calculated to be 0.86 L kg -1 and the mean residence time (MRT iv ) was 30.2 h. Following oral administration, the maximum plasma concentration (C max ) of 55.4 μg mL -1 was reached at 12 h (T max ). The absorption constant (k a ) was 0.158 h -1 . The bioavailability was estimated to be 57.1%. The low bioavailability observed at higher doses was explained by the saturation of the mechanisms of absorption. The drug absorption process was limited by its inherent low solubility, which limited the amount of available FF absorbed in the gastrointestinal tract. Based on the pharmacokinetic data, an optimal dosing schedule for FF administration is hereby provided. Based on the minimum inhibitory concentration found for susceptible strains of Aeromonas salmonicida, oral FF administration of first, an initial dose of 30 mg FF kg -1 , followed by 6 maintenance doses at 18 mg kg -1 /daily could be effective against furunculosis in turbot. © 2016 John Wiley & Sons Ltd.

  16. 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.)

  17. 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.

  18. 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

  19. 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

  20. 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.

  1. A Need to Know: An Ethical Decision-Making Model for Research Administrators

    Science.gov (United States)

    Lincoln, Sarah Hope; Holmes, Elizabeth K.

    2008-01-01

    When faced with a morally charged situation, individuals engage in an ethical decision-making process to resolve the ethical dilemma. This paper outlines a model that describes the steps in the ethical decision-making process and identifies situational factors, collectively termed moral intensity, which may influence this process. The use of a…

  2. A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D-2 receptor antagonists in rats

    NARCIS (Netherlands)

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R. H.; Danhof, Meindert; De Lange, Elizabeth C. M.; Proost, Johannes H.

    2016-01-01

    We compared the model performance of two semi-mechanistic pharmacokinetic-pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model, to describe prolactin response following the administration of the dopamine D-2 receptor antagonists risperidone, paliperidone or

  3. 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.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Intermittent Administration of Parathyroid Hormone [1-34] Prevents Particle-Induced Periprosthetic Osteolysis in a Rat Model.

    Directory of Open Access Journals (Sweden)

    Fanggang Bi

    Full Text Available We examined whether intermittent administration of parathyroid hormone [1-34] (PTH[1-34]; 60 μg/kg/day can prevent the negative effects of titanium (Ti particles on implant fixation and periprosthetic osteolysis in a rat model. Eighteen adult male rats (12 weeks old, bones still growing received intramedullary Ti implants in their bilateral femurs; 6 rats from the blank group received vehicle injections, and 12 rats from the control group and PTH treatment group received Ti particle injections at the time of operation and intra-articular injections 2 and 4 weeks postoperatively. Six of the rats that received Ti particles from the PTH group also received PTH[1-34] treatment. Six weeks postoperatively, all specimens were collected for assessment by X-ray, micro-CT, biomechanical, scanning electron microscopy (SEM, and dynamic histomorphometry. A lower BMD, BV/TV, Tb.N, maximal fixation strength, and mineral apposition rate were observed in the control group compared to the blank group, demonstrating that a periprosthetic osteolysis model had been successfully established. Administration of PTH[1-34] significantly increased the bone mineral density of the distal femur, BV/TV, Tb.N, Tb.Th, Tb.Sp, Con.D, SMI, and maximal fixation strength in the PTH group compared to that in the control group. SEM revealed higher bone-implant contact, thicker lamellar bone, and larger trabecular bone area in the PTH group than in the control group. A higher mineral apposition rate was observed in the PTH group compared to both the blank and control groups. These findings imply that intermittent administration of PTH[1-34] prevents periprosthetic osteolysis by promoting bone formation. The effects of PTH[1-34] were evaluated at a suprapharmacological dosage to the human equivalent in rats; therefore, additional studies are required to demonstrate its therapeutic potential in periprosthetic osteolysis.

  9. 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.

  10. Enterprise Architecture Modeling of Core Administrative Systems at KTH : A Modifiability Analysis

    OpenAIRE

    Rosell, Peter

    2012-01-01

    This project presents a case study of modifiability analysis on the Information Systems which are central to the core business processes of Royal Institution of Technology in Stockholm, Sweden by creating, updating and using models. The case study was limited to modifiability regarding only specified Information Systems. The method selected was Enterprise Architecture together with Enterprise Architecture Analysis research results and tools from the Industrial Information and Control Systems ...

  11. The Food and Drug Administration and Drug Legalization: A Brief Model of Regulation

    OpenAIRE

    Kalam, Murad

    2002-01-01

    This paper offers a brief model of FDA regulation of currently illegal narcotics in the United States. Given that nearly three out of four Americans believe that the drug war has failed, recent calls from prominent liberal and conservative thinkers to legalize drugs, and state “compassionate use†ballot initiatives, future drug legalization is at least conceivable in the United States. Yet, how would the FDA regulate NLD’s under its current st...

  12. Bayesian models and meta analysis for multiple tissue gene expression data following corticosteroid administration

    Directory of Open Access Journals (Sweden)

    Kelemen Arpad

    2008-08-01

    Full Text Available Abstract Background This paper addresses key biological problems and statistical issues in the analysis of large gene expression data sets that describe systemic temporal response cascades to therapeutic doses in multiple tissues such as liver, skeletal muscle, and kidney from the same animals. Affymetrix time course gene expression data U34A are obtained from three different tissues including kidney, liver and muscle. Our goal is not only to find the concordance of gene in different tissues, identify the common differentially expressed genes over time and also examine the reproducibility of the findings by integrating the results through meta analysis from multiple tissues in order to gain a significant increase in the power of detecting differentially expressed genes over time and to find the differential differences of three tissues responding to the drug. Results and conclusion Bayesian categorical model for estimating the proportion of the 'call' are used for pre-screening genes. Hierarchical Bayesian Mixture Model is further developed for the identifications of differentially expressed genes across time and dynamic clusters. Deviance information criterion is applied to determine the number of components for model comparisons and selections. Bayesian mixture model produces the gene-specific posterior probability of differential/non-differential expression and the 95% credible interval, which is the basis for our further Bayesian meta-inference. Meta-analysis is performed in order to identify commonly expressed genes from multiple tissues that may serve as ideal targets for novel treatment strategies and to integrate the results across separate studies. We have found the common expressed genes in the three tissues. However, the up/down/no regulations of these common genes are different at different time points. Moreover, the most differentially expressed genes were found in the liver, then in kidney, and then in muscle.

  13. Long-term vascular access ports as a means of sedative administration in a rodent fMRI survival model

    Science.gov (United States)

    Hettinger, Patrick C.; Li, Rupeng; Yan, Ji-Geng; Matloub, Hani S.; Cho, Younghoon R.; Pawela, Christopher P.; Rowe, Daniel B.; Hyde, James S.

    2011-01-01

    The purpose of this study is to develop a rodent functional magnetic resonance imaging (fMRI) survival model with the use of heparin-coated vascular access devices. Such a model would ease the administration of sedative agents, reduce the number of animals required in a survival experiment, and eliminate animal-to-animal variability seen in previous designs. Seven male Sprague-Dawley rats underwent surgical placement of an MRI-compatible vascular access port, followed by implantable electrode placement on the right median nerve. Functional MRI during nerve stimulation and resting-state functional connectivity MRI (fcMRI) were performed at times 0, 2, 4, 8, and 12 weeks postoperatively using a 9.4 T scanner. Anesthesia was maintained using intravenous dexmedetomidine and reversed using atipamezole. There were no fatalities or infectious complications during this study. All vascular access ports remained patent. Blood oxygen level dependent (BOLD) activation by electrical stimulation of the median nerve using implanted electrodes was seen within the forelimb sensory region (S1FL) for all animals at all time points. The number of activated voxels decreased at time points 4 and 8 weeks, returning to a normal level at 12 weeks, which is attributed to scar tissue formation and resolution around the embedded electrode. The applications of this experiment extend far beyond the scope of peripheral nerve experimentation. These vascular access ports can be applied to any survival MRI study requiring repeated medication administration, intravenous contrast, or blood sampling. PMID:21726581

  14. Systemic Administration of Propentofylline, Ibudilast, and (+)-Naltrexone Each Reverses Mechanical Allodynia in a Novel Rat Model of Central Neuropathic Pain

    Science.gov (United States)

    Ellis, Amanda; Wieseler, Julie; Favret, Jacob; Johnson, Kirk W.; Rice, Kenner C.; Maier, Steven F.; Falci, Scott; Watkins, Linda R.

    2014-01-01

    Central neuropathic pain (CNP) is a debilitating consequence of central nervous system (CNS) damage for which current treatments are ineffective. To explore mechanisms underlying CNP, we developed a rat model involving T13/L1 dorsal root avulsion. The resultant dorsal horn damage creates bilateral below-level (L4-6) mechanical allodynia. This allodynia, termed spinal neuropathic avulsion pain (SNAP), occurs in the absence of confounding paralysis. To characterize this model, we undertook a series of studies aimed at defining whether SNAP could be reversed by any of 3 putative glial activation inhibitors, each with distinct mechanisms of action. Indeed, the phosphodiesterase inhibitor propentofylline, the macrophage migration inhibitory factor (MIF) inhibitor ibudilast, and the toll-like receptor 4 (TLR4) antagonist (+)-naltrexone each reversed below-level allodynia bilaterally. Strikingly, none of these impacted SNAP upon first administration but required 1–2 wk of daily administration before pain reversal was obtained. Given reversal of CNP by each of these glial modulatory agents, these results suggest that glia contribute to the maintenance of such pain and enduring release of MIF and endogenous agonists of TLR4 is important for sustaining CNP. The markedly delayed efficacy of all 3 glial modulatory drugs may prove instructive for interpretation of apparent drug failures after shorter dosing regimens. PMID:24412802

  15. The applicability of Bass's model of transformational, transactional, and laissez-faire leadership in the hospital administrative environment.

    Science.gov (United States)

    Spinelli, Robert J

    2006-01-01

    The purpose of this study is to evaluate empirically in the hospital administrative environment the relationship of leadership behaviors to subordinate manager's perceived outcomes, through examination of B. M. Bass's (1985) model of transformational, transactional, and laissez-faire leadership. The author measured leadership orientation and outcome factors through subordinate managers' ratings of hospital CEOs using a questionnaire, which asked: Is there a relationship between the leadership styles of hospital CEOs and subordinate managers' self-reported willingness to exert extra effort, perception of leader effectiveness and satisfaction with their leader? Findings revealed that the relationship between transformational leadership and the outcome factors were stronger and more positive than were the transactional and laissez-faire styles. These findings are consistent with the hierarchal patterns reported and support the universality of the model.

  16. 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

  17. Prophylactic effect of administration of human gamma globulins in a mouse model of tuberculosis.

    Science.gov (United States)

    Olivares, Nesty; Puig, Alina; Aguilar, Diana; Moya, Aniel; Cádiz, Armando; Otero, Oscar; Izquierdo, Luis; Falero, Gustavo; Solis, Rosa L; Orozco, Hector; Sarmiento, Maria E; Norazmi, Mohd Nor; Hernández-Pando, Rogelio; Acosta, Armando

    2009-05-01

    The protective effect of human gamma globulins on Mycobacterium tuberculosis infection was evaluated in a mouse model of intratracheal infection. Animals receiving human gamma globulins intranasally, 2h before intratracheal challenge showed a significant decrease in lung bacilli load compared to non-treated animals in different time intervals of up to 2 months after challenge. The same effect was obtained when M. tuberculosis was pre-incubated with the gamma globulin before challenge. The protective effect of the gamma-globulin formulation was abolished after pre-incubation with M. tuberculosis. These results suggest a potential role of specific antibodies in the defence against mycobacterial infections.

  18. 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.

  19. Ex vivo administration of trimetazidine improves post-transplant lung function in pig model.

    Science.gov (United States)

    Cosgun, Tugba; Iskender, Ilker; Yamada, Yoshito; Arni, Stephan; Lipiski, Miriam; van Tilburg, Koen; Weder, Walter; Inci, Ilhan

    2017-07-01

    Ex vivo lung perfusion (EVLP) is not only used to assess marginal donor lungs but is also used as a platform to deliver therapeutic agents outside the body. We previously showed the beneficial effects of trimetazidine (TMZ) on ischaemia reperfusion (IR) injury in a rat model. This study evaluated the effects of TMZ in a pig EVLP transplant model. Pig lungs were retrieved and stored for 24 h at 4°C, followed by 4 h of EVLP. Allografts were randomly allocated to 2 groups ( n  = 5 each). TMZ (5 mg/kg) was added to the prime solution prior to EVLP. After EVLP, left lungs were transplanted and recipients were observed for 4 h. Allograft gas exchange function and lung mechanics were recorded hourly throughout reperfusion. Microscopic lung injury and inflammatory and biochemical parameters were assessed. There was a trend towards better oxygenation during EVLP in the TMZ group ( P  = 0.06). After transplantation, pulmonary gas exchange was significantly better during the 4-h reperfusion period and after isolation of the allografts for 10 min ( P  Ex vivo treatment of donor lungs with TMZ significantly improved immediate post-transplant lung function. Further studies are warranted to understand the effect of this strategy on long-term lung function. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  20. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes.

    Science.gov (United States)

    Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

    2014-06-30

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen.

  1. Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

    Science.gov (United States)

    Liu, Chi; Kurokawa, Ryosuke; Fujino, Masayuki; Hirano, Shinichi; Sato, Bunpei; Li, Xiao-Kang

    2014-01-01

    Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using high-quality sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. PMID:24975958

  2. A Population Pharmacokinetic Model for Disposition in Plasma, Saliva and Urine of Scopolamine after Intranasal Administration to Healthy Human Subjects

    Science.gov (United States)

    Wu, L.; Tam, V. H.; Chow, D. S. L.; Putcha, L.

    2014-01-01

    An intranasal gel formulation of scopolamine (INSCOP) was developed for the treatment of Space Motion Sickness. The bioavailability and pharmacokinetics (PK) were evaluated under the Food and Drug Administration guidelines for clinical trials with an Investigative New Drug (IND) protocol. The aim of this project was to develop a PK model that can predict the relationship between plasma, saliva and urinary scopolamine concentrations using data collected from the IND clinical trials with INSCOP. Methods: Twelve healthy human subjects were administered three dose levels (0.1, 0.2 and 0.4 mg) of INSCOP. Serial blood, saliva and urine samples were collected between 5 min and 24 h after dosing and scopolamine concentrations were measured by using a validated LC-MS-MS assay. Pharmacokinetic Compartmental models, using actual dosing and sampling times, were built using Phoenix (version 1.2). Model selection was based on the likelihood ratio test on the difference of criteria (-2LL) and comparison of the quality of fit plots. Results: The best structural model for INSCOP (minimal -2LL= 502.8) was established. It consisted of one compartment each for plasma, saliva and urine, respectively, which were connected with linear transport processes except the nonlinear PK process from plasma to saliva compartment. The best-fit estimates of PK parameters from individual PK compartmental analysis and Population PK model analysis were shown in Tables 1 and 2, respectively. Conclusion: A population PK model that could predict population and individual PK of scopolamine in plasma, saliva and urine after dosing was developed and validated. Incorporating a non-linear transfer from plasma to saliva compartments resulted in a significantly improved model fitting. The model could be used to predict scopolamine plasma concentrations from salivary and urinary drug levels, allowing non-invasive therapeutic monitoring of scopolamine in space and other remote environments.

  3. 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.

  4. Restoration of Tear Secretion in a Murine Dry Eye Model by Oral Administration of Palmitoleic Acid

    Directory of Open Access Journals (Sweden)

    Shigeru Nakamura

    2017-04-01

    Full Text Available Sea buckthorn (Hippophae rhamnoides–derived products have traditionally been used as food and medicinal ingredients in Eastern countries. The purpose of this study was to investigate the effect of oral intake of sea buckthorn oil products on tear secretion using a murine dry eye model. Orally administered sea buckthorn pulp oil (not seed oil restored aqueous tear secretion to its normal value under a dry eye condition. Palmitoleate (C16:1, a fatty acid present in sea buckthorn pulp oil, preserved tear secretion and suppressed inflammatory cytokines in the lacrimal gland to the same extent as that by pulp oil. These results suggest that an oral intake of sea buckthorn pulp oil has a potency to preserve tear secretion capacity in the dry eye state and palmitoleate, its main constituent fatty acid, is an active component of the oil. This effect may enable a potent diet-based treatment for the prevention of dry eye.

  5. Persistent Dystrophin Protein Restoration 90 Days after a Course of Intraperitoneally Administered Naked 2′OMePS AON and ZM2 NP-AON Complexes in mdx Mice

    Directory of Open Access Journals (Sweden)

    Elena Bassi

    2012-01-01

    Full Text Available In Duchenne muscular dystrophy, the exon-skipping approach has obtained proof of concept in animal models, myogenic cell cultures, and following local and systemic administration in Duchenne patients. Indeed, we have previously demonstrated that low doses (7.5 mg/Kg/week of 2′-O-methyl-phosphorothioate antisense oligoribonucleotides (AONs adsorbed onto ZM2 nanoparticles provoke widespread dystrophin restoration 7 days after intraperitoneal treatment in mdx mice. In this study, we went on to test whether this dystrophin restoration was still measurable 90 days from the end of the same treatment. Interestingly, we found that both western blot and immunohistochemical analysis (up to 7% positive fibres were still able to detect dystrophin protein in the skeletal muscles of ZM2-AON-treated mice at this time, and the level of exon-23 skipping could still be assessed by RT real-time PCR (up to 10% of skipping percentage. In contrast, the protein was undetectable by western blot analysis in the skeletal muscles of mdx mice treated with an identical dose of naked AON, and the percentage of dystrophin-positive fibres and exon-23 skipping were reminiscent of those of untreated mdx mice. Our data therefore demonstrate the long-term residual efficacy of this systemic low-dose treatment and confirm the protective effect nanoparticles exert on AON molecules.

  6. Comparison and validation of two mathematical models for the impact of mass drug administration on Ascaris lumbricoides and hookworm infection.

    Science.gov (United States)

    Coffeng, Luc E; Truscott, James E; Farrell, Sam H; Turner, Hugo C; Sarkar, Rajiv; Kang, Gagandeep; de Vlas, Sake J; Anderson, Roy M

    2017-03-01

    The predictions of two mathematical models of the transmission dynamics of Ascaris lumbricoides and hookworm infection and the impact of mass drug administration (MDA) are compared, using data from India. One model has an age structured partial differential equation (PDE) deterministic framework for the distribution of parasite numbers per host and sexual mating. The second model is an individual-based stochastic model. Baseline data acquired prior to treatment are used to estimate key transmission parameters, and forward projections are made, given the known MDA population coverage. Predictions are compared with observed post-treatment epidemiological patterns. The two models could equally well predict the short-term impact of deworming on A. lumbricoides and hookworm infection levels, despite being fitted to different subsets and/or summary statistics of the data. As such, the outcomes give confidence in their use as aids to policy formulation for the use of PCT to control A. lumbricoides and hookworm infection. The models further largely agree in a qualitative sense on the added benefit of semi-annual vs. annual deworming and targeting of the entire population vs. only children, as well as the potential for interruption of transmission. Further, this study also illustrates that long-term predictions are sensitive to modelling assumptions about which age groups contribute most to transmission, which depends on human demography and age-patterns in exposure and contribution to the environmental reservoir of infection, the latter being notoriously difficult to empirically quantify. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa) administration enhances the wound healing in the model of chronic skin wounds in rabbits

    Science.gov (United States)

    Shevtsov, Maxim A; Smagina, Larisa V; Kudriavtceva, Tatiana A; Petlenko, Sergey V; Voronkina, Irina V

    2015-01-01

    The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa) and its acylated analogue (R-Glu-Trp-ONa) were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin–eosin, Mallory’s staining) confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs’ activity, indicating their role in wound healing. PMID:25848208

  8. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

    2012-01-01

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

  9. Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model

    DEFF Research Database (Denmark)

    Kristensen, Jens; Mæng, Michael; Rehling, Michael

    2005-01-01

    preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology. METHODS: A control group and two rhEPO groups were studied. EPO1 pigs were given EPO corresponding...... by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion). RESULTS: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically...... (mean+/-SD for C: 0.64+/-0.20; EPO1: 0.75+/-0.17; EPO2: 0.80+/-0.07). In the EPO2 group mean arterial pulmonary pressure and dP/dtmax were increased compared with control group. CONCLUSION: Despite promising results from studies in rodents, rhEPO did not reduce infarct size measured after 2.5 h...

  10. Chronic administration of fluoxetine and pro-inflammatory cytokine change in a rat model of depression.

    Directory of Open Access Journals (Sweden)

    Yanxia Lu

    Full Text Available This study evaluated the chronic effects of fluoxetine, a commonly prescribed SSRI antidepressant, on the peripheral and central levels of inflammatory cytokines including IL-1β, IL-6, TNF-α and IL-17 over a 4-interval in a rat model of chronic mild stress (CMS which resembles the human experience of depression. Twenty-four Sprague-Dawley rats were randomly assigned to CMS+vehicle (n = 9, CMS+fluoxetine (n = 9 and the control (n = 6 groups. Sucrose preference and forced swim tests were performed to assess behavioral change. Blood samples were collected on day 0, 60, 90 and 120 for measurement of cytokine levels in plasma. On day 120, the brain was harvested and central level of cytokines was tested using Luminex. Four months of fluoxetine treatment resulted in changes in the sucrose preference and immobility time measurements, commensurate with antidepressant effects. The CMS+vehicle group exhibited elevated plasma levels of IL-1β, IL-17, and TNF-α on day 60 or 120. Rats treated with fluoxetine demonstrated lower IL-1β in plasma and brain after 90 and 120-day treatment respectively (p<0.05. There was a trend of reduction of IL-6 and TNF-α concentration. This study revealed the potential therapeutic effects of fluoxetine by reducing central and peripheral levels of IL-1β in the alleviation of depressive symptoms.

  11. 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.

  12. Locally administrated perindopril improves healing in an ovariectomized rat tibial osteotomy model.

    Directory of Open Access Journals (Sweden)

    Xiong Zhao

    Full Text Available Angiotensin-converting enzyme inhibitors are widely prescribed to regulate blood pressure. High doses of orally administered perindopril have previously been shown to improve fracture healing in a mouse femur fracture model. In this study, perindopril was administered directly to the fracture area with the goal of stimulating fracture repair. Three months after being ovariectomized (OVX, tibial fractures were produced in Sprague-Dawley rats and subsequently stabilized with intramedullary wires. Perindopril (0.4 mg/kg/day was injected locally at the fractured site for a treatment period of 7 days. Vehicle reagent was used as a control. Callus quality was evaluated at 2 and 4 weeks post-fracture. Compared with the vehicle group, perindopril treatment significantly increased bone formation, increased biomechanical strength, and improved microstructural parameters of the callus. Newly woven bone was arranged more tightly and regularly at 4 weeks post-fracture. The ultimate load increased by 66.1 and 76.9% (p<0.01, and the bone volume over total volume (BV/TV increased by 29.9% and 24.3% (p<0.01 at 2 and 4 weeks post-fracture, respectively. These findings suggest that local treatment with perindopril could promote fracture healing in ovariectomized rats.

  13. 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.

  14. 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…

  15. 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

  16. Intratracheal Bleomycin Aerosolization: The Best Route of Administration for a Scalable and Homogeneous Pulmonary Fibrosis Rat Model?

    Directory of Open Access Journals (Sweden)

    Alexandre Robbe

    2015-01-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a chronic disease with a poor prognosis and is characterized by the accumulation of fibrotic tissue in lungs resulting from a dysfunction in the healing process. In humans, the pathological process is patchy and temporally heterogeneous and the exact mechanisms remain poorly understood. Different animal models were thus developed. Among these, intratracheal administration of bleomycin (BML is one of the most frequently used methods to induce lung fibrosis in rodents. In the present study, we first characterized histologically the time-course of lung alteration in rats submitted to BLM instillation. Heterogeneous damages were observed among lungs, consisting in an inflammatory phase at early time-points. It was followed by a transition to a fibrotic state characterized by an increased myofibroblast number and collagen accumulation. We then compared instillation and aerosolization routes of BLM administration. The fibrotic process was studied in each pulmonary lobe using a modified Ashcroft scale. The two quantification methods were confronted and the interobserver variability evaluated. Both methods induced fibrosis development as demonstrated by a similar progression of the highest modified Ashcroft score. However, we highlighted that aerosolization allows a more homogeneous distribution of lesions among lungs, with a persistence of higher grade damages upon time.

  17. Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model.

    Science.gov (United States)

    Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

    2013-01-01

    Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and possible adverse effects on the oral administration of obtained tobacco seeds were evaluated in a mouse model. Tobacco was transformed via Agrobacteium tumefaciens with chimeric constructs containing structural parts of the major subunit FedA of the F18 adhesive fimbriae and VT2e B-subunit genes under control of a seed specific GLOB promoter. We showed that the foreign Vt2e-B and F18 genes were stably accumulated in storage tissue by the immunostaining method. In addition, Balb-C mice receiving transgenic tobacco seeds via the oral route showed a significant increase in IgA-positive plasma cell presence in tunica propria when compared to the control group with no observed adverse effects. Our findings encourage future studies focusing on swine for evaluation of the protective effects of transformed tobacco seeds against E. coli infection.

  18. A murine model of dry eye induced by topical administration of erlotinib eye drops.

    Science.gov (United States)

    Yang, Qi-Chen; Bao, Jing; Li, Cheng; Tan, Gang; Wu, An-Hua; Ye, Lei; Ye, Lin-Hong; Zhou, Qiong; Shao, Yi

    2018-03-01

    In the present study, the effects of erlotinib on mouse tear function and corneal epithelial tissue structure were investigated. Throughout the 3 weeks of treatment, no notable differences were observed in the body, eye or lacrimal gland weights of the control and experimental mice. However, in the experimental group, the tear volume and break‑up times of tear film were significantly lower following treatment with erlotinib compared with the control group. Corneal fluorescein staining in the experimental group revealed patchy staining, and the Lissamine green staining and inflammatory index were significantly higher in the experimental group at 3 weeks than in the control group. In the experimental group, the number of corneal epithelium layers increased significantly following treatment with erlotinib for 3 weeks and a significant increase in the number of vacuoles was observed compared with the control group. Treatment with erlotinib significantly increased the corneal epithelial cell apoptosis, and led to a significantly increased number of epithelial cell layers and increased keratin 10 expression. It also significantly reduced the number of conjunctival goblet cells. Transmission electron microscopy and scanning electron microscopy revealed that the corneal epithelial surface was irregular and there was a substantial reduction and partial loss of the microvilli in the experimental group. Mice treated with erlotinib also exhibited an increased protein expression of tumor necrosis factor‑α and decreased protein expression of phosphorylated‑epidermal growth factor receptor in the corneal epithelial cells. The topical application of erlotinib eye drops was revealed to induce dry eyes in mice. This is a novel method of developing a model of dry eyes in mice.

  19. Effect of administration of antibodies against nerve growth factor in a rat model of muscle injury.

    Science.gov (United States)

    Suzuki, Masahiro; Inage, Kazuhide; Sakuma, Yoshihiro; Orita, Sumihisa; Yamauchi, Kazuyo; Suzuki, Takane; Suzuki, Miyako; Kubota, Go; Oikawa, Yasuhiro; Sainoh, Takeshi; Sato, Jun; Fujimoto, Kazuki; Shiga, Yasuhiro; Abe, Koki; Kanamoto, Hirohito; Takahashi, Kazuhisa; Ohtori, Seiji

    2016-03-01

    Although muscle injury is a common source of pain, the mechanism causing such pain is not completely known. We have previously reported nerve growth factor (NGF) as a proinflammatory mediator involved in acute pain, and clinical trials have shown the effectiveness of anti-NGF antibodies for management of low back pain. Here, we aim to examine the effects of anti-NGF antibodies on muscle-derived pain by studying their effects on sensory innervation in a rat muscle injury model. A nervous system tracer, Fluoro-Gold, was applied to both gastrocnemius muscles of 24 male Sprague Dawley rats to stain the sensory nerves. Then, the drop-mass method was used to damage the right gastrocnemius muscle of the posterior limb. Anti-NGF antibodies (50μL) were injected into the injured muscles in 12 rats. Tissues were evaluated 1, 3, and 7 days post-injury by performing haematoxylin-and-eosin (HE) staining. The percentage of the total number of FG-positive cells that were also positive for a pain-related neuropeptide, calcitonin gene-related peptide (CGRP), was determined for the bilateral dorsal root ganglia from L1 to L6 7 days post-injury. HE staining showed active inflammation, indicated by increased basophil and eosinophil accumulation, at the injury site 1 and 3 days post-injury, as well as scar tissue formation 7 days post-injury. Injection of anti-NGF reduced muscle necrosis 1 and 3 days post-injury, and resulted in replacement of granulation tissue and muscle fibre regeneration 7 days post-injury. Anti-NGF also significantly inhibited CGRP among FG-positive cells (treatment group 38.2%, control group 49.6%; Pinjury. Anti-NGF antibodies successfully suppressed the pain mediator NGF and inhibited inflammation, suggesting NGF as a target for control in pain management. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. 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.

  1. Changes in cerebral [18F]-FDG uptake induced by acute alcohol administration in a rat model of alcoholism.

    Science.gov (United States)

    Gispert, Juan D; Figueiras, Francisca P; Vengeliene, Valentina; Herance, José R; Rojas, Santiago; Spanagel, Rainer

    2017-06-01

    Several [ 18 F]-FDG positron emission tomography (PET) studies in alcoholics have consistently reported decreases in overall brain glucose metabolism at rest and following acute alcohol administration. However, changes in cerebral glucose utilization associated with the transition to addiction are not well understood and require longitudinal translational imaging studies in animal models of alcoholism. Here, we studied brain glucose uptake in alcohol drinking rats in order to provide convergent evidence to what has previously been reported in human studies. Brain glucose metabolism was measured by [ 18 F]-FDG microPET imaging in different male Wistar rat groups: short-term drinking (three months), long-term drinking (twelve months) and alcohol-naïve. Global and regional cerebral glucose uptake was measured at rest and following acute alcohol administration. We showed that alcohol significantly reduced the whole-brain glucose metabolism. This effect was most pronounced in the parietal cortex and cerebellum. Alcohol-induced decreases in brain [ 18 F]-FDG uptake was most apparent in alcohol-naïve rats, less intense in short-term drinkers and absent in long-term drinkers. The latter finding indicates the occurrence of tolerance to the intoxicating effects of alcohol in long-term drinking individuals. In contrast, some regions, like the ventral striatum and entorhinal cortex, showed enhanced metabolic activity, an effect that did not undergo tolerance during long-term alcohol consumption. Our findings are comparable to those described in human studies using the same methodology. We conclude that [ 18 F]-FDG PET studies in rat models of alcoholism provide good translation and can be used for future longitudinal studies investigating alterations in brain function during different stages of the addiction cycle. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Intratracheal Administration of Mesenchymal Stem Cells Modulates Tachykinin System, Suppresses Airway Remodeling and Reduces Airway Hyperresponsiveness in an Animal Model.

    Directory of Open Access Journals (Sweden)

    Konrad Urbanek

    Full Text Available The need for new options for chronic lung diseases promotes the research on stem cells for lung repair. Bone marrow-derived mesenchymal stem cells (MSCs can modulate lung inflammation, but the data on cellular processes involved in early airway remodeling and the potential involvement of neuropeptides are scarce.To elucidate the mechanisms by which local administration of MSCs interferes with pathophysiological features of airway hyperresponsiveness in an animal model.GFP-tagged mouse MSCs were intratracheally delivered in the ovalbumin mouse model with subsequent functional tests, the analysis of cytokine levels, neuropeptide expression and histological evaluation of MSCs fate and airway pathology. Additionally, MSCs were exposed to pro-inflammatory factors in vitro.Functional improvement was observed after MSC administration. Although MSCs did not adopt lung cell phenotypes, cell therapy positively affected airway remodeling reducing the hyperplastic phase of the gain in bronchial smooth muscle mass, decreasing the proliferation of epithelium in which mucus metaplasia was also lowered. Decrease of interleukin-4, interleukin-5, interleukin-13 and increase of interleukin-10 in bronchoalveolar lavage was also observed. Exposed to pro-inflammatory cytokines, MSCs upregulated indoleamine 2,3-dioxygenase. Moreover, asthma-related in vivo upregulation of pro-inflammatory neurokinin 1 and neurokinin 2 receptors was counteracted by MSCs that also determined a partial restoration of VIP, a neuropeptide with anti-inflammatory properties.Intratracheally administered MSCs positively modulate airway remodeling, reduce inflammation and improve function, demonstrating their ability to promote tissue homeostasis in the course of experimental allergic asthma. Because of a limited tissue retention, the functional impact of MSCs may be attributed to their immunomodulatory response combined with the interference of neuropeptide system activation and tissue

  3. 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...

  4. A mathematical model for long-term effect of diethylcarbamazine-albendazole mass drug administration on lymphatic filariasis

    Science.gov (United States)

    Tasman, H.; Supali, T.; Supriatna, A. K.; Nuraini, N.; Soewono, E.

    2015-03-01

    In this paper we discuss a mathematical model for the transmission of lymphatic filariasis disease. The human population is divided into susceptible, latent, acute and chronic subpopulations. Treatment is carried out within the scheme of mass drug administration (MDA) by giving the diethylcarbamazine (DEC) and albendazole (ALB) to all individuals. In the model, we assume that the treatments have direct killing effect to microfilariae, increase of immune-mediated effect. The treated individuals are assumed to remain susceptible to the disease. This is due to the fact that the treatment is only partially effective against macrofilaria. Simulations of the model reveals that DEC-ALB treatment does give significant reduction of acute and chronic compartments at the end of the treatment period and slow down the growth after the treatment before eventually tend to the endemic state. It showed that repeated treatment during MDA is effective to decrease the transmission. This suggests that terminating MDA program after a long period of its application may still effective in controlling the disease.

  5. 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.

  6. 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)

  7. Modelling control of Schistosoma haematobium infection: predictions of the long-term impact of mass drug administration in Africa.

    Science.gov (United States)

    Gurarie, David; Yoon, Nara; Li, Emily; Ndeffo-Mbah, Martial; Durham, David; Phillips, Anna E; Aurelio, H Osvaldo; Ferro, Josefo; Galvani, Alison P; King, Charles H

    2015-10-22

    Effective control of schistosomiasis remains a challenging problem for endemic areas of the world. Given knowledge of the biology of transmission and past experience with mass drug administration (MDA) programs, it is important to critically evaluate the likelihood that MDA programs will achieve substantial reductions in Schistosoma prevalence. In implementing the World Health Organization Roadmap for Neglected Tropical Diseases it would useful for policymaking to model projections of the status of Schistosoma control in MDA-treated areas in the next 5-10 years. Calibrated mathematical models were used to project the effects of different frequency and coverage of MDA for schistosomiasis haematobia control in present-day endemic communities, taking into account uncertainties of parasite biology and input data. The modeling approach in this analysis was the Stratified Worm Burden model developed in our earlier works, calibrated using data from longitudinal S. haematobium control trials in Kenya. Model-based simulations of MDA control in typical low-risk and higher-risk communities indicated that infection prevalence can be substantially reduced within 10 years only when there is a high degree of community participation (>70 %) with at least annual MDA. Significant risk for re-emergence of infection remains if MDA is suspended. In a stable (stationary) ecosystem, Schistosoma reproduction and transmission are sufficiently robust that the process of human infection continues, even under pressure from aggressive MDA. MDA alone is unlikely to interrupt transmission, and once mass treatment is suspended, the prevalence of human infection is likely to rebound to pre-control levels over a period of 25-30 years. MDA success in achieving very low levels of infection prevalence is highly dependent on treatment coverage and frequency within the local human population, and requires that both adults and children be included in drug delivery coverage. Ultimately, supplemental

  8. 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...

  9. 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...

  10. Extracts of Renealmia alpinia (Rottb.) MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection.

    Science.gov (United States)

    Patiño, Arley Camilo; Quintana, Juan Carlos; Gutiérrez, José María; Rucavado, Alexandra; Benjumea, Dora María; Pereañez, Jaime Andrés

    2015-04-30

    Renealmia alpinia (Rottb.) MAAS, obtained by micropropagation (in vitro) and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50) values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05) for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract) and 34.7% (wild extract), in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.

  11. Extracts of Renealmia alpinia (Rottb. MAAS Protect against Lethality and Systemic Hemorrhage Induced by Bothrops asper Venom: Insights from a Model with Extract Administration before Venom Injection

    Directory of Open Access Journals (Sweden)

    Arley Camilo Patiño

    2015-04-01

    Full Text Available Renealmia alpinia (Rottb. MAAS, obtained by micropropagation (in vitro and wild forms have previously been shown to inhibit some toxic activities of Bothrops asper snake venom if preincubated before injection. In this study, assays were performed in a murine model in which extracts were administered for three days before venom injection. R. alpinia extracts inhibited lethal activity of B. asper venom injected by intraperitoneal route. Median Effective Dose (ED50 values were 36.6 ± 3.2 mg/kg and 31.7 ± 5.4 mg/kg (p > 0.05 for R. alpinia wild and in vitro extracts, respectively. At a dose of 75 mg/kg, both extracts totally inhibited the lethal activity of the venom. Moreover, this dose prolonged survival time of mice receiving a lethal dose of venom by the intravenous route. At 75 mg/kg, both extracts of R. alpinia reduced the extent of venom-induced pulmonary hemorrhage by 48.0% (in vitro extract and 34.7% (wild extract, in agreement with histological observations of lung tissue. R. alpinia extracts also inhibited hemorrhage in heart and kidneys, as evidenced by a decrease in mg of hemoglobin/g of organ. These results suggest the possibility of using R. alpinia as a prophylactic agent in snakebite, a hypothesis that needs to be further explored.

  12. Administration of 4-(α-L-Rhamnosyloxy-benzyl Isothiocyanate Delays Disease Phenotype in SOD1G93A Rats: A Transgenic Model of Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Maria Galuppo

    2015-01-01

    Full Text Available 4-(α-L-Rhamnosyloxy-benzyl glucosinolate (glucomoringin, GMG is a compound found in Moringa oleifera seeds. Myrosinase-catalyzed hydrolysis at neutral pH of GMG releases the biologically active compound 4-(α-L-rhamnosyloxy-benzyl isothiocyanate (GMG-ITC. The present study was designed to test the potential therapeutic effectiveness of GMG-ITC to counteract the amyotrophic lateral sclerosis (ALS using SOD1tg rats, which physiologically develops SOD1G93A at about 16 weeks of life, and can be considered a genetic model of disease. Rats were treated once a day with GMG (10 mg/Kg bioactivated with myrosinase (20 µL/rat via intraperitoneal (i.p. injection for two weeks before disease onset and the treatment was prolonged for further two weeks before the sacrifice. Immune-inflammatory markers as well as apoptotic pathway were investigated to establish whether GMG-ITC could represent a new promising tool in clinical practice to prevent ALS. Achieved data display clear differences in molecular and biological profiles between treated and untreated SOD1tg rats leading to guessing that GMG-ITC can interfere with the pathophysiological mechanisms at the basis of ALS development. Therefore, GMG-ITC produced from myrosinase-catalyzed hydrolysis of pure GMG could be a candidate for further studies aimed to assess its possible use in clinical practice for the prevention or to slow down this disease.

  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. 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...

  15. 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...

  16. 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

  17. Grande Ronde Model Watershed Program Administration and Habitat Projects, Annual Progress Report, Project Period: Program Administration: January 1, 1997 - December 31, 1997 Habitat Projects: January 1, 1997 - March 31, 1998.

    Energy Technology Data Exchange (ETDEWEB)

    Noyes, Cecilia; Kuchenbecker, Lyle; Perry, Patty

    1998-10-28

    This agreement provided funding for operation and administration of the Grande Ronde Model Watershed Program including staffing of an Executive Director, Program Planner, and clerical personnel. The contract covers maintaining program services, project planning, subwatershed plans (CRMP's), public involvement and education, interagency coordination/clearing house, monitoring, and technical support activities that have taken place in the Grande Ronde basin. Cost-share has been received from the Bureau of Reclamation and the Governor's Watershed Enhancement Board.

  18. Drinking typography established by scheduled induction predicts chronic heavy drinking in a monkey model of ethanol self-administration.

    Science.gov (United States)

    Grant, Kathleen A; Leng, Xiaoyan; Green, Heather L; Szeliga, Kendall T; Rogers, Laura S M; Gonzales, Steven W

    2008-10-01

    We have developed an animal model of alcohol self-administration that initially employs schedule-induced polydipsia (SIP) to establish reliable ethanol consumption under open access (22 h/d) conditions with food and water concurrently available. SIP is an adjunctive behavior that is generated by constraining access to an important commodity (e.g., flavored food). The induction schedule and ethanol polydipsia generated under these conditions affords the opportunity to investigate the development of drinking typologies that lead to chronic, excessive alcohol consumption. Adult male cynomolgus monkeys (Macaca fascicularis) were induced to drink water and 4% (w/v in water) ethanol by a Fixed-Time 300 seconds (FT-300 seconds) schedule of banana-flavored pellet delivery. The FT-300 seconds schedule was in effect for 120 consecutive sessions, with daily induction doses increasing from 0.0 to 0.5 g/kg to 1.0 g/kg to 1.5 g/kg every 30 days. Following induction, the monkeys were allowed concurrent access to 4% (w/v) ethanol and water for 22 h/day for 12 months. Drinking typographies during the induction of drinking 1.5 g/kg ethanol emerged that were highly predictive of the daily ethanol intake over the next 12 months. Specifically, the frequency in which monkeys ingested 1.5 g/kg ethanol without a 5-minute lapse in drinking (defined as a bout of drinking) during induction strongly predicted (correlation 0.91) subsequent ethanol intake over the next 12 months of open access to ethanol. Blood ethanol during induction were highly correlated with intake and with drinking typography and ranged from 100 to 160 mg% when the monkeys drank their 1.5 g/kg dose in a single bout. Forty percent of the population became heavy drinkers (mean daily intakes >3.0 g/kg for 12 months) characterized by frequent "spree" drinking (intakes >4.0 g/kg/d). This model of ethanol self-administration identifies early alcohol drinking typographies (gulping the equivalent of 6 drinks) that evolve into

  19. Effects of Systemic Administration of Oxytocin on Contextual Fear Extinction in a Rat Model of Post-Traumatic Stress Disorder

    Directory of Open Access Journals (Sweden)

    Sharaf Eskandarian

    2013-11-01

    Full Text Available Introduction: One of the hallmark symptoms of posttraumatic stress disorder (PTSD is the impaired extinction of traumatic memory. Single prolonged stress (SPS has been suggested as an animal model of PTSD, since SPS rats exhibited the impaired fear extinction. Oxytocin (OXT has been recently suggested as a potential pharmacotherapy for treatment of PTSD. In this study, using SPS rats we investigated the effects of multiple systemic administration of OXT on contextual fear extinction. Methods: SPS was conducted in three stages: restraint for 2 h, forced swim for 20 min, and diethyl ether anesthesia, and then left undisturbed in their home cage for 7 days. In the SPS group, 7 days after SPS treatment, contextual fear conditioning was performed (on day 0, and then extinction training was performed on each of four consecutive days following fear conditioning. In the sham group, the procedures were similar except that SPS treatment was not performed. Results: During extinction trial (10 min freezing behavior was recorded. OXT (1, 10, 100 and 1000μg/kg was administrated (I.P immediately after each extinction trial. SPS rats exhibited significant impairment of contextual fear extinction as compared with sham rats. While there was no significant difference in the freezing levels between SPS and Sham rats 24 h after the fear conditioning, the freezing levels in SPS rats were significantly higher than those in sham rats after the second extinction training. Systemic OXT delayed fear extinction in sham rats as compared with sham-saline treated animals. No effect of OXT was found in SPS rats. Discussion: These findings indicate that increasing OXT transmission during fear memory reactivation delays fear extinction, and thus, the recommendation of OXT for PTSD treatment should be considered with caution.

  20. Intestinal alkaline phosphatase administration in newborns decreases systemic inflammatory cytokine expression in a neonatal necrotizing enterocolitis rat model.

    Science.gov (United States)

    Rentea, Rebecca M; Liedel, Jennifer L; Fredrich, Katherine; Welak, Scott R; Pritchard, Kirkwood A; Oldham, Keith T; Simpson, Pippa M; Gourlay, David M

    2012-10-01

    Supplementation of intestinal alkaline phosphatase (IAP), an endogenous protein expressed in the intestines, decreases the severity of necrotizing enterocolitis (NEC)-associated intestinal injury and permeability. We hypothesized that IAP administration is protective in a dose-dependent manner of the inflammatory response in a neonatal rat model. Pre- and full-term newborn Sprague-Dawley rat pups were sacrificed on day of life 3. Control pups were vaginally delivered and dam fed. Preterm pups were delivered via cesarean section and exposed to intermittent hypoxia and formula feeds containing lipopolysaccharide (NEC) with and without IAP. Three different standardized doses were administered to a group of pups treated with 40, 4, and 0.4U/kg of bovine IAP (NEC+IAP40, IAP4, or IAP0.4U). Reverse transcription-real-time polymerase chain reaction (RT-PCR) for inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α on liver and lung tissues and serum cytokine analysis for interleukin (IL)-1β, IL-6, IL-10, and TNF-α were performed. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests, expressed as mean±standard error of the mean and P≤0.05 considered significant. Levels of cytokines IL-1β, IL-6, and TNF-α increased significantly in NEC versus control, returning to control levels with increasing doses of supplemental enteral IAP. Hepatic and pulmonary TNF-α and iNOS messenger ribonucleic acid expressions increased in NEC, and the remaining elevated despite IAP supplementation. Proinflammatory cytokine expression is increased systemically with intestinal NEC injury. Administration of IAP significantly reduces systemic proinflammatory cytokine expression in a dose-dependent manner. Early supplemental enteral IAP may reduce NEC-related injury and be useful for reducing effects caused by a proinflammatory cascade. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. The Development of the Academic Administration Model of Basic Primary Educational Institutions under the Office of Sakon Nakhon Educational Service Area Office 3

    Directory of Open Access Journals (Sweden)

    Kamonlrat Kaenchan

    2017-09-01

    Full Text Available The research aimed to 1 examine the current conditions, problems and academic administration of basic education schools under the office of Sakon Nakhon educational service area office 3, 2 develop the academic administration model of basic educational schools under the office of Sakon Nakhon educational service area office 3. The study was divided into 2 phases. Phase 1: Study the researches and literatures concerning the framework, the current conditions and the problems of academic administration to gain the concept for constructing a set of questionnaire. The questionnaire was then used to collect data from 50 administrators, 83 heads of academic sections and 198 heads of learning areas ; and interviewed the administrators of 5 schools that ranked top-five of the national education test scores (O-NET and were certified by the office of educational standard assurance and quality assessment in the third-round inspection. Phase 2: Construct the model of educational administration of basic education schools under the office of Sakon Nakhon educational service area office 3, held a focus group discussion of which the participants were 2 educational administrators and 5 school directors on the constructed model, evaluated the educational administration models of the schools under the office of Sakon Nakhon educational service area office 3 by 30 school administrators and teachers. The instruments used to collect data were a set of questionnaire, interviewing forms, recording forms and evaluating forms. The data were analyzed by a computer application. The statistics used to analyze the data were percentage, mean and standard deviation. The results were as follows: 1 The current conditions of academic administration of basic education schools under the office of Sakon Nakhon educational service area office 3, overall, were at a high level. The highest mean was the development of the learning process. The problems of academic administration, overall

  9. Peritoneal administration of Met-RANTES attenuates inflammatory and nociceptive responses in a murine neuropathic pain model.

    Science.gov (United States)

    Liou, Jiin-Tarng; Mao, Chih-Chieh; Ching-Wah Sum, Daniel; Liu, Fu-Chao; Lai, Ying-Shu; Li, Jui-Chin; Day, Yuan-Ji

    2013-01-01

    The C-C motif chemokine ligand 5 (CCL5; also known as regulated on activation, normal T expressed and secreted, or RANTES) is a member of the CC family of chemokines that specifically attract and activate leukocytes to sites of inflammation. Although CCL5 has been implicated in the processing of pain, its detailed mechanisms of action are still unknown. In this study, we investigated the potential of the Met-RANTES, a selective CCL5 receptor antagonist, via peritoneal administration to modulate the recruitment of inflammatory cells in injured sites and attenuate nociceptive responses in a neuropathic pain model in mice. Nociceptive sensitization, immune cell infiltration, multiple cytokine secretion, and opioid peptide expression in damaged nerves were studied. Our results indicated that Met-RANTES-treated mice had less behavioral hypersensitivity after partial sciatic nerve ligation. Macrophage infiltration, pro-inflammatory cytokine (TNFα, IL-1β, IL-6, and IFNγ) protein secretion, and enkephalin, β-endorphin, and dynorphin mRNA expression in damaged nerves following partial sciatic nerve ligation were significantly decreased, and anti-inflammatory cytokine (IL-10) protein was significantly increased in Met-RANTES-treated mice. These results suggest that CCL5 is capable of regulating the microenvironment that controls behavioral hypersensitivity at the level of the peripheral injured site in a murine chronic neuropathic pain model. The present study identifies the potent pro-inflammatory potential of CCL5 and verifies the possible role of selective CCL5 receptor inhibitor in a murine neuropathic pain model. Copyright © 2013 American Pain Society. Published by Elsevier Inc. All rights reserved.

  10. Experimental osteoarthritis model by means of medial meniscectomy in rats and effects of diacerein administration and hyaluronic acid injection

    Directory of Open Access Journals (Sweden)

    Marcia Uchôa Rezende

    Full Text Available CONTEXT AND OBJECTIVE: The development of a slow and progressive mechanical model for osteoarthritis is important for correlation with clinical practice, and for evaluating the effects of disease-modifying medications. A mechanical osteoarthritis model was developed to evaluate the effects of intra-articular hyaluronic acid (HA injection and oral diacerein administration. DESIGN AND SETTING: Experimental study at the Department of Orthopedics and Traumatology, Universidade de São Paulo. METHOD: Total medial meniscectomy was performed on seven groups of ten Wistar rats each, comprising four control groups (C and three study groups (S. C.I: operated, non-medicated; C.II: operated, injections of HA vehicle; C.III: non-operated, non-medicated; C.IV: operated, non-medicated, sacrificed three months post-meniscectomy; S.I: operated, receiving intra-articular HA injections; S.II: operated, oral diacerein from the third to the seventh postoperative month; S.III: operated, received both medications. All the animals (except C.IV were sacrificed seven months post-meniscectomy. All femurs and tibias were assessed histologically. RESULTS: The most severe degenerative histological changes were in the tibias of the operated knees. On the contralateral side, all groups had mild changes on the tibial surface. The femoral surface had slight changes. C.I showed severe changes. S.II results matched those of C.IV. HA protected the tibial surface. S.II and S.III had similar results. CONCLUSIONS: 1 The experimental model produced mild arthritis after three months and severe arthritis after seven months; 2 diacerein reduced the degenerative changes in both knees; 3 HA protected the joint cartilage; 4 Combining the two drugs did not improve the results.

  11. Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction.

    Science.gov (United States)

    Ren, Wei; Zuo, Ran; Wang, Yao-Nan; Wang, Hong-Jie; Yang, Jian; Xin, Shao-Kun; Han, Ling-Yu; Zhao, Hai-Yu; Han, Shu-Yan; Gao, Bo; Hu, Hao; Hu, Yuan-Jia; Bian, Bao-Lin; Si, Nan

    2016-01-01

    Huang-Lian-Jie-Du Decoction (HLJDD) is a classical Traditional Chinese Medicine (TCM) formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK) and pharmacodynamic (PD) data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR) of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM) method. Additionally, the levels of 7 cytokines (CKs) in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax) and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, IL-10, and macrophage inflammatory protein-2 (MIP-2) and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that HLJDD may

  12. Pharmacokinetic-Pharmacodynamic Analysis on Inflammation Rat Model after Oral Administration of Huang Lian Jie Du Decoction.

    Directory of Open Access Journals (Sweden)

    Wei Ren

    Full Text Available Huang-Lian-Jie-Du Decoction (HLJDD is a classical Traditional Chinese Medicine (TCM formula with heat-dissipating and detoxifying effects. It is used to treat inflammation-associated diseases. However, no systematic pharmacokinetic (PK and pharmacodynamic (PD data concerning the activity of HLJDD under inflammatory conditions is available to date. In the present study, the concentration-time profiles and the hepatic clearance rates (HCR of 41 major components in rat plasma in response to the oral administration of a clinical dose of HLJDD were investigated by LC-QqQ-MS using a dynamic multiple reaction monitoring (DMRM method. Additionally, the levels of 7 cytokines (CKs in the plasma and the body temperature of rats were analyzed. Furthermore, a PK-PD model was established to describe the time course of the hemodynamic and anti-inflammatory effects of HLJDD. As one of the three major active constituents in HLJDD, iridoids were absorbed and eliminated more easily and quickly than alkaloids and flavonoids. Compared with the normal controls, the flavonoids, alkaloids and iridoids in inflamed rats exhibited consistently changing trends of PK behaviors, such as higher bioavailability, slower elimination, delays in reaching the maximum concentration (Tmax and longer substantivity. The HCR of iridoids was different from that of alkaloids and flavonoids in inflamed rats. Furthermore, excellent pharmacodynamic effects of HLJDD were observed in inflamed rats. The levels of tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, IL-1β, IL-10, and macrophage inflammatory protein-2 (MIP-2 and body temperature significantly decreased after the administration of HLJDD. Based on PK-PD modeling with the three-phase synchronous characterization of time-concentration-effect, flavonoids exhibited one mechanism of action in the anti-inflammatory process, while iridoids and alkaloids showed another mechanism of action. Taken together, the results demonstrated that

  13. Effect of hyaluronic acid on postoperative intraperitoneal adhesion formation and reformation in the rat model

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

    The local application of 0.25% or 0.4% HA before the induction of a measured laser injury on the rat uterine horn was associated with a significant reduction (P less than 0.05) in postoperative IP adhesions when compared with the group of animals pretreated with the diluent vehicle PBS or received no pretreatment. However, 0.4% HA, when applied in a similar manner, was ineffective in reducing reformation of adhesions after microsurgical adhesiolysis.

  14. Degradation of mesh coatings and intraperitoneal adhesion formation in an experimental model

    NARCIS (Netherlands)

    Schreinemacher, M. H. F.; Emans, P. J.; Gijbels, M. J. J.; Greve, J.-W. M.; Beets, G. L.; Bouvy, N. D.

    2009-01-01

    In laparoscopic ventral hernia repair a mesh is placed in direct contact with the viscera, often leading to substantial adhesions. In this experimental study the ability of different coated and uncoated meshes to attenuate adhesion formation was examined. Six commercially available meshes were

  15. The pharmacokinetic-pharmacodynamic model of telmisartan and hydrochlorothiazide on blood pressure and plasma potassium after long-term administration in spontaneously hypertensive rats.

    Science.gov (United States)

    Yu, Dan; Chen, Yuancheng; Hao, Kun

    2015-12-01

    A pharmacokinetic-pharmacodynamic model was developed to describe the time course of blood pressure and plasma potassium after long-term telmisartan and/or hydrochlorothiazide administration in spontaneously hypertensive rats. The spontaneously hypertensive rats were administered once daily for 6 weeks. The drug concentration, blood pressure and plasma potassium were monitored for several points. The time courses of blood pressure and plasma potassium were described by indirect response pharmacokinetic-pharmacodynamic model. The synergistic antihypertensive pharmacodynamic interaction between telmisartan and hydrochlorothiazide was observed, which was simulated by the inhibitory function of telmisartan and stimulatory function of hydrochlorothiazide after co-administration of the two drugs. For plasma potassium, when hydrochlorothiazide administrated alone, the plasma potassium reached to a low steady-state level at 4.64 mmol/L for 6 weeks. The plasma potassium increased to a steady-state level at 4.84 mmol/L after co-administration of telmisartan. The time courses of plasma potassium were successfully characterized by indirect response pharmacokinetic-pharmacodynamic model after long-term administration of telmisartan and/or hydrochlorothiazide. The model captured turnovers of blood pressure and plasma potassium in the different time phases and dose conditions. © 2015 Société Française de Pharmacologie et de Thérapeutique.

  16. Corticosteroid administration reduces the concentration of hyaluronan in bronchoalveolar lavage in a murine model of eosinophilic airway inflammation.

    Science.gov (United States)

    Ernst, Glenda; Lompardía, Silvina; Cordo Russo, Rosalía; Gentilini, Virginia; Venturiello, Stella; Galíndez, Fernando; Grynblat, Pedro; Hajos, Silvia E

    2012-12-01

    To analyze the effect of corticosteroid administration on the concentration of hyaluronan (HA) in bronchoalveolar lavage (BAL) in a murine model of eosinophilic airway inflammation and to study the mechanisms involved. Untreated-mice or mice treated with 1 μg/g/day betamethasone (Bm) or 0.25 μg/g/day(-1) budesonide (Bd) were sensitized and challenged with Dermatophagoides pteronyssinus (Dp) or saline (control group). The concentration of HA in BAL was determined by ELISA. In vitro migration assays were performed using a Boyden chamber and the expression of HA synthases (HAS) was analyzed by RT-PCR. We found a significant increase (P mice that was prevented by Bm or Bd. Corticosteroids also inhibited the increase in HAS expression, and the phosphorylation of Akt and ERK in the lungs of challenged mice. Finally, we found that low molecular weight HA induces the chemotaxis of BAL cells in vitro through a mechanism mediated by CD44. We conclude that corticosteroids prevent the increase in HA in BAL from Dp-challenged mice. This effect is associated with reduced expression of HAS and reduced phosphorylation of Akt and ERK in the lungs of challenged mice.

  17. Dopamine D1 and D3 receptors mediate reconsolidation of cocaine memories in mouse models of drug self-administration.

    Science.gov (United States)

    Yan, Y; Newman, A H; Xu, M

    2014-10-10

    Memories of drug experience and drug-associated environmental cues can elicit drug-seeking and taking behaviors in humans. Disruption of reconsolidation of drug memories dampens previous memories and therefore may provide a useful way to treat drug abuse. We and others previously demonstrated that dopamine D1 and D3 receptors play differential roles in acquiring cocaine-induced behaviors. Moreover, D3 receptors contribute to the reconsolidation of cocaine-induced conditioned place preference. In the present study, we examined effects of manipulating D1 or D3 receptors on reconsolidation of cocaine memories in mouse models of drug self-administration. We found that pharmacological blockade of D1 receptors or a genetic mutation of the D3 receptor gene attenuated reconsolidation that lasted for at least 1week after the memory retrieval. In contrast, with no memory retrieval, pharmacological antagonism of D1 receptors or the D3 receptor gene mutation did not significantly affect reconsolidation of cocaine memories. Pharmacological blockade of D3 receptors also attenuated reconsolidation in wild-type mice that lasted for at least 1week after the memory retrieval. These results suggest that D1 and D3 receptors and related signaling mechanisms play key roles in reconsolidation of cocaine memories in mice, and that these receptors may serve as novel targets for the treatment of cocaine abuse in humans. Copyright © 2014 IBRO. All rights reserved.

  18. Glu-Trp-ONa or its acylated analogue (R-Glu-Trp-ONa administration enhances the wound healing in the model of chronic skin wounds in rabbits

    Directory of Open Access Journals (Sweden)

    Shevtsov MA

    2015-03-01

    Full Text Available Maxim A Shevtsov,1,2 Larisa V Smagina,1 Tatiana A Kudriavtceva,3 Sergey V Petlenko,4 Irina V Voronkina1 1Institute of Cytology of the Russian Academy of Sciences (RAS, St Petersburg, Russia; 2IP Pavlov State Medical University of St Petersburg, St Petersburg, Russia; 3Institute of Experimental Medicine of the North-West Branch of the Russian Academy of Medical Sciences (IEM NWB RAMS, St Petersburg, Russia; 4Military Medical Academy, St Petersburg, Russia Abstract: The management of chronic skin wounds represents a major therapeutic challenge. The synthesized dipeptide (Glu-Trp-ONa and its acylated analogue (R-Glu-Trp-ONa were assessed in the model of nonhealing dermal wounds in rabbits in relation to their healing properties in wound closure. Following wound modeling, the rabbits received a course of intraperitoneal injections of Glu-Trp-ONa or R-Glu-Trp-ONa. Phosphate-buffered saline and Solcoseryl® were applied as negative and positive control agents, respectively. An injection of Glu-Trp-ONa and R-Glu-Trp-ONa decreased the period of wound healing in animals in comparison to the control and Solcoseryl-treated groups. Acylation of Glu-Trp-ONa proved to be beneficial as related to the healing properties of the dipeptide. Subsequent zymography analyses showed that the applied peptides decreased the proteolytic activity of matrix metalloproteinases MMP-9, MMP-8, and MMP-2 in the early inflammatory phase and reversely increased the activity of MMP-9, MMP-8, and MMP-1 in the remodeling phase. Histological analyses of the wound sections (hematoxylin–eosin, Mallory’s staining confirmed the enhanced formation of granulation tissue and re-epithelialization in the experimental groups. By administering the peptides, wound closures increased significantly through the modulation of the MMPs’ activity, indicating their role in wound healing. Keywords: chronic wound, matrix metalloproteinases, small peptides

  19. 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

  20. Model-based drug administration : current status of target-controlled infusion and closed-loop control

    NARCIS (Netherlands)

    Kuizenga, Merel H.; Vereecke, Hugo E. M.; Struys, Michel M. R. F.

    Purpose of review Drug administration might be optimized by incorporating pharmacokinetic-dynamic (PK/PD) principles and control engineering theories. This review gives an update of the actual status of target-controlled infusion (TCI) and closed-loop computer-controlled drug administration and the

  1. Population pharmacokinetic and pharmacodynamic modeling of high-dose intermittent ticarcillin-clavulanate administration in pediatric cystic fibrosis patients.

    Science.gov (United States)

    Zobell, Jeffery T; Stockmann, Chris; Young, David C; Cash, Jared; McDowell, Brittany J; Korgenski, Kent; Sherwin, Catherine M T; Spigarelli, Michael; Chatfield, Barbara A; Ampofo, Krow

    2011-11-01

    The Intermountain Cystic Fibrosis Pediatric Center utilizes ticarcillin-clavulanate 400 mg/kg/d divided every 6 hours, (maximum 24 g/d). This dosing strategy is higher than the Food and Drug Administration (FDA)-approved package labeling. We evaluated the microbiologic efficacy of this dosing regimen. The primary study objective was to predict the pharmacokinetic (PK) and pharmacodynamic (PD) MIC breakpoints (the highest MIC with a probability of target attainment [PTA] of at least 90%) for the bacteriostatic and bactericidal targets of ticarcillin activity against Pseudomonas aeruginosa using the study dosing regimen. A secondary objective was to evaluate the tolerability profile of the higher ticarcillin-clavulanate dosing regimen in children with cystic fibrosis (CF). This was a population-based PK-PD modeling study of pediatric CF patients admitted from January 1, 2005 to December 31, 2009 who received the dosing regimen for at least 7 days. Population PK and PD models were used to estimate PK and PD parameters for 127 clinically evaluable patients. A 10,000-patient Monte Carlo simulation was performed to estimate the target time in which free drug concentrations exceeded the MIC of the infecting organism. The 2 PK-PD targets of microbiologic efficacy included ≥30% for bacteriostasis and ≥50% for bactericidal effects of ticarcillin-clavulanate at higher than FDA-approved doses. A total of 127 patients (age, 0-19 years) met inclusion criteria. Serum concentration levels were modeled in this patient population using published PK parameters with intermittent ticarcillin peak concentrations reaching 288 (93.4) mg/L. The model predicted the PTA of the MICs for P. aeruginosa with a near-maximal bactericidal PK-PD MIC breakpoint of 16 μg/mL and a bacteriostasis PK-PD MIC breakpoint of 32 μg/mL. The results of our simulation suggest that in this select pediatric population, higher than FDA-approved doses of ticarcillin-clavulanate were effective in achieving

  2. The brain 5-HT4 receptor binding is down-regulated in the Flinders Sensitive Line depression model and in response to paroxetine administration

    DEFF Research Database (Denmark)

    Licht, Cecilie Löe; Marcussen, Anders Bue; Wegener, Gregers

    2009-01-01

    The 5-hydroxytryptamine (5-HT(4)) receptor may be implicated in depression and is a new potential target for antidepressant treatment. We have investigated the brain 5-HT(4) receptor [(3)H]SB207145 binding in the Flinders Sensitive Line rat depression model by quantitative receptor autoradiography...... cortices after chronic paroxetine administration, and markedly reduced in several regions after 5-HT depletion. Thus, the 5-HT(4) receptor binding was decreased in the Flinders Sensitive Line depression model and in response to chronic paroxetine administration....

  3. Effects of oral administration of di-(2-ethylhexyl) and diisononyl phthalates on atopic dermatitis in NC/Nga mice.

    Science.gov (United States)

    Sadakane, Kaori; Ichinose, Takamichi; Takano, Hirohisa; Yanagisawa, Rie; Koike, Eiko

    2014-02-01

    Subcutaneous injection of low dose of phthalates causes adjuvant effects on immunoglobulin production. Moreover, intraperitoneal injection of di-(2-ethylhexyl) phthalate (DEHP) and diisononyl phthalate (DINP) at doses lower than the no-observed-adverse-effect level (NOAEL) causes aggravation of atopic dermatitis-like skin lesions (ADSLs) in mouse models. However, the effects of oral exposure to these phthalates, including their effect on atopic dermatitis (AD) symptoms, remain unclear. To investigate the effects of oral administration of DEHP and DINP at doses lower than the NOAEL on AD in an NC/Nga mouse model. NC/Nga mice were subcutaneously injected with mite-allergen (Dermatophagoides pteronyssinus) to induce ADSLs and orally administered varying doses of DEHP (0, 8.3, 166.3 or 3325 µg/animal) or DINP (0, 6.6, 131.3 or 2625 µg/animal) once a week for four weeks. Skin disease symptomatology was subsequently evaluated and immunoglobulin production levels in serum and inflammatory cytokine levels in lesion sites were measured. Oral administration of low doses of both DEHP and DINP tended to increase infiltration of eosinophils; degranulation of mast cells and local expression of inflammatory cytokines, interleukin-13 and macrophage inflammatory protein-1 alpha in subcutaneous tissue, whereas DINP administration tended to aggravate allergen-induced ADSL production. Oral administration of both DEHP and DINP at doses lower than the NOAEL tends to increase the allergic response in animal AD models, but only DINP administration slightly aggravates allergen-induced ADSL production.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. 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....

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Effects of sublingual immunotherapy in a murine asthma model sensitized by intranasal administration of house dust mite extracts.

    Science.gov (United States)

    Shima, Kenjiro; Koya, Toshiyuki; Tsukioka, Keisuke; Sakagami, Takuro; Hasegawa, Takashi; Fukano, Chiharu; Ohashi-Doi, Katsuyo; Watanabe, Satoshi; Suzuki, Eiichi; Kikuchi, Toshiaki

    2017-01-01

    Sublingual immunotherapy (SLIT) has received attention as a method for allergen immunotherapy. However, the mechanism of SLIT has not yet been fully investigated. Therefore, we evaluated the effects of SLIT in a murine asthma model, sensitized by intranasal administration of house dust mite (HDM) extracts. Female BALB/c mice were intranasally exposed to HDM for either 3 or 5 weeks (5 consecutive days per week). Mice were administered either low-dose (0.5 mg/day) or high-dose (5 mg/day) sublingual HDM extracts for 2 weeks, followed by an additional week of intranasal exposure. Airway hyperresponsiveness (AHR), bronchoalveolar lavage fluid (BALF) cell count, cytokine levels in the BALF and lymph node cell culture supernatants, and allergen-specific antibodies were measured. Lung histology was also investigated. In mice sensitized for 5 weeks, high-dose SLIT ameliorated AHR, airway eosinophilia and goblet cell metaplasia. In mice sensitized for 3 weeks, even low dose SLIT ameliorated AHR and airway eosinophilia. Th2 cytokine levels in culture supernatants of submandibular lymph node cells in high-dose SLIT mice decreased, whereas IL-10 levels increased. Total IgA in BALF increased in mice sensitized for 3 or 5 weeks, and high-dose SLIT also increased allergen-specific IgG2a in mice sensitized for 5 weeks. These data suggest that earlier induction of SLIT in HDM-sensitized mice provides superior suppression of AHR and goblet cell metaplasia. The modulation of allergen specific IgG2a and local IgA might play a role in the amelioration of AHR and airway inflammation. Copyright © 2016 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

  18. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Weiner, H L; Lemere, C A; Maron, R

    2000-01-01

    Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated ......Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease...

  19. 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...

  20. 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.

  1. GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome

    DEFF Research Database (Denmark)

    Pereira-Fantini, Prue M; Nagy, Eva S; Thomas, Sarah L

    2008-01-01

    in a juvenile short bowel syndrome model. Contrary to adult rodent studies, administration of GLP-2 resulted in adverse outcomes including reduced ability to gain weight; decreased serum albumin, tissue maltase, and sucrase; and villous atrophy. We anticipate this information will have important implications...

  2. Ohio 4-H Agents' Perceptions of the Level of Importance and Frequency of Use of the Eighteen Components of the GEMS Model of Volunteer Administration.

    Science.gov (United States)

    Deppe, Catherine A.; Culp, Ken, III

    2001-01-01

    4-H youth development agents (n=81) identified the importance and frequency of use of the phases in the GEMS (Generate, Educate, Motivate, Sustain) model of volunteer administration. The greatest discrepancy between importance and frequency was in sustaining volunteer involvement. Areas for agents' professional development were identified.…

  3. GLP-2 administration results in increased proliferation but paradoxically an adverse outcome in a juvenile piglet model of short bowel syndrome

    DEFF Research Database (Denmark)

    Pereira-Fantini, Prue M; Nagy, Eva S; Thomas, Sarah L

    2008-01-01

    OBJECTIVE: The objective of the present study was to examine the effect of glucagon-like peptide-2 (GLP-2) administration in a piglet, juvenile model of short bowel syndrome. MATERIALS AND METHODS: Four-week-old piglets underwent either a sham operation or 75% small bowel resection. Postoperative...

  4. A mouse model of pathological small intestinal epithelial cell apoptosis and shedding induced by systemic administration of lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Jonathan M. Williams

    2013-11-01

    The gut barrier, composed of a single layer of intestinal epithelial cells (IECs held together by tight junctions, prevents the entrance of harmful microorganisms, antigens and toxins from the gut lumen into the blood. Small intestinal homeostasis is normally maintained by the rate of shedding of senescent enterocytes from the villus tip exactly matching the rate of generation of new cells in the crypt. However, in various localized and systemic inflammatory conditions, intestinal homeostasis can be disturbed as a result of increased IEC shedding. Such pathological IEC shedding can cause transient gaps to develop in the epithelial barrier and result in increased intestinal permeability. Although pathological IEC shedding has been implicated in the pathogenesis of conditions such as inflammatory bowel disease, our understanding of the underlying mechanisms remains limited. We have therefore developed a murine model to study this phenomenon, because IEC shedding in this species is morphologically analogous to humans. IEC shedding was induced by systemic lipopolysaccharide (LPS administration in wild-type C57BL/6 mice, and in mice deficient in TNF-receptor 1 (Tnfr1−/−, Tnfr2 (Tnfr2−/−, nuclear factor kappa B1 (Nfκb1−/− or Nfĸb2 (Nfĸb2−/−. Apoptosis and cell shedding was quantified using immunohistochemistry for active caspase-3, and gut-to-circulation permeability was assessed by measuring plasma fluorescence following fluorescein-isothiocyanate–dextran gavage. LPS, at doses ≥0.125 mg/kg body weight, induced rapid villus IEC apoptosis, with peak cell shedding occurring at 1.5 hours after treatment. This coincided with significant villus shortening, fluid exudation into the gut lumen and diarrhea. A significant increase in gut-to-circulation permeability was observed at 5 hours. TNFR1 was essential for LPS-induced IEC apoptosis and shedding, and the fate of the IECs was also dependent on NFκB, with signaling via NFκB1 favoring cell survival and

  5. Estimated economic benefits from low-frequency administration of atypical antipsychotics in treatment of schizophrenia: a decision model

    Directory of Open Access Journals (Sweden)

    Furiak Nicolas M

    2012-11-01

    Full Text Available Abstract The objective of this study was to quantify the direct medical resources used and the corresponding burden of disease in the treatment of patients with schizophrenia. Because low-frequency administration (LFA of risperidone guarantees adherence during treatment intervals and offers fewer opportunities to discontinue, adherence and persistence were assumed to improve, thereby reducing relapses of major symptoms. A decision tree model including Markov processes with monthly cycles and a five-year maximum timeframe was constructed. Costs were adapted from the literature and discounted at a 3% annual rate. The population is a demographically homogeneous cohort of patients with schizophrenia, differentiated by initial disease severity (mildly ill, moderately ill, and severely ill. Treatment parameters are estimated using published information for once-daily risperidone standard oral therapy (RIS-SOT and once-monthly risperidone long-acting injection (RIS-LAI with LFA therapy characteristics derived from observed study trends. One-year and five-year results are expressed as discounted direct medical costs and mean number of relapses per patient (inpatient, outpatient, total and are estimated for LFA therapies given at three, six, and nine month intervals. The one-year results show that LFA therapy every 3 months (LFA-3 ($6,088 is less costly than either RIS-SOT ($10,721 or RIS-LAI ($9,450 with similar trends in the 5-year results. Moreover, the model predicts that LFA-3 vs. RIS-SOT vs. RIS LAI therapy will reduce costly inpatient relapses (0.16 vs. 0.51 vs. 0.41. Extending the interval to six (LFA-6 and nine (LFA-9 months resulted in further reductions in relapse and costs. Limitations include the fact that LFA therapeutic options are hypothetical and do not yet exist and limited applicability to compare one antipsychotic agent versus another as only risperidone therapy is evaluated. However, study results have quantified the potential health

  6. The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model.

    Science.gov (United States)

    Aragón, Félix; Carino, Silvia; Perdigón, Gabriela; de Moreno de LeBlanc, Alejandra

    2014-06-01

    Antitumour activity is one of the health-promoting effects attributed to probiotics specially analysed from preclinical models, mostly murine. Here, the effect of milk fermented by the probiotic bacterium Lactobacillus casei CRL 431, on a murine breast cancer model was analysed. Mice were fed with milk fermented by Lactobacillus casei or unfermented milk before and after tumour injection. Rate of tumour development, cytokines in serum, IgA, CD4, CD8, F4/80 and cytokines positive cells in mammary glands were determined. Microvasculature in the tumour tissues was monitored. The effect of fermented milk administration after tumour injection was also evaluated. It was observed that probiotic administration delayed or blocked tumour development. This effect was associated to modulation of the immune response triggered by the tumour. The area occupied by blood vessels decreased in the tumours from mice given fermented milk which agrees with their small tumours, and fewer side effects. Finally, it was observed that probiotic administration after tumour detection was also beneficial to delay the tumour growth. In conclusion, we showed in this study the potential of milk fermented by the probiotic Lactobacillus casei CRL431 to stimulate the immune response against this breast tumour, avoiding or delaying its growth when it was preventively administrated and also when the administration started after tumour cells injection. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. 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...

  8. 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 ...

  9. Efficacy of phosphocreatine pre-administration on XIAP and Smac in ischemic penumbra of rats with focal cerebral ischemia reperfusion injury.

    Science.gov (United States)

    Wang, Wei; Wang, Qi; Yu, Wanyou; Chen, Lianhua; Li, Zhong

    2018-02-01

    To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.

  10. D-Galactose High-Dose Administration Failed to Induce Accelerated Aging Changes in Neurogenesis, Anxiety, and Spatial Memory on Young Male Wistar Rats.

    Science.gov (United States)

    Cardoso, Armando; Magano, Sara; Marrana, Francisco; Andrade, José P

    2015-12-01

    The model of accelerated senescence with the prolonged administration of d-galactose is used in anti-aging studies because it mimics several aging-associated alterations such as increase of oxidative stress and decline of cognition. However, there is no standardized protocol for this aging model, and recently some reports have questioned its effectiveness. To clarify this issue, we used a model of high-dose d-galactose on 1-month-old male Wistar rats and studied the hippocampus, one of the most affected brain regions. In one group (n = 10), d-galactose was daily administered intraperitoneally (300 mg/kg) during 8 weeks whereas age-matched controls (n = 10) were injected intraperitoneally with saline. A third group (n = 10) was treated with the same dose of d-galactose and with oral epigallocatechin-3-gallate (EGCG) (2 grams/L), a green tea catechin with anti-oxidant and neuroprotective properties. After treatments, animals were submitted to open-field, elevated plus-maze and Morris water maze tests, and neurogenesis in the dentate gyrus subgranular layer was quantified. There were no significant alterations when the three groups were compared in the number of doublecortin- and Ki-67-immunoreactive cells, and also on anxiety levels, spatial learning, and memory. Therefore, d-galactose was not effective in the induction of accelerated aging, and EGCG administered to d-galactose-treated animals did not improve behavior and had no effects on neurogenesis. We conclude that daily 300 mg/kg of d-galactose administered intraperitoneally may not be a suitable model for inducing age-related neurobehavioral alterations in young male Wistar rats. More studies are necessary to obtain a reliable and reproducible model of accelerated senescence in rodents using d-galactose.

  11. Is Forced Swimming Immobility a Good Endpoint for Modeling Negative Symptoms of Schizophrenia? - Study of Sub-Anesthetic Ketamine Repeated Administration Effects

    Directory of Open Access Journals (Sweden)

    GILDA NEVES

    2017-08-01

    Full Text Available ABSTRACT Immobility time in the forced swimming has been described as analogous to emotional blunting or apathy and has been used for characterizing schizophrenia animal models. Several clinical studies support the use of NMDA receptor antagonists to model schizophrenia in rodents. Some works describe the effects of ketamine on immobility behavior but there is variability in the experimental design used leading to controversial results. In this study, we evaluated the effects of repeated administration of ketamine sub-anesthetic doses in forced swimming, locomotion in response to novelty and novel object recognition, aiming a broader evaluation of the usefulness of this experimental approach for modeling schizophrenia in mice. Ketamine (30 mg/kg/day i.p. for 14 days induced a not persistent decrease in immobility time, detected 24h but not 72h after treatment. This same administration protocol induced a deficit in novel object recognition. No change was observed in mice locomotion. Our results confirm that repeated administration of sub-anesthetic doses of ketamine is useful in modeling schizophrenia-related behavioral changes in mice. However, the immobility time during forced swimming does not seem to be a good endpoint to evaluate the modeling of negative symptoms in NMDAR antagonist animal models of schizophrenia.

  12. The utilization of oropharyngeal intratracheal PAMP administration and bronchoalveolar lavage to evaluate the host immune response in mice.

    Science.gov (United States)

    Allen, Irving C

    2014-04-02

    The host immune response to pathogens is a complex biological process. The majority of in vivo studies classically employed to characterize host-pathogen interactions take advantage of intraperitoneal injections of select bacteria or pathogen associated molecular patterns (PAMPs) in mice. While these techniques have yielded tremendous data associated with infectious disease pathobiology, intraperitoneal injection models are not always appropriate for host-pathogen interaction studies in the lung. Utilizing an acute lung inflammation model in mice, it is possible to conduct a high resolution analysis of the host innate immune response utilizing lipopolysaccharide (LPS). Here, we describe the methods to administer LPS using nonsurgical oropharyngeal intratracheal administration, monitor clinical parameters associated with disease pathogenesis, and utilize bronchoalveolar lavage fluid to evaluate the host immune response. The techniques that are described are widely applicable for studying the host innate immune response to a diverse range of PAMPs and pathogens. Likewise, with minor modifications, these techniques can also be applied in studies evaluating allergic airway inflammation and in pharmacological applications.

  13. 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…

  14. 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.

  15. Oral administration of the KATP channel opener diazoxide ameliorates disease progression in a murine model of multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Mahy Nicole

    2011-11-01

    Full Text Available Abstract Background Multiple Sclerosis (MS is an acquired inflammatory demyelinating disorder of the central nervous system (CNS and is the leading cause of nontraumatic disability among young adults. Activated microglial cells are important effectors of demyelination and neurodegeneration, by secreting cytokines and others neurotoxic agents. Previous studies have demonstrated that microglia expresses ATP-sensitive potassium (KATP channels and its pharmacological activation can provide neuroprotective and anti-inflammatory effects. In this study, we have examined the effect of oral administration of KATP channel opener diazoxide on induced experimental autoimmune encephalomyelitis (EAE, a mouse model of MS. Methods Anti-inflammatory effects of diazoxide were studied on lipopolysaccharide (LPS and interferon gamma (IFNγ-activated microglial cells. EAE was induced in C57BL/6J mice by immunization with myelin oligodendrocyte glycoprotein peptide (MOG35-55. Mice were orally treated daily with diazoxide or vehicle for 15 days from the day of EAE symptom onset. Treatment starting at the same time as immunization was also assayed. Clinical signs of EAE were monitored and histological studies were performed to analyze tissue damage, demyelination, glial reactivity, axonal loss, neuronal preservation and lymphocyte infiltration. Results Diazoxide inhibited in vitro nitric oxide (NO, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6 production and inducible nitric oxide synthase (iNOS expression by activated microglia without affecting cyclooxygenase-2 (COX-2 expression and phagocytosis. Oral treatment of mice with diazoxide ameliorated EAE clinical signs but did not prevent disease. Histological analysis demonstrated that diazoxide elicited a significant reduction in myelin and axonal loss accompanied by a decrease in glial activation and neuronal damage. Diazoxide did not affect the number of infiltrating lymphocytes positive for CD3 and CD20

  16. Tumor Penetrating Theranostic Nanoparticles for Enhancement of Targeted and Image-guided Drug Delivery into Peritoneal Tumors following Intraperitoneal Delivery.

    Science.gov (United States)

    Gao, Ning; Bozeman, Erica N; Qian, Weiping; Wang, Liya; Chen, Hongyu; Lipowska, Malgorzata; Staley, Charles A; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2017-01-01

    The major obstacles in intraperitoneal (i.p.) chemotherapy of peritoneal tumors are fast absorption of drugs into the blood circulation, local and systemic toxicities, inadequate drug penetration into large tumors, and drug resistance. Targeted theranostic nanoparticles offer an opportunity to enhance the efficacy of i.p. therapy by increasing intratumoral drug delivery to overcome resistance, mediating image-guided drug delivery, and reducing systemic toxicity. Herein we report that i.p. delivery of urokinase plasminogen activator receptor (uPAR) targeted magnetic iron oxide nanoparticles (IONPs) led to intratumoral accumulation of 17% of total injected nanoparticles in an orthotopic mouse pancreatic cancer model, which was three-fold higher compared with intravenous delivery. Targeted delivery of near infrared dye labeled IONPs into orthotopic tumors could be detected by non-invasive optical and magnetic resonance imaging. Histological analysis revealed that a high level of uPAR targeted, PEGylated IONPs efficiently penetrated into both the peripheral and central tumor areas in the primary tumor as well as peritoneal metastatic tumor. Improved theranostic IONP delivery into the tumor center was not mediated by nonspecific macrophage uptake and was independent from tumor blood vessel locations. Importantly, i.p. delivery of uPAR targeted theranostic IONPs carrying chemotherapeutics, cisplatin or doxorubicin, significantly inhibited the growth of pancreatic tumors without apparent systemic toxicity. The levels of proliferating tumor cells and tumor vessels in tumors treated with the above theranostic IONPs were also markedly decreased. The detection of strong optical signals in residual tumors following i.p. therapy suggested the feasibility of image-guided surgery to remove drug-resistant tumors. Therefore, our results support the translational development of i.p. delivery of uPAR-targeted theranostic IONPs for image-guided treatment of peritoneal tumors.

  17. 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...

  18. 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)

  19. 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.

  20. 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...

  1. 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

  2. Disruption of the M2 gene of murine gammaherpesvirus 68 alters splenic latency following intranasal, but not intraperitoneal, inoculation.

    Science.gov (United States)

    Jacoby, Meagan A; Virgin, Herbert W; Speck, Samuel H

    2002-02-01

    Infection of mice with murine gammaherpesvirus 68 (gamma HV68; also referred to as MHV68) provides a tractable small-animal model with which to address the requirements for the establishment and maintenance of gammaherpesvirus infection in vivo. The M2 gene of gamma HV68 is a latency-associated gene that encodes a protein lacking discernible homology to any known viral or cellular proteins. M2 gene transcripts have been detected in latently infected splenocytes (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999; H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999) and peritoneal exudate cells (H. W. Virgin IV, R. M. Presti, X. Y. Li, C. Liu, and S. H. Speck, J. Virol. 73:2321-2332, 1999), as well as in a latently gamma HV68-infected B-lymphoma cell line (S. M. Husain, E. J. Usherwood, H. Dyson, C. Coleclough, M. A. Coppola, D. L. Woodland, M. A. Blackman, J. P. Stewart, and J. T. Sample, Proc. Natl. Acad. Sci. USA 96:7508-7513, 1999). Here we describe the generation of gamma HV68 mutants with disruptions in the M2 gene. Mutation of the M2 gene did not affect the ability of the virus to replicate in tissue culture, nor did it affect gamma HV68 virulence in B6.Rag1 deficient mice. However, we found that M2 was differentially required for acute replication in vivo. While mutation of M2 did not affect acute phase of virus replication in the lungs of mice following intranasal inoculation, acute-phase virus replication in the spleen was decreased compared to that of the wild-type and marker rescue viruses following intraperitoneal inoculation. Upon intranasal inoculation, M2 mutant viruses exhibited a significant decrease in the establishment of latency in the spleen on day 16 postinfection, as measured by the frequency of viral genome-positive cells. In addition, M2 mutant viral genome

  3. 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.

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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

  8. 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.

  9. 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.

  10. 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)

  11. 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.

  12. The Cultural Context of Administration.

    Science.gov (United States)

    Ortiz, Flora Ida

    To explicate the relevance of cultural context to educational administration practices, this paper contrasts United States cultural attitudes and administrative practices with those of Latin America. Drawing on Leslie A. White's definition of culture, the author presents the Weberian model of administration as exemplary for the United States,…

  13. Further standardisation in Land Administration

    NARCIS (Netherlands)

    Lemmen, Christiaan; van Oosterom, P.J.M.; Kalantari, Mohsen; Unger, Eva-Maria; Teo, Chee Hai; Zeeuw, Kees de

    2017-01-01

    The paper describes the ongoing developments and standardisation in land administration. Standards are relevant in relation to build as well as maintain and develop a land administration.

    Standards like the ISO 19152 Land Administration Domain Model (LADM) are helping to jump-start new

  14. Mitigation of chlorine gas lung injury in rats by postexposure administration of sodium nitrite.

    Science.gov (United States)

    Yadav, Amit K; Doran, Stephen F; Samal, Andrey A; Sharma, Ruchita; Vedagiri, Kokilavani; Postlethwait, Edward M; Squadrito, Giuseppe L; Fanucchi, Michelle V; Roberts, L Jackson; Patel, Rakesh P; Matalon, Sadis

    2011-03-01

    Nitrite (NO(2)(-)) has been shown to limit injury to the heart, liver, and kidneys in various models of ischemia-reperfusion injury. Potential protective effects of systemic NO(2)(-) in limiting lung injury or enhancing repair have not been documented. We assessed the efficacy and mechanisms by which postexposure intraperitoneal injections of NO(2)(-) mitigate chlorine (Cl(2))-induced lung injury in rats. Rats were exposed to Cl(2) (400 ppm) for 30 min and returned to room air. NO(2)(-) (1 mg/kg) or saline was administered intraperitoneally at 10 min and 2, 4, and 6 h after exposure. Rats were killed at 6 or 24 h. Injury to airway and alveolar epithelia was assessed by quantitative morphology, protein concentrations, number of cells in bronchoalveolar lavage (BAL), and wet-to-dry lung weight ratio. Lipid peroxidation was assessed by measurement of lung F(2)-isoprostanes. Rats developed severe, but transient, hypoxemia. A significant increase of protein concentration, neutrophil numbers, airway epithelia in the BAL, and lung wet-to-dry weight ratio was evident at 6 h after Cl(2) exposure. Quantitative morphology revealed extensive lung injury in the upper airways. Airway epithelial cells stained positive for terminal deoxynucleotidyl-mediated dUTP nick end labeling (TUNEL), but not caspase-3. Administration of NO(2)(-) resulted in lower BAL protein levels, significant reduction in the intensity of the TUNEL-positive cells, and normal lung wet-to-dry weight ratios. F(2)-isoprostane levels increased at 6 and 24 h after Cl(2) exposure in NO(2)(-)- and saline-injected rats. This is the first demonstration that systemic NO(2)(-) administration mitigates airway and epithelial injury.

  15. 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

    The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use...... 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......-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high...

  16. Expression of verocytotoxic Escherichia coli antigens in tobacco seeds and evaluation of gut immunity after oral administration in mouse model

    OpenAIRE

    Rossi, Luciana; Di Giancamillo, Alessia; Reggi, Serena; Domeneghini, Cinzia; Baldi, Antonella; Sala, Vittorio; Dell'Orto, Vittorio; Coddens, Annelies; Cox, Eric; Fogher, Corrado

    2013-01-01

    Verocytotoxic Escherichia (E.) coli strains are responsible for swine oedema disease, which is an enterotoxaemia that causes economic losses in the pig industry. The production of a vaccine for oral administration in transgenic seeds could be an efficient system to stimulate local immunity. This study was conducted to transform tobacco plants for the seed-specific expression of antigenic proteins from a porcine verocytotoxic E. coli strain. Parameters related to an immunological response and ...

  17. Lymphotropic administration of photosensitizer as a model of target therapy of testicle inflammation: Experimental and clinical data.

    Science.gov (United States)

    Yagudaev, Daniel M; Brechov, Eugene I; Saidov, Ayubdzhon C; Kalyagina, Nina A; Kuznetsova, Julia O; Loschenov, Victor B

    2016-03-01

    The existence of zones of humoral skin-subskin tissue linkage with internal organs as well as the possibility of targeted administration of preparation into the affected organs were studied. An experimental study of preparation and distribution in the bodies of mice was held by both intravenous and lymphotropic methods of administration. By means of detection with a photosensitizer (as a marker), the study was conducted on healthy mice and mice with testicle inflammation. Based on the experimental results, the study has been implemented into the clinical practice of treatment of acute inflammatory diseases of testicle and its epididymis. Patients were administered antibiotics either by the lymphotropic method, or by traditional methods. The concentration of the preparation, administered by the lymphotropic method, maintained in target organs (testicles) at a high level for a longer time, while the intravenous injections provided fast achievement of high concentrations. Moreover there was a lower level of accumulation of the photosensitizer in parenchymal organs after subcutaneous (lymphotropic) administration. The presence of humoral connection of certain areas of skin and subcutaneous tissue with testicles and their epididymis was proved. It was found that the lymphotropic administration leads to earlier clinical improvement and normalization of laboratory indices, and, thus, to significant reduction in hospital stay. Such results open the possibility of targeted drug delivery to the diseased organs. In perspective, the method may be used in treating patients not only in urology, but also in surgery, as well as for many acute, chronic or cancer diseases. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Nasal administration of amyloid-beta peptide decreases cerebral amyloid burden in a mouse model of Alzheimer's disease

    DEFF Research Database (Denmark)

    Weiner, H L; Lemere, C A; Maron, R

    2000-01-01

    Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease-implicated ......Progressive cerebral deposition of amyloid-beta (Abeta) peptide, an early and essential feature of Alzheimer's disease (AD), is accompanied by an inflammatory reaction marked by microgliosis, astrocytosis, and the release of proinflammatory cytokines. Mucosal administration of disease......-implicated proteins can induce antigen-specific anti-inflammatory immune responses in mucosal lymphoid tissue which then act systemically. We hypothesized that chronic mucosal administration of Abeta peptide might induce an anti-inflammatory process in AD brain tissue that could beneficially affect...... Abeta plaque burden and Abeta42 levels in mice treated intranasally with Abeta peptide versus controls treated with myelin basic protein or left untreated. This lower Abeta burden was associated with decreased local microglial and astrocytic activation, decreased neuritic dystrophy, serum anti...

  19. Intraarterial route increases the risk of cerebral lesions after mesenchymal cell administration in animal model of ischemia

    Science.gov (United States)

    Argibay, Bárbara; Trekker, Jesse; Himmelreich, Uwe; Beiras, Andrés; Topete, Antonio; Taboada, Pablo; Pérez-Mato, María; Vieites-Prado, Alba; Iglesias-Rey, Ramón; Rivas, José; Planas, Anna M.; Sobrino, Tomás; Castillo, José; Campos, Francisco

    2017-01-01

    Mesenchymal stem cells (MSCs) are a promising clinical therapy for ischemic stroke. However, critical parameters, such as the most effective administration route, remain unclear. Intravenous (i.v.) and intraarterial (i.a.) delivery routes have yielded varied outcomes across studies, potentially due to the unknown MSCs distribution. We investigated whether MSCs reached the brain following i.a. or i.v. administration after transient cerebral ischemia in rats, and evaluated the therapeutic effects of both routes. MSCs were labeled with dextran-coated superparamagnetic nanoparticles for magnetic resonance imaging (MRI) cell tracking, transmission electron microscopy and immunohistological analysis. MSCs were found in the brain following i.a. but not i.v. administration. However, the i.a. route increased the risk of cerebral lesions and did not improve functional recovery. The i.v. delivery is safe but MCS do not reach the brain tissue, implying that treatment benefits observed for this route are not attributable to brain MCS engrafting after stroke.

  20. Vitamin A is systemically bioavailable after intratracheal administration with surfactant in an animal model of newborn respiratory distress.

    Science.gov (United States)

    Singh, Avash J; Bronshtein, Vadim; Khashu, Minesh; Lee, Kyle; Potts, James E; Friel, James; Chessex, Philippe

    2010-06-01

    Chronic lung disease (CLD) is a major cause of long-term morbidity in extremely LBW infants with respiratory distress syndrome. Parenteral vitamin A administration decreases the risk of CLD. We tested the hypothesis that intratracheal vitamin A administration with surfactant is systemically bioavailable without interfering with the functional properties of exogenous surfactant. Newborn piglets were ventilated with 100% FiO2 and sequential saline lavage induced respiratory distress syndrome. During lung injury induction, ventilator changes were allowed, but none were made following treatment allocation. Animals were assigned by chance in a blinded control trial to three groups: I=control; II=surfactant; III=surfactant+vitamin A. Hemodynamics, lung mechanics, and blood gases were measured following instrumentation, pre- and posttreatment for 4 h, at which time the liver was sampled for retinol determination. All parameters improved in animals receiving surfactant. A significant interaction existed between time and group for PaO2 and alveolar-arterial oxygen difference (A-aDO2). Hepatic levels of retinol were higher (p<0.001) in animals receiving retinyl acetate. Intratracheal administration of surfactant+vitamin A did not alter the beneficial effects of surfactant on lung compliance and gas exchange. Intratracheal Vitamin A was associated with rapid hepatic uptake. Further studies are warranted.

  1. 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.

  2. 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...

  3. BRAZILIAN ADMINISTRATION, ADMINISTRATIVE REFORM AND THE NEW STATE: THE ROLE OF ADMINISTRATIVE APPARATUS IN VARGAS ADMINISTRATION

    Directory of Open Access Journals (Sweden)

    Emerson Moura

    2016-07-01

    Full Text Available The role played by the administrative apparatus through the Department of Administrative Services in the Government policy Vargas is the object put in debate. Analyzes the theme from the the investigation of patrimonial, authoritarian and inefficient context which marks the formation and development of administrative bureaucracy, the tenders of professionalization and efficiency brought by the administrative reforms of the 1930s and 1940s with the contrast of the limitations of the import of the Weberian model in the Brazilian context and analysis of the establishment of the New State DASP and their assignments. Search the work demonstrate the control position he held directly and through the State Departments in the Brazilian Public Administration ensuring centralized and developmental policy of the government. For this is adopted as the research method of approach structuralism in order to identify the deconstruction of the phenomenon - of administrative reforms - in the superficial perception - the proposed impersonality and efficiency as the best way of achieving the public interest - its invariant structure - the search for the adequacy of the administrative apparatus and bureaucracy for pursuit of political ends pursued by the Government.

  4. 75 FR 6433 - Federal Aviation Administration

    Science.gov (United States)

    2010-02-09

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Notice of Availability of a Draft... 9, West Chicago, IL AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of... Surveillance Radar, Model 9, West Chicago, Illinois. SUMMARY: The Federal Aviation Administration (FAA...

  5. 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

  6. Therapeutic effect of intravesical administration of paclitaxel solubilized with poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate) in an orthotopic bladder cancer model

    International Nuclear Information System (INIS)

    Tamura, Koetsu; Kikuchi, Eiji; Konno, Tomohiro; Ishihara, Kazuhiko; Matsumoto, Kazuhiro; Miyajima, Akira; Oya, Mototsugu

    2015-01-01

    To evaluate the effects of intravesical administration of paclitaxel (PTX-30W), which was prepared by solubilization with a water-soluble amphiphilic polymer composed of PMB30W, a copolymer of 2-methacryloyloxyethyl phosphorylcholine and n-butyl methacrylate, in an orthotopic bladder cancer model. The cytotoxicities of PMB30W were examined in MBT-2 cell cultures and the results were compared with those of the conventional paclitaxel solubilizer Cremophor. In an orthotopic MBT-2 bladder cancer model, the effect of intravesical administration of PTX-30W was compared with that of paclitaxel solubilized with Cremophor (PTX-CrEL). The paclitaxel concentration in bladder tumors after the intravesical treatment was also evaluated using liquid chromatography tandem mass spectrometry (LC-MS/MS) system. In vitro, Cremophor exhibited dose-dependent cytotoxicity towards MBT-2 cells, whereas no cytotoxicity was observed with PMB30W. In the orthotopic bladder cancer model, intravesical administration of PTX-30W resulted in a significant reduction of bladder wet weight compared with that of PTX-CrEL. The paclitaxel concentration in bladder tumors after the intravesical treatment was significantly higher in PTX-30W treated mice than in PTX-CrEL treated mice. Intravesically administered PTX-30W can elicit stronger antitumor effects on bladder tumors than conventional paclitaxel formulated in Cremophor, presumably because of its better penetration into tumor cells. PTX-30W might be a promising antitumor agent for intravesical treatment of non-muscle invasive bladder cancer

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. Micro-dose hCG as luteal phase support without exogenous progesterone administration: mathematical modelling of the hCG concentration in circulation and initial clinical experience.

    Science.gov (United States)

    Andersen, C Yding; Fischer, R; Giorgione, V; Kelsey, Thomas W

    2016-10-01

    For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the GnRHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential advances and disadvantages. Based on the pharmacokinetic characteristics of hCG, the mathematical modelling of the concentration profiles of hCG during the luteal phase has been evaluated in connection with several different approaches for hCG administration as LPS. It is suggested that the currently employed LPS provided in connection with the GnRHa trigger (i.e. 1.500 IU) is too strong, and that daily micro-dose hCG administration is likely to provide an optimised LPS with the current available drugs. Initial clinical results with the micro-dose hCG approach are presented.

  18. Feasibility and Efficacy of Autologous Bone Marrow Aspirate Transplantation Combined with Human Parathyroid Hormone 1-34 Administration to Treat Osteonecrosis in a Rabbit Model.

    Science.gov (United States)

    Makihara, Takeshi; Yoshioka, Tomokazu; Sugaya, Hisashi; Aoto, Katsuya; Wada, Hiroshi; Uemura, Kenta; Tanaka, Kenta; Akaogi, Hiroshi; Yamazaki, Masashi; Mishima, Hajime

    2017-01-01

    No studies have examined the transplantation of a bone marrow aspirate (BMA) containing mesenchymal stem cells (MSCs) combined with human parathyroid hormone 1-34 (hPTH1-34) administration. Therefore, we evaluated the feasibility and efficacy of autologous BMA transplantation combined with hPHT1-34 administration in a bone necrosis model. The metatarsal bones of rabbits were necrotized using liquid nitrogen, and the rabbits received a BMA transplantation or saline injection followed by hPTH1-34 (30  μ g/kg) or saline administration three times per week ( n = 3-4 per group). The rabbits were euthanized at 12 weeks after the initiation of treatment. No systemic adverse effects or local neoplastic lesions were observed. Importantly, the rabbits in the BMA transplantation plus hPTH1-34 group showed the highest bone volumes and histological scores of new bone. These data confirmed the feasibility of BMA transplantation combined with hPTH1-34, at least during the experimental period. The observed efficacy may be explained by a synergistic effect from the stimulation of MSC differentiation to osteoblasts with hPTH1-34-mediated suppression of apoptosis in osteoblasts. These results indicate the promising potential for BMA transplantation combined with hPTH1-34 administration in bone necrosis treatment. Longer term experiments are needed to confirm the safety of this therapeutic strategy.

  19. An Organization Model to Assist Individual Physicians, Scientists, and Senior Health Care Administrators With Personal and Professional Needs.

    Science.gov (United States)

    Shanafelt, Tait D; Lightner, Deborah J; Conley, Christopher R; Petrou, Steven P; Richardson, Jarrett W; Schroeder, Pamela J; Brown, William A

    2017-11-01

    Working as a physician, scientist, or senior health care administrator is a demanding career. Studies have demonstrated that burnout and other forms of distress are common among individuals in these professions, with potentially substantive personal and professional consequences. In addition to system-level interventions to promote well-being globally, health care organizations must provide robust support systems to assist individuals in distress. Here, we describe the 15-year experience of the Mayo Clinic Office of Staff Services (OSS) providing peer support to physicians, scientists, and senior administrators at one center. Resources for financial planning (retirement, tax services, college savings for children) and peer support to assist those experiencing distress are intentionally combined in the OSS to normalize the use of the Office and reduce the stigma associated with accessing peer support. The Office is heavily used, with approximately 75% of physicians, scientists, and senior administrators accessing the financial counseling and 5% to 7% accessing the peer support resources annually. Several critical structural characteristics of the OSS are specifically designed to minimize potential stigma and reduce barriers to seeking help. These aspects are described here with the hope that they may be informative to other medical practices considering how to create low-barrier access to help individuals deal with personal and professional challenges. We also detail the results of a recent pilot study designed to extend the activity of the OSS beyond the reactive provision of peer support to those seeking help by including regular, proactive check-ups for staff covering a range of topics intended to promote personal and professional well-being. Copyright © 2017 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  20. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kwon Joong Yong

    2016-05-01

    Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

  1. Stabilization of tooth movement by administration of reveromycin A to osteoprotegerin-deficient knockout mice.

    Science.gov (United States)

    Yabumoto, Takahiro; Miyazawa, Ken; Tabuchi, Masako; Shoji, Satsuki; Tanaka, Miyuki; Kadota, Manami; Yoshizako, Mamoru; Kawatani, Makoto; Osada, Hiroyuki; Maeda, Hatsuhiko; Goto, Shigemi

    2013-09-01

    In this study, mechanical stress in the form of tooth movement was applied to osteoprotegerin-deficient knockout mice, which served as an animal model for juvenile Paget's disease. To compare and evaluate bone turnover and response of the surrounding bony tissue, we administered reveromycin A. We also investigated the ability of reveromycin A to control osteoclastic activity in juvenile Paget's disease. Eight-week-old male osteoprotegerin-deficient knockout and wild-type mice were injected with reveromycin A (15 mg/kg of body weight) intraperitoneally twice daily. An elastic module was inserted interproximally between the maxillary left first and second molars. Administration of reveromycin A to osteoprotegerin-deficient knockout mice reduced tooth movement distances, increased bone volumes at the interradicular septum, decreased osteoclast counts, and reduced serum alkaline phosphatase and tartrate resistant acid phosphatase. Reveromycin A administration also caused a temporal shift in peak Runx2 staining in osteoprotegerin-deficient knockout mice so that the overall staining time course was similar to that observed for wild-type mice. Reveromycin A administration in osteoprotegerin-deficient knockout mice inhibited bone resorption and normalized bone formation. As a result, normal bone turnover was obtained. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

  2. 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.

  3. 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...

  4. Intratracheal co-administration of antioxidants and ceftriaxone reduces pulmonary injury and mortality rate in an experimental model of sepsis.

    Science.gov (United States)

    Galvão, Andre M; Wanderley, Marcela S O; Silva, Roberto A; Filho, Carlos A M; Melo-Junior, Mário R; Silva, Luciano A; Streck, Emílio L; Dornelas de Andrade, Armele F; Souza Maia, Maria B; Barbosa de Castro, Celia M M

    2014-10-01

    Recent studies showed that both sepsis and antibiotic therapy are associated with cell death and linked to reactive oxygen species generation. This study investigated the effects of intratracheal administration of combinations of antioxidants (n-acetyl cysteine (NAC), vitamins C and E) in the treatment of sepsis-induced lung injury. Ninety-six male Wistar rats subjected to sepsis were treated with ceftriaxone plus NAC with or without vitamins C and E and compared to appropriate controls. As an index of oxidative damage protein carbonyls, sulfhydryl groups, lipid peroxidation and superoxide anion were measured, as well as superoxide dismutase and catalase. Histopathological alterations and mortality rate were also analyzed. Twenty-four hours after sepsis induction, markers of oxidative stress increased in all lungs examined. Ceftriaxone plus intratracheal combination of NAC, vitamins C and E decreased lung injury in infected animals by reducing superoxide anion production (54%), lipid peroxidation (53%) and protein carbonyl (58%) and restored the redox status (7.5 times). This therapy also reduced the imbalance of antioxidant enzymes activities and attenuated the alveolar architectural disorganization, inflammatory cell infiltration and pulmonary oedema. Survival increased from 66.6% with ceftriaxone to 83.2% with ceftriaxone plus antioxidants. Ceftriaxone plus intratracheal co-administration of antioxidants provides better protection, by decreasing pulmonary oxidative stress, limiting histophatological alterations and improving survival. Antioxidants should be explored as a co-adjuvant in the treatment of severe lung injury. © 2014 Asian Pacific Society of Respirology.

  5. 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.

  6. A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D2 receptor antagonists in rats.

    Science.gov (United States)

    Taneja, Amit; Vermeulen, An; Huntjens, Dymphy R H; Danhof, Meindert; De Lange, Elizabeth C M; Proost, Johannes H

    2016-10-15

    We compared the model performance of two semi-mechanistic pharmacokinetic-pharmacodynamic models, the precursor pool model and the agonist-antagonist interaction model, to describe prolactin response following the administration of the dopamine D2 receptor antagonists risperidone, paliperidone or remoxipride in rats. The time course of pituitary dopamine D2 receptor occupancy was also predicted. Male Wistar rats received a single dose (risperidone, paliperidone, remoxipride) or two consecutive doses (remoxipride). Population modeling was applied to fit the pool and interaction models to the prolactin data. The pool model was modified to predict the time course of pituitary D2 receptor occupancy. Unbound plasma concentrations of the D2 receptor antagonists were considered the drivers of the prolactin response. Both models were used to predict prolactin release following multiple doses of paliperidone. Both models described the data well and model performance was comparable. Estimated unbound EC50 for risperidone and paliperidone was 35.1nM (relative standard error 51%) and for remoxipride it was 94.8nM (31%). KI values for these compounds were 11.1nM (21%) and 113nM (27%), respectively. Estimated pituitary D2 receptor occupancies for risperidone and remoxipride were comparable to literature findings. The interaction model better predicted prolactin profiles following multiple paliperidone doses, while the pool model predicted tolerance better. The performance of both models in describing the prolactin profiles was comparable. The pool model could additionally describe the time course of pituitary D2 receptor occupancy. Prolactin response following multiple paliperidone doses was better predicted by the interaction model. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Comparison between male and female rats in a model of self-administration of a chocolate-flavored beverage: Behavioral and neurochemical studies.

    Science.gov (United States)

    Contini, Andrea; Sanna, Fabrizio; Maccioni, Paola; Colombo, Giancarlo; Argiolas, Antonio

    2018-05-15

    The existence of sex differences was studied in a rat model of operant self-administration of a chocolate-flavored beverage (CFB), which possesses strong reinforcing properties and is avidly consumed by rats. Whether these differences occurred concomitantly to changes in extracellular dopamine in the dialysate obtained from the nucleus accumbens, was assessed by intracerebral microdialysis. Male, ovariectomized and intact female rats showed similar self-administration profiles, with minor differences in both acquisition and maintenance phases. Intact females self-administered larger amounts of CFB, when expressed per body weight, than males and ovariectomized females, in spite of similar values of lever-responding, latency to the first lever-response and consumption efficiency (a measure of rat's licking effectiveness) in males, ovariectomized and intact females and no difference in breakpoint value and number of lever-responses emerged when males, ovariectomized and intact females were exposed to a progressive ratio schedule of reinforcement. Intracerebral microdialysis revealed a slight but significant increase in dopamine activity in the shell of the nucleus accumbens of male rats when compared to intact female rats during CFB self-administration. The above differences may be caused by the hormonal (mainly estradiol) fluctuations that occur during the estrus cycle in intact females. Accordingly, in intact females CFB self-administration and dopamine activity were found to fluctuate across the estrus cycle, with lower parameters of CFB self-administration and lower dopamine activity in the Proestrus and Estrus phases vs. the Metestrus and Diestrus phases of the cycle. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Knowledge Management Implementation at the Women’s Branch of the Institute of Public Administration in Saudi Arabia: A Proposed Model

    Directory of Open Access Journals (Sweden)

    Eiman Saud Abokhodiar

    2014-05-01

    Full Text Available This article aims to introduce a proposed model of knowledge management implementation at the Women’s Branch of the Institute of Public Administration (WIPA. The model was built after a review and analysis of literature related to knowledge management implementation in higher education institutions. The research includes three sections. The first section deals with a theoretical framework of knowledge management, including a knowledge management definition, components of knowledge management systems, an academic knowledge framework, an organizational knowledge framework, and processes of knowledge management. The second section reviews and discusses the proposed model of knowledge management implementation at WIPA. Finally, the article concludes with a discussion of the success factors and expected barriers to the proposed model.

  9. Sodium borocaptate (BSH) for Boron Neutron Capture Therapy (BNCT) in the hamster cheek pouch oral cancer model: boron biodistribution at 9 post administration time-points

    International Nuclear Information System (INIS)

    Garabalino, M.A.; Heber, E.M.; Monti, Hughes A.; Molinari, A.J.; Pozzi, E.C.C.; Trivillin, V.A.; Schwint, Amanda E.

    2011-01-01

    The therapeutic success of Boron Neutron Capture Therapy (BNCT) depends centrally on boron concentration in tumor and healthy tissue. We previously demonstrated the therapeutic efficacy of boronophenylalanine (BPA) and sodium decahydrodecaborate (GB-10) as boron carriers for BNCT in the hamster cheek pouch oral cancer model. Given the clinical relevance of sodium mercaptoundecahydro-closo-dodecaborate (BSH) as a boron carrier, the aim of the present study was to expand the ongoing BSH biodistribution studies in the hamster cheek pouch oral cancer model. In particular, we studied 3 additional post-administration time-points and increased the sample size corresponding to the time-points evaluated previously, to select more accurately the post-administration time at which neutron irradiation would potentially confer the greatest therapeutic advantage. BSH was dissolved in saline solution in anaerobic conditions to avoid the formation of the dimer BSSB and its oxides which are toxic. The solution was injected intravenously at a dose of 50 mg 10 B/kg (88 mg BSH / kg). Different groups of animals were killed humanely at 7, 8, and 10 h after administration of BSH. The sample size corresponding to the time-points 3, 4, 6, 9 and 12 h was increased. Samples of blood, tumor, precancerous tissue, normal pouch tissue, cheek mucosa, parotid gland, palate, skin, tongue, spinal cord marrow, brain, liver, kidney, spleen and lung were processed for boron measurement by Optic Emission Spectroscopy (ICP-OES). Boron concentration in tumor peaked to 24-34 ppm, 3-10 h post-administration of BSH, with a spread in values that resembled that previously reported in other experimental models and human subjects. The boron concentration ratios tumor/normal pouch tissue and tumor/blood ranged from 1.3 to 1.8. No selective tumor uptake was observed at any of the time points evaluated. The times post-administration of BSH that would be therapeutically most useful would be 5, 7 and 9 h. The

  10. 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.