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Sample records for antibody catumaxomab intraperitoneally

  1. A phase I trial of intravenous catumaxomab

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    Mau-Sørensen, Morten; Dittrich, Christian; Dienstmann, Rodrigo;

    2015-01-01

    design in epithelial cancers with known EpCAM expression. The dose-limiting toxicity (DLT) period consisted of 4 weeks, with weekly intravenous administration of catumaxomab. Key DLTs were ≥grade 3 optimally treated non-hematological toxicity; ≥grade 3 infusion-related reactions refractory to supportive....... A reversible decrease in liver function test (prothrombin time) at the 7-µg dose level was considered a DLT. The first patient at 10 µg experienced a fatal hepatic failure related to catumaxomab that led to the termination of the study. CONCLUSIONS: The MTD of weekly intravenous catumaxomab was 7 µg. Major...

  2. Palliative treatment of malignant ascites: profile of catumaxomab

    Directory of Open Access Journals (Sweden)

    Lila Ammouri

    2010-05-01

    Full Text Available Lila Ammouri, Eric E PrommerMayo Clinic Hospice and Palliative Medicine Program, Mayo Clinic College of Medicine, Mayo Clinic Hospital, Scottsdale, AZ, USAAbstract: Malignant ascites is the abnormal accumulation of fluid in the peritoneal cavity associated with several intrapelvic and intra-abdominal malignancies. The development of ascites leads to significant symptoms and poor quality of life for the cancer patient. Available therapies for palliation include treatment of the underlying disease, but when there are no treatment options, the use of diuretics, implantation of drainage catheters, and surgical shunting techniques are considered. None of these symptom palliation options affect the course of disease. The development of trifunctional antibodies, which attach to specific overexpressed surface markers on tumor cells, and trigger an immune response leading to cytoreductive effects, represents a new approach to the management of malignant ascites. The purpose of this review is to highlight current therapies for malignant ascites and review data as to the effectiveness of a new trifunctional antibody, catumaxomab.Keywords: catumaxomab, ascites, trifunctional

  3. Therapeutic considerations in the use of intraperitoneal radiolabelled monoclonal antibodies in ovarian carcinoma

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    Crowther, M.E.; Ward, B.G.; Granowska, M.; Mather, S.; Britton, K.E.; Shepherd, J.H.; Slevin, M.L.

    1989-03-01

    Eleven patients with ovarian cancer have been treated with a radiolabelled monoclonal antibody directed against human milk fat globule membrane (HMFG2). All patients had Stage III disease and had previously undergone debulking surgery followed by chemotherapy. Although 16 patients have been referred, 5 could not be treated. This paper discusses the criteria for patient selection and treatment, and describes the technical difficulties of this form of therapy and the complications sustained following the intraperitoneal instillation of up to 150 mCi iodine-131 labelled HMFG2. Significant complications included two ileo-cutaneous fistulae and peritonitis in one patient which prevented treatment from being given.

  4. Investigations into the route of uptake and pharmacokinetics of intraperitoneally-administered monoclonal antibodies: I. Transdiaphragmatic blockade of the terminal lymphatics in the rat.

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    Barrett, J S; Wahl, R L; Wagner, J G; Brown, R; Fisher, S J

    1990-01-01

    Recent studies on the intraperitoneal administration of radiolabeled monoclonal antibodies indicate that the diaphragm and, in particular, the lymphatics associated with the diaphragm are more involved in the transport of such high-molecular-mass moieties than was earlier suspected. The current study examines the role of the diaphragm in the i.p. transport of an IgG2a murine monoclonal antibody, 5G6.4, by observing the effect on the absorption of the antibody produced when the diaphragm has been scarred. Normal, sham-operated, and diaphragmatically scarred (abrasions made with 600-grade sandpaper) female Sprague Dawley rats (150-250 g) were administered intraperitoneal injections of 125labeled 5G6.4 in a volume of 2.0 cm3. Approximately 5 micrograms antibody protein was administered in the individual 19-microCi injections per rat. Scarring was effective in partially blocking the amount of labeled antibody that crossed the diaphragm. Mean diaphragm levels (% injected dose/g) of 125I-labeled 5G6.4 from the scarred group were 16.8% lower than values from the sham-operated rats and 37.2% lower than those from the control rats. The blockade was effective in slowing the appearance of the labeled antibody in the systemic circulation. The half-time to absorption was significantly prolonged in the scarred group; mean t1/2 absorption values of 2.5 h for the control group, 5.3 h for the sham-operated group, and 9.6 h for the diaphragmatically blocked group were recorded. Scarring the diaphragm reduced the mean maximum blood concentration by 27.6% over the control group and 23.9% over the sham-operated group. The mean time to maximum blood concentration was lengthened by 93..0% over the control group and 35.3% over the sham-operated group due as a result of scarification. Presumably this impedence to absorption would increase the time that the radiolabeled antibody bathed the peritoneal space. The scarred group also had the largest "system mean residence time" (162.5 h

  5. Quantitative Immuno-SPECT Monitoring of Pretargeted Radioimmunotherapy with a Bispecific Antibody in an Intraperitoneal Nude Mouse Model of Human Colon Cancer

    NARCIS (Netherlands)

    Schoffelen, R.; Graaf, W.T. van der; Sharkey, R.M.; Franssen, G.M.; McBride, W.J.; Chang, C.H.; Bos, D.L.; Goldenberg, D.M.; Oyen, W.J.G.; Boerman, O.C.

    2012-01-01

    The prospects for using pretargeted immuno-SPECT to monitor the response to pretargeted radioimmunotherapy were examined. In this study, a bispecific anticarcinoembryonic antigen (CEACAM5; CD66e) x antihapten monoclonal antibody, TF2, was used in combination with a small (1.5 kD) peptide, IMP288, la

  6. Antibody

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    An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... microorganisms (bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

  7. Drug: D09207 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D09207 Drug Catumaxomab (INN); Removab (TN) Monoclonal antibody ATC code: L01XC09 a...TIC AGENTS L01X OTHER ANTINEOPLASTIC AGENTS L01XC Monoclonal antibodies L01XC09 Catumaxomab D09207 Catumaxom...plastics [BR:br08308] Molecularly targeted agents Monoclonal antibody Catumaxomab [ATC:L01XC09] D09207 Catumaxomab (INN) CAS: 509077-98-9 PubChem: 96025887 ...

  8. Intraperitoneal explosion following gastric perforation.

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    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.

  9. Intraperitoneal schwannoma. Three cases. Schwanoma intraperitoneal. Tres casos

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    Sanchez Lafuente, J.; Rodriguez Sanpedro, F.; Varela, R.; Lopez Ojeda, J.; Martinez, J. (Hospital regional. Servicio de Radiodignostico. Malaga (Spain))

    1993-01-01

    Schwanomas are nerve sheath tumors which can spread throughout the entire organism, although their intraperitoneal localization is exceptional. Three cases are presented of schwannoma originating in jejunal mesentery, 2 of which were predominantly cystic, with histological features of malignancy, while the third was seen to be solid, non homogenous and histologically benign. The literature is reviewed and the difficulties involved in establishing radiological criteria for benignity or malignity in these tumors are discussed, as is the differential diagnosis with regard to other abdominal cystic or solid masses. (Author) 14 refs.

  10. INTRAPERITONEAL LYSIS OF TUBERCLE BACILLI.

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    Manwaring, W H; Bronfenbrenner, J

    1913-12-01

    1. Tubercle bacilli injected into the peritoneal cavities of tuberculous guinea pigs, rats, rabbits, dogs, and monkeys, rapidly disappear from the peritoneal fluids, while persisting in the peritoneal fluids of normal control animals. 2. This disappearance is in part due to an adhesion of the injected bacilli to the peritoneal leucocytes and a fixation of the leucocytes on the omentum. 3. The injected tubercle bacilli can be recovered quantitatively from the peritoneal cavities of normal guinea pigs from one and one half to two hours after the injection, while from tuberculous guinea pigs only 65 per cent. of the bacilli can be recovered at this time. 4. Isolated peritoneal tissues from tuberculous guinea pigs have the power of destroying tubercle bacilli in vitro. 5. A second factor reducing the number of tubercle bacilli free in the peritoneal fluid is therefore an actual lysis of the bacilli. 6. The intraperitoneal lysis is not due solely to substances present in the circulating fluids, since the phenomenon cannot be produced by these fluids in vitro, and since a lytic power cannot be passively conferred even by a direct transfusion of blood from tuberculous to normal animals. 7. The intraperitoneal lysis is apparently due to specific changes in the fixed peritoneal cells of the tuberculous animals.

  11. Intraperitoneal administration of gonadotropin-releasing hormone-PE40 induces castration in male rats

    Institute of Scientific and Technical Information of China (English)

    Li Yu; Zhong-Fang Zhang; Chun-Xia Jing; Feng-Lin Wu

    2008-01-01

    AIM: To evaluate the long-term effects of gonadotropin-releasing hormone (GnRH)-based vaccine on levels of GnRH antibody and testosterone, and vaccine-induced immunocastration on sexual behavior of male rats.METHODS: The rats were treated with GnRH-PE40 intraperitoneally every other day for 12 wk. GnRH antibody and testosterone level in rat blood were determined by ELISA and radioimmunoassay, respectively. Morphological changes in testes and sexual behavior of rats were evaluated.RESULTS: GnRH-PE40 induced a high production in GnRH antibody, decreased the serum testosterone level, testis atrophy and sexual function in rats.CONCLUSION: Intraperitoneal administration of GnRH-PE40 produces structural and functional castration of male rat reproductive system by inducing anti-GnRH antibody.

  12. Intraperitoneal desmoid tumor: achievements in CT. Tumor demoide intraperitoneal: hallazgos en TC

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    Soto Aguilar, M.C.; Navarro Sanchis, E.; Sanchez-Lafuente Rubio, J.; Vicente Romo, J.; Fuentes Limpiaez, J.J. (Hospital Regional Carlos Haya. Servicio de Radiodiagnostico. Malaga (Spain))

    1993-01-01

    We present two cases of intraperitoneal desmoid tumor studied by means of CT. Both presented in the form of solid masses with involvement of small bowel loops in asympthmatic patients. CT is useful for locating the mass and studying possible tumor recurrences, but there is no semiological data to differentiate them from other intraperitoneal solid neoplasms. (Author)

  13. Delayed presentation of traumatic intraperitoneal bladder rupture

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    Brown, D.; Magill, H.L.; Black, T.L.

    1986-03-01

    A child with urine ascites as a delayed manifestation of post-traumatic intraperitoneal bladder rupture is presented. The diagnosis was suggested by abdominal CT scan and confirmed with a cystogram. While uncommon, late presentation of intraperitoneal bladder rupture following trauma may occur from masking of a primary laceration or development of secondary rupture at the site of a hematoma in the bladder wall. Since CT may be a primary diagnostic study performed following abdominal trauma, the radiologist should be aware of CT findings suggesting bladder rupture and of the possibility of delayed presentation of this injury.

  14. Intraperitoneal stone migration during percutaneos nephrolithotomy

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    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.

  15. Antithyroglobulin antibody

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    Thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Hypothyroidism - thyroglobulin antibody; Thyroiditis - thyroglobulin antibody; Graves disease - thyroglobulin antibody; Underactive thyroid - thyroglobulin antibody

  16. Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoneal recurrence after gastrointestinal cancer resection

    Institute of Scientific and Technical Information of China (English)

    Qing-Guo Fu; Fan-Dong Meng; Xiao-Dong Shen; Ren-Xuan Guo

    2002-01-01

    AIM: To investigate the prophylactic and therapeutic efficacy of intraperitoneal IL-2 immunotherapy following intraperitoneal thermochemotherapy in the metastasis and recurrence of gastric and colorectal cancer after operation.METHODS: Forty-two gastric cancer patients at T3Ⅱ-T4 ⅢB stages and 96 patients with colorectal cancer at B to D stages admitted from January1996 to October 1998 were randomly divided into control group (group Ⅰ, 65 cases) receiving intraperitoneal thermochemotherapy, and group Ⅱ (73cases) receiving both intraperitoneal thermochemotherapy andintraperitoneal IL-2 immunotherapy. Distilled water at 43-45℃ containing 5-Fu 0.5 g/L and MMC 8 mg/L was perfused into peritoneal cavity before closure at the end of operation for 1 h, and from the third day, IL-2 10 million IU in 500 ml 0.9 % sodium chloride was intraperitoneallyadministrated daily for 10 times. One month after operation, all the patients underwent regular intravenous chemotherapy. Before and after the IL-2 immunotherapy, some Th1 type cytokines in the peripheral blood of the patients in the two groups were detected by ELISA, and the intraperitoneal recurrence and liver metastasis rates and the 3-year survival rate were statistically evaluated after intensive follow-up. RESULTS: IL-2 intraperitoneal immunotherapy significantly elevated the level of some Th1 type cytokines (P<0.01compared with that of control group), and the 3-year survival rate of group Ⅱ was 18.1% higher and the rates of intraperitoneal recurrence and liver metastasis were 16.9 % and 6.0 % lower than those of group I significantly (P<0.05-0.01).CONCLUSION: The combination of intraperitoneal IL-2 immunotherapy and thermochemotherapy could promote Th1 immune paradigm and enforce anti-tumor activity of bodies, which plays a positive role in preventing gastric and colorectal cancer from intraperitoneal recurrence and development.

  17. Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study

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    Royer, B.; Kalbacher, E; Onteniente, S; Jullien, V; Montange, D; Piedoux, S; Thiery-Vuillemin, A; Delroeux, D; Pili-Floury, S.; Guardiola, E; Combe, M.; Muret, P.; Nerich, V; Heyd, B; Chauffert, B

    2011-01-01

    Background: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. Methods: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. Results: Epinephrine halves...

  18. Intraperitoneal tuberculous abscess: computed tomography features

    Institute of Scientific and Technical Information of China (English)

    Peng; Dong; Jing-Jing; Chen; Xi-Zhen; Wang; Ya-Qin; Wang

    2015-01-01

    AIM: To evaluate the computed tomography(CT) features of intraperitoneal tuberculous abscess(IPTA). METHODS: Eight patients with IPTA confirmed by pathology were analyzed retrospectively. The clinical symptoms, medical images, and surgical findings were evaluated. Involvement of the intestine, peritoneum, viscera, and lymph nodes was also assessed. RESULTS: All 8 patients had a history of abdominal discomfort for 1 to 6 mo. Physical examination revealed a palpable abdominal mass in 6 patients. Three patients had no evidence of pulmonary tuberculosis(TB). All IPTAs(11 abscesses) were seen as a multiseptated, peripherally enhanced, hypodense mass with enlarged, rim-enhanced lymph nodes. The largest abscess diameter ranged from 4.5 cm to 12.2 cm. CT showed 2 types of IPTA: Lymph node fusion and encapsulation. Of the 8 patients, one had liver tuberculosis and one had splenic and ovarian tuberculosis. Two cases showed involvement of the terminal ileum and ileocecal junction. Ascites were found in 4 cases. Three patients had peritonitis and mesenteritis. Three patients showed involvement of the omentum. Three patients had histological evidence of caseating granuloma, and 5 had histological evidence of acid-fast bacilli. CONCLUSION: CT is crucial in the detection and characterization of IPTA. Certain CT findings are necessary for correct diagnosis.

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

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    Philipp Horvath; Stefan Beckert; Florian Struller; Alfred K?nigsrainer; Ingmar K?nigsrainer

    2016-01-01

    AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: 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 bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 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 < 4000 cells/m3. RESULTS: 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). Thelength of hospital stay tended to be higher in the MMCgroup 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 postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC

  20. Single Center Experience With Hyperthermic Intraperitoneal Chemotherapy

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    Kim, Woo Ram; Hur, Hyuk; Min, Byung Soh; Baik, Seung Hyuk; Lee, Kang Young

    2017-01-01

    Purpose Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been proposed for controlling peritoneal seeding metastasis in some kinds of cancers, including those of colorectal origin, but their safety and oncological benefits are subjects of debate. We present our early experience with those procedures. Methods Data were retrospectively collected from all patients with peritoneal carcinomatosis (PC) and pseudomyxoma peritonei (PMP) treated using CRS and HIPEC at Yonsei Cancer Center between July 2014 and July 2015. Short-term outcomes and risk factors for postoperative complications were analyzed. Results Twenty-three patients with PC (n = 18) and PMP (n = 5) underwent CRS and HIPEC. Median follow-up and age were 2 months and 54 years, respectively. The median peritoneal carcinomatosis index score was 15, and CC0-1 was achieved in 78.3% of all patients. The median operation time and bleeding loss were 590 minutes and 570 mL, respectively. Grade-IIIa/grade-IIIb complications occurred in 4.3% (n = 1)/26.1% (n = 6) of the patients within 30 days postoperatively, and no 30-day mortalities were reported. Factors related to postoperative complications with CRS and HIPEC were number of organ resection (P = 0.013), longer operation time (P patients treated with cetuximab for recurred colorectal cancer had grade-III postoperative complication. Conclusion Our initial experience with CRS and HIPEC presented about 30% grade-III postoperative complications. Therefore, expert surgeons need to perform those procedures with great caution in selected patients who might benefit from it.

  1. Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

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    Anders Lyngvi Fougner

    2016-04-01

    Full Text Available Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP sensor sites, as an alternative to the SC location. Intraarterial (IA and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L. Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s, and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min. IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

  2. Natural Killer (NK- and T-Cell Engaging Antibody-Derived Therapeutics

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    Christoph Stein

    2012-06-01

    Full Text Available Unmodified antibodies (abs have been successful in the treatment of hematologic malignancies, but less so for the treatment of solid tumors. They trigger anti-tumor effects through their Fc-domains, and one way to improve their efficacy is to optimize their interaction with the effectors through Fc-engineering. Another way to empower abs is the design of bispecific abs and related fusion proteins allowing a narrower choice of effector cells. Here we review frequently chosen classes of effector cells, as well as common trigger molecules. Natural Killer (NK- and T-cells are the most investigated populations in therapeutical approaches with bispecific agents until now. Catumaxomab, the first bispecific ab to receive drug approval, targets the tumor antigen Epithelial Cell Adhesion Molecule (EpCAM and recruits T-cells via a binding site for the cell surface protein CD3. The next generation of recombinant ab-derivatives replaces the broadly reactive Fc-domain by a binding domain for a single selected trigger. Blinatumomab is the first clinically successful member of this class, targeting cancer cells via CD19 and engaging T-cells by CD3. Other investigators have developed related recombinant fusion proteins to recruit effectors, such as NK-cells and macrophages. The first such agents currently in preclinical and clinical development will be discussed.

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

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

    2016-01-01

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

  4. Meta-analysis of intraperitoneal chemotherapy for gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Da-Zhi Xu; You-Qing Zhan; Xiao-Wei Sun; Su-Mei Cao; Qi-Rong Geng

    2004-01-01

    AIM: To assess the efficacy and safety of intraperitoneal chemotherapy in patients undergoing curative resection for gastric cancer through literature review. METHODS: Medline (PubMed) (1980-2003/1), Embase (1980-2003/1), Cancerlit Database (1983-2003/1) and Chinese Biomedicine Database (1990-2003/1) were searched. Language was restricted to Chinese and English. The statistical analysis was performed by RevMan4.2 software provided by the Cochrane Collaboration. The results were expressed with odds ratio for the categorical variables. RESULTS: Eleven trials involving 1 161 cases were included. The pooled odds ratio was 0.51, with a 95% confidence interval (0.40-0.65). Intraperitoneal chemotherapy may benefit the patients after curative resection for locally advanced gastric cancer, and the combination of intraperitoneal chemotherapy with hyperthermia or activated carbon particles may provide more benefits to patients due to the enhanced antitumor activity of drugs. Sensitivity analysis and fail-safe number suggested that the result was comparatively reliable. However, of 11 trials, only 3 studies were of high quality. CONCLUSION: Intraperitoneal chemotherapy after curative resection for locally advanced gastric cancer may be beneficial to patients. Continuous multicenter, randomized, double blind, rigorously designed trials should be conducted to draw definitive conclusions.

  5. Intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis: review of animal models.

    Science.gov (United States)

    Gremonprez, Félix; Willaert, Wouter; Ceelen, Wim

    2014-02-01

    The development of suitable animal models is essential to experimental research on intraperitoneal chemotherapy (IPC). This review of the English literature (MEDLINE) presents a detailed analysis of current animal models and gives recommendations for future experimental research. Special consideration should be given to cytotoxic drug dose and concentration, tumor models, and outcome parameters.

  6. Validation of Intraluminal and Intraperitoneal microdialysis in ischemic small intestine

    DEFF Research Database (Denmark)

    Pynnönen, Lauri; Minkkinen, Minna; Perner, Anders;

    2013-01-01

    We sought to define the sensitivity and specificity of intraperitoneal (IP) and intraluminal (IL) microdialysate metabolites in depicting ex vivo small intestinal total ischemia during GI-tract surgery. We hypothesized that IL as opposed to IP microdialysis detects small intestinal ischemia...

  7. Selection of chemotherapy for hyperthermic intraperitoneal use in gastric cancer

    NARCIS (Netherlands)

    Braam, H. J.; Schellens, J. H.; Boot, H.; van Sandick, J. W.; Knibbe, C. A.; Boerma, D.; van Ramshorst, B.

    2015-01-01

    Purpose: Several studies have shown the potential benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients. At present the most effective chemotherapeutic regime in HIPEC for gastric cancer is unknown. The aim of this review was to p

  8. Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.

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    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.

  9. Intraperitoneal insulin infusion: on the way to the artificial pancreas

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    Vladimir Aleksandrovich Karpel'ev

    2015-06-01

    Full Text Available Creating an "artificial pancreas" (a "closed loop" insulin pump, with self-adjusting insulin abilities, based on real time continuous glucose monitoring data – is one of the most actual medical challenges of modern engineering and cybernetics.Artificial pancreas (AP prototypes based on wearable insulin pump with subcutaneous insulin delivery are still problematic, mainly because of slow insulin pharmacokinetics. Intravenous insulin infusion via AP allows effectively maintain euglycaemia for inpatients, due to insulin pharmacokinetics and pharmacodynamics advantages. Unfortunately, it can’t be used for outpatients. Intraperitoneal insulin infusion is still relatively infrequently used in the world, but it is a promising alternative, compared to both previous methods due to a physiological action profile, fast insulin pharmacokinetics, relatively better safety and availability for outpatient usage.The purpose of this review is to describe the intraperitoneal insulin infusion features for diabetes patients at a point of AP creation perspectives. 

  10. Learning curve in cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

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    Moradi, Bijan N; Esquivel, Jesus

    2009-09-15

    Cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy have achieved good long-term results in patients with complete surgical eradication of their peritoneal dissemination but at the expense of significant perioperative morbidity and mortality. The high complication rate has been attributed to the steep learning curve associated with this procedure. We report on the current literature regarding the learning curve for this procedure and the key components that determine the success in learning this new skill.

  11. Intraperitoneal Local Anesthetic in Pediatric Surgery: A Systematic Review.

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    Hamill, James K; Rahiri, Jamie-Lee; Liley, Andrew; Hill, Andrew G

    2016-12-01

    Introduction Systematic reviews report intraperitoneal local anesthetic (IPLA) effective in adults but until now no review has addressed IPLA in children. The objective of this review was to answer the question, does IPLA compared with control reduce pain after pediatric abdominal surgery. Materials and Methods Data sources: MEDLINE, EMBASE, Cochrane databases, trials registries, ProQuest, Web of Science, Google Scholar, and Open Gray.

  12. Kinetics of intraperitoneally infused insulin in rats - Functional implications for the bioartificial pancreas

    NARCIS (Netherlands)

    DeVos, P; Vegter, D; DeHaan, BJ; Strubbe, JH; Bruggink, JE; VanSchilfgaarde, R

    1996-01-01

    Intraperitoneal transplantation of encapsulated islets can restore normoglycemia in diabetic recipients but not normal glucose tolerance nor normal insulin responses to a physiological stimulus. This study investigates whether the intraperitoneal implantation site as such contributes to the interfer

  13. Efficacy of intraperitoneal thermochemotherapy and immunotherapy in intraperitoeal recurrence after grastrointestinal cancer resecction

    Institute of Scientific and Technical Information of China (English)

    Qing-GuoFu; Fan-DongMeng; Xiao-DognShen; Ren-XuanGuo

    2002-01-01

    AIM:To investigate the prophylactic and therapeutic efficacy of intraperitoneal IL-2 innunotherapy following intraperitoneal thermochemotheray int the metastasis and recurrence of gastric and colorectal cancer after operation.

  14. Antimitochondrial antibody

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    ... page: //medlineplus.gov/ency/article/003529.htm Antimitochondrial antibody To use the sharing features on this page, please enable JavaScript. Antimitochondrial antibodies (AMA) are substances ( antibodies ) that form against mitochondria. ...

  15. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: Where are we?

    Institute of Scientific and Technical Information of China (English)

    Ingmar K(o)nigsrainer; Stefan Beckert

    2012-01-01

    Peritoneal surface malignancies are generally associated with poor prognosis.In daily clinical routine,systemic chemotherapy is still considered the only reasonable therapy despite of encouraging results of cytoreductive surgery (CRS) along with intraperitoneal hyperthermic chemotherapy (HIPEC).The Achilles heel of CRS and HIPEC is appropriate patient selection and precise surgical technique preventing patients from excessive morbidity and mortality.Given these findings,new concepts of second look surgery for high risk patients allow detection of peritoneal spread ahead of clinical symptoms or presence of peritoneal masses reducing perioperative morbidity.In addition,personalized intraperitoneal chemotherapy might further improve outcome by appreciating individual tumor biology.These days,every physician should be aware of CRS and HIPEC for treatment of peritoneal surface malignancies.Since there is now sufficient data for the superiority of CRS and HIPEC to systemic chemotherapy in selected patients,our next goal should be providing this strategy with minimal morbidity and mortality even in the presence of higher tumor load.

  16. 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.

  17. 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

    .001). Relatively low levels for quality of life were found, as well as a higher than expected number of patients with psychiatric symptoms. CONCLUSIONS: CIPII proved effective in complex patients with a history of poor control and hospital admission. Despite a substantial long-term improvement in glycaemic control......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......-term glycaemic response were sought. Self-report questionnaires were administered at 58 months follow-up only, to assess current psychopathology and quality of life. RESULTS: Mean HbA(1c) decreased from 10.0 +/- 2.3% to 9.0 +/- 1.8% (P = 0.039) 1 year after implantation and stabilized at 9.0 +/- 1.6% (P = 0...

  18. Intraperitoneal lidocaine & tenoxicam for pain relief after gynaecological laparoscopy

    Institute of Scientific and Technical Information of China (English)

    Ibrahim A Abdelazim; Mohammed Al-Kadi; Maged Mahmoud El Shourbagy; Ahmed Abdelazim Mohamed; Mohannad Lutfi Abu faza

    2013-01-01

    Objective: To detect the effect of intra-peritoneal instillation of local anesthetic with or without NSAIDs on pain relief after gynecological laparoscopy. Methods: Seventy five patients scheduled for laparoscopy were included in the study and randomly divided into three groups. At the end of the laparoscopic procedure, 100 mL normal saline in the first group, or 100 mL normal saline contains 200 mg lidocaine in the second group, or 100 mL normal slaine containing 200 mg lidocaine and 20 mg tenoxicam in the third group were splashed into the pelvis by the surgeon. Post-operative pain were monitored and compared. Results: The incidence and severity of immediate postoperative shoulder pain reduced from 44% of patients scoring 2-5 in saline group to 16% scoring 2-3 in lidocaine group and 8% scoring 2-3 in lidocaine-tenoxicam group. Compared with saline group, abdominal pain scores were significantly lower in lidocaine group and lidocaine-tenoxicam group over 24 hours after surgery. At 12 and 24 hours after surgery, abdominal pain scores were significantly reduced in lidocaine-tenoxicam group compared with lidocaine group. No pain on deep respiration was reported in 84%, and 68% in lidocaine-tenoxicam and lidocaine groups respectively compared to 12% in those in the saline group. The mean time to first request for analgesia was increased from (2.3 ±1.9) hours in saline group to (4.4 ± 2.4) hours in lidocaine group and to (8.3 ± 10.2) hours in lidocaine-tenoxicam group. Conclusion: Intraperitoneal balanced analgesia (local anesthetics ± NSAIDS) is a simple and safe technique for analgesia following gynaecological Laparoscopy.

  19. Intraperitoneal alpha-radioimmunotherapy in mice using different specific activities

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Haglund, Elin;

    2009-01-01

    The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At.......The aim of this study was to investigate the therapeutic efficacy of the alpha-radioimmunotherapy of ovarian cancer in mice, using different specific activities. This study was performed by using the monoclonal antibody, MX35 F(ab')(2), labeled with the alpha-particle-emitter, 211At....

  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...

  1. Mouse model of sublethal and lethal intraperitoneal glanders (Burkholderia mallei).

    Science.gov (United States)

    Fritz, D L; Vogel, P; Brown, D R; Deshazer, D; Waag, D M

    2000-11-01

    Sixty male BALB/c mice were inoculated intraperitoneally with either a sublethal or a lethal dose of Burkholderia mallei China 7 strain, then killed at multiple time points postinoculation. Histopathologic changes were qualitatively similar in both groups and consisted of pyogranulomatous inflammation. In sublethal study mice, changes were first seen at 6 hours in mediastinal lymph nodes, then in spleen, liver, peripheral lymph nodes, and bone marrow at day 3. These changes generally reached maximal incidence and severity by day 4 but decreased by comparison in all tissues except the liver. Changes were first seen in lethal study mice also at 6 hours in mediastinal lymph nodes and in spleens. At day 1, changes were present in liver, peripheral lymph nodes, and bone marrow. The incidence and severity of these changes were maximal at day 2. In contrast to sublethal study mice, the incidence and severity of the changes did not decrease through the remainder of the study. The most significant difference between the two groups was the rapid involvement of the spleen in the lethal study mice. Changes indicative of impaired vascular perfusion were more frequently seen in the sublethal study mice. Our findings indicate that mice are susceptible to B. mallei infection and may serve as an appropriate model for glanders infection in a resistant host such as human beings. Additionally, by immunoelectron microscopy, we showed the presence of type I O-antigenic polysaccharide (capsular) antigen surrounding B. mallei.

  2. Intraperitoneal photodynamic therapy for peritoneal carcinomatosis and sarcomatosis

    Science.gov (United States)

    Hahn, Stephen M.; Fraker, Douglas L.; Zhu, Timothy C.; Yodh, Arjun G.; Rodriguez, Carmen E.; Smith, Debbie; Currens, Ann; Glatstein, Eli

    2000-03-01

    The preliminary results of an ongoing Phase II trial of Photofrin-mediated intraperitoneal PDT (IP PDT) are presented. The clinical endpoints of this trial are to determine the response rates of patients with carcinomatosis and sarcomatosis to IP PDT and to document the toxicities of IP PDT in a defined patient population. Photofrin, 2.5 mg/kg, was administered intravenously 48 hours prior to debulking surgery and light delivery, 57 patients with ovarian cancer, gastrointestinal cancers, and sarcomas were enrolled. 44 patients received Photofrin and received light treatment. 39 patients are valuable for response. 8 of 39 patients had a complete radiographic response to IP PDT 3 months after treatment. 3 patients are alive without evidence of disease 6, 6 and 9 months after treatment. 1 patient is alive and has no evidence of intra-abdominal disease but has developed lung metastases. Toxicities include post-operative fluid shifts, hypotension, hydronephrosis, pleural effusions, enteric fistula, transient liver function test elevation, thrombocytopenia, and wound dehiscence. Toxicity is related to pre-operative tumor bulk and to the extensiveness of surgery required. IP PDT is feasible and leads to an initial clinical response rate of 25 percent in patients with incurable peritoneal carcinomatosis and sarcomatosis.

  3. Aging-related Changes of Microglia and Astrocytes in Hypothalamus after Intraperitoneal Injection of Hypertonic Saline in Rats

    Institute of Scientific and Technical Information of China (English)

    WANG Xiaoli; XU Yun; WANG Fang; TANG Lihua; LIU Zhilong; LI Honglian; LIU Shenghong

    2006-01-01

    To examine the aging-related changes of microglia and astrocytes in hypothalamus of rats after intraperitoneal injection of hypertonic saline in rats, old- and young-aged rats were injected with hypertonic saline solution into peritoneal cavity. Lectin histochemical techniques using Ricinus communis agglutinin-1 (RCA-1) and immunocytochemical method employing antibody against glial fibrillary acidic protein (GFAP) were used to demonstrate microglia and astrocytes in the hypothalamus of the rats, and the positively-stained cells were analyzed by computer-assisted image analysis system. Our results showed that the numbers of microglia and astrocytes were significantly increased in the hypothalamus of old-aged rats. After intraperitoneal injection of hypertonic saline,the number of microglia was significantly decreased in the hypothalamus of both young- and oldaged groups. After introperitoneal injection of hypertonic saline, the number of GFAP positive cells was significantly increased in the hypothalamus of young rats, but the number of GFAP positive cells did not show significant change in the hypothalamus of old rats. It is concluded that in the hypothalamus of old-aged rats, the increase of microglia may be related with the aging or degeneration of neurons, and the increase of astrocytes may provide more nourishment required by the aged neurons. The microglia and astrocytes in the hypothalamus of the two group rats may be affected by hypertonic saline, and the response of these cells to the stimuli is characterized by some aging-related changes.

  4. Adjuvant treatment with dexamethasone plus anti-C5 antibodies improves outcome of experimental pneumococcal meningitis: a randomized controlled trial

    OpenAIRE

    2015-01-01

    Background We compared adjunctive treatment with placebo, dexamethasone, anti-C5 antibodies, and the combination of dexamethasone plus anti-C5 antibodies in experimental pneumococcal meningitis. Methods In this prospective, investigator-blinded, randomized trial, 96 mice were infected intracisternally with 107 CFU/ml Streptococcus pneumoniae serotype 3, treated with intraperitoneal ceftriaxone at 20 h, and randomly assigned to intraperitoneal adjunctive treatment with placebo (saline), dexame...

  5. Detection and localization of rabbit hepatitis e virus and antigen in systemic tissues from experimentally intraperitoneally infected rabbits.

    Science.gov (United States)

    Mao, Jingjing; Zhao, Yue; She, Ruiping; Cao, Binbin; Xiao, Peng; Wu, Qiaoxing; Guo, Zhaojie; Ma, Longhuan; Soomro, Majid Hussain

    2014-01-01

    Rabbit hepatitis E virus (HEV) is a novel genotype of HEV, and is considered to pose a risk of zoonotic transmission. Research into the systemic distribution of rabbit HEV in rabbits during different periods of infection has rarely been reported. To better understand this virus, we infected rabbits with second-passage rabbit HEV via an intraperitoneal route. After inoculation, the infection showed two types, temporary and constant infection. The detection of HEV RNA in the feces varied with time, and serum antigen correlated with fecal HEV RNA. Viremia only appeared 72 days after inoculation. The rabbits remained antibody negative throughout the experimental period. When HEV was localized, several organs besides the liver were HEV RNA positive. Tissue antigen was observed immunohistochemically in the different cells of various organs, especially in parts of the small intestine and the characteristic rabbit gut-associated lymphoid tissue. These data provide valuable information for future research into the pathogenesis of HEV.

  6. Pharmacokinetics of bupivacaine after intraperitoneal administration to cats undergoing ovariohysterectomy.

    Science.gov (United States)

    Benito, Javier; Monteiro, Beatriz P; Beaudry, Francis; Lavoie, Anne-Marie; Lascelles, B Duncan X; Steagall, Paulo V

    2016-06-01

    OBJECTIVE To evaluate pharmacokinetics of bupivacaine after IP administration to cats undergoing ovariohysterectomy. ANIMALS 8 healthy cats. PROCEDURES Anesthesia was induced with propofol and maintained with isoflurane. Buprenorphine (0.02 mg/kg, IV) and meloxicam (0.2 mg/kg, SC) were administered. A 20-gauge catheter was inserted into a jugular vein for blood sample collection. A ventral midline incision was made, and a solution of 0.5% bupivacaine (2 mg/kg) diluted with an equal volume of saline (0.9% NaCl) solution (final concentration, 0.25% bupivacaine) was injected into the peritoneal space over the right and left ovarian pedicles and caudal aspect of the uterus before ovariohysterectomy. Cats were monitored for signs of bupivacaine toxicosis. Venous blood samples (2 mL) were collected before (time 0) and 2, 5, 10, 15, 20, 30, 60, 120, and 240 minutes after bupivacaine administration. Plasma bupivacaine concentrations were determined with a liquid chromatography-tandem mass spectrometry method. Pharmacokinetic parameters were determined by data plotting followed by analysis with a noncompartmental model. RESULTS No signs of bupivacaine toxicosis were observed. Maximum bupivacaine plasma concentration was 1,030 ± 497.5 ng/mL at a mean ± SD value of 30 ± 24 minutes after administration. Mean elimination half-life was 4.79 ± 2.7 hours. Mean clearance indexed by bioavailability and volume of distribution indexed by bioavailability were 0.35 ± 0.18 L•h/kg and 2.10 ± 0.84 L/kg, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Intraperitoneal administration of bupivacaine resulted in concentrations that did not cause observable toxicosis. Studies to investigate analgesic effects for this technique in cats are warranted.

  7. 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.

  8. Intraperitoneal administration of thioredoxin decreases brain damage from ischemic stroke.

    Science.gov (United States)

    Wang, Bin; Tian, Shilai; Wang, Jiayi; Han, Feng; Zhao, Lei; Wang, Rencong; Ning, Weidong; Chen, Wei; Qu, Yan

    2015-07-30

    Recent studies demonstrate that Thioredixin (Trx) possesses a neuronal protective effect and closely relates to oxidative stress and apoptosis of cerebral ischemia injury. The present study was conducted to validate the neuroprotective effect of recombinant human Trx-1 (rhTrx-1) and its potential mechanisms against ischemia injury at middle cerebral artery occlusion (MCAO) in mice. rhTrx-1 was administrated intraperitoneally at a dose of 5, 10 and 20mg/kg 30 min before MCAO in mice, and its neuronal protective effect was evaluated by neurological deficit score, brain dry-wet weight, 2,3,5-triphenyltetrazolium chloride (TTC) staining. The protein carbonyl content and HO-1 were detected to investigate its potential anti-oxidative and anti-inflammatory property, and the anti-apoptotic ability of rhTrx-1 was assessed by casepase-3 and TUNEL staining. The results demonstrated that rhTrx-1 significantly improved neurological functions and reduced cerebral infarction and apoptotic cell death at 24h after MCAO. Moreover, rhTrx-1 resulted in a significant decrease in carbonyl contents and HO-1 against oxidative stress, which turned to be fast reduction during the first 24h and tended to be stable from 24h to 72h after MCAO. The study shows that rhTrx-1 exerts an neuroprotective effect in cerebral ischemia injury. The anti-oxidative, anti-apoptotic and anti-inflammatory properties of rhTrx-1 are more likely to succeed as a therapeutic approach to diminish oxidative stress-induced neuronal apoptotic cell death in acute ischemic stroke.

  9. Anti-sperm antibodies and fertility of turkey hens.

    Science.gov (United States)

    McCorkle, F M; Christensen, V L; Thaxton, J P

    1983-11-01

    Anti-sperm antibody titers increase with time in serum of turkey hens following a standard production schedule of artificial insemination (AI). In hens receiving intravenous (IV) or intraperitoneal (IP) additional AI, serum anti-sperm antibody levels increase more rapidly after a lag phase. A single injury to the oviduct also resulted in increased anti-sperm antibodies similar to IV and IP groups. This is a new observation that a single injury increased antibody titers to spermatozoa equal in IV and/or IP injections. A negative correlation between serum anti-sperm antibody titers for IV, IP and injury to oviduct and fertility of these groups was observed. Hens of IV and injury to oviduct groups with high levels of anti-sperm antibodies in the last 2 weeks of production had significantly lower fertility than hens with low levels of antibodies and control hens.

  10. Local Release of Highly Loaded Antibodies from Functionalized Nanoporous Support for Cancer Immunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lei, Chenghong; Liu, P.; Chen, Baowei; Mao, Yumeng; Engelmann, Heather E.; Shin, Yongsoon; Jaffar, Jade; Hellstrom, Ingegerd; Liu, Jun; Hellstrom, Karl E.

    2010-05-26

    We report that antibodies can be loaded in functionalized mesoporous silica (FMS) with super-high density to provide long-lasting local release at a given site. Preliminary data indicate that FMS-antibody injected directly into a mouse melanoma induces a greater inhibition of tumor growth than seen in various controls, including the antibody injected intraperitoneally. Our findings introduce a novel approach for local delivery of therapeutically active proteins to tumors and potentially, other diseases.

  11. 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 in...

  12. Thyroid Antibodies

    Science.gov (United States)

    ... e.g., at regular intervals after thyroid cancer treatment) Thyroid stimulating hormone receptor antibody, Thyroid Stimulating Immunoglobulin TRAb, TSHR Ab, TSI Graves disease When a person has symptoms of hyperthyroidism If a pregnant woman has a known autoimmune ...

  13. Posttraumatic Haematuria with Pseudorenal Failure: A Diagnostic Lead for Intraperitoneal Bladder Rupture

    Science.gov (United States)

    Vagholkar, Suvarna

    2016-01-01

    Bladder rupture is a very morbid injury following blunt or penetrating lower abdominal trauma. Prompt diagnosis is crucial to initiate optimal treatment. Intraperitoneal bladder rupture is associated with haematuria and biochemical features of renal failure. Cystogram is diagnostic. Immediate open surgical repair is the main stay of treatment. A case of intraperitoneal rupture diagnosed preoperatively by the presence of haematuria and pseudorenal failure is presented to highlight the association of posttraumatic haematuria and pseudorenal failure in such injuries. PMID:27547477

  14. Posttraumatic Haematuria with Pseudorenal Failure: A Diagnostic Lead for Intraperitoneal Bladder Rupture

    Directory of Open Access Journals (Sweden)

    Ketan Vagholkar

    2016-01-01

    Full Text Available Bladder rupture is a very morbid injury following blunt or penetrating lower abdominal trauma. Prompt diagnosis is crucial to initiate optimal treatment. Intraperitoneal bladder rupture is associated with haematuria and biochemical features of renal failure. Cystogram is diagnostic. Immediate open surgical repair is the main stay of treatment. A case of intraperitoneal rupture diagnosed preoperatively by the presence of haematuria and pseudorenal failure is presented to highlight the association of posttraumatic haematuria and pseudorenal failure in such injuries.

  15. Chemotherapy with laparoscope-assisted continuous circulatory hyperthermic intraperitoneal perfusion for malignant ascites

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate the procedure, feasibility and effects of laparoscopeassisted continuous circulatory hyperthermic intraperitoneal perfusion chemotherapy (CHIPC) in treatment of malignant ascites induced by peritoneal carcinomatosis from gastric cancers. METHODS: From August 2006 to March 2008, the laparoscopic approach was used to perform CHIPC on 16 patients with malignant ascites induced by gastric cancer or postoperative intraperitoneal seeding. Each patient underwent CHIPC three times after laparosco...

  16. 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

  17. Preparation and evaluation of chitosan based thermoreversible gels for intraperitoneal delivery of 5-fluorouracil (5-FU).

    Science.gov (United States)

    Depani, Bhavesh P; Naik, Anuja A; Nair, Hema A

    2013-12-01

    Sterile thermoreversibly gelling systems based on chitosan- glycerol phosphate were developed for intraperitoneal delivery of the antineoplastic agent 5-FU. The formulation was evaluated for gelling characteristics and in vitro drug release. Drug free gels were evaluated for in vitro cytotoxicity in L-929 mouse fibroblast cells. Drug loaded gels were subjected to acute toxicity studies in Swiss albino mice via intraperitoneal route and efficacy studies via intratumoral injections in subcutaneous colon carcinoma bearing BALB/c mice. The formulations gelled reversibly in 8 min at 37 °C and provided prolonged release of the drug. Drug free systems showed dose dependent cytotoxicity in fibroblast cells, while in vivo studies revealed a 2.8-fold increase in LD50 of 5-FU administered intraperitoneally as the developed system. Tumor volume measurements showed comparable efficacy of 5-FU administered as gel and commercial injection with a greatly improved safety profile of the former as adjudged from mortality and body weight measurements.

  18. Antiparietal cell antibody test

    Science.gov (United States)

    APCA; Anti-gastric parietal cell antibody; Atrophic gastritis - anti-gastric parietal cell antibody; Gastric ulcer - anti-gastric parietal cell antibody; Pernicious anemia - anti-gastric parietal cell antibody; ...

  19. The Sentinel Clot Sign: a Useful CT Finding for the Evaluation of Intraperitoneal Bladder Rupture Following Blunt Trauma

    Energy Technology Data Exchange (ETDEWEB)

    Shin, Sang Soo; Jeong, Yong Yeon; Chung, Tae Woong; Yoon, Woong; Kang, Heoung Keun; Kang, Taek Won; Shin, Hee Young [Chonnam National University Medical School, Gwangju (Korea, Republic of)

    2007-12-15

    To evaluate the frequency and relevance of the 'sentinel clot' sign on CT for patients with traumatic intraperitoneal bladder rupture in a retrospective study. During a recent 42-month period, 74 consecutive trauma patients (45 men, 29 women; age range, 12 84 years; mean age, 50.8 years) with gross hematuria were examined by the use of intravenous contrast enhanced CT of the abdomen and pelvis, followed by retrograde cystography. Contrast-enhanced CT scanning was performed by using a helical CT scanner. CT images were retrospectively reviewed in consensus by two radiologists. The CT findings including the sentinel clot sign, pelvic fracture, traumatic injury to other abdominal viscera, and the degree of intraperitoneal free fluid were assessed and statistically analyzed using the two-tailed x{sup 2} test. Twenty of the 74 patients had intraperitoneal bladder rupture. The sentinel clot sign was seen for 16 patients (80%) with intraperitoneal bladder rupture and for four patients (7%) without intraperitoneal bladder rupture (p < 0.001). Pelvic fracture was noted in five patients (25%) with intraperitoneal bladder rupture and in 39 patients (72%) without intraperitoneal bladder rupture (p < 0.001). Intraperitoneal free fluid was found in all patients (100%) with intraperitoneal bladder rupture, irrespective of an associated intraabdominal visceral injury, whereas 19 (35%) of the 54 patients without intraperitoneal bladder rupture had intraperitoneal free fluid (p < 0.001). Detection and localization of the sentinel clot sign abutting on the bladder dome may improve the accuracy of CT in the diagnosis of traumatic intraperitoneal bladder rupture, especially when the patients present with gross hematuria.

  20. The Efficacy of Intraperitoneal Pancreatic Islet Isografts in the Reversal of Diabetes in Rats

    NARCIS (Netherlands)

    Fritschy, Wilbert M.; Straaten, Jeanette F.M. van; Vos, Paul de; Strubbe, Jan H.; Wolters, Gerrit H.J.; Schilfgaarde, Reinout van

    1991-01-01

    The peritoneal cavity is of renewed interest for pancreatic islet transplantation, since it is the preferable site for transplantation of immunoisolated islets. In this study we investigated the minimum islet graft volume needed to restore normoglycemia after free intraperitoneal isogenic transplant

  1. Intraincisional vs intraperitoneal infiltration of local anaesthetic for controlling early post-laparoscopic cholecystectomy pain

    Directory of Open Access Journals (Sweden)

    Gouda M El-labban

    2011-01-01

    Full Text Available Background: The study was designed to compare the effect of intraincisional vs intraperitoneal infiltration of levobupivacaine 0.25% on post-operative pain in laparoscopic cholecystectomy. Materials and Methods: This randomised controlled study was carried out on 189 patients who underwent laparoscopic cholecystectomy. Group 1 was the control group and did not receive either intraperitoneal or intraincisional levobupivacaine. Group 2 was assigned to receive local infiltration (intraincisional of 20 ml solution of levobupivacaine 0.25%, while Group 3 received 20 ml solution of levobupivacaine 0.25% intraperitoneally. Post-operative pain was recorded for 24 hours post-operatively. Results: Post-operative abdominal pain was significantly lower with intraincisional infiltration of levobupivacaine 0.25% in group 2. This difference was reported from 30 minutes till 24 hours post-operatively. Right shoulder pain showed significantly lower incidence in group 2 and group 3 compared to control group. Although statistically insignificant, shoulder pain was less in group 3 than group 2. Conclusion: Intraincisional infiltration of levobupivacaine is more effective than intraperitoneal route in controlling post-operative abdominal pain. It decreases the need for rescue analgesia.

  2. 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.

    2009-01-01

    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 th

  3. 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 in

  4. 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.

    2010-01-01

    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

  5. Intraperitoneal versus subcutaneous insulin therapy in the treatment of type 1 diabetes mellitus

    DEFF Research Database (Denmark)

    van Dijk, P R; Logtenberg, S J J; Hendriks, S H

    2015-01-01

    BACKGROUND: Continuous intraperitoneal insulin infusion (CIPII), a last-resort type 1 diabetes mellitus (T1DM) treatment, has only been investigated in small or controlled studies. We aimed to investigate glycaemia and quality of life (QoL) with CIPII versus subcutaneous (SC) insulin therapy duri...

  6. The Effect of an Intraperitoneal Injection of Melatonin on Serum Amylase Levels in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Cavit Çöl

    2009-05-01

    Full Text Available Context Several experimental studies have been carried out to explain the ph ysiopathological mechan isms and to introduce endocrinological, enzymatic, biochemical and histopathol ogical changes in organism s during acute pancreatitis. Objective To evaluate the effect of an intraperitoneal injection of melatonin on serum amylase levels. Design Experimental acut e pancreatitis was experimentally caused through panc reatic duct ligation in 20 Winstar Albino rats . The rats were then divided into two groups: control and melatonin groups. Intervention The serum amylase level was measured on the 7 th day after acute pancreatitis had developed. In the melatonin group, an intraperitoneal injecti on of melatonin (20 mg/kg/day was performed starting from the 2 nd day after pancreatic duct ligation. Main outcome measure The levels of serum amylase were measured with an auto analyzer. Results It was found that the mean (±SD level of serum amylase in th e control group was 947±182 IU/mL wh ile it was 358±177 IU/mL in the experimental group (P<0.001. Conclusions The 20 mg/kg/day intraperitoneal injection of melatonin which was carried out for one week attenuated the serum amylase levels to a statistically si gnificant degree. The researchers believe that intraperitoneal in jections of melatonin decrease the severity of acute pancreatitis.

  7. 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.

  8. 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

  9. Role Guided Intraperitoneal Port-A-Cath Insertion in The Managment of Cancer Ovary of Fluoroscopic

    Directory of Open Access Journals (Sweden)

    Ahmed H Soliman *, Saad Ali Abd-Rabou *, Maged Abou Seada *,

    2013-07-01

    Full Text Available Introduction : The use of intraperitoneal (IP chemotherapy as a treatment for ovarian cancer has been demonstrated to result in improved survival. Aim of the work: The aim of this work is to evaluate the applicability and efficacy of fluoroscopic placed intraperitoneal port-A-cath and to assess the response rate to intraperitoneal chemotherapy in cases of ovarian carcinoma .Methods: The studied group included ,22 female patients with malignant ovarian cancer whom referred from gynecological surgery and gynecological oncology units to the Vascular and Interventional Radiology Unit, Ain Shams University Hospitals, for peritoneal port-A-cath application. All the patients were known cases of either primary or recurrent ovarian cancer , underwent cytoreductive surgery and referred to us .Results: Intraperitoneal port-A-cath with the aid of fluoroscopy showed highest technical success ( 91.9% and lowest complication rate on the long run compared to other methods of peritoneal access . Patients with cancer ovary showed significant improvement of the disease process denoted by changes in the degree of ascites , peritoneal nodules and tumor marker level after receiving combined IV/ IP chemotherapy. Conclusion: Port catheters proved to be the most safe method of long term access to the peritoneal cavity with the lowest complication rate compared to other methods of access to the peritoneal cavity

  10. Severe Intraperitoneal Haemorrhage following Suprapubic Catheter Insertion in a Patient Treated with Iloprost

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    R. A. J. Spence

    2013-01-01

    Full Text Available Suprapubic catheter (SPC insertion is a common urological procedure, performed both in the elective and emergency settings. The authors present an unusual case of severe intraperitoneal bleeding following the insertion of an SPC under direct vision, where the use of prostacyclin analogue may have been a contributing factor.

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

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    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.

  12. The effect of consolidation treatment with intraperitoneal carboplatin in advanced epithelial ovarian cancers

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    Azamsadat Mousavi

    2014-07-01

    Conclusion: It seems that consolidation therapy with intraperitoneal carboplatin may not increase overall survival, reduce relapse rate or decrease mortality, though it does not induce considerable side effects. Since the mean survival in the intervention group was nine months more than controls, this difference may be clinically significant.

  13. Oral immunization of mice with gamma-irradiated Brucella neotomae induces protection against intraperitoneal and intranasal challenge with virulent B. abortus 2308.

    Science.gov (United States)

    Dabral, Neha; Martha-Moreno-Lafont; Sriranganathan, Nammalwar; Vemulapalli, Ramesh

    2014-01-01

    Brucella spp. are Gram-negative, facultative intracellular coccobacilli that cause one of the most frequently encountered zoonosis worldwide. Humans naturally acquire infection through consumption of contaminated dairy and meat products and through direct exposure to aborted animal tissues and fluids. No vaccine against brucellosis is available for use in humans. In this study, we tested the ability of orally inoculated gamma-irradiated B. neotomae and B. abortus RB51 in a prime-boost immunization approach to induce antigen-specific humoral and cell mediated immunity and protection against challenge with virulent B. abortus 2308. Heterologous prime-boost vaccination with B. abortus RB51 and B. neotomae and homologous prime-boost vaccination of mice with B. neotomae led to the production of serum and mucosal antibodies specific to the smooth LPS. The elicited serum antibodies included the isotypes of IgM, IgG1, IgG2a, IgG2b and IgG3. All oral vaccination regimens induced antigen-specific CD4(+) and CD8(+) T cells capable of secreting IFN-γ and TNF-α. Upon intra-peritoneal challenge, mice vaccinated with B. neotomae showed the highest level of resistance against virulent B. abortus 2308 colonization in spleen and liver. Experiments with different doses of B. neotomae showed that all tested doses of 10(9), 10(10) and 10(11) CFU-equivalent conferred significant protection against the intra-peritoneal challenge. However, a dose of 10(11) CFU-equivalent of B. neotomae was required for affording protection against intranasal challenge as shown by the reduced bacterial colonization in spleens and lungs. Taken together, these results demonstrate the feasibility of using gamma-irradiated B. neotomae as an effective and safe oral vaccine to induce protection against respiratory and systemic infections with virulent Brucella.

  14. Induction of mammary tumors in rat by intraperitoneal injection of NMU: histopathology and estral cycle influence.

    Science.gov (United States)

    Rivera, E S; Andrade, N; Martin, G; Melito, G; Cricco, G; Mohamad, N; Davio, C; Caro, R; Bergoc, R M

    1994-11-11

    In order to obtain an experimental model we induced mammary tumors in female Sprague-Dawley rats. The carcinogen N-nitroso-N-methylurea (NMU) was injected intraperitoneally (i.p.) at doses of 50 mg/kg body weight when animals were 50, 80 and 110 days old. Tumor sizes were measured with a caliper and their growth parameters and histopathological properties were tested. For 100 rats, 88.4% of developed lesions were ductal carcinomas, histologically classified as 52.8% cribiform variety, 30.6% solid carcinoma. Metastases in liver, spleen and lung were present. Other primary tumors were detected with low incidence. The influence of the rat estrous cycle during the first exposure to intraperitoneal NMU injection was studied. The latency period in estrus, proestrus and diestrus was 82 +/- 15, 77 +/- 18 and 79 +/- 18 days, respectively. Tumor incidence was significantly higher in estrus (95.2%) than proestrus (71.4%) or diestrus (77.4), (P rats.

  15. Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery in Mice

    Science.gov (United States)

    2012-09-01

    small transmitter group; model G2 Emitter, Mini Mitter, Bend, OR). Surgical preparation con- sisted of shaving the abdominal fur and scrubbing the...Sl , No 5 September 2012 Pages 600-608 Effect of Intraperitoneal Radiotelemetry Instrumentation on Voluntary Wheel Running and Surgical Recovery...of the diaphragm, large intestine, and duodenum. These results demonstrate that the large transmitter delayed surgical recovery, disrupted normal

  16. Outcome following incomplete surgical cytoreduction combined with intraperitoneal chemotherapy for colorectal peritoneal metastases

    Institute of Scientific and Technical Information of China (English)

    Roisin; Mary; Heaney; Conor; Shields; Jurgen; Mulsow

    2015-01-01

    Cytoreductive surgery combined with intraperitoneal chemotherapy can improve survival in appropriately selected patients with colorectal peritoneal metastases. Outcomes are best in those patients in whom a complete cytoreduction can be achieved. Unresectabledisease is however encountered in approximately one-quarter of patients at laparotomy. The merits, or otherwise, of proceeding with an incomplete cytoreduction in this setting are unclear. We performed a review of published outcomes following incomplete cytoreduction for colorectal peritoneal metastases. Using the electronic databases, Pub Med and MEDLINE, a systematic search of available literature published during the period January 1997 to September 2014 was conducted. Following application of exclusion criteria, 19 papers were identified and included in this review. These comprised fifteen case series, 3 case control studies and one randomised control trial. In the nineteen studies included in this review, 2790 patients underwent cytoreductive surgery with or without intraperitoneal chemotherapy for peritoneal metastases of colorectal origin. Of these, 1732(62%) underwent a complete cytoreduction while 986(35%) patients underwent an incomplete cytoreduction. Median survival in the complete cytoreduction group ranged from 11 to 62 mo while survival in the latter group ranged from 2.4 to 32 mo. Of the 986 patients with an incomplete cytoreduction, 331 patients received intraperitoneal chemotherapy and survival in this cohort ranged from 4.5 to 32 mo. An incomplete cytoreduction, with or without intraperitoneal chemotherapy, does not appear to confer a survival benefit. The limited available data points to a palliative benefit in a subset of patients. In the absence of high quality data, the decision as to whether or not to proceed with surgery should be made on an individual patient basis.

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

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    Mithat Günaydın

    2015-09-01

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

  18. Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Ingmar Konigsrainer

    2011-01-01

    Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis. Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier. Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients. Patient selection for this multimodal approach is one of the most critical issues, and calls for interdisciplinary evaluation by radiologists, medical and surgical oncologists, and anaesthetists. This article sets forth criteria for selection of gastric cancer patients suffering from peritoneal carcinomatosis.

  19. Combined laparoscopic cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in a patient with peritoneal mesothelioma.

    Science.gov (United States)

    Esquivel, Jesus; Averbach, Andrew

    2009-08-01

    The role of minimally invasive, laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been reported by several centers around the world, mainly to palliate intractable ascites in patients with extensive peritoneal surface malignancies who are not candidates for a complete cytoreduction. In this paper, we report on the first case of combined laparoscopic cytoreductive surgery and HIPEC with curative intent in a patient with limited peritoneal mesothelioma.

  20. Influence of emotional stress on pharmacokinetics of isosorbide dinitrate intraperitoneally administered to rats.

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    Gomita,Yutaka

    1990-02-01

    Full Text Available The plasma level of isosorbide dinitrate intraperitoneally administered to rats stressed by foot-shock was almost the same as that in non-stressed control rats. However, levels of its metabolites, 5-isosorbide mononitrate and 2-isosorbide mononitrate, were lower in stressed rats than in non-stressed rats, suggesting that stress may influence the metabolism and/or excretion of the metabolites.

  1. Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis Secondary to Mucinous Adenocarcinoma of the Appendix

    OpenAIRE

    Sparks, David S.; Morris, Bradley; Xu, Wen; Fulton, Jessica; Atkinson, Victoria; Meade, Brian; Lutton, Nicholas

    2015-01-01

    Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical but effective treatment option for select peritoneal malignancies. We sought to determine our early experience with this method for peritoneal carcinomatosis secondary to mucinous adenocarcinomas of appendiceal origin. As such, we performed a retrospective clinical study of 30 consecutive patients undergoing CRS with planned HIPEC at the Princess Alexandra Hospital, between June 2009 to Dece...

  2. Delivery Induced Intraperitoneal Rupture of a Cystic Ovarian Teratoma and Associated Chronic Chemical Peritonitis

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    Reine Nader

    2014-01-01

    Full Text Available Intraperitoneal rupture of cystic ovarian teratoma is a rare complication. We report a case in a 29-year-old female, with increased abdominal circumference 2 months after vaginal delivery. MRI/CT raised this diagnosis associated to chemical peritonitis. A malignant ovarian mass with peritoneal carcinomatosis was excluded. Laparoscopic oophorectomy was performed and histologic analysis confirmed imaging findings. This case demonstrates the interest of imaging before surgery in pelvic masses to avoid misdiagnosing and to provide adequate treatment.

  3. Intraperitoneal cytostatics impair early post-operative collagen synthesis in experimental intestinal anastomosesP6.

    OpenAIRE

    Martens, M F; Hendriks, T; Wobbes, T; DE PONT J.J.

    1992-01-01

    Collagen synthesis in intestinal anastomoses has been measured in rats after in vivo administration of cytostatics. The cytostatics were administered during 5 consecutive days either intravenously or intraperitoneally. On day 3 of the course the rats received both an ileal and a colonic anastomosis. The animals were sacrificed 3 and 7 days after operation. The cytostatics regimen used was a combination of 5-fluorouracil, bleomycin and cisplatinum in a dose of 10, 2 and 0.35 mg kg-1 day-1, res...

  4. Effect of Monocyte Chemotactic Protein-1 on the Intraperitoneal Adhesion Formation

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    In order to study the role of monocyte chemotactic protein-1 (MCP-1) in the intra-peritoneal adhesion formation, 23 infertile patients undergoing laparoscopic operation were divided into two groups: experimental group including 12 patients with intra-peritoneal adhesion and control group including 11 patients without intra-peritoneal adhesion. Peritoneal fluid (PF) and peritoneum were collected from these patients during laparoscopic examination. The expression levels of MCP-l protein and MCP-1 mRNA were detected by using enzyme-linked immunosorbent assay (ELISA) and dot blot analysis method respectively. It was found that the levels of MCP-1 protein in PF of the patients with peritoneal adhesion were significantly higher than in the control group (0. 44±0.11 ng/ml vs 0. 19+0. 09 ng/ml respectively, P<0. 01 ). The level of MCP-1 mRNA in the peritoneum of the patients with peritoneal adhesion was significantly higher than in the control group (48.61±3.72 vs 19. 87±2.54 respectively, P<0. 01). It was suggested that MCP-1 might play a role in the adhesion formation, and chemotactic cytokines expressing in the peritoneal mesothelial cells might be take part in the process.

  5. ESTABLISHMENT OF INTRAPERITONEAL TRANSPLANTATION MODEL OF CISPLATIN-RESISTANT OVARIAN CARCINOMA CELL IN SCID MICE

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hui; ZHAO Qun; ZUO Lian-fu; WANG Xiao-ling; WANG Yong-jun; JIA Jin-hua; KANG Shan

    2006-01-01

    Objective: to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency (SCID) mouse and to study its biologic characteristics. Methods: Sixteen qualified C.B17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×107 cells (0.5 mL) per mouse. The behaviors of mice,tumor growth and morphology were analyzed. The expression of cancer antigen 125 (CA125), GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results: In this experimental study, transplanted tumors are formed in 100%SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher (P<0.05). Conclusion: An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

  6. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy: a review of factors contributing to morbidity and mortality

    Science.gov (United States)

    Newton, Andrew D.; Bartlett, Edmund K.

    2016-01-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with prolonged survival for appropriately selected patients with peritoneal dissemination of abdominal malignancies. CRS and HIPEC has been criticized for perceived high rates of morbidity and mortality. Morbidity and mortality rates of CRS and HIPEC, however, do not appear dissimilar to those of other large abdominal surgeries, particularly when relevant patient and operative factors are accounted for. The risk of morbidity and mortality following this surgery for a given individual can be predicted in part by a variety of patient and operative factors. While strong data are lacking, the limited data that exists on the matter suggests that the independent contribution of the heated intraperitoneal chemotherapy to CRS and HIPEC morbidity is relatively small. A more thorough understanding of the patient and operative factors associated with CRS and HIPEC morbidity and mortality, as well as the specific complications related to the intraperitoneal chemotherapy, can better inform clinicians in multidisciplinary teams and patients alike in the decision-making for this surgery. PMID:26941988

  7. The influence of intraperitoneal transplantation of free and encapsulated Langerhans islets on the second set phenomenon.

    Science.gov (United States)

    Orłowski, Tadeusz; Godlewska, Ewa; Mościcka, Maria; Sitarek, Elzbieta

    2003-12-01

    To protect the allografts or xenografts against transplant rejection special semipermeable membranes are applied. So far, there are only a few studies on the influence of an immunoisolated graft on the recipient immune system. Therefore, the possibility that an intraperitoneally grafted alginate/poly L-lysine/alginate (APA) coated pancreatic islets graft can effectively sensitize the recipient and provoke second set phenomenon was studied. C3H male mice and male WAG rats were used as donors of full-thickness skin and of free or encapsulated islet intraperitoneal grafts. Male BALB/c mice served as recipients. Skin grafts were performed following the method of Billingham and Medawar. The length of the second skin graft survival time served as the criterion for the sensitizing capacity of the primary graft. APA encapsulation of islets delayed but has not prevented the development of the second set phenomenon. However, the second skin graft rejection time was significantly longer after grafting of encapsulated islets than after free islets transplantation. APA microencapsulation of intraperitoneally transplanted islets delayed but did not prevent the development of the second set phenomenon. Encapsulation does not ensure complete immunoisolation, but only creates "an artificially immunoprivileged site of transplantation."

  8. Technology of hyperthermic intraperitoneal chemotherapy in the United States, Europe, China, Japan, and Korea.

    Science.gov (United States)

    Esquivel, Jesus

    2009-01-01

    Significant improvements in the understanding of the biologic behavior of peritoneal surface malignancies in addition to the combination of peritonectomy procedures that allow complete eradication of macroscopic peritoneal disease and hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of surgery, directed at residual microscopic disease, have change the therapeutic strategy from a palliative approach to a curative intent in a selected group of patients with peritoneal carcinomatosis.The rationale for adding HIPEC is supported by the strong pharmacological advantage over systemic therapy. Because of the peritoneal-plasma barrier, intraperitoneal administration of chemotherapy results in intraperitoneal levels that are 20 to 1000 times higher than plasma levels. The chemotherapy not only directly destroys tumor cells, but also eliminates viable platelets, neutrophils, and monocytes from the peritoneal cavity. This diminishes the promotion of tumor growth associated with the wound healing process. In addition, combining the intraperitoneal chemotherapy with hyperthermia has several advantages. Heat by itself has more toxicity for cancerous tissue than for normal tissue, and this predominant effect on cancer increases as the vascularity of the malignancy decreases. Also, hyperthermia increases the penetration of chemotherapy into tissues. As tissues soften in response to heat, the elevated interstitial pressure of a tumor mass may decrease and allow improved drug penetration. Lastly, and probably most important, heat increases the cytotoxicity of selected chemotherapy agents. This synergism occurs only at the interface of heat and body tissue at the peritoneal surface.However, despite the wider acceptance to combine extensive cytoreductive surgery with intraoperative intraperitoneal heated chemotherapy, the specifics of the HIPEC administration continue to lack uniformity. The most recent consensus statement issued by the Peritoneal Surface Oncology Group

  9. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  10. Selection of antibodies from synthetic antibody libraries.

    Science.gov (United States)

    Harel Inbar, Noa; Benhar, Itai

    2012-10-15

    More than 2 dozen years had passed since the field of antibody engineering was established, with the first reports of bacterial [1-3] and mammalian cells [4] expression of recombinant antibody fragments, and in that time a lot of effort was dedicated to the development of efficient technological means, intended to assist in the creation of therapeutic monoclonal antibodies (mAbs). Research focus was given to two intertwined technological aspects: the selection platform and the recombinant antibody repertoires. In accordance with these areas of interest, it is the goal of this chapter to describe the various selection tools and antibody libraries existing, with emphasis on the later, and their applications. This chapter gives a far from exhaustive, subjective "historic account" of the field, describing the selection platforms, the different formats of antibody repertoires and the applications of both for selecting recombinant antibodies. Several excellent books provide detailed protocols for constructing antibody libraries and selecting antibodies from those libraries [5-13]. Such books may guide a newcomer to the field in the fine details of antibody engineering. We would like to offer advice to the novice: although seemingly simple, effective library construction and antibody isolation provide best benefits in the hands of professionals. It is an art as much as it is science.

  11. Effect of intraperitoneal antimicrobials on the concentration of bacteria, endotoxin, and tumor necrosis factor in abdominal fluid and plasma in rats

    NARCIS (Netherlands)

    Rosman, C; Westerveld, GJ; vanOeveren, W; Kooi, K; Bleichrodt, RP

    1996-01-01

    The efficacy of intraperitoneal instillation of antimicrobial agents in eliminating the bacterial contaminant in patients with generalized peritonitis remains controversial. We determined the effect of intraperitoneal instillation of taurolidine or imipenem on mortality, and on the concentration of

  12. Breakthrough therapy for peritoneal carcinomatosis of gastric cancer:Intraperitoneal chemotherapy with taxanes

    Institute of Scientific and Technical Information of China (English)

    Hironori; Yamaguchi; Joji; Kitayama; Hironori; Ishigami; Shinsuke; Kazama; Hiroaki; Nozawa; Kazushige; Kawai; Keisuke; Hata; Tomomichi; Kiyomatsu; Toshiaki; Tanaka; Junichiro; Tanaka; Takeshi; Nishikawa; Kensuke; Otani; Koji; Yasuda; Soichiro; Ishihara; Eiji; Sunami; Toshiaki; Watanabe

    2015-01-01

    The effect of chemotherapy on peritoneal carcinomatosis(PC) of gastric cancer remains unclear.Recently,the intraperitoneal(IP) administration of taxanes [e.g.,paclitaxel(PTX) and docetaxel(DOC)] during the perioperative period has shown promising results.Herein,we summarized the rationale and methodology for using IP chemotherapy with taxanes and reviewed the clinical results.IP administered taxanes remain in the IP space at an extremely high concentration for 48-72 h.The drug directly infiltrates peritoneal metastatic nodules from the surface and then produces antitumor effects,making it ideal for IP chemotherapy.There are two types of perioperative IP chemotherapy with taxanes: neoadjuvant intraperitoneal and systemic chemotherapy and sequential perioperative intraperitoneal chemotherapy(SPIC).In SPIC,patients receive neoadjuvant IP chemotherapy and the same regimen of IP chemotherapy after cytoreductive surgery(CRS) until disease progression.Usually,a taxane dissolved in 500-1000 m L of saline at ordinary temperature is administered through an IP access port on an outpatient basis.According to phase Ⅰ?studies,the recommended doses(RD) are as follows: IP DOC,45-60 mg/m2; IP PTX [without intravenous(IV) PTX],80 mg/m2; and IP PTX(with IV PTX),20 mg/m2.Phase Ⅱ studies have reported a median survival time of 14.4-24.6 mo with a 1-year overall survival of 67%-78%.A phase Ⅲ study comparing S-1 in combination with IP and IV PTX to S-1 with IV cisplatin started in 2011.The prognosis of patients who underwent CRS was better than that of those who did not; however,this was partly due to selection bias.Although several phase Ⅱ studies have shown promising results,a randomized controlled study is needed to validate the effectiveness of IP chemotherapy with taxanes for PC of gastric cancer.

  13. Pharmacokinetics of mitomycin C after resection of peritoneal carcinomatosis and intraperitoneal chemohyperthermic perfusion.

    Science.gov (United States)

    Cerretani, D; Nencini, C; Urso, R; Giorgi, G; Marrelli, D; De Stefano, A; Pinto, E; Cioppa, T; Nastri, G; Roviello, F

    2005-12-01

    Over the last few years surgery on patients with abdominal malignancies has become more aggressive but the majority of patients present locoregional recurrence as peritoneal dissemination. Cytoreductive surgery followed by intraperitoneal chemohyperthermic perfusion (ICHP) has been described for treatment and prevention of locoregional cancer spread from various origins. This paper reports our study of the pharmacokinetics of mitomycin C (MMC) administered by intraperitoneal chemohyperthermic perfusion (ICHP) in patients with peritoneal carcinomatosis. 28 patients received MMC 20 mg/m2 intraperitoneally as a perfusion over 60 min. MMC was determined in perfusate, plasma and urine samples with a UV-HPLC method. A compartmental model was used to fit the drug concentrations in plasma and perfusate. Our results showed a mean maximum plasma concentration (Cmax) of 0.14 +/- 0.086 microg/ml with a peak time (Tmax) of 48..7 +/- 5.61 min. The mean area under the curve (AUC) and terminal half-life (t1/2) were 15.8 +/- 9.8 mg x min/L and 83.7 +/- 31.74 min respectively. Clearance (CL) was estimated by fitting the data by a compartmental model and the mean value was 72 +/- 66 L/h. The percent of the dose absorbed was very variable and ranged between 14 and 57% (mean 37 +/- 14%). The mean percentage of dose recovered unchanged in the urine during 24 hours was 7.21 +/- 3.73%. We conclude that ICHP in patients with peritoneal surface malignancies seems to have clinical value since it gives high peritoneal and tumor MMC concentrations with limited systemic exposure and toxicity.

  14. 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.

  15. Conservatively managed spontaneous intraperitoneal bladder perforation in a patient with chronic bladder outflow obstruction

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    Abeyna L. C. Jones

    2014-01-01

    Full Text Available We present the unusual case of a spontaneous intraperitoneal bladder rupture as a first presentation of chronic bladder outflow obstruction secondary to benign prostatic hyperplasia. A contributing factor to diagnostic delay was unfamiliarity with the classical presentation of abdominal pain, abdominal distension and urinary ascites leading to autodialysis represented by an unusually high serum creatinine. A cystogram was performed after a non-contrast computed tomography (CT scan originally performed to determine the cause of abdominal pain, failed to confirm the diagnosis. The patient′s initial acute presentation was successfully managed conservatively with prolonged urinary catheterization.

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

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    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.

  17. Time course of antibodies against IgG and type II collagen in adjuvant arthritis. Role of mycobacteria administration in antibody production.

    Science.gov (United States)

    Franch, A; Cassany, S; Castellote, C; Castell, M

    1994-02-01

    The aim of this study was to elucidate, during the time course of adjuvant arthritis, the existence of antibodies directed to IgG (rheumatoid factor-like) and antibodies against type II collagen. In a second study, we also studied the relation between antibody production, arthritic process and mycobacteria administration. We have demonstrated the presence of antibodies to IgG and type II collagen by means of ELISA techniques. This reactivity appeared on day 7 post-induction, decreased later, and increased progressively from day 21 until last day studied (day 56 post-induction). We have also quantified antibodies against a soluble fraction of Mycobacterium butyricum, the inductor of the disease. Anti-mycobacteria antibodies appeared during the first seven days after induction, but from day 14, when systemic inflammation began, their levels suddenly increased. There is a positive correlation between anti-mycobacteria antibody levels and articular swelling. Anti-IgG and anti-collagen antibody production was not directly linked to arthritic process since these antibodies were synthesized when M. butyricum was administered intraperitoneally, which does not induce arthritis. Anti-mycobacteria antibody concentration was higher when arthritis induction by mycobacterial was successful than when it was unsuccessful.

  18. Non-specific immune response of bullfrog Rana catesbeiana to intraperitoneal injection of bacterium Aeromonas hydrophila

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    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.

  19. Does intraperitoneal medical ozone preconditioning and treatment ameliorate the methotrexate induced nephrotoxicity in rats?

    Science.gov (United States)

    Aslaner, Arif; Çakır, Tuğrul; Çelik, Betül; Doğan, Uğur; Mayir, Burhan; Akyüz, Cebrail; Polat, Cemal; Baştürk, Ahmet; Soyer, Vural; Koç, Süleyman; Şehirli, Ahmet Özer

    2015-01-01

    Methotrexate is a chemotherapeutic agent used for many cancer treatments. It leads to toxicity with its oxidative injury. The purpose of our study is investigating the medical ozone preconditioning and treatment has any effect on the methotrexate-induced kidneys by activating antioxidant enzymes in rats. Eighteen rats were divided into three equal groups; control, Mtx without and with medical ozone. Nephrotoxicity was performed with a single dose of 20 mg/kg Mtx intraperitoneally at the fifteenth day of experiment on groups 2 and 3. Medical ozone preconditioning was performed at a dose of 25 mcg/ml (5 ml) intraperitoneally everyday in the group 3 and treated with medical ozone for five more days while group 2 was received only 5 ml of saline everyday for twenty days. All rats were sacrificed at the end of third week and the blood and kidney tissue samples were obtained to measure the levels of TNF-α, IL-1β, malondialdehyde, glutathione and myeloperoxidase. Kidney injury score was evaluated histolopatologically. Medical ozone preconditioning and treatment ameliorated the biochemical parameters and kidney injury induced by Mtx. There was significant increase in tissue MDA, MPO activity, TNF-α and IL-1β (Pnephrotoxicity induced by Mtx in rats by activating antioxidant enzymes and prevented renal tissue.

  20. Intraperitoneal spontaneous rupture of the bladder subsequent to irradiation for the uterus. A case report

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    Ishii, Tokumi; Kadowaki, Teruo; Sugiyama, Takahide.

    1988-12-01

    We report a case of spontaneous intraperitoneal rupture of the bladder. A 54-year-old woman was admitted to our hospital with the chief complaints of severe lower abdominal pain, dysuria and macroscopic hematuria in October, 1985. In 1969, she had had a radical hysterectomy and postoperative irradiation for cancer of the uterus. Two years later she had undergone additional irradiation. On physical examination, the abdomen was tender with guarding and signs of peritonitis. Laboratory data revealed a blood urea nitrogen of 32.8 mg/dl and all electrolytes were normal. Excretory urogram showed normal upper urinary tract but irregularity of the bladder dome. Cystoscopy revealed acute inflammation of the bladder mucosa. Consequently, we made a presumptive diagnosis of radiation cystitis and she was treated with antibiotics and drip infusion. Within a week her general condition was improved and she had discharged. In June, 1986 she was admitted again with the same chief complaints as at her first admission. Cystoscopic findings showed a hole on the postero-superior wall and retrograde cystogram revealed an intraperitoneal rupture of the bladder. At exploration a necrotic bladder wall resected and closed in 3 layers. The post operative course was uneventful.

  1. A comparison of virulence of intraperitoneal infection of Burkholderia mallei strains in guinea-pigs

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    Eslampanah, M.

    2015-12-01

    Full Text Available Male guinea pigs show high susceptibility to Burkholderia mallei and have been used as animal models in glanders studies. The purpose of our study was to elucidate glanders comparative pathogenesis in guinea pigs. We present here the histological changes and bacterial isolation that develop over time in guinea pigs inoculated intraperitoneally (IP with two strain of B. mallei. Ten male guinea pigs were inoculated intraperitoneally with either the standard strain of Burkholderia mallei or B. mallei strain from Siberian tiger at the Tehran zoo individually, then euthanized at multiple time points post inoculation. Histopathologic changes were similar in both groups and consisted of pyogranulomatous inflammation. In the standard strain study guinea pigs, changes were first seen at 48 hours in liver and heart then in spleen, lung, and kidney at day 3. These changes generally reached maximal incidence and severity by day 3 but decreased by comparison in all tissues except the liver, lung and kidney. Changes were first seen in Siberian tiger strain study guinea pigs also at 48 hours in lung, liver and spleen. At day 3, changes were present in liver, spleen and mediastinal lymph nodes. These changes were maximal at day 4 and 5. In contrast there are differences in incidence and severity between the two strain study guinea pigs. Our findings based on histopathological study indicate that Siberian tiger strain has more severity in gross and necropsy examination but in pathologic lesion was qualitatively similar generally. Additionally, by bacterial isolation, we confirmed the presence of B. mallei.

  2. Operating personnel safety during the administration of Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

    Science.gov (United States)

    Kyriazanos, Ioannis; Kalles, Vasileios; Stefanopoulos, Anastasios; Spiliotis, John; Mohamed, Faheez

    2016-09-01

    Cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is increasingly used in the treatment of peritoneal malignancies. The administration of HIPEC after complete cytoreduction offers the combination of the pharmacokinetic advantages inherent to the intraperitoneal delivery of cytotoxic chemotherapy, with the direct cytotoxic effects of hyperthermia, and has been reported to offer significantly improved patient outcomes. As a result, this novel method disseminates rapidly, with many surgical teams having developed peritoneal malignancy treatment programs. Protocols are needed for the introduction, handling, and management of chemotherapeutic agents in the operating room to minimize risk to the staff involved in the procedure. The personnel exposure during CRS and HIPEC may arise from different routes, such as air contamination, direct contact, manipulation of perfusates or chemotherapy solutions, and manipulation of objects/tissues exposed to chemotherapeutics. Guidelines for safe administration of HIPEC including environmental contamination risk management, personal protective equipment, and occupational health issues are yet to be established. This review summarizes the existing evidence regarding the safety considerations of HIPEC administration.

  3. 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.

  4. 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.

  5. Intraperitoneal Infusion of Mesenchymal Stem/Stromal Cells Prevents Experimental Autoimmune Uveitis in Mice

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    Joo Youn Oh

    2014-01-01

    Full Text Available Autoimmune uveitis is one of the leading causes of blindness. We here investigated whether intraperitoneal administration of human mesenchymal stem/stromal cells (hMSCs might prevent development of experimental autoimmune uveitis (EAU in mice. Time course study showed that the number of IFN-γ- or IL-17-expressing CD4+ T cells was increased in draining lymph nodes (DLNs on the postimmunization day 7 and decreased thereafter. The retinal structure was severely disrupted on day 21. An intraperitoneal injection of hMSCs at the time of immunization protected the retina from damage and suppressed the levels of proinflammatory cytokines in the eye. Analysis of DLNs on day 7 showed that hMSCs decreased the number of Th1 and Th17 cells. The hMSCs did not reduce the levels of IL-1β, IL-6, IL-12, and IL-23 which are the cytokines that drive Th1/Th17 differentiation. Also, hMSCs did not induce CD4+CD25+Foxp3+ cells. However, hMSCs increased the level of an immunoregulatory cytokine IL-10 and the population of IL-10-expressing B220+CD19+ cells. Together, data demonstrate that hMSCs attenuate EAU by suppressing Th1/Th17 cells and induce IL-10-expressing B220+CD19+ cells. Our results support suggestions that hMSCs may offer a therapy for autoimmune diseases mediated by Th1/Th17 responses.

  6. Hepatic Histopathological Characteristics and Antioxidant Response of Phytoplanktivorous Silver Carp Intraperitoneally Injected with Extracted Microcystins

    Institute of Scientific and Technical Information of China (English)

    LI LI; PING XIE

    2009-01-01

    Objectives To investigate the hispathological characteristics and antioxidant responses in liver of silver carp after intraperitoneal administration of microcystins (MCs) for further understanding hepatic intoxication and antioxidation mechanism in fish. Methods Phytoplanktivorous silver carp was injected intraperitoneally (i.p.) with extracted hepatotoxic microcystins (mainly MC-RR and-LR) at a dose of 1000μg MC-LReq./kg body weight, and liver histopathological changes and antioxidant responses were studied at 1, 3, 12, 24, and 48 h, respectively, after injection. Results The damage to liver structure and the activities of hepatic antioxidant enzymes including catalase (CAT), superoxide dismutase (SOD), and ghitathione peroxide (GPX) were increased in a time-dependent manner. Conclusion In terms of clinical and histological signs of intoxication and LD50 (i.p.) dose of MC-LR, silver carp appears rather resistant to MCs exposure than other fishes. Also, the significantly increased SOD activity in the liver of silver carp suggests a higher degree of response to MCs exposure than CAT and GPX.

  7. Intraperitoneally administered biliverdin protects against UVB-induced skin photo-damage in hairless mice.

    Science.gov (United States)

    Bai, Bingxue; Liu, Yingdi; You, Yan; Li, Yuzhen; Ma, Liangjuan

    2015-03-01

    Oxidative stress is shown to be responsible for ultraviolet B (UVB) irradiation-induced skin cancer and premature aging. Biliverdin (BVD), a product of heme oxygenase-1, has strong anti-oxidant and anti-inflammatory properties. In the present study, we investigated the effects of BVD on UVB-induced skin photo-damage in hairless mice. Mice were divided into three groups: control group, UVB group (only UVB irradiation) and BVD+UVB group (mice were intraperitoneally injected with BVD before each UVB irradiation). Intraperitoneal BVD injection resulted in a significant photoprotective effect by reducing morphological and histopathological changes to the skin. BVD also exhibited a significant antioxidant effect by increasing the superoxide dismutase (SOD) level and decreasing the thiobarbituric acid reactive substances (TBARS) level compared with the control group. In addition, BVD activated biliverdin reductase (BVR) expression and inhibited the UVB-induced increase of p38 mitogen-activated protein kinase phosphorylation (p-p38MAPK), MMP (matrix metalloproteinase)-1 and MMP-3 expression (pskin photo-damage in hairless mice and that this is likely mediated by its antioxidant and anti-inflammatory mechanisms and cell signal regulatory action.

  8. Intraperitoneal insemination of the guinea pig with synchronized estrus induced by progesterone implant.

    Science.gov (United States)

    Ueda, H; Kosaka, T; Takahashi, K W

    1998-10-01

    Female guinea pigs with synchronized ovulation by means of implantation of progesterone-filled tubing (P-tube) followed by a progesterone injection, were inseminated by intraperitoneal injection with sperm suspension. First, to obtain the optimum conditions for insemination, the females were inseminated singly over the range of 1-10 x 10(7) spermatozoa before and after the synchronized ovulation. The incidence of conception and implantation was 100% in the females given more than 5 x 10(7)/animal at 9:00 h on the 5th day after removal of the P-tube. Second, the reproductive ability of the inseminated females under this optimal condition was observed throughout the pregnancy to delivery. Inseminated females had a mean +/- S.D. gestation period of 68.7 +/- 0.5 days, a litter size of 2.8 +/- 0.6 pups and body weight of 110 +/- 14 g. These data were comparable to those of naturally-mated females. Our findings suggest that the artificial insemination by intraperitoneal injection in combination with the synchronized estrus technique is very useful for production control in a small colony of guinea pigs.

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

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    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

  10. Acetylcholine receptor antibody

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    ... page: //medlineplus.gov/ency/article/003576.htm Acetylcholine receptor antibody To use the sharing features on this page, please enable JavaScript. Acetylcholine receptor antibody is a protein found in the blood ...

  11. Antinuclear antibody panel

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    ... page: //medlineplus.gov/ency/article/003535.htm Antinuclear antibody panel To use the sharing features on this page, please enable JavaScript. The antinuclear antibody panel is a blood test that looks at ...

  12. Lyme disease antibody

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    ... JavaScript. The Lyme disease blood test looks for antibodies in the blood to the bacteria that causes ... needed. A laboratory specialist looks for Lyme disease antibodies in the blood sample using the ELISA test . ...

  13. Adeno-associated virus serotype rh.10 displays strong muscle tropism following intraperitoneal delivery.

    Science.gov (United States)

    Ai, Jianzhong; Li, Jia; Gessler, Dominic J; Su, Qin; Wei, Qiang; Li, Hong; Gao, Guangping

    2017-01-09

    Recombinant adeno-associated virus (rAAV) is an attractive tool for basic science and translational medicine including gene therapy, due to the versatility in its cell and organ transduction. Previous work indicates that rAAV transduction patterns are highly dependent on route of administration. Based on this relationship, we hypothesized that intraperitoneal (IP) administration of rAAV produces unique patterns of tissue tropism. To test this hypothesis, we investigated the transduction efficiency of 12 rAAV serotypes carrying an enhanced green fluorescent protein (EGFP) reporter gene in a panel of 12 organs after IP injection. Our data suggest that IP administration emphasizes transduction patterns that are different from previously reported intravascular delivery methods. Using this approach, rAAV efficiently transduces the liver, pancreas, skeletal muscle, heart and diaphragm without causing significant histopathological changes. Of note, rAAVrh.10 showed excellent muscle transduction following IP administration, highlighting its potential as a new muscle-targeting vector.

  14. Generalized seizure: A rare etiology of intraperitoneal rupture of the urinary bladder

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    Bipin C Pal

    2007-01-01

    Full Text Available Seizures can lead to different types of injuries which can be as simple as minor lacerations and at times as serious as fractures and head injuries. We are reporting a case wherein a female patient presented with a history of abdominal pain and not passing urine for 24h following an attack of seizure. After catheterization the urine drained was blood-stained. On clinical suspicion a cystogram was done which showed intraperitoneal rupture of the bladder. At laparotomy an isolated rent in the dome of the bladder was found which was repaired in three layers. Postoperative period was uneventful. To our knowledge this is the second case of its kind reported in the literature. Our case illustrates that a thorough abdominal examination is desirable while examining a patient following an episode of generalized seizure.

  15. 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.

  16. Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This article is to offer a concise review on the use of cytoreductive surgery (CRS) plus intraperitoneal hyperthermic chemotherapy (IPHC) for the treatment of peritoneal carcinomatosis (PC). Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 mo. With the establishment of several phase studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.

  17. Intraperitoneal Hemorrhage in a Peritoneal Dialysis Patient Using Dabigatran: A Case Report

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    Egemen Cebeci

    2016-06-01

    Full Text Available Dabigatran is used for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. It is still unclear whether the use of dabigatran leads to more bleeding compared with warfarin. In this paper, we present a case of intraperitoneal hemorrhage in a 54-years-old male peritoneal dialysis patient using dabigatran for paroxysmal atrial fibrillation because international normalized ratio level could not be kept at target levels during follow-up. The use of dabigatran in atrial fibrillation has become widespread in recent years. Despite the low risk of intracranial hemorrhage, clinicians should be careful in patients with chronic kidney disease because coagulation monitoring is not possible.

  18. Polyethylene Glycol (PEG-3350, Colyte Poisoning due to Intra-Peritoneal Leakage in an Elderly Patient

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    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.

  19. Catheter-related Complications in Postoperative Intraperitoneal Chemotherapy for Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To analyze catheter-related complications during postoperative Intraperitoneal chemotherapy (IPCT) for gastric cancer. Methods: From December 2003 to April 2007, 80 patients with gastric cancer were treated with postoperative IPCT using central venous catheters (CVCs), during which the complications that occurred in association with CVCs were documented and analyzed. Results: Catheter-related complications were seen in 10 out of the 80 patients, yielding a total complication rate of 12.5%. Main complications included abdominal pain (3.8%), local infection (1.3%), catheter obstruction (2.5%), leakage (2.5%) and dislocation (2.5%). All patients successfully finished their IPCT, the success rate was 100%. There occurred no severe complications or treatment-related deaths. Conclusion: It is convenient and safe to carry out postoperative IPCT for gastric cancer using CVCs, which, with a low catheter-related complication rate, should be recommended for more clinic use.

  20. Intraperitoneal pseudocyst formation: complication of fungal peritonitis in continuous ambulatory peritoneal dialysis.

    Science.gov (United States)

    Sahpazova, E; Ruso, B; Kuzmanovska, D

    2007-10-01

    A 14-year-old girl, with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) the last 4 years, after an episode of Candida albicans was switched to hemodialysis. One month later she came back because of a palpable-painful abdominal mass and abdominal distention. Computed tomography (CT) and ultrasound examination demonstrated a demarkated fluid collection in the lower abdomen and pelvis. The cyst was drained percutaneously and the culture disclosed candida albicans which was treated with fluconasole. Two months later, the girl was admitted again with the same symptoms. An investigative laparotomy was undergone and the cyst was drained again. Fluid cultures were negative. CT abdomen examination six months later was negative for cyst relapse. In conclusion, intraperitoneal pseudocyst is a serious complication of CAPD. Surgical intervention may be preferable to percutaneous drainage.

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

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    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.

  2. Catheterization-associated complications of intraperitoneal chemotherapy in advanced gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Meng Ye; Hong-Ming Pan; Hai-Yun Wang; Fang Lou; Wei Jin; Yu Zheng; Jin-Ming Wu

    2004-01-01

    AIM: To assess the catheterization-associated complications during intraperitoneal chemotherapy (IPCT) for advanced gastric cancer.METHODS: From 1998 to 2002, 80 patients with advanced gastric cancer received a total of 320 courses of IPCT using a large bore central venous catheter and associated complications were analyzed.RESULTS: Catheterization-associated complications occurred in 11 of the 80 patients (13.8%), including abdominal pain caused by catheter in 2 cases (0.63%), insertion failure in 2 cases (0.63%), bowel perforation in 1 case (0.31%)and abdominal pain during chernotherapy in 6 cases (1.88%).No serious complications required surgical intervention.CONCLUSION: IPCT using central venous catheters can be performed safely and simply without severe associated complications.

  3. 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...... 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. RESULTS: 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...

  4. Near fatal spontaneous intraperitoneal bleeding: A rare manifestation in a congenital factor X deficiency carrier

    Directory of Open Access Journals (Sweden)

    K V Vinod

    2015-01-01

    Full Text Available Congenital factor X (FX deficiency is a rare coagulation disorder of autosomal recessive inheritance, characterized by bleeding of variable severity. Bleeding severity generally correlates with the level of FX functional activity and severe bleeding usually occurs in moderate and severe deficiency, when FX coagulant activity is <5%. FX activity above 10% is infrequently associated with severe bleeding. Here we report the rare occurrence of life-threatening massive spontaneous intraperitoneal bleeding with hypovolemic shock, resulting from spontaneous rupture of an ovarian luteal cyst in a 25-year-old FX deficiency carrier woman, with a FX activity of 26%. She was managed successfully conservatively, with fresh frozen plasma and packed red blood cell transfusions and she showed gradual improvement. The case is being reported to discuss the diagnosis and management of this rare inherited coagulation disorder.

  5. Intraperitoneal pseudocyst formation: Complication of fungal peritonitis in continuous ambulatory peritoneal dialysis

    Science.gov (United States)

    Sahpazova, E; Ruso, B; Kuzmanovska, D

    2007-01-01

    A 14-year-old girl, with end-stage renal disease on continuous ambulatory peritoneal dialysis (CAPD) the last 4 years, after an episode of Candida albicans was switched to hemodialysis. One month later she came back because of a palpable painful abdominal mass and abdominal distention. Computed tomography (CT) and ultrasound examination demonstrated a demarkated fluid collection in the lower abdomen and pelvis. The cyst was drained percutaneously and the culture disclosed candida albicans which was treated with fluconasole. Two months later, the girl was admitted again with the same symptoms. An investigative laparotomy was undergone and the cyst was drained again. Fluid cultures were negative. CT abdomen examination six months later was negative for cyst relapse. In conclusion, intraperitoneal pseudocyst is a serious complication of CAPD. Surgical intervention may be preferable to percutaneous drainage. PMID:19582199

  6. The antibody mining toolbox

    OpenAIRE

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D.; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

    2013-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput ...

  7. Dosimetric model for intraperitoneal targeted liposomal radioimmunotherapy of ovarian cancer micrometastases

    Energy Technology Data Exchange (ETDEWEB)

    Syme, A M [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta T6G 2J1 (Canada); McQuarrie, S A [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3118 Dentistry/Pharmacy Centre, Edmonton, Alberta T6G 2N8 (Canada); Middleton, J W [Department of Physics, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario K1N 6N5 (Canada); Fallone, B G [Departments of Physics and Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2 (Canada)

    2003-05-21

    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. Lung-Derived Microscaffolds Facilitate Diabetes Reversal after Mouse and Human Intraperitoneal Islet Transplantation.

    Directory of Open Access Journals (Sweden)

    Nasser Abualhassan

    Full Text Available There is a need to develop three-dimensional structures that mimic the natural islet tissue microenvironment. Endocrine micro-pancreata (EMPs made up of acellular organ-derived micro-scaffolds seeded with human islets have been shown to express high levels of key beta-cell specific genes and secrete quantities of insulin per cell similar to freshly isolated human islets in a glucose-regulated manner for more than three months in vitro. The aim of this study was to investigate the capacity of EMPs to restore euglycemia in vivo after transplantation of mouse or human islets in chemically diabetic mice. We proposed that the organ-derived EMPs would restore the extracellular components of the islet microenvironment, generating favorable conditions for islet function and survival. EMPs seeded with 500 mouse islets were implanted intraperitoneally into streptozotocin-induced diabetic mice and reverted diabetes in 67% of mice compared to 13% of controls (p = 0.018, n = 9 per group. Histological analysis of the explanted grafts 60 days post-transplantation stained positive for insulin and exhibited increased vascular density in a collagen-rich background. EMPs were also seeded with human islets and transplanted into the peritoneal cavity of immune-deficient diabetic mice at 250 islet equivalents (IEQ, 500 IEQ and 1000 IEQ. Escalating islet dose increased rates of normoglycemia (50% of the 500 IEQ group and 75% of the 1000 IEQ group, n = 3 per group. Human c-peptide levels were detected 90 days post-transplantation in a dose-response relationship. Herein, we report reversal of diabetes in mice by intraperitoneal transplantation of human islet seeded on EMPs with a human islet dose as low as 500 IEQ.

  9. Cytoreductive Surgery and Heated Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis Secondary to Mucinous Adenocarcinoma of the Appendix

    Science.gov (United States)

    Sparks, David S.; Morris, Bradley; Xu, Wen; Fulton, Jessica; Atkinson, Victoria; Meade, Brian; Lutton, Nicholas

    2015-01-01

    Cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is a radical but effective treatment option for select peritoneal malignancies. We sought to determine our early experience with this method for peritoneal carcinomatosis secondary to mucinous adenocarcinomas of appendiceal origin. As such, we performed a retrospective clinical study of 30 consecutive patients undergoing CRS with planned HIPEC at the Princess Alexandra Hospital, between June 2009 to December 2012, with mucinous adenocarcinomas of the appendix. CRS was performed in 30 patients, 13 received HIPEC intraoperatively and 17 received early postoperative intra-peritoneal chemotherapy (EPIC) in addition. Mean age was 52.3 years and median hospital stay was 26 days (range 12–190 days). Peritoneal cancer index scores were 0–10 in 6.7% of patients, 11–20 in 20% of patients and >20 in 73.3% of patients. Complete cytoreduction was achieved overall in 21 patients. In total, 106 complications were observed in 28 patients. Ten were grade 3-A, five were grade 3-B and one grade-5 secondary to a fatal PE on day 97. In patients who received HIPEC, there was no difference in disease-free survival (P = 0.098) or overall survival (P = 0.645) between those who received EPIC versus those who did not. This study demonstrates that satisfactory outcomes with regards to morbidity and survival can be achieved with CRS and HIPEC, at a single-centre institution with growing expertise in the technique. Our results are comparable with outcomes previously described in the international literature. PMID:25594636

  10. Laparoscopic Diagnosis and Laparoscopic Hyperthermic Intraoperative Intraperitoneal Chemotherapy for Pseudomyxoma Peritonei Detected by CT Examination

    Directory of Open Access Journals (Sweden)

    Masamitsu Hirano

    2012-01-01

    Full Text Available Background. Patients with early stage of pseudomyxoma peritonei (PMP are sometimes difficult to diagnose the primary sites and intraperitoneal spread of tumor and to perform a cytological study. Methods. Patients without a definitive diagnosis and with unknown extent of peritoneal spread of tumor underwent laparoscopy. Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC was administered as part of the same intervention. The results of treatment were evaluated at the time of second-look laparotomy (SLL as a subsequent intervention. Results. Eleven patients were managed by diagnostic laparoscopy followed by laparoscopic HIPEC (LHIPEC. The operation time of laparoscopic examination and LHIPEC was 177 ± 26 min (range 124–261 min. No intraoperative complication was experienced. The peritoneal carcinomatosis index (PCI score by laparoscopic observation was 16.5 ± 6.4 (range 0–30. One patient with localized pseudomyxoma peritonei (PMP mucocele did not received LHIPEC; the other 10 patients with peritoneal metastases (PM were treated with LHIPEC. After LHIPEC, ascites disappeared in 2 cases and decreased in the amount in the other 8 cases. Nine patients underwent SLL and cytoreductive surgery (CRS combined with HIPEC. The duration between LHIPEC and SLL ranged from 40 to 207 days (97 ± 40 days. The PCI at the SLL ranged from 4 to 27 (12.9 ± 7.1. The PCI at the time of SLL decreased as compared to PCI at the time of diagnostic laparotomy in 7 of 9 patients. Median follow-up period is 22 months (range 7–35. All 11 patients are alive. Conclusion. The early results suggest that laparoscopic diagnosis combined with LHIPEC is useful to determine the surgical treatment plan and reduce the tumor burden before definitive CRS at SLL.

  11. Laparoscopic intraperitoneal mesh fixation with fibrin sealant (Tisseel®) vs. titanium tacks: a randomised controlled experimental study in pigs

    DEFF Research Database (Denmark)

    Eriksen, J.R.; Bech, Jakob Ilsted; Linnemann, D.

    2008-01-01

    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 had...... two pieces of MotifMESH (R) and two pieces of Proceed (R) mesh fixed in the intraperitoneal position by a laparoscopic technique. The two pieces of the same mesh were fixed with fibrin glue (Tisseel) and titanium tacks, respectively. All pigs were euthanised on the 30th postoperative day and the mesh...... feasible in a pig model. There is still no evidence that fibrin-sealing alone is appropriate for intraperitoneal mesh fixation in hernia repair, but the technique might become an alternative or supplement to mechanical mesh fixation. Until then, further experimental research in animal hernia models...

  12. 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

    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...... had two pieces of MotifMESH((R)) and two pieces of Proceed((R)) mesh fixed in the intraperitoneal position by a laparoscopic technique. The two pieces of the same mesh were fixed with fibrin glue (Tisseel) and titanium tacks, respectively. All pigs were euthanised on the 30th postoperative day...... with Tisseel is safe and technically feasible in a pig model. There is still no evidence that fibrin-sealing alone is appropriate for intraperitoneal mesh fixation in hernia repair, but the technique might become an alternative or supplement to mechanical mesh fixation. Until then, further experimental...

  13. EXPERIENCE WITH INTRAPERITONEAL CHEMOTHERAPY USING ASCITIC FLUID AS A SOLVENT OF CHEMICALS IN THE TREATMENT OF OVARIAN CANCER

    Directory of Open Access Journals (Sweden)

    Yu. S. Sidorenko

    2009-01-01

    Full Text Available Thirty two with the ascitic form of Stages IIIC—IV ovarian cancer underwent 1 to 3 courses of intraperitoneal multidrug therapy using a protein ascitic fluid concentrate (PAFC as a solvent of drugs (cisplatin, cyclophosphan, doxorubicin according to the CAP regimen. The induction chemotherapy allowed remission to be achieved in 78.1% of cases (against 40% with standard intraperitoneal therapy, the stan- dard volume of surgical treatment was performed in 28 (87.5% patients (21 (70% receiving the control regime; with the use of PAFC, the size of minimum residual tumour (less than 1 cm was achieved in 81.3% versus 63.3% with standard intraperitoneal chemotherapy. This treatment enables the use large-dose chemotherapy regimens that cause no severe systemic toxic reactions. The method is highly-effective, low-toxic and may be recommended for the treatment of patients with the ascitic form of Stages III—IV ovarian cancer.

  14. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  15. Pharmacokinetics and tissue distribution of intraperitoneal 5-fluorouracil with a novel carrier solution in rats

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Wei; Guo-Xin Li; Xiang-Cheng Huang; Li Zhen; Jiang Yu; Hai-Jun Deng; Shan-Hua Qing; Ce Zhang

    2008-01-01

    AIM: To compare the pharmacokinetics and tissue distribution of 5-fluorouracil administered intraperitoneally with two isotonic carrier solutions: HAES-steri (neotype 6% hydroxyethyl starch), a novel carrier solution with middle molecular weight and physiologic saline (0.9%sodium chloride solution), a traditional carrier solution for intraperitoneal chemotherapy, in rats.METHODS: A total of 60 Sprague Dawley rats were randomized into groups according to the carrier solution administered. Each group was further randomized according to the intraperitoneal dwell period (1, 3, 6, 12,18 and 24 h). At the end of the procedure the rats were killed, the peritoneal fluid was withdrawn completely and quantitated. Drug concentrations in peritoneal fluid, plasma, and tissues were determined by highperformance liquid chromatography.RESULTS: The mean volumes remaining in the peritoneal cavity were significantly higher with HAESsteri than those with physiologic saline at 1, 6, 12, 18,and 24 h (P=0.047, 0.009, 0.005, 0.005 and 0.005respectively, the percentages of remaining peritoneal fluid volume were 89.9 ± 5.6 vs 83.4 ± 4.9, 79.9 ± 2.8 vs 56.2 ± 15.7, 46.8 ± 5.5 vs 24.7± 9.7, 23.0 ± 2.8 0.0 ± 0.0 and 4.2 ± 1.7 vs 0.0 ± 0.0 respectively). Mean concentrations in peritoneal fluid were significantly higher with HAES-steri than those with physiologic saline at 3,12 and 18 h (P = 0.009, 0.009 and 0.005 respectively,the concentrations were 139.2768 ± 28.2317 mg/L vs mg/L, 11.5427 ± 3.0976 mg/L vs 0.0000 ± 0.0000 mg/L and 4.7724 ± 1.0936 mg/L vs 0.0000 ± 0.0000 mg/L respectively). Mean plasma 5-fiuorouracil concentrations in portal vein were significantly higher with HAES-steri at 3, 12, 18 and 24 h (P = 0.009, 0.034, 0.005 and 0.019 respectively, the concentrations were 3.3572 ± 0.8128 mg/L vs 0.8794 ± 0.2394 mg/L, 0.6203 ± 0.9935 mg/L vs 0.0112 ± 0.0250 mg/L, 0.3725 ± 0.3871 mg/L vs 0.0000 ± 0.0000 mg/L, and 0.2469 ± 0.1457 mg/L 0.0000 ± 0.0000 mg

  16. Obese and lean Zucker rats respond similarly to intraperitoneal administration of gastrin-releasing peptides.

    Science.gov (United States)

    Washington, Martha C; Park, Karen H; Sayegh, Ayman I

    2014-08-01

    The Zucker rat is an animal model used to study obesity and the control of food intake by various satiety peptides. The amphibian peptide bombesin (Bn) reduces cumulative food intake similarly in both obese and lean weanling Zucker rats. Here, we hypothesized that intraperitoneal (i.p) administration of gastrin-releasing peptides-10, -27 and -29 (GRP-10, GRP-27, GRP-29), which are the mammalian forms of Bn, would reduce first meal size (MS, 10% sucrose) and prolong the intermeal interval (IMI, time between first and second meals) similarly in obese and lean adult Zucker rats. To test this hypothesis, we administered GRP-10, GRP-27 and GRP-29 (0, 2.1, 4.1 and 10.3 nmol/kg) i.p. to obese and lean male Zucker rats (who were deprived of overnight food but not water) and then measured the first and second MS, IMI and satiety ratio (SR, IMI/MS). We found that in both obese and lean rats, all forms of GRP reduced the first MS, and in lean rats, they also decreased the second MS. Additionally, GRP-10 and GRP-29 prolonged the IMI in both obese and lean rats, but GRP-27 only prolonged it in lean rats. Finally, we found that all forms of GRP increased the SR in both obese and lean rats. In agreement with our hypothesis, we conclude that all forms of GRP reduce food intake in obese and lean adult Zucker rats similar to Bn in weanling rats.

  17. Continuous intraperitoneal carboplatin delivery for the treatment of late-stage ovarian cancer.

    Science.gov (United States)

    Zhidkov, Nickholas; De Souza, Raquel; Ghassemi, Amir H; Allen, Christine; Piquette-Miller, Micheline

    2013-09-01

    The rate of failure of chemotherapy treatment in ovarian cancer remains high, resulting in a low 5-year survival rate of 20-40% in patients that present with advanced-stage disease. Treatment-free periods between cycles of chemotherapy may contribute to accelerated tumor cell proliferation and decreased treatment response. The elimination of treatment-free breaks has been deemed beneficial in the context of cell-cycle-specific agents. The potential benefit of this approach for non-cell-cycle-specific agents has not yet been elucidated. The present study is the first to address this issue by investigating the impact of continuous versus intermittent intraperitoneal administration of carboplatin over a 14 day period to SCID mice bearing SKOV-3 ovarian cancer xenografts. Immunostaining of tumor sections was employed to quantify tumor proliferation, angiogenesis, and apoptosis using Ki-67, CD-31, caspase-3 (CASP3), and terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL). Continuous ip administration of carboplatin resulted in greater tumor growth inhibition than intermittent therapy (p < 0.05). Significantly greater tumor cell apoptosis and less cell proliferation and angiogenesis were measured in tumors of mice treated with continuous carboplatin as compared to both intermittent and control groups. These results indicate that continuous local administration may be a promising approach to improve the effectiveness of platinum-based chemotherapy regimens.

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

    Energy Technology Data Exchange (ETDEWEB)

    Syme, A M [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); Kirkby, C [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); Riauka, T A [Department of Medical Physics, Cross Cancer Institute, University of Alberta, 11560 University Avenue, Edmonton, Alberta, T6G 1Z2 (Canada); Fallone, B G [Department of Physics, University of Alberta, 412 Avadh Bhatia Physics Laboratory, Edmonton, Alberta, T6G 2J1 (Canada); McQuarrie, S A [Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, 3118 Dentistry/Pharmacy Centre, Edmonton, Alberta, T6G 2N8 (Canada)

    2004-05-21

    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.

  19. Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion.

    Science.gov (United States)

    Wang, Xinhe; McGovern, Gillian; Zhang, Yi; Wang, Fei; Zha, Liang; Jeffrey, Martin; Ma, Jiyan

    2015-07-01

    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.

  20. 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.

  1. 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.

  2. Spontaneous Intraperitoneal Rupture of a Hepatic Hydatid Cyst with Subsequent Anaphylaxis: A Case Report

    Directory of Open Access Journals (Sweden)

    Benjamin Tinsley

    2013-01-01

    Full Text Available Hydatid cyst rupture into the abdomen is a serious complication of cystic hydatid disease of the liver (Cystic Echinococcosis with an incidence of up to 16% in some series and can result in anaphylaxis or anaphylactoid reactions in up to 12.5% of cases. At presentation, 36–40% of hydatid cysts have ruptured or become secondarily infected. Rupture can be microscopic or macroscopic and can be fatal without surgery. Hydatid disease of the liver is primarily caused by the tapeworm Echinococcus granulosus and occurs worldwide, with incidence of up to 200 per 100,000 in endemic areas. Our case describes a 24-year-old Bulgarian woman presenting with epigastric pain and evidence of anaphylaxis. Abdominal CT demonstrated a ruptured hydatid cyst in the left lobe of the liver. A partial left lobe hepatectomy, cholecystectomy, and peritoneal washout was performed with good effect. She was treated for anaphylaxis and received antihelminthic treatment with Albendazole and Praziquantel. She made a good recovery following surgery and medical treatment and was well on follow-up. Intraperitoneal rupture with anaphylaxis is a rare occurrence, and there do not seem to be any reported cases from UK centres prior to this.

  3. [Clinical practice guideline on peritoneal carcinomatosis treatment using surgical cytoreduction and hyperthermic intraoperative intraperitoneal chemotherapy].

    Science.gov (United States)

    Kavanagh, Mélanie; Ouellet, Jean-François

    2006-09-01

    In 2005, the Comité de l'évolution des pratiques en oncologie (CEPO) took it upon itself to develop a clinical practice guideline to determine the clinical value of surgical cytoreduction followed by hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) for treating peritoneal carcinomatosis stemming from colorectal cancer, cancers of the appendix and stomach, pseudomyxoma peritonei, and mesothelioma of the peritoneum. A review of the scientific literature was performed using the PubMed search engine. The period covered extended from January 1990 to January 2006, inclusively. The scientific literature search was limited to clinical trials (minimum phase II) and organizations elaborating clinical practice recommendations. Twenty-six studies were identified. Of these, only one was phase III. Although some of these studies have demonstrated a benefit from this treatment in terms of patient survival, HIPEC remains a complex procedure whose optimal use is uncertain. Given the morbidity and mortality associated with this treatment, this procedure requires a high level of expertise. Considering the evidence available, the CEPO recommends: 1) that complete cytoreduction followed by HIPEC be used in a clinical research context only, preferably in the presence of an isolated peritoneal carcinomatosis stemming from colorectal cancer, cancer of the appendix, peritoneal pseudomyxoma, or mesothelioma of the peritoneum; 2) that studies be conducted only in specialized centers with the necessary expertise and technical resources.

  4. Acute toxicity assessment of choline by inhalation, intraperitoneal and oral routes in Balb/c mice.

    Science.gov (United States)

    Mehta, Amit Kumar; Arora, Naveen; Gaur, Shailendra Nath; Singh, Bhanu Pratap

    2009-08-01

    Studies suggest that choline has potential to be used as a dietary supplement and a drug for immune inflammatory diseases like asthma and rhinitis. But there are apprehensions regarding adverse effects of choline when given orally in high doses. To address this knowledge gap, toxicity assessment of choline chloride was carried out by intranasal (i.n.), oral and intraperitoneal (i.p.) routes in Balb/c mice for 28days. Body weight, food and water consumption of mice were recorded daily. Hematology and clinical chemistry were assessed to check hepatocellular functions and morphological alterations of the cells. Splenocyte counts were analysed for evaluating cellular immunity. Liver function test was performed by assaying different enzyme systems in serum such as, urea, blood urea nitrogen (BUN), creatinine, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Body weight, food and water consumption did not differ between mice treated with choline and the saline control group. Hematologic and biochemical variables were not affected with any increase in serum toxicity marker enzymes indicating normal liver functioning. Choline administration did not affect total cholesterol and high density lipoprotein levels as compared to their respective controls. Urea and blood urea nitrogen levels in choline treated mice were not different than controls. Creatinine level was, however, higher than control in i.p. treatment group, but other parameters were normal. In conclusion, the repeated consumption of choline chloride via i.n. and oral or i.p. routes did not cause toxicity in mice in the toxicological endpoints examined.

  5. Intensive Care Unit Admission after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy. Is It Necessary?

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    Horacio N. López-Basave

    2014-01-01

    Full Text Available Introduction. Cytoreductive surgery (CS with hyperthermic intraperitoneal chemotherapy (HIPEC is a new approach for peritoneal carcinomatosis. However, high rates of complications are associated with CS and HIPEC due to treatment complexity; that is why some patients need stabilization and surveillance for complications in the intensive care unit. Objective. This study analyzed that ICU stay is necessary after HIPEC. Methods. 39 patients with peritoneal carcinomatosis were treated according to strict selection criteria with CS and HIPEC, with closed technique, and the chemotherapy administered were cisplatin 25 mg/m2/L and mitomycin C 3.3 mg/m2/L for 90-minutes at 40.5°C. Results. 26 (67% of the 39 patients were transferred to the ICU. Major postoperative complications were seen in 14/26 patients (53%. The mean time on surgical procedures was 7.06 hours (range 5−9 hours. The mean blood loss was 939 ml (range 100–3700 ml. The mean time stay in the ICU was 2.7 days. Conclusion. CS with HIPEC for the treatment of PC results in low mortality and high morbidity. Therefore, ICU stay directly following HIPEC should not be standardized, but should preferably be based on the extent or resections performed and individual patient characteristics and risk factors. Late complications were comparable to those reported after large abdominal surgery without HIPEC.

  6. Intraperitoneal Infection of Wild-Type Mice with Synthetically Generated Mammalian Prion.

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    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.

  7. Effect of an intraperitoneal injection with activated Hymenolepis nana and H. diminuta cysticercoids on homologous challenge.

    Science.gov (United States)

    Gabriele, F; Bortoletti, G; Conchedda, M; Palmas, C

    1995-04-01

    The intraperitoneal injection of excysted-activated cysticercoids of Hymenolepis nana and H. diminuta stimulates a protective immunity in mice and rats against an oral homologous challenge with different levels of effectiveness. The immunizing dose reduced only worm growth in the natural host (i.e. H. nana/mouse and H. diminuta/rat models), while in the unnatural host (i.e. H. diminuta/mouse model) expulsion of the worms from the intestine was accelerated. In mice infected with H. nana the effect appeared about 20 days after injection, but a greater effect was found in both models 40 days later even at low dose (1 cysticercoid). In rats the effect appeared 40 days after injection when a large inoculum (50 or 100 cysticercoids) was used. The induced immunity was slow in developing and only partially effective: this was probably related to host difficulties in processing somatic worm antigens, or to the slow production of metabolites by the worms in the peritoneal cavity.

  8. Sustained, low-dose intraperitoneal cisplatin improves treatment outcome in ovarian cancer mouse models.

    Science.gov (United States)

    Ye, Hongye; Tanenbaum, Laura M; Na, Young Jeong; Mantzavinou, Aikaterini; Fulci, Giulia; del Carmen, Marcela G; Birrer, Michael J; Cima, Michael J

    2015-12-28

    Intraperitoneal (IP) chemotherapy for ovarian cancer treatment prolongs overall survival by 16 months compared to intravenous chemotherapy but is not widely practiced due to catheter-related complications and complexity of administration. An implantable, nonresorbable IP microdevice was used to release chemotherapeutic agent at a constant rate of approximately 1.3 μg/h in vitro and 1.0 μg/h in vivo. Studies conducted in two orthotopic murine models bearing human xenografts (SKOV3 and UCI101) demonstrate that continuous dosing reduces tumor burden to the same extent as weekly IP bolus drug injections. Treatment-induced toxicity was quantified via body weight loss and complete blood count. The microdevice resulted in significantly less toxicity than IP bolus injections, despite administration of higher cumulative doses (total area under the concentration-time curve of 3049 ng day/mL with the microdevice vs. 2118 ng-day/mL with IP bolus injections). This preclinical study supports the concept that reduced toxicity with similar efficacy outcomes can be achieved by continuous dosing in ovarian cancer patients currently treated with IP therapy.

  9. Intraperitoneal injection of microencapsulated Sertoli cells restores muscle morphology and performance in dystrophic mice.

    Science.gov (United States)

    Chiappalupi, Sara; Luca, Giovanni; Mancuso, Francesca; Madaro, Luca; Fallarino, Francesca; Nicoletti, Carmine; Calvitti, Mario; Arato, Iva; Falabella, Giulia; Salvadori, Laura; Di Meo, Antonio; Bufalari, Antonello; Giovagnoli, Stefano; Calafiore, Riccardo; Donato, Rosario; Sorci, Guglielmo

    2016-01-01

    Duchenne muscular dystrophy (DMD) is a genetic disease characterized by progressive muscle degeneration leading to impaired locomotion, respiratory failure and premature death. In DMD patients, inflammatory events secondary to dystrophin mutation play a major role in the progression of the pathology. Sertoli cells (SeC) have been largely used to protect xenogeneic engraftments or induce trophic effects thanks to their ability to secrete trophic, antiinflammatory, and immunomodulatory factors. Here we have purified SeC from specific pathogen-free (SPF)-certified neonatal pigs, and embedded them into clinical grade alginate microcapsules. We show that a single intraperitoneal injection of microencapsulated SPF SeC (SeC-MC) in an experimental model of DMD can rescue muscle morphology and performance in the absence of pharmacologic immunosuppressive treatments. Once i.p. injected, SeC-MC act as a drug delivery system that modulates the inflammatory response in muscle tissue, and upregulates the expression of the dystrophin paralogue, utrophin in muscles through systemic release of heregulin-β1, thus promoting sarcolemma stability. Analyses performed five months after single injection show high biocompatibility and long-term efficacy of SeC-MC. Our results might open new avenues for the treatment of patients with DMD and related diseases.

  10. Carcinogenicity studies on natural and man-made fibres with the intraperitoneal test in rats.

    Science.gov (United States)

    Pott, F; Roller, M; Ziem, U; Reiffer, F J; Bellmann, B; Rosenbruch, M; Huth, F

    1989-01-01

    Female Wistar rats were injected intraperitoneally (i.p.) with a suspension of 11 fibrous and 3 granular dusts. A dose of 0.25 mg actinolite or UICC chrysotile induced tumours of the peritoneum in more than 50% of the animals. Even 0.05 and 0.01 mg proved to be carcinogenic, although no adhesions of the abdominal organs could be observed. The findings are in conflict with the hypothesis that a scar is always the morphological precondition for the development of an asbestos-induced tumour. Actinolite injected i.p. in a solution of polyvinylpyridine-N-oxide gave a lower tumour incidence than when suspended only in saline, possibly due to inactivation of the fibre surface. Persistent glass fibres were less effective than actinolite having a similar fibre size distribution. On the other hand, relatively thick basalt fibres and ceramic fibres gave higher tumour incidences than expected. Wollastonite fibres were not carcinogenic, probably because of their low durability. Large amounts of polyvinylchloride, alpha-ferric oxide hydrate and wood dust also led only to adhesions of the abdominal organs and fibrosis; a definite carcinogenic effect was not detected.

  11. Oxidative stress in blood and testicle of rat following intraperitoneal administration of aluminum and indium.

    Science.gov (United States)

    Maghraoui, S; Clichici, Simona; Ayadi, A; Login, C; Moldovan, R; Daicoviciu, D; Decea, N; Mureşan, A; Tekaya, L

    2014-03-01

    Aluminum (Al) and indium (In) have embryotoxic, neurotoxic and genotoxic effects, oxidative stress being one of the possible mechanisms involved in their cytotoxicity. We have recently demonstrated that indium intraperitoneal (ip) administration induced histological disorganization of testicular tissue. In the present research we aimed at investigating the effect of Al and In ip administration on systemic and testicular oxidative stress status. Studies were performed on Wistar rats ip injected with Al, In or physiological solution for two weeks. Our results showed that In significantly decreased the absolute weight of testicles. Measurements of lactate dehydrogenase (LDH) and paraoxonase (PON) activities showed that In induced a significant augmentation in the first parameter but no changes were observed in the second. Both Al and In caused oxidative stress in testicles by increasing malondialdehyde (MDA) and protein carbonyls (PC) production. Concomitantly, thiol group (-SH) and glutathione (GSH) level were enhanced in the testicles. In the blood, while concentrations of MDA was not changed, those of GSH was significantly decreased in the Al and In groups. Our results indicated that Al and In cause oxidative stress both in blood and testicles but In has cytotoxic effect as well as negative impact on testicle weights. These findings could explain the testicular histological alterations previously described after In ip administration.

  12. Experience after 100 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

    Institute of Scientific and Technical Information of China (English)

    Ingmar K(o)nigsrainer; Derek Zieker; J(o)rg Glatzle; Olivia Lauk; Julia Klimek; Stephan Symons; Bj(o)rn Brücher; Stefan Beckert; Alfred K(o)nigsrainer

    2012-01-01

    AIM:To investigate perioperative patient morbidity/mortality and outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).METHODS:Of 150 patients 100 were treated with cytoreductive surgery and HIPEC and retrospectively analyzed.Clinical and postoperative follow-up data were evaluated.Body mass index (BMI),age and peritoneal carcinomatosis index (PCI) were chosen as selection criteria with regard to tumor-free survival and perioperative morbidity for this multimodal therapy.RESULTS:CRS with HIPEC was successfully performed in 100 out of 150 patients.Fifty patients were excluded because of intraoperative contraindication.Median PCI was 17 (1-39).In 89% a radical resection (CC0/CC1)was achieved.One patient died postoperatively due to multiorgan failure.Neither PCI,age nor BMI was a risk factor for postoperative complications/outcome according to the DINDO classification.In 9% Re-CRS with HIPEC was performed during the follow-up period.CONCLUSION:Patient selection remains the most important issue.Neither PCI,age nor BMI alone should be an exclusion criterion for this multimodal therapy.

  13. Time Savings and Surgery Task Load Reduction in Open Intraperitoneal Onlay Mesh Fixation Procedure

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    Sanjoy Roy

    2015-01-01

    Full Text Available Background. This study assessed the reduction in surgeon stress associated with savings in procedure time for mechanical fixation of an intraperitoneal onlay mesh (IPOM compared to a traditional suture fixation in open ventral hernia repair. Study Design. Nine general surgeons performed 36 open IPOM fixation procedures in porcine model. Each surgeon conducted two mechanical (using ETHICON SECURESTRAPTM Open and two suture fixation procedures. Fixation time was measured using a stopwatch, and related surgeon stress was assessed using the validated SURG-TLX questionnaire. T-tests were used to compare between-group differences, and a two-sided 95% confidence interval for the difference in stress levels was established using nonparametric methodology. Results. The mechanical fixation group demonstrated an 89.1% mean reduction in fixation time, as compared to the suture group (p<0.00001. Surgeon stress scores measured using SURG-TLX were 55.5% lower in the mechanical compared to the suture fixation group (p<0.001. Scores in five of the six sources of stress were significantly lower for mechanical fixation. Conclusions. Mechanical fixation with ETHICON SECURESTRAPTM Open demonstrated a significant reduction in fixation time and surgeon stress, which may translate into improved operating efficiency, improved performance, improved surgeon quality of life, and reduced overall costs of the procedure.

  14. Controlled infection of Poecilia reticulata Peters (guppy) with Tetrahymena by immersion and intraperitoneal injection.

    Science.gov (United States)

    Sharon, G; Pimenta-Leibowitz, M; Vilchis, M C L; Isakov, N; Zilberg, D

    2015-01-01

    Tetrahymena is a protozoan parasite, which infects guppy, Poecilia reticulata Peters, and causes substantial economical losses in commercial farms worldwide. Studies of guppy infected by Tetrahymena require standardized infection protocols. The LD50 for Tetrahymena infection of guppies by intraperitoneal (IP) injection was calibrated, and the level obtained was 946 parasites per fish. Guppy infection with Tetrahymena by immersion, imitating the natural route of infection via the integument, was studied under normal or stress conditions. Exposure to cold and netting (CNI) and to cold only (CI) followed by immersion exposure to 10 000 Tetrahymena per mL resulted in 22.5% and 19.2% mortality, respectively, as compared to 14.2% and 10% in groups that were netted only (NI) or non-stressed (I). Histopathology revealed that immersion infection resulted in a systemic infection. Lysozyme levels, measured 3 weeks after infection, were significantly higher in the CNI group (288 μg per mg protein) compared with CI-, NI- and I-treated groups (94.5, 64 and 62.3 μg mg(-1), respectively). There was no evident parasite immobilization activity in body homogenates, suggesting no development of acquired immunity. Re-infection by IP injection revealed no increase in protection in any of the treatment groups, mortality range of 56.3-75%, higher than in the non-exposed control (40.6% mortality).

  15. Influence of the intraperitoneal administration of antitumor Abarema auriculata extract on mice behavior

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    Daniela F. Gusmão

    2013-12-01

    Full Text Available The organic extract EB689, obtained from the stem of Abarema auriculata (Benth. Barneby & J.W.Grimes, Fabaceae, commonly known as "saboeiro-ferro", was chemically studied, as well as its influence over behavioral effects such as locomotion, emotionality and anxiety, after intra-peritonial administration were assessed. The open-field and elevated-plus maze were used in experiments divided into two stages. The first stage aimed for the identification of the main effects over behavior using a reduced number of animals against half-fold diluted doses of EB689. The same variables were also tested in a second stage of the experiment using the non-lethal intra-peritoneal dose of 4.8 mg/kg in a larger number of animals. It was observed that EB689 clearly decreased locomotion, which was probably caused by internal hemorrhage causing hypovolemic shock. Although it is the first time lupeol and eucryphin are described in A. auriculata, it is still not clear if they are involved in the toxicology of A. auriculata. The undesirable effects of EB689 are better understood, the basis for further pharmacological assays aiming antitumor activity are supported.

  16. 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)

  17. Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats.

    Science.gov (United States)

    Mete, Fatih; Tarhan, Huseyin; Celik, Orcun; Akarken, Ilker; Vural, Kamil; Ekin, Rahmi Gokhan; Aydemir, Isil; Ilbey, Yusuf Ozlem

    2017-01-01

    We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone (O-IP), and torsion/detorsion plus intratesticular ozone (O-IT). The O-IP ozone group received a 4 mg kg-1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system. i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level. e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.

  18. Comparison of intraperitoneal and intratesticular ozone therapy for the treatment of testicular ischemia-reperfusion injury in rats

    Directory of Open Access Journals (Sweden)

    Fatih Mete

    2017-01-01

    Full Text Available We compare the efficacy of intratesticular ozone therapy with intraperitoneal ozone therapy in an experimental rat model. For this purpose, 24 rats were divided into four groups including sham-operated, torsion/detorsion, torsion/detorsion plus intraperitoneal ozone (O-IP, and torsion/detorsion plus intratesticular ozone (O-IT. The O-IP ozone group received a 4 mg kg−1 intraperitoneal injection of ozone, and the O-IT group received the same injection epididymally. At 4 h after detorsion, the rats were sacrificed and orchiectomy materials were assessed histopathologically. Spermatogenesis in the seminiferous tubules and damage to the Sertoli cells were histopathologically evaluated in the testes using the Johnsen scoring system. i-NOS and e-NOS activities in the testis tissue were also evaluated. Torsion-detorsion caused a decreased Johnsen score and increased apoptosis of spermatogonial and Sertoli cells. Ozone injection prevented increases in Johnsen score and i-NOS level. e-NOS level of the O-IP group was significantly lower than that of the O-IP group, and i-NOS level of the O-IT group was significantly lower than that of the O-IP group. Local ozone therapy is more effective than systemic ozone therapy at improving IRI-related testicular torsion. Our study is the first to show that the efficacy of intratesticular implementation of ozone therapy is higher than that of intraperitoneal ozone therapy.

  19. Refractory ascites in systemic lupus erythematosus: further biological support of intraperitoneal steroid treatment as a suitable therapeutical option.

    Science.gov (United States)

    Atisha-Fregoso, Yemil; Hernández-Ramírez, Diego F; Olivares-Martínez, Elizabeth; Núñez-Alvarez, Carlos A; Llorente, Luis; Hernández-Molina, Gabriela

    2017-03-01

    The objective of this report was to evaluate the ascitic fluid of a patient with refractory lupus ascites (proband) at different time points-pre- and post-intraperitoneal treatment with dexamethasone-using a multiparametric approach which included the presence of autoantibodies and pro- and anti-inflammatory cytokines and chemokines, and a proteomic analysis. As controls, we studied two additional patients also with lupus ascites (only at basal evaluation) and two patients with ascites due to alcoholic liver cirrhosis. High levels of anti-dsDNA and anti-nucleosomes autoantibodies were detected in the ascitic fluid of all lupus patients and remained elevated in the proband throughout the follow-up. All lupus patients have detectable ascitic high levels of IL-6, IL-8, IL-10, TNF-α, MCP-1, and IGF-1 which diminished gradually in the proband after intraperitoneal dexamethasone. In the proteomic analysis of the ascitic fluid, a marked increment of apolipoprotein A1 was observed and again, it diminished gradually after intraperitoneal treatment. Our findings further support the use of intraperitoneal steroids as an effective therapeutic option for refractory ascites in systemic lupus erythematosus.

  20. LOW COMPLICATION RATE DURING INTRAPERITONEAL THERAPY THROUGH A TOTALLY IMPLANTED PERITONEAL ACCESS PORT IN PATIENTS WITH OVARIAN-CANCER

    NARCIS (Netherlands)

    NANNINGA, AG; WILLEMSE, PHB; DEVRIES, EGE; Boonstra, J.

    1992-01-01

    Fifty-three patients with histologically proven ovarian cancer were treated with intraperitoneally administered cisplatin or human recombinant interferon-alpha through a totally implanted peritoneal access port. A total of 281 treatment courses were given. No complications related to surgical implan

  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

    2002-01-01

    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 wit

  2. Pharmacokinetic and pharmacodynamic analysis of hyperthermic intraperitoneal oxaliplatin-induced neutropenia in subjects with peritoneal carcinomatosis.

    Science.gov (United States)

    Valenzuela, Belén; Nalda-Molina, Ricardo; Bretcha-Boix, Pere; Escudero-Ortíz, Vanesa; Duart, Maria José; Carbonell, Vicente; Sureda, Manuel; Rebollo, José Pascual; Farré, Josep; Brugarolas, Antonio; Pérez-Ruixo, Juan José

    2011-03-01

    The objective of this study was to characterize the pharmacokinetics and the time course of the neutropenia-induced by hyperthermic intraperitoneal oxaliplatin (HIO) after cytoreductive surgery in cancer patients with peritoneal carcinomatosis. Data from 30 patients who received 360 mg/m(2) of HIO following cytoreductive surgery were used for pharmacokinetic-pharmacodynamic (PK/PD) analysis. The oxaliplatin plasma concentrations were characterized by an open two-compartment pharmacokinetic model after first-order absorption from peritoneum to plasma. An oxaliplatin-sensitive progenitor cell compartment was used to describe the absolute neutrophil counts in blood. The reduction of the proliferation rate of the progenitor cells was modeled by a linear function of the oxaliplatin plasma concentrations. The typical values of oxaliplatin absorption and terminal half-lives were estimated to be 2.2 and 40 h, with moderate interindividual variability. Oxaliplatin reduced the proliferation rate of the progenitor cells by 18.2% per mg/L. No patient's covariates were related to oxaliplatin PK/PD parameters. Bootstrap and visual predictive check evidenced the model was deemed appropriate to describe oxaliplatin pharmacokinetics and the incidence and severity of neutropenia. A peritoneum oxaliplatin exposure of 65 and 120 mg·L/h was associated with a 20% and 33% incidence of neutropenia grade 4. The time course of neutropenia following HIO administration was well described by the semiphysiological PK/PD model. The maximum tolerated peritoneum oxaliplatin exposure is 120 mg L/h and higher exposures should be avoided in future studies. We suggest the prophylactic use of granulocyte colony stimulating factor for patients treated with HIO exposure higher than 65 mg L/h.

  3. Intraperitoneal Bilirubin Administration Decreases Infarct Area in a Rat Coronary Ischemia/Reperfusion Model

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    Ron eBen-Amotz

    2014-02-01

    Full Text Available Bilirubin was previously considered a toxin byproduct of heme catabolism. However, a mounting body of evidence suggests that at physiological doses, bilirubin is a powerful antioxidant and anti-atherosclerotic agent. Recent clinical studies have shown that human beings with genetically-induced hyperbilirubinemia (Gilbert Syndrome are protected against coronary heart disease. The purpose of this study was to investigate whether administration of exogenous bilirubin to normal rats would convey similar protective effects in an experimental model of coronary ischemia. We hypothesized that intraperitoneal bilirubin administration 1 hour before injury would decrease infarct area and preserve left ventricular (LV systolic function when compared to non-treated rats. Coronary ischemia was induced by temporary (30 min ligation of the left anterior descending coronary artery in control or bilirubin treated rats, followed by a 1-hour period of reperfusion. LV function was estimated by measurements of fractional shortening and fractional area shortening using echocardiography. LV function decreased in both experimental groups after ischemia and reperfusion, although in bilirubin-treated rats fractional shortening was less depressed during the period of ischemia (18.8 vs 25.8%, p = 0.034. Infarct size was significantly reduced in the bilirubin treated group compared to the non-treated group (13.34% vs 25.5%, p = 0.0067. Based on the results of this study, bilirubin supplementation appears to provide significant decrease in infarct size although protective effects on LV function were noted only during the period of ischemia. This result also suggests that lipid soluble antioxidant bilirubin prevents the oxidation of cardiolipin and decreases the infarct size in the heart during ischemia.

  4. 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

    2014-03-28

    Cancers originating from the 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 (Lu et al., 2008; Tsai et al., 2007; Tsai et al., 2013). 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% of 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 cancers. 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.

  5. 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.

  6. Glycemic and insulin responses in white sea bream Diplodus sargus, after intraperitoneal administration of glucose.

    Science.gov (United States)

    Enes, P; Peres, H; Pousão-Ferreira, P; Sanchez-Gurmaches, J; Navarro, I; Gutiérrez, J; Oliva-Teles, A

    2012-06-01

    A glucose tolerance test was performed in white sea bream Diplodus sargus, juveniles to evaluate the effect of a glucose load on plasma glucose, insulin, triacylglyceride levels, and on liver glycogen storage in order to study the capability of glucose utilization by this species. After being fasted for 48 h, fish were intraperitoneally injected with either 1 g of glucose per kg body weight or a saline solution. Plasma glucose rose from a basal level of 4 to a peak of 18-19 mmol l(-1), 2-4 h after glucose injection and fish exhibited hyperglycemia for 9 h. An insulin peak (from 0.5 to 0.8 ng ml(-1)) was observed 2-6 h after glucose injection, and basal value was attained within 9 h. Liver glycogen peaked 6-12 h after the glucose load and thereafter decreased to the basal value which was attained 24 h after injection. Plasma triacylglycerides in glucose-injected fish were only significantly higher than the basal value 12 h after injection. Glucose-injected fish generally showed lower plasma triacylglyceride levels than control fish. Our results indicate that under these experimental conditions, glucose acts as an insulin secretagogue in white sea bream juveniles. Moreover, insulin may have contributed to restoring basal plasma glucose levels by enhancing glucose uptake in the liver. Further studies are needed to corroborate the lipolytic action of glucose. Clearance of glucose from the blood stream was fast, comparatively to other species, indicating that white sea bream has a good capability of glucose utilization.

  7. Pharmacokinetics of cefquinome in tilapia (Oreochromis niloticus) after a single intramuscular or intraperitoneal administration.

    Science.gov (United States)

    Shan, Q; Zhu, X; Liu, S; Bai, Y; Ma, L; Yin, Y; Zheng, G

    2015-12-01

    The pharmacokinetics of cefquinome was studied in plasma after a single dose (10 mg/kg) of intramuscular (i.m.) or intraperitoneal (i.p.) administration to tilapia (Oreochromis niloticus) in freshwater at 30 °C. Ten fish per sampling point were examined after treatment. The data were fitted to two-compartment open models following both routes of administration. The estimates of total body clearance (CL/F), volume of distribution (Vd/F), and absorption half-life (T1/2ka ) were 0.049 and 0.037 L/h/kg, 0.41 and 0.33 L/kg, and 0.028 and 0.035 h following i.m. and i.p. administration, respectively. After i.m. injection, the elimination half-life (T1⁄2β ) was calculated to be 5.81 h, the maximum plasma concentration (Cmax ) to be 49.40 μg/mL, the time to peak plasma cefquinome concentration (Tmax ) to be 0.14 h, and the area under the plasma concentration-time curve (AUC) to be 204.6 μg h/mL. Following i.p. administration, the corresponding estimates were 6.05 h, 44.39 μg/mL, 0.17 h and 267.8 μg h/mL. The minimum inhibitory concentrations of cefquinome, determined for 30 strains of Streptococcus agalactiae isolated from diseased tilapia, ranged from 0.015 to 0.12 μg/mL. Results from these studies support that 10 mg cefquinome/kg body weight daily could be expected to control tilapia bacterial pathogens inhibited in vitro by a minimal inhibitory concentration value of ≤2 μg/mL.

  8. Expression of recombinant antibodies.

    Science.gov (United States)

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with "human-like" post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

  9. Therapeutic Recombinant Monoclonal Antibodies

    Science.gov (United States)

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  10. Recombinant renewable polyclonal antibodies.

    Science.gov (United States)

    Ferrara, Fortunato; D'Angelo, Sara; Gaiotto, Tiziano; Naranjo, Leslie; Tian, Hongzhao; Gräslund, Susanne; Dobrovetsky, Elena; Hraber, Peter; Lund-Johansen, Fridtjof; Saragozza, Silvia; Sblattero, Daniele; Kiss, Csaba; Bradbury, Andrew R M

    2015-01-01

    Only a small fraction of the antibodies in a traditional polyclonal antibody mixture recognize the target of interest, frequently resulting in undesirable polyreactivity. Here, we show that high-quality recombinant polyclonals, in which hundreds of different antibodies are all directed toward a target of interest, can be easily generated in vitro by combining phage and yeast display. We show that, unlike traditional polyclonals, which are limited resources, recombinant polyclonal antibodies can be amplified over one hundred million-fold without losing representation or functionality. Our protocol was tested on 9 different targets to demonstrate how the strategy allows the selective amplification of antibodies directed toward desirable target specific epitopes, such as those found in one protein but not a closely related one, and the elimination of antibodies recognizing common epitopes, without significant loss of diversity. These recombinant renewable polyclonal antibodies are usable in different assays, and can be generated in high throughput. This approach could potentially be used to develop highly specific recombinant renewable antibodies against all human gene products.

  11. Pharmacokinetics of {sup 99m} Tc-thalidomide in BALB/c mice: comparison of endovenous and intraperitoneal administration; Farmacocinetica da talidomida marcada com tecnecio-99m em camundongos BALB/C: comparacao entre via endovenosa e intraperitoneal

    Energy Technology Data Exchange (ETDEWEB)

    Moreno, Silvana R.F.; Motta, Ana Paula R.; Cardoso, Rejane C.; Bernardo-Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    1999-11-01

    Thalidomide is a teratogenic agent that is being used in the treatment of lung tuberculosis infection, HIV-1, lupus eritomatosus and host graft disease. This is due to its efficient immunosuppressive action. We have chosen the technetium-99 m, for the labeling of thalidomide for to test the possibility of the thalidomide as a radiopharmaceutical. Furthermore, we are studying the behaviour of this labeled drug through the biodistribution in mice (intraperitoneal and endovenous via). The percentage of radioactivity per gram was determined for each organ. So much the inoculation by intraperitoneal as endovenous via showed that kidney had the largest uptake of {sup 99m} Tc-thalidomide in each period of time tested. In the control animal, free {sup 99m} Tc was found in the stomach. (author) 13 refs., 8 tabs.; e-mail: bernardo at uerj.br

  12. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  13. Monoclonal Antibody Production against Human Spermatozoal Surface Antigens

    Directory of Open Access Journals (Sweden)

    M Jedi-Tehrani

    2005-10-01

    Full Text Available Introduction: As monoclonal antibodies are potential tools for characterization of soluble or cellular surface antigens, use of these proteins has always been considered in infertility and reproduction research. Therefore, in this study, monoclonal antibodies against human sperm surface antigens were produced. Material and Methods: To produce specific clones against human sperm surface antigens, proteins were extracted using solubilization methods. Balb/c mice were immunized intraperitoneally with the proteins using complete Freund’s adjuvant in the first injection and incomplete Adjuvant in the following booster injections. Hybridoma cells producing ASA were cloned by limiting dilution. Results: Five stable ASA producing hybridoma clones were achieved and their antibody isotypes were determined by ELISA. All the isotypes were of IgG class. Their cross reactivity with rat and mice spermatozoa was examined but they did not have any cross reactivity. Conclusion: The produced antibodies can be used in further studies to characterize and evaluate each of the antigens present on human sperm surface and determining their role in fertilization.

  14. 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

  15. Cell envelope components of Yersinia pestis grown in intraperitoneal diffusion chambers

    Directory of Open Access Journals (Sweden)

    Rita C. C. Ferreira

    1998-09-01

    Full Text Available The electrophoretic profiles of penicillin binding proteins (PBPs and outer membrane proteins (OMPs of Yersinia pestis EV 76 were determined following in vivo growth in diffusion chambers implanted in the peritoneal cavity of mice. In contrast to Y. pestis grown under in vitro conditions which activate the low calcium response (LCR regulon there was no significant qualitative or quantitative change of the PBP profile of Y. pestis cells during growth in diffusion chambers for up to 72 h following implantation in mice. Three OMPs, with molecular weight of 100, 60 and 58 kDa, were expressed in Y. pestis cells grown for 24 h, but not at 48 h or at 72 h, in diffusion chambers. These results indicate that growth of Y. pestis in intraperitoneal diffusion chambers activates genes which might be relevant to the growth in the mammal host.Os perfis eletroforéticos de proteínas ligadoras de penicilina (PLPs e proteínas de membrana externa (PMEs de Yersinia pestis EV 76 foram determinados após crescimento in vivo em câmaras de difusão implantadas na cavidade peritoneal de camundongos. Em contraste com o observado em amostras de Y. pestis crescidas in vitro em condições que ativem a resposta ao baixo nível de cálcio (RBC, não houve mudanças qualitativas ou quantitativas no perfil de PLPs de Y. pestis durante o crescimento em câmaras de difusão por até 72 h após a implantação em camundongos. Três PMEs, com peso molecular de 100, 60 e 58 kDa, foram expressas por células de Y. pestis em 24 h, mas não em 48 e 72 h, após a implantação das câmaras de difusão. Estes resultados indicam que o crescimento de células de Y. pestis em câmaras de difusão intraperitoniais podem resultar na ativação de genes relevantes para o crescimento no hospedeiro mamífero.

  16. Protection of carbon monoxide intraperitoneal administration from rat intestine injury induced by lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    LIU Shao-hua; MA Ke; XU Bing; XU Xin-rong

    2010-01-01

    Background Treatment with inhaled carbon monoxide (CO) has been shown to ameliorate intestinal injury in experimental animals induced by lipopolysaccharide (LPS) or ischemia-reperfusion. We hypothesized that CO intraperitoneal administration (i.p.) might provide similar protection to inhaled gas. This study aimed to investigate the effects of continuous 2 L/min of 250 ppm CO i.p. on rat intestine injury induced by LPS and to try to develop a more practical means of delivering the gas.Methods A total of 72 male Sprague-Dawley rats were randomly assigned to 4 groups: control group, CO i.p. group, LPS group and LPS+CO i.p. group. One hour after intravenously received 5 mg/kg LPS, the rats in LPS group and LPS+CO i.p. group were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively, and the rats of control group and CO i.p. group intravenously received an equal volume of 0.9% NaClI and 1 hour later, were exposed to room air and 2 L/min of 250 ppm CO i.p., respectively. One, 3 and 6 hour of each group after treated with room air or CO i.p., the animals (n=6 for each time point) were sacrificed and intestinal tissues were collected for determinating the levels of platelet activator factor (PAF) and intercellular adhesion molecule-1 (ICAM-1) with enzyme-lined immunosorbent assays. The maleic dialdehyde (MDA) content and the myeloperoxidase (MPO) activity were determined with a chemical method. The phosphorylated p38 mitogen activated protein kinase (MAPK) expression was assayed with Western blotting and the cell apoptotic rate with flow cytometery. The arterial oxygenation was measured by blood gas analysis, and the pathology determined by light microscope.Results After treatment with 2 L/min of 250 ppm CO i.p., the increase of PAF, ICAM-1, MDA, MPO, and cell apoptotic rate induced by LPS was markedly reduced (P<0.05 or 0.01), and accompanied by ameliorating intestine injury. Western blotting showed that these effects of CO i.p. were mediated by p38 MAPK

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

    Energy Technology Data Exchange (ETDEWEB)

    Marsteller, Douglas A. [Graduate Program in Molecular and Cellular Pharmacology, SUNY Stony Brook, Stony Brook, NY 11794-8651 (United States) and Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States)]. E-mail: marst@bnl.gov; Barbarich-Marsteller, Nicole C. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Graduate Program in Neuroscience, Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, NY 11794-5230 (United States); Fowler, Joanna S. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Schiffer, Wynne K. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Alexoff, David L. [Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Rubins, Daniel J. [Imaging Department, Merck Research Laboratories, West Point, PA 19486 (United States); Dewey, Stephen L. [Graduate Program in Molecular and Cellular Pharmacology, SUNY Stony Brook, Stony Brook, NY 11794-8651 (United States); Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973-5000 (United States); Graduate Program in Neuroscience, Department of Neurobiology and Behavior, SUNY Stony Brook, Stony Brook, NY 11794-5230 (United States); Psychiatry Department, New York University School of Medicine, New York, NY 10016 (United States)

    2006-01-15

    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-[{sup 18}F]-fluoro-D-glucose ({sup 18}FDG) was used to determine the variability of a 50-min brain {sup 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 {sup 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 {sup 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 {sup 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 {sup 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.

  18. 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 betwee...... in the 'lymph-imbalance' theory of ascites formation, whereas a 'fluid equilibrium' theory seems to be too simple, especially with respect to explain protein sequestration in the peritoneal cavity....

  19. Monoclonal antibody "gold rush".

    Science.gov (United States)

    Maggon, Krishan

    2007-01-01

    The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush.

  20. Induction of lupus-related specific autoantibodies by non-specific inflammation caused by an intraperitoneal injection of n-hexadecane in BALB/c mice.

    Science.gov (United States)

    Kuroda, Yoshiki; Ono, Nobutaka; Akaogi, Jun; Nacionales, Dina C; Yamasaki, Yoshioki; Barker, Tolga T; Reeves, Westley H; Satoh, Minoru

    2006-02-01

    A single intraperitoneal (i.p.) injection of pristane, incomplete Freund's adjuvant (IFA), or the adjuvant oil squalene, but not high molecular weight medicinal mineral oils, induces lupus-related autoantibodies to nRNP/Sm and -Su in non-autoimmune strains of mice. This ability appears to be associated with the low molecular weight and adjuvanticity of hydrocarbon. n-Hexadecane (C(16)H(34)), which is present in petroleum, has adjuvant activity and induces arthritis in rodents like other lupus-inducing oils. In addition to dietary exposure to n-hexadecane in mineral oils, exposure also occurs via inhalation of oil mist, jet fuel, or diesel exhaust or by absorption through the skin. Since n-hexadecane is a low molecular weight adjuvant hydrocarbon oil similar to other lupus-inducing hydrocarbons, the present study examined whether it can also induce lupus-related autoantibodies in mice. Female BALB/cJ mice received a single i.p. injection of 0.5 ml of n-hexadecane, pristane, or saline (control). Pathology and serology (immunoglobulin levels, autoantibodies by immunofluorescence, immunoprecipitation, and ELISA) were examined 3 months later. Unexpectedly, all n-hexadecane-treated mice, but none in the other groups, developed inflammatory ascites within 2.5 months. n-Hexadecane induced hypergammaglobulinemia (IgG1, IgG2a), antinuclear (titer>1:160, 67%) and -cytoplasmic antibodies (58%) and autoantibodies to nRNP/Sm (25%), Su (33%), ssDNA (83%), and chromatin (100%). Therefore, non-specific inflammation caused by n-hexadecane resulted in the production of a limited set of specific autoantibodies. These previously unrecognized immunological effects of n-hexadecane may have implications in monitoring human exposure to hydrocarbons and in the pathogenesis of autoimmune diseases.

  1. Comparison between the Effects of Intraperitoneal Injection of LDL and Intravenous Injection of LDL on Arterial Endothelial Cells Apoptosis

    Institute of Scientific and Technical Information of China (English)

    王丽; 秦瑾; 刘正湘

    2003-01-01

    Summary: To observe the effect of oxidized low density lipoprotein (OxLDL) on arterial endothelialcells apoptosis in vivo, we established a model in which Sprague-Dawley rats were given intraperi-toneal and intravenous injection of unmodified LDL (8 mg/kg every day) via the tail vein. Sevendays after the injection, the aortic endothelial cells specimens were prepared by an en face preparationof rat aorta. The apoptotic cells were identified and counted by in situ nick and labelling (TUNEL)method and light microcopy. The numbers of the apoptotic cells were 12.52±4.71/field in the in-traperitoneal injection control group, 11.41±2.94/field in the intravenous injection control group,22.98±8. 01/field in the intraperitoneal injection LDL group and 103. 8 ± 11.5/field in the intra-venous injection LDL group, respectively. The difference was significant between injection LDLgroup and control (P<0. 01), and the difference was also significant between two LDL injectiongroups (P<0. 01). These findings suggest that injection of LDL can induce apoptosis in arterial en-dothelial cells and the effect is especially significant with intravenous injection LDL. After injection,oxidative modification of LDL may occur in local arteries and causes injury to the endothelial cells.

  2. Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.

    Directory of Open Access Journals (Sweden)

    Morgana T L Castelo-Branco

    Full Text Available BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs and bone marrow-derived mesenchymal stromal cells (BM-MSCs in rats with trinitrobenzene sulfonic acid (TNBS-induced colitis. METHODS: After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. RESULTS: Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1β decreased, while VEGF and TGF-β did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. CONCLUSIONS: Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

  3. Antiphospholipid antibody syndrome.

    Science.gov (United States)

    Kutteh, William H; Hinote, Candace D

    2014-03-01

    Antiphospholipid antibodies (aPLs) are acquired antibodies directed against negatively charged phospholipids. Obstetric antiphospholipid antibody syndrome (APS) is diagnosed in the presence of certain clinical features in conjunction with positive laboratory findings. Obstetric APS is one of the most commonly identified causes of recurrent pregnancy loss. Thus, obstetric APS is distinguished from APS in other organ systems where the most common manifestation is thrombosis. Several pathophysiologic mechanisms of action of aPLs have been described. This article discusses the diagnostic and obstetric challenges of obstetric APS, proposed pathophysiologic mechanisms of APS during pregnancy, and the management of women during and after pregnancy.

  4. Effects of intraperitoneal nitroglycerin on the strength and healing attitude of anastomosis of rat intestines with ischemia-reperfusion injury

    Directory of Open Access Journals (Sweden)

    Ahmet Oktay Cihan

    2011-01-01

    Full Text Available Background: Ischemic conditions in the intestine result in deterioration of anastomosis healing process. In this study, our aim was to evaluate the possible effects of intraperitoneal nitroglycerin on the intestinal anastomosis healing and anastomosis burst pressures in rats with ischemia and reperfusion injury (I/R. Materials and Methods: Fifty four Wistar albino rats were divided into six groups. In the first two groups, the rats underwent I/R. In the Group 1, the rats had normal saline (S and in Group 2, the rats had nitroglycerin (N injection. In the 3 rd and 4 th groups, an intestinal anastomosis was made at the 10 cm proximally to the ileocecal valve. In Group 3, S and in Group 4, N were injected. In Group 5, the rats received I/R, intestinal anastomosis and intraperitoneal S injection. I/R, intestinal anastomosis and intraperitoneal N injection were made in Group 6 rats. All nitroglycerin (50 ΅g/kg injections were made at postoperative days of 0, 1, 2, 3, 4, 5 consecutively. On the sixth day, all rats were killed. In all rats with anastomosis, anastomotic burst pressure (ABP was measured. Histopathological specimens were collected from all rats and evaluated under light microscopy. Results: Serious tissue damage was only detected in the Group 1 histopathologically (8 rats had grade 4 damage. In Group 2, there was a decrease in tissue damage according to histopathologic examination (5 rats had grade 1 damage. The effect onto the healing was similar in S and N groups. Nitroglycerin was noted to have a positive effect on collagen production. Nitroglycerin increased the ABP levels in rats both with and without I/R (the means are 17.93, 21.10, 14.67, and 17.63 in Groups 3, 4, 5, and 6, respectively. Conclusion: I/R may weaken the strength of intestinal anastomosis. Intraperitoneal application of nitroglycerin may prevent the histopathologic changes within a limited degree. Intraperitoneal nitroglycerin has also positive effects on the healing

  5. Inhibition of ascitic ehrlich tumor cell growth by intraperitoneal injection of Pfaffia paniculata (Brazilian ginseng butanolic residue

    Directory of Open Access Journals (Sweden)

    Juliana Vieira

    2010-06-01

    Full Text Available This study aimed to investigate the effects of the administration of butanolic residue (BR of Pfaffia paniculata by intraperitoneal route to Ehrlich ascitis tumor bearing mice. Initially, a toxicity study of P. paniculata BR was performed in which doses of 12.5; 25 and 50mg/Kg were administered by intraperitoneal injection for seven days to Swiss mice. The treatment did not show toxicity. Then, Swiss male mice received, by intraperitoneal injection, once a day, 12.5; 25 or 50mg/Kg of P. paniculata BR for seven days. This protocol started in the same day of tumor inoculation with 5X10(6 cells i.p. The treatment with butanolic residue of P.paniculata i.p caused a significant increase in the ascitic volume; however, a significant decrease in tumor cells number per ml (pNeste estudo, foi avaliado o efeito do tratamento intraperitoneal com Resíduo Butanólico de Pfaffia paniculata, sobre o crescimento do Tumor de Ehrlich, forma ascítica. Foram utilizados dois grupos de 15 camundongos cada, sendo um grupo controle e o outro grupo tratado com RB 50mg/Kg. Todos os animais foram inoculados intraperitonealmente, com 5X10(6 células tumorais O tratamento iniciou-se no mesmo dia da inoculação do tumor. Assim, os animais receberam diariamente, por via intraperitoneal, 0,1 ml de RB na concentrações 50 mg/Kg, ou PBS como controle. Após 7 dias da inoculação do tumor, os animais foram eutanasiados e foi colhido o fluído ascítico total, para a contagem do número de células tumorais presentes neste fluído e estudo da morfologia destas células . Neste experimento observou-se aumento significante da quantidade de fluido ascítico nos animais tratados com RB, e diminuição significativa em relação ao número de células tumorais/ml e células tumorais totais, presentes no fluído ascítico, comparativamente com os animais controle. Estes resultados sugerem efeito inibitório tópico do RB levando à morte as células neoplásicas.

  6. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  7. Antithyroid microsomal antibody

    Science.gov (United States)

    ... to confirm the cause of thyroid problems, including Hashimoto thyroiditis . The test is also used to find ... positive test may be due to: Granulomatous thyroiditis Hashimoto thyroiditis High levels of these antibodies have also ...

  8. Serum herpes simplex antibodies

    Science.gov (United States)

    ... 2. HSV-1 most often causes cold sores (oral herpes). HSV-2 causes genital herpes. How the Test ... whether a person has ever been infected with oral or genital herpes . It looks for antibodies to herpes simplex virus ...

  9. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  10. [New antibodies in cancer treatment].

    Science.gov (United States)

    Pestalozzi, B C; Knuth, A

    2004-09-22

    Since the development of hybridoma technology in 1975 monoclonal antibodies with pre-defined specificity can be produced. Only twenty years later did it become possible to make therapeutic use of monoclonal antibodies in oncology. To this end it was necessary to attach the antigen-binding site of a mouse antibody onto the scaffold of a human antibody molecule. Such chimeric or "humanized" antibodies may be used in passive immunotherapy without eliciting an immune response. Rituximab and trastuzumab are such humanized antibodies. They are used today routinely in the treatment of malignant lymphoma and breast cancer, respectively. These antibodies are usually used in combination with conventional cytostatic anticancer drugs.

  11. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  12. Echinococcus granulosus: the potential use of specific radiolabelled antibodies in diagnosis by immunoscintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Rogan, M.T.; Morris, D.L.; Pritchard, D.I.; Perkins, A.C. (Nottingham Univ. (UK))

    1990-05-01

    Diagnosis of hydatid disease in man is frequently dependent on the imaging of cysts in situ by techniques such as ultrasonography and CAT scans. Such methods are useful but are not specific and can lead to errors in diagnosis. The present work reports preliminary experiments on the development of a specific imaging technique for hydatid cysts using radiolabelled antibodies. A purified preparation of antigen B of hydatid fluid was used to raise polyclonal antisera in rabbits and the resulting affinity-purified IgG labelled with {sup 131}I. Gerbils with an established Echinococcus granulosus infection were injected intraperitoneally with the labelled antibody and imaged 48 h later with a gamma camera. Hydatid cysts could be identified within the peritoneal cavity and post-mortem assessment of activity showed the cysts to contain approximately four times as much activity as the surrounding organs thereby indicating successful targeting of the antibody to the cysts. (author).

  13. Natural and Man-made Antibody Repertories for Antibody Discovery

    Directory of Open Access Journals (Sweden)

    Juan C eAlmagro

    2012-11-01

    Full Text Available Antibodies are the fastest-growing segment of the biologics market. The success of antibody-based drugs resides in their exquisite specificity, high potency, stability, solubility, safety and relatively inexpensive manufacturing process in comparison with other biologics. We outline here the structural studies and fundamental principles that define how antibodies interact with diverse targets. We also describe the antibody repertoires and affinity maturation mechanisms of human, mice and chickens, plus the use of novel single-domain antibodies in camelids and sharks. These species all utilize diverse evolutionary solutions to generate specific and high affinity antibodies and illustrate the plasticity of natural antibody repertoires. In addition, we discuss the multiple variations of man-made antibody repertoires designed and validated in the last two decades, which have served as tools to explore how the size, diversity and composition of a repertoire impact the antibody discovery process.

  14. Clinical Study on Early Post-operational Intraperitoneal Chemotherapy and Salviae in Treating Patients of Gastric Cancer

    Institute of Scientific and Technical Information of China (English)

    于庆生; 王炜; 汪小明; 王汉明; 帅剑峰

    2002-01-01

    Objective: To evaluate the safety, feasibility and short-term efficacy of early post-operational intraperitoneal chemotherapy (EPIC) combined with Salviae miltiorrhizae (SM) in treating patients with gastric cancer. Methods: The 136 patients enrolled were divided into 3 groups: the EPIC group, the EPVC group and the control group. The former two groups were treated with SM plus 5-FU started from the second or third day after operation for 5 continuous days by intraperitoneal infusion or intravenous dripping respectively, and the control group was untreated but conventional chemotherapy was given 3 weeks after surgical operation. Toxic and adverse effects of chemotherapy, post-operational complications, short-term survival rate and intra-abdominal tumor recurrence rate were observed and compared.Results: (1) Toxic adverse effects of chemotherapy that occurred in the EPIC group were less than those in the EPVC group significantly (P<0.05-0.01). (2) Occurrence of serious complications in the EPIC group was not higher than that in the other two groups. (3) The 1- and 2-year survival rate in the EPIC group was higher than those in the other two groups respectively (P<0.01), while the post-operational intra-abdominal recurrence rate in EPIC group was significantly lower than that in the other two groups (P<0.05). Conclusions: Combined therapy of SM and 5-FU in treating patients with gastric cancer by intraperitoneal infusion is not only safe and feasible with mild toxic and side effect, but also produces a more beneficial effects, including less intra-abdominal recurrence and satisfactory short-term survival rate .

  15. Acute intraperitoneal injection of caffeine improves endurance exercise performance in association with increasing brain dopamine release during exercise.

    Science.gov (United States)

    Zheng, Xinyan; Takatsu, Satomi; Wang, Hongli; Hasegawa, Hiroshi

    2014-07-01

    The purpose of this study was to examine changes of thermoregulation, neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH), which is the thermoregulatory center, and endurance exercise performance after the intraperitoneal injection of caffeine in rats. Core body temperature (Tcore), oxygen consumption (VO₂) and tail skin temperature (Ttail) were measured. A microdialysis probe was inserted in the PO/AH, and samples for the measurements of extracellular dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels were collected. During the rest experiment, 1 h after baseline collections in the chamber (23 °C), the rats were intraperitoneally injected with saline, or 3 mg kg(-1) or 10 mg kg(-1) caffeine. The duration of the test was 4 h. During the exercise experiment, baseline collections on the treadmill were obtained for 1 h. One hour before the start of exercise, rats were intraperitoneally injected with either 10 mg kg(-1) caffeine (CAF) or saline (SAL). Animals ran until fatigue at a speed of 18 m min(-1), at a 5% grade, on the treadmill in a normal environment (23 °C). At rest, 3 mg kg(-1) caffeine did not influence Tcore, Ttail, VO₂, extracellular DA, NA and 5-HT. 10 mg kg(-1) caffeine caused significant increases in Tcore, VO₂, Ttail and extracellular DA in the PO/AH. In addition, 10 mg kg(-1) caffeine increased the run time to fatigue (SAL: 104.4 ± 30.9 min, CAF: 134.0 ± 31.1 min, pexercise increased Tcore, VO₂, Ttail and extracellular DA in the PO/AH. NA increased during exercise, while neither caffeine nor exercise changed 5-HT. These results indicate that caffeine has ergogenic and hyperthermic effects, and these effects may be related to changes of DA release in the brain.

  16. Immune reactions and nerve repair in mice with sciatic nerve injury 14 days after intraperitoneal injection of Brazil

    Institute of Scientific and Technical Information of China (English)

    Jian Cao; Zhongping Niu; Yongan Wang; Yiwen Jiang; Haoyu Liu; Binfeng Wang; Weitian Yin; Lisen Li

    2012-01-01

    BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

  17. Gastrostomy Intraperitoneal Bumper Migration in a Three-Year-Old Child: A Rare Complication following Gastrostomy Tube Replacement.

    Science.gov (United States)

    Guanà, Riccardo; Lonati, Luca; Barletti, Claudio; Cisarò, Fabio; Casorzo, Ilaria; Carbonaro, Giulia; Lezo, Antonella; Delmonaco, Angelo Giovanni; Mussa, Alessandro; Capitanio, Martina; Cussa, Davide; Lemini, Riccardo; Schleef, Jürgen

    2014-09-01

    Feeding gastrostomy is used worldwide for adults and children with feeding impairment to obtain long-term enteral nutrition. Percutaneous endoscopic gastrostomy insertion is considered the gold standard, but after the first months requires gastrostomy tube replacement with a low-profile button. The replacement is known as an easy procedure, but several minor and major complications may occur during and after the manoeuvre. We describe intraperitoneal bumper migration in a 3-year-old boy, a rare complication following gastrostomy tube replacement, and we discuss the recent literature regarding similar cases.

  18. Gastrostomy Intraperitoneal Bumper Migration in a Three-Year-Old Child: A Rare Complication following Gastrostomy Tube Replacement

    Directory of Open Access Journals (Sweden)

    Riccardo Guanà

    2014-12-01

    Full Text Available Feeding gastrostomy is used worldwide for adults and children with feeding impairment to obtain long-term enteral nutrition. Percutaneous endoscopic gastrostomy insertion is considered the gold standard, but after the first months requires gastrostomy tube replacement with a low-profile button. The replacement is known as an easy procedure, but several minor and major complications may occur during and after the manoeuvre. We describe intraperitoneal bumper migration in a 3-year-old boy, a rare complication following gastrostomy tube replacement, and we discuss the recent literature regarding similar cases.

  19. Plasma-to-ascitic fluid transport rate of albumin in patients with decompensated cirrhosis. Relation to intraperitoneal albumin

    DEFF Research Database (Denmark)

    Henriksen, J H; Ring-Larsen, Helmer; 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...... (plasma minus ascitic fluid) oncotic pressure (rlin = 0.74, P less than 0.001) but significantly higher than that (P less than 0.005), indicating a 'non-equilibrium' in the splanchnic Starling forces. The results point to a multivariate genesis and perpetuation of cirrhotic ascites as laid down...

  20. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    surface expression of various antibody formats in the generated knockout strain. Functional scFv and scFab fragments were efficiently displayed on yeast whereas impaired chain assembly and heavy chain degradation was observed for display of full-length IgG molecules. To identify the optimal polypeptide...... linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  1. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    to the antibody science in every project in antibody drug discovery. Recent experimental technologies allow for the rapid generation of large-scale data on antibody sequences, affinity, potency, structures, and biological functions; this should accelerate drug discovery research. Therefore, a robust bioinformatic...... infrastructure for these large data sets has become necessary. In this article, we first identify and discuss the typical obstacles faced during the antibody drug discovery process. We then summarize the current status of three sub-fields of antibody informatics as follows: (i) recent progress in technologies...... for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  2. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  3. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    Antibodies recognize their cognate antigens in a precise and effective way. In order to do so, they target regions of the antigenic molecules that have specific features such as large exposed areas, presence of charged or polar atoms, specific secondary structure elements, and lack of similarity...... to self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  4. Compositions, antibodies, asthma diagnosis methods, and methods for preparing antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Jin, Hongjun; Zangar, Richard C.

    2017-01-17

    Methods for preparing an antibody are provided with the method including incorporating 3-bromo-4-hydroxy-benzoic acid into a protein to form an antigen, immunizing a mammalian host with the antigen, and recovering an antibody having an affinity for the antigen from the host. Antibodies having a binding affinity for a monohalotyrosine are provided as well as composition comprising an antibody bound with monohalotyrosine. Compositions comprising a protein having a 3-bromo-4-hydroxy-benzoic acid moiety are also provided. Methods for evaluating the severity of asthma are provide with the methods including analyzing sputum of a patient using an antibody having a binding affinity for monohalotyrosine, and measuring the amount of antibody bound to protein. Methods for determining eosinophil activity in bodily fluid are also provided with the methods including exposing bodily fluid to an antibody having a binding affinity for monohalotyrosine, and measuring the amount of bound antibody to determine the eosinophil activity.

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

    Directory of Open Access Journals (Sweden)

    Sills E Scott

    2002-11-01

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

  6. Rare cause of acute surgical abdomen with free intraperitoneal air: Spontaneous perforated pyometra. A report of 2 cases

    Science.gov (United States)

    Lim, Siew Fung; Lee, Song Liang; Chiow, Adrian Kah Heng; Foo, Chek Siang; Wong, Andrew Siang Yih; Tan, Su-Ming

    2012-01-01

    Summary Background: The acute abdomen accounts for up to 40% of all emergency surgical hospital admissions and a large proportion are secondary to gastrointestinal perforation. Studies have shown the superiority of the abdominal CT over upright chest radiographs in demonstrating free intraperitoneal air. Spontaneous perforated pyometra is a rare cause of the surgical acute abdomen with free intraperitoneal air. Only 38 cases have been reported worldwide. Case Report: We report 2 cases of spontaneously perforated pyometra in our hospital’s general surgery department. Both underwent exploratory laparotomy: one had a total hysterectomy and bilateral salpingo-oophorectomy, while the other had an evacuation of the uterine cavity, primary repair of uterine perforation and a peritoneal washout. A literature search was conducted and all reported cases reviewed in order to describe the clinical presentations and management of the condition. Of the 40 cases to date, including 2 of our cases, the most common presenting symptoms were abdominal pain (97.5%), fever (37.5%) and vomiting (25.0%). The main indication for exploratory laparotomy was pneumoperitoneum (97.5%). Conclusions: Pyometra is an unusual but serious condition in elderly women presenting with an acute abdomen. A high index of suspicion is needed to make the appropriate diagnosis. PMID:23569488

  7. 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.

  8. Assessment of Ovarian Cancer Tumors Treated with Intraperitoneal Cisplatin Therapy by Nanoscopic X-ray Fluorescence Imaging

    Science.gov (United States)

    Laforce, Brecht; Carlier, Charlotte; Vekemans, Bart; Villanova, Julie; Tucoulou, Rémi; Ceelen, Wim; Vincze, Laszlo

    2016-07-01

    Ovarian cancer is amongst the most common types of cancer in women, with a relatively low overall cure rate of approximately 30%. This is therefore an important incentive to urge for further research in order to maximize the chances of survival for these patients. Intraperitoneal chemotherapy with Cisplatin is an effective treatement for ovarian cancer; however, many questions still remain concerning the ideal treatment protocol and tumor resistance towards the drug, which should be resolved for optimal application of this therapy. For the first time in-vivo grown tumors treated with both hyper- and normothermic intraperitoneal chemotherapy have been studied using nano-XRF spectroscopy to examine the platinum (Pt) distribution within the analyzed tissues. These measurements prove Pt resides predominantly outsides the cancer cells in the stroma of the tissue. These findings indicate the resistance mechanism of the cancer cells prevents Cisplatin from diffusing through their cell membranes. This is an important addition to the existing knowledge on the resistance mechanism providing insights which might help to overcome this effect. In our aim to find the optimal treatment protocol, no significant differences were found between the two examined procedures. A more extensive data set will be needed to draw definite conclusions.

  9. 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.

  10. 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.

  11. Human germline antibody gene segments encode polyspecific antibodies.

    Science.gov (United States)

    Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens

    2013-04-01

    Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding.

  12. Prediction of antibody persistency from antibody titres to natalizumab

    DEFF Research Database (Denmark)

    Jensen, Poul Erik H; Koch-Henriksen, Nils; Sellebjerg, Finn Thorup;

    2012-01-01

    In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients.......In a subgroup of patients with multiple sclerosis natalizumab therapy causes generation of anti-natalizumab antibodies that may be transient or persistent. It is recommended to discontinue natalizumab therapy in persistently antibody-positive patients....

  13. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  14. Antibody Blood Tests

    Science.gov (United States)

    ... What do I do if I have a negative blood test (or panel) but I’m still having symptoms? While it is rare, it is possible for patients to have a negative antibody test results and still have celiac disease. ...

  15. RBC Antibody Screen

    Science.gov (United States)

    ... test also may be used to help diagnose autoimmune-related hemolytic anemia in conjunction with a DAT. This condition may be caused when a person produces antibodies against his or her own RBC antigens. This can happen with some autoimmune disorders , such as lupus , with diseases such as ...

  16. What Is Antiphospholipid Antibody Syndrome?

    Science.gov (United States)

    ... page from the NHLBI on Twitter. What Is Antiphospholipid Antibody Syndrome? Antiphospholipid (AN-te-fos-fo-LIP-id) antibody ... weeks or months. This condition is called catastrophic antiphospholipid syndrome (CAPS). People who have APS also are at ...

  17. Red Blood Cell Antibody Identification

    Science.gov (United States)

    ... ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin Test ; RBC ... I should know? How is it used? Red blood cell (RBC) antibody identification is used as a follow- ...

  18. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  19. Anti-smooth muscle antibody

    Science.gov (United States)

    ... gov/ency/article/003531.htm Anti-smooth muscle antibody To use the sharing features on this page, please enable JavaScript. Anti-smooth muscle antibody is a blood test that detects the presence ...

  20. Antibody Engineering and Therapeutics Conference

    OpenAIRE

    Larrick, James W; Parren, Paul WHI; Huston, James S; Plückthun, Andreas; Bradbury, Andrew; Tomlinson, Ian M; Chester, Kerry A.; Burton, Dennis R.; Adams, Gregory P.; Weiner, Louis M.; Scott, Jamie K.; Alfenito, Mark R; Veldman, Trudi; Reichert, Janice M.

    2013-01-01

    The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Bi...

  1. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptides...... can be modified to obtain desired properties or conformation, tagged for purification, isotopically labeled for protein quantitation or conjugated to immunogens for antibody production. The antibodies that bind to these peptides represent an invaluable tool for biological research and discovery...

  2. Synthetic peptides for antibody production

    NARCIS (Netherlands)

    Zegers, N.D.

    1995-01-01

    Synthetic peptides are useful tools for the generation of antibodies. The use of antibodies as specific reagents in inununochemical assays is widely applied. In this chapter, the application of synthetic peptides for the generation of antibodies is described. The different steps that lead to the uni

  3. Protective effects of intraperitoneal vitamin C, aprotinin and melatonin administration on retinal edema during experimental uveitis in the guinea pig.

    Science.gov (United States)

    Kükner, A Sahap; Kükner, Aysel; Naziroğlu, Mustafa; Colakoğlu, Neriman; Celebi, Serdal; Yilmaz, Turgut; Aydemir, Orhan

    2004-01-01

    A considerable amount of clinical and experimental evidence exists suggesting the involvement of reactive oxygen substances (ROS) in the aetiology of uveitis. The activated phagocytic system of polymorphonuclear leucocytes in uveitis is involved in the generation of ROS. In addition to their direct free radical scavenging action, aprotinin, melatonin and vitamin C are known to protect against oedema formation and can preserve plasma membrane fluidity and free radical production. Histological changes in the retina that occur during uveitis are not well explained. The purpose of this study was to determine whether vitamin C, aprotinin and melatonin can protect the retina from damage accompanying experimental uveitis (EU). Thirty adult male guinea pigs were divided into five groups of six animals each. The first group was used as control. The right eyes of groups 2, 3, 4 and 5 received an intravitreal injection of bovine serum albumin for induction of experimental uveitis. At the same time and also on the consecutive third day, groups 3, 4 and 5 received intraperitoneal injections of vitamin C (ascorbic acid, 100 mg kg(-1) body wt), aprotinin (20,000 kIU kg(-1) body wt) and melatonin (10 mg kg(-1) body wt), respectively. The animals were killed on the sixth day. The average thickness of the retina and inner plexiform layer for each eye was measured in sagittal section near the optic nerve and expressed in microns. The thickness of the retina and inner plexiform layer in the control group was significantly (p vitamin C, group EU plus aprotinin, group EU plus melatonin (p vitamin C, group EU plus aprotinin and group EU plus melatonin were significantly (p 0.05). In conclusion, this study demonstrated that oedematous effects of EU on the retina were reduced by the administration of intraperitoneal vitamin C, aprotinin and melatonin, i.e. these antioxidants had significant protective effects on the retina of guinea pigs against oedematous damage in EU. However, the

  4. Successful Intra-peritoneal Antibiotic Therapy for Primary Abdominal Nocardiosis in an Immunocompetent Young Female Masquerading as Carcinoma Ovary

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    Ravi N Patil

    2012-01-01

    Full Text Available Nocardiosis is a common opportunistic infection in the immunocompromised and in patients with chronic debilitating diseases,e.g continuous ambulatory peritoneal dialysis (CAPD patients. Primary abdominal nocardiosis is rare and is indeed a very rare infection in immunocompetent persons. Only two cases have been reported in immunocompetent patients so far and this may be third case to the best of our knowledge and first in India. About 11 cases have been reported in CAPD patients and AIDS patients.We report a case of Nocardiosis in an immunocompetent young female who presented with an abdomino-pelvic mass masquerading as carcinoma ovary.After initial resistance to various antibiotics, she responded to intraperitoneal and oral linezolid and oral ciprofloxacin.

  5. Pattern of distribution of dimethylbenz(a)anthracene in the Amazon molly, Poecilia formosa (Girard), after intraperitoneal injection

    Energy Technology Data Exchange (ETDEWEB)

    Woodhead, A.D.; Bornbusch, A.

    1983-01-01

    The present paper describes the distribution and accumulation labelled dimethylbenz(a)anthracene (DMBA) in the Amazon molly after intraperitoneal injection. The study was made to see whether there was preferential accumulation of the compound in the spleen; the findings showed that this was not the case. Two hours after injection, DMBA was present throughout the body, except in the brain and the ovary. There was enhanced deposition at four sites, in the macrophages of the atrium of the heart and the peritoneum, the liver and the exocrine pancreas. DMBA was taken up by reticuloendothelial macrophages for 78 h after injection, then it was lost. The accumulation and disappearance of radioactive label seen in the liver and pancreatic cells probably represented the pattern of metabolism of the compound. By 400 h after injection there was little DMBA remaining. Label accumulated in the ameloblasts, which secrete the enamel capping of the teeth. 12 references, 3 figures, 1 table.

  6. SPECT/NIRF Dual Modality Imaging for Detection of Intraperitoneal Colon Tumor with an Avidin/Biotin Pretargeting System.

    Science.gov (United States)

    Dong, Chengyan; Yang, Sujuan; Shi, Jiyun; Zhao, Huiyun; Zhong, Lijun; Liu, Zhaofei; Jia, Bing; Wang, Fan

    2016-01-06

    We describe herein dual-modality imaging of intraperitoneal colon tumor using an avidin/biotin pretargeting system. A novel dual-modality probe, (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin, was designed, synthesized and characterized. Single-photon emission computed tomography/ computed tomography (SPECT/CT) imaging and near infrared fluorescence (NIRF) imaging were developed using intraperitoneal LS180 human colon adenocarcinoma xenografts. Following avidin preinjection for 4 hours, (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin could successfully detect colon tumors of different sizes inside the abdominal region using both modalities, and the imaging results showed no differences. Biodistribution studies demonstrated that the tumors had a very high uptake of the probe (99m)Tc-HYNIC-lys(Cy5.5)-PEG4-biotin (12.74 ± 1.89% ID/g at 2 h p.i.), and the clearance from blood and other normal tissues occured very fast. The low tumor uptake in the non-pretargeted mice (1.63 ± 0.50% ID/g at 2 h p.i.) and tumor cell staining results showed excellent tumor binding specificity of the pretargeting system. The ability of the novel probe to show excellent imaging quality with high tumor-to-background contrast, a high degree of binding specificity with tumors and excellent in vivo biodistribution pharmacokinetics should prove that the avidin/biotin based dual-modality pretargeting probe is a promising imaging tool during the entire period of tumor diagnosis and treatment.

  7. In vivo biodistribution and toxicology of functionalized nano-graphene oxide in mice after oral and intraperitoneal administration.

    Science.gov (United States)

    Yang, Kai; Gong, Hua; Shi, Xiaoze; Wan, Jianmei; Zhang, Youjiu; Liu, Zhuang

    2013-04-01

    Graphene oxide (GO) and its functionalized derivatives have attracted great attention in biomedicine in recent years. A number of groups including ours have studied the in vivo behaviors of functionalized nano-graphene after intravenous injection or inhalation, and uncovered the surface coating & size dependent biodistribution and toxicology profiles for this type of nanomaterials. However, the fate of GO derivatives in animals after oral feeding and intraperitoneal (i.p.) injection, which are two other major drug administration routes, remain unclear. Therefore, in this work, we sought to systematically investigate in vivo biodistribution and potential toxicity of as-made GO and a number of polyethylene glycol (PEG) functionalized GO derivatives with different sizes and surface coatings, after oral and intraperitoneal administration at high doses. It is found that (125)I labeled PEGylated GO derivatives show no obvious tissue uptake via oral administration, indicating the rather limited intestinal adsorption of those nanomaterials. In contrast, high accumulation of PEGyalted GO derivatives, but not as-made GO, in the reticuloendothelial (RES) system including liver and spleen is observed after i.p. injection. Further investigations based on histological examination of organ slices and hematological analysis discover that although GO and PEGylated GO derivatives would retain in the mouse body over a long period of time after i.p. injection, their toxicity to the treated animals is insignificant. Our work is an important fundamental study that offers a deeper understanding of in vivo behaviors and toxicology of functionalized nano-graphene in animals, depending on their different administration routes.

  8. 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.

  9. Intraperitoneal Alpha-Lipoic Acid to prevent neural damage after crush injury to the rat sciatic nerve

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    Ozbag Davut

    2009-01-01

    Full Text Available Abstract Objective Crush injury to the sciatic nerve causes oxidative stress. Alfa Lipoic acid (a-LA is a neuroprotective metabolic antioxidant. This study was designed to investigate the antioxidant effects of pretreatment with a-LA on the crush injury of rat sciatic nerve. Methods Forty rats were randomized into four groups. Group I and Group II received saline (2 ml, intraperitoneally and a-LA (100 mg/kg, 2 ml, intraperitoneally in the groups III and IV at the 24 and 1 hour prior to the crush injury. In groups II, III and IV, the left sciatic nerve was exposed and compressed for 60 seconds with a jeweler's forceps. In Group I (n = 10, the sciatic nerve was explored but not crushed. In all groups of rats, superoxide dismutase (SOD and catalase (CAT activities, as well as malondialdehyde (MDA levels were measured in samples of sciatic nerve tissue. Results Compared to Group I, Group II had significantly decreased tissue SOD and CAT activities and elevated MDA levels indicating crush injury (p < 0.05. In the a-LA treatment groups (groups III and IV, tissue CAT and SOD activities were significantly increased and MDA levels significantly decreased at the first hour (p < 0.05 and on the 3rd day (p < 0.05. There was no significant difference between a-LA treatment groups (p > 0.05. Conclusion A-LA administered before crush injury of the sciatic nerve showed significant protective effects against crush injury by decreasing the oxidative stress. A-LA should be considered in the treatment of peripheral nerve injuries, but further studies are needed to explain the mechanism of its neuroprotective effects.

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

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    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

  11. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  12. Engineering antibodies by yeast display.

    Science.gov (United States)

    Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

    2012-10-15

    Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering.

  13. Antibody responses to allergen Lol pIV are suppressed following adoptive transfer of B lymphocytes from the internal image anti-idiotypic antibody-treated mice.

    Science.gov (United States)

    Zhou, E M; Kisil, F T

    1995-10-01

    An internal image anti-idiotypic antibody, designated B1/1, was generated against an idiotope (Id91) of the monoclonal antibody (mAb91) specific for Lol pIV. The administration of B1/1 in PBS, at doses ranging from 100 ng to 100 micrograms/mouse, to syngeneic Balb/c mice resulted in the suppression of the formation of anti-Lol pIV antibodies that possessed the Id91. Spleen cells obtained from the mice 2 weeks after the treatment with B1/1 (25 micrograms/mouse) were adoptively transferred intravenously into the syngeneic recipients which were challenged intraperitoneally with Lol pIV in alum 2 hr after the transfer. The recipients were boosted with Lol pIV 14 days later. It was demonstrated that the transfer of splenic B cells (but not of T cells) from B1/1-treated donors induced a significant suppression of not only the level of IgE and IgG antibodies to Lol pIV, but also the level of antibodies possessing the Id91. Treatment of the B cells with mAb91 plus complement abrogated their ability to transfer the suppression. This study indicates that the treatment with the anti-Id B1/1 generated B cells that were characterized, serologically, as possessing the anti-Id-like antibodies on their surface and were responsible for transferring the suppression of the formation of antibodies to allergen Lol pIV and the expression of Id91.

  14. Efficacy of Antibody to PNAG Against Keratitis Caused by Fungal Pathogens

    Science.gov (United States)

    Zhao, Ge; Zaidi, Tanweer S.; Bozkurt-Guzel, Cagla; Zaidi, Tauqeer H.; Lederer, James A.; Priebe, Gregory P.; Pier, Gerald B.

    2016-01-01

    Purpose Developing immunotherapies for fungal eye infections is a high priority. We analyzed fungal pathogens for expression of the surface polysaccharide, poly-N-acetyl glucosamine (PNAG), and used a mouse model of ocular keratitis caused by Aspergillus flavus, A. fumigatus, or Fusarium solani to determine if PNAG was an immunotherapy target and requirements for ancillary cellular and molecular immune effectors. Methods Enzyme-linked immunosorbent assay (ELISA) or immunofluorescence was used to detect PNAG on fungal cells. Keratitis was induced by scratching corneas of C57BL/6, IL-17R KO, RAG-1 KO, or IL-22 KO mice followed by inoculation with fungal pathogens. Goat antibodies to PNAG, a PNAG-specific human IgG1 monoclonal antibody, or control antibodies were injected either prophylactically plus therapeutically or therapeutically only, and corneal pathology and fungal levels determined in infected eyes at 24 or 48 hours after infection. Results All tested fungal species produced PNAG. Prophylactic or therapeutic treatment by intraperitoneal (IP) injection of antibody to PNAG combined with post-infection topical application of antibody, the latter also used for A. fumigatus, led to reduced fungal levels, corneal pathology, and cytokine expression. Topical administration only of the PNAG monoclonal antibodies (MAb) reduced fungal loads and corneal pathology. There was no antibody protection in IL-17R KO, RAG-1 KO, or IL-22 KO mice. Conclusions Poly-N-acetyl glucosamine is produced by clinically important fungal ocular pathogens. Antibody to PNAG demonstrated protection against Aspergillus and Fusarium keratitis, requiring T cells producing IL-17 and IL-22. These findings indicate the potential to prevent or treat fungal infections by vaccines and immunotherapeutics to PNAG. PMID:28002842

  15. Effects of Monoclonal Antibody Against Porcine 40-kDa Adipocyte-Specific Membrane Protein on Endocrine Secretion in Pigs

    Institute of Scientific and Technical Information of China (English)

    LIU Ling-yun; HU Hong-mei; ZHAO Su-mei; ZHANG Xi; DUAN Gang; GAO Shi-zheng

    2009-01-01

    The present study was to investigate the effect of monocional antibody against porcine 40-kDa adipocyte-specific membrane protein on endocrine secretion in pigs, in order to provide the evidence for application of this antibody to reduce excessive fat deposition in pig production. 40 Landrace × Saba pigs were randomly divided into 8 groups: 2 control groups were given saline with 10 mL, respectively, and the 6 treatment groups were given monoclonal antibody against porcine 40-kDa adipocyte-specific membrane protein with 0.1,0.5, and 1.0 mg kg-1 body weight at 15 or 60 kg body weight,respectively, all treatments were performed by intraperitoneal injection. The results showed that this monoclonal antibody could significantly reduce serum insulin level and increase levels of serum growth hormone (GH), insulin-like growth factor-1 (IGF-1), triiodothyronine (T3), and tetraiodothyronine (T4) either at 15 or 60 kg body weight injection. However,more marked effect was observed at 15 kg body weight treatment. Moreover, the dose-dependent effect of this monoclonal antibody on endocrine secretion was also observed. This result revealed that this monoclonal antibody increased secretion of hormones regulating fat lysis and reduced secretion of hormones regulating fat synthesis, suggests the reduction of porcine excessive fat deposition by this monoclonal antibody was carried out through affecting hormones regulating fat metabolism.

  16. Passive Immunization in JNPL3 Transgenic Mice Using an Array of Phospho-Tau Specific Antibodies.

    Directory of Open Access Journals (Sweden)

    Cristina d'Abramo

    Full Text Available Recent work from our lab and few others have strongly suggested that immunotherapy could be an effective means of preventing the development of tau accumulation in JNPL3 transgenic mice, carrying the human P301L mutation. The aim of this study was to test the efficacy of a variety of specific tau monoclonal antibodies in JNPL3. Starting at 3 months of age, mice were treated for 4 months with weekly intraperitoneal injections of saline or purified tau monoclonal antibodies (10 mg/Kg different in specificity for pathological tau: CP13 (pSer202, RZ3 (pThr231 and PG5 (pSer409. As expected, not all the antibodies tested showed efficacy at preventing the development of tau pathology at the described dose, with some of them even worsening the pathological scenario. Only by targeting the pSer202 epitope with CP13 was a conspicuous reduction of insoluble or soluble tau in cortex and hindbrain obtained. Here we report about the importance of screening in vivo multiple tau antibodies in order to select the antibodies to direct into future clinical studies.

  17. Anti-idiotypic antibodies function as a surrogate surface epitope of Brugia malayi infective larvae.

    Science.gov (United States)

    Carlow, C K; Busto, P; Storey, N; Philipp, M

    1990-07-01

    Anti-idiotypic (AB2) antibodies were generated in rabbits following immunization with a murine IgM monoclonal antibody (AB1) recognizing a surface determinant of Brugia malayi infective stage larvae. AB2 specifically inhibited the binding of AB1 to B. malayi larvae. Furthermore, AB2 had the ability to mimic the original antigen since mice immunized with AB2 possessed serum antibodies (AB3) specific for the B. malayi surface determinant. The presence of anti-surface antibodies (AB3 and AB1) induced either by AB2 immunization or by administration of AB1, did not alter the outcome of an intraperitoneal infection of B. malayi larvae in BABL/c mice when compared to untreated animals. AB3 antibodies like AB1, were IgM, thus indicating an isotype restricted response to the B. malayi epitope. There were no detectable cell mediated responses to the surface determinant in mice immunized with AB2, assessed by lymphocyte blastogenesis or IL3 production in vitro in response to the idiotope as presented by living larvae. The lack of cellular responses and/or the previously demonstrated rapid shedding of the epitope may explain the inability of AB1 or AB2 to protect mice against larval challenge in this study.

  18. Large Scale Generation and Characterization of Anti-Human IgA Monoclonal Antibody in Ascitic Fluid of Balb/c Mice

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    Fatemeh Ezzatifar

    2015-03-01

    Full Text Available Purpose: Monoclonal antibodies are potentially powerful tools used in biomedical research, diagnosis, and treatment of infectious diseases and cancers. The monoclonal antibody against Human IgA can be used as a diagnostic application to detect infectious diseases. The aim of this study was to improve an appropriate protocol for large-scale production of mAbs against IgA. Methods: For large-scale production of the monoclonal antibody, hybridoma cells that produce monoclonal antibodies against Human IgA were injected intraperitoneally into Balb/c mice that were previously primed with 0.5 ml Pristane. After ten days, ascitic fluid was harvested from the peritoneum of each mouse. The ELISA method was carried out for evaluation of the titration of produced mAbs. The ascitic fluid was investigated in terms of class and subclass by a mouse mAb isotyping kit. MAb was purified from the ascitic fluid by ion exchange chromatography. The purity of the monoclonal antibody was confirmed by SDS-PAGE, and the purified monoclonal antibody was conjugated with HRP. Results: Monoclonal antibodies with high specificity and sensitivity against Human IgA were prepared by hybridoma technology. The subclass of antibody was IgG1 and its light chain was the kappa type. Conclusion: This conjugated monoclonal antibody could have applications in designing ELISA kits in order to diagnose different infectious diseases such as toxoplasmosis and H. Pylori.

  19. How antibodies use complement to regulate antibody responses.

    Science.gov (United States)

    Sörman, Anna; Zhang, Lu; Ding, Zhoujie; Heyman, Birgitta

    2014-10-01

    Antibodies, forming immune complexes with their specific antigen, can cause complete suppression or several 100-fold enhancement of the antibody response. Immune complexes containing IgG and IgM may activate complement and in such situations also complement components will be part of the immune complex. Here, we review experimental data on how antibodies via the complement system upregulate specific antibody responses. Current data suggest that murine IgG1, IgG2a, and IgG2b upregulate antibody responses primarily via Fc-receptors and not via complement. In contrast, IgM and IgG3 act via complement and require the presence of complement receptors 1 and 2 (CR1/2) expressed on both B cells and follicular dendritic cells. Complement plays a crucial role for antibody responses not only to antigen complexed to antibodies, but also to antigen administered alone. Lack of C1q, but not of Factor B or MBL, severely impairs antibody responses suggesting involvement of the classical pathway. In spite of this, normal antibody responses are found in mice lacking several activators of the classical pathway (complement activating natural IgM, serum amyloid P component (SAP), specific intracellular adhesion molecule-grabbing non-integrin R1 (SIGN-R1) or C-reactive protein. Possible explanations to these observations will be discussed.

  20. Induction of anti-tumor immunity by trifunctional antibodies in patients with peritoneal carcinomatosis

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    Lindhofer Horst

    2009-02-01

    Full Text Available Abstract Peritoneal carcinomatosis (PC from epithelial tumors is a fatal diagnosis without efficient treatment. Trifunctional antibodies (trAb are novel therapeutic approaches leading to a concerted anti-tumor activity resulting in tumor cell destruction. In addition, preclinical data in mouse tumor models demonstrated the induction of long lasting tumor immunity after treatment with trAb. We describe the induction of anti-tumor specific T-lymphocytes after intraperitoneal administration of trAb in patients with PC. 9 patients with progressive PC from gastric (n = 6 and ovarian cancer (n = 2, and cancer of unknown primary (n = 1 received 3 escalating doses of trAb after surgery and/or ineffective chemotherapy. The trAb EpCAM × CD3 (10, 20, 40 μg or HER2/neu × CD3 (10, 40, 80 μg were applicated by intraperitoneal infusion. Four weeks after the last trAb application, all patients were restimulated by subdermal injection of trAb + autologous PBMC + irradiated autologous tumor cells. Immunological reactivity was tested by analyzing PBMC for specific tumor reactive CD4+/CD8+ T lymphocytes using an IFN-γ secretion assay. In 5 of 9 patients, tumor reactive CD4+/CD8+ T-lymphocytes increased significantly, indicating specific anti-tumor immunity. A clinical response (stable disease, partial regression has been observed in 5 of 9 patients, with a mean time to progression of 3.6 months. Follow-up showed a mean survival of 11.8 months (median 8.0 months after trAb therapy. TrAb are able to induce anti-tumor immunity after intraperitoneal application and restimulation. The induction of long-lasting anti-tumor immunity may provide an additional benefit of the intraperitoneal therapy with trAb and should be further elevated in larger clinical trials.

  1. The antibody Hijikata Tatsumi

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    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  2. Cancer imaging with radiolabeled antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Goldenberg, D.M. (Center for Molecular Medicine and Immunology, Newark, NJ (US))

    1990-01-01

    This book presents a perspective of the use of antibodies to target diagnostic isotopes to tumors. Antibodies with reasonable specificity can be developed against almost any substance. If selective targeting to cancer cells can be achieved, the prospects for a selective therapy are equally intriguing. But the development of cancer detection, or imaging, with radiolabeled antibodies has depended upon advances in a number of different areas, including cancer immunology and immunochemistry for identifying suitable antigen targets and antibodies to these targets, tumor biology for model systems, radiochemistry for he attachment of radionuclides to antibodies, molecular biology for reengineering the antibodies for safer and more effective use in humans, and nuclear medicine for providing the best imaging protocols and instrumentation to detect minute amounts of elevated radioactivity against a background of considerable noise. Accordingly, this book has been organized to address the advances that are being made in many of these areas.

  3. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

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    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  4. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival of gastric cancer with peritoneal carcinomatosis: evidence from an experimental study

    Directory of Open Access Journals (Sweden)

    Yonemura Yutaka

    2011-05-01

    Full Text Available Abstract Background Cytoreductive surgery (CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been considered as a promising treatment modality for gastric cancer with peritoneal carcinomatosis (PC. However, there have also been many debates regarding the efficacy and safety of this new approach. Results from experimental animal model study could help provide reliable information. This study was to investigate the safety and efficacy of CRS + HIPEC to treat gastric cancer with PC in a rabbit model. Methods VX2 tumor cells were injected into the gastric submucosa of 42 male New Zealand rabbits using a laparotomic implantation technique, to construct rabbit model of gastric cancer with PC. The rabbits were randomized into control group (n = 14, CRS alone group (n = 14 and CRS + HIPEC group (n = 14. The control group was observed for natural course of disease progression. Treatments were started on day 9 after tumor cells inoculation, including maximal removal of tumor nodules in CRS alone group, and maximal CRS plus heperthermic intraperitoneal chemoperfusion with docetaxel (10 mg/rabbit and carboplatin (40 mg/rabbit at 42.0 ± 0.5°C for 30 min in CRS + HIPEC group. The primary endpoint was overall survival (OS. The secondary endpoints were body weight, biochemistry, major organ functions and serious adverse events (SAE. Results Rabbit model of gastric cancer with PC was successfully established in all animals. The clinicopathological features of the model were similar to human gastric PC. The median OS was 24.0 d (95% confidence interval 21.8 - 26.2 d in the control group, 25.0 d (95% CI 21.3 - 28.7 d in CRS group, and 40.0 d (95% CI 34.6 - 45.4 d in CRS + HIPEC group (P = 0.00, log rank test. Compared with CRS only or control group, CRS + HIPEC could extend the OS by at least 15 d (60%. At the baseline, on the day of surgery and on day 8 after surgery, the peripheral blood cells counts, liver and kidney functions, and biochemistry

  5. Antibodies against antibodies: immunogenicity of adalimumab as a model

    NARCIS (Netherlands)

    van Schouwenburg, P.A.

    2012-01-01

    Upon repeated adalimumab exposure part of the patients start to produce ADA. The antibody response is polyclonal and consists mainly of antibodies of IgG1 and IgG4 isotype. In the majority of ADA positive patients ADA are already produced within the first 28 weeks of treatment and in part of the pat

  6. 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

    beta on insulin release from the perfused pancreas as shown for isolated islets. To test whether periodical exposure of the endocrine pancreas to circulating IL-1 beta in vivo affects insulin release from the intact perfused pancreas, rats were treated with daily intraperitoneal injections of 4......Previous studies have demonstrated a stimulatory effect of interleukin-1 beta (IL-1 beta) on insulin and glucagon release from the perfused rat pancreas, accompanied by selective lysis of 20% of beta-cells as assessed by electronmicroscopy. However, we have not observed an inhibitory action of IL-1...... micrograms IL-1 beta/kg or saline for 5 days. On day 5 the pancreata were isolated 2 h after the last injection and perfused from 0 to 72 min with 11 mmol/l D-glucose and from 72 to 84 min with 20 mmol/l D-glucose. Saline or IL-1 beta was added from 12 to 72 min. In pancreata from animals pre-treated with IL...

  7. Expression of apoptosis-Related genes bcl-2 and bax in rat brain hippocampus, followed by intraperitoneal injection of nanosilver

    Directory of Open Access Journals (Sweden)

    Maryam Ghoshcian

    2016-05-01

    Full Text Available Background: Silver nanoparticles are small scale substance (<100 nm used in food technology and medical industry. The data suggest that nanosilver may produce neurotoxicity by generating free radical-induced oxidative stress and by altering gene expression producing apoptosis and neurotoxicity. In this study, the apoptotic effects of Nano silver on apoptosis- related genes expression bcl-2 and bax on rat hippocampus, which is involved in memory and learning, was investigated. Materials & Methods: 28 male Wistar rats were divided into four groups of control and three groups of the treatment. The control group received saline and the treatment groups received intraperitoneal injections of silver nanoparticles at doses of 100, 200 and 400ppm. Ten days after the last injection, the hippocampal region was dissected and removed and then the expression of bcl-2 and bax genes was evaluated using semi-qualitative RT-PCR and Densitometry assay. Results: The expression of anti- apoptotic b-cl2 gene was reduced in the treatment groups compared to the control group. In comparison, the expression of pro- apoptotic bax gene was increased in the treatment groups compared to the control group. This apoptotic affects was increased at higher doses. Conclusion: The data suggest that silver nanoparticles may produce apoptosis by altering apoptosis- related genes expression, in rat brain hippocampus cells.

  8. Intraperitoneal delivery of platinum with in-situ crosslinkable hyaluronic acid gel for local therapy of ovarian cancer.

    Science.gov (United States)

    Cho, Eun Jung; Sun, Bo; Doh, Kyung-Oh; Wilson, Erin M; Torregrosa-Allen, Sandra; Elzey, Bennett D; Yeo, Yoon

    2015-01-01

    Intraperitoneal (IP) chemotherapy is a promising post-surgical therapy of solid carcinomas confined within the peritoneal cavity, with potential benefits in locoregional and systemic management of residual tumors. In this study, we intended to increase local retention of platinum in the peritoneal cavity over a prolonged period of time using a nanoparticle form of platinum and an in-situ crosslinkable hyaluronic acid gel. Hyaluronic acid was chosen as a carrier due to the biocompatibility and biodegradability. We confirmed a sustained release of platinum from the nanoparticles (PtNPs) and nanoparticle/gel hybrid (PtNP/gel), receptor-mediated endocytosis of PtNPs, and retention of the gel in the peritoneal cavity over 4 weeks: conditions desirable for a prolonged local delivery of platinum. However, PtNPs and PtNP/gel did not show a greater anti-tumor efficacy than CDDP solution administered at the same dose but rather caused a slight increase in tumor burdens at later time points, which suggests a potential involvement of empty carriers and degradation products in the growth of residual tumors. This study alerts that although several materials considered biocompatible and safe are used as drug carriers, they may have unwanted biological effects on the residual targets once the drug is exhausted; therefore, more attention should be paid to the selection of drug carriers.

  9. Small bowel involvement is a prognostic factor in colorectal carcinomatosis treated with complete cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy

    Directory of Open Access Journals (Sweden)

    Benizri Emmanuel I

    2012-04-01

    Full Text Available Abstract Background Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC is a promising treatment for patients with peritoneal carcinomatosis (PC. Our objective was to identify new prognostic factors in patients with PC from colorectal cancer treated with this procedure. Methods All patients with PC from colorectal cancer treated by HIPEC from January 2000 to December 2007 were prospectively included. The tumor extension was assessed by the Peritoneal Cancer Index (PCI and the residual disease was recorded using the completeness cytoreductive score (CCs. All clinical and treatment data were computed in univariate and multivariable analyses using survival as primary end point. Results We carried out 51 complete procedures in 49 consecutive patients. The mean PCI was 10. The allocation of CCs was: CC-0 = 37, CC-1 = 14. The five-year overall and progression-free survival rate were 40% and 20%, respectively. Several prognostic factors for survival were identified by univariate analysis: PCI P P P = 0.06, area 5 (P = 0.031, area 7 (P = 0.014, area 8 (P = 0.022, area 10 (P P = 0.02. Only the involvement of the distal jejunum (area 10 was significant in the multivariable analysis (P = 0.027. Conclusions We demonstrated that the involvement of area 10 (distal jejunum of the PCI score was an independent factor associated with poor prognosis.

  10. Intraperitoneal Administration of Low Dose Aluminium in The Rat: How Good is It to Produce a Model for Alzheimer Disease.

    Science.gov (United States)

    Ulusoy, H B; Sonmez, M F; Kilic, E; Caliskan, K; Karaca, B; Kara, M; Ercal, O; Gunduz, Y; Karabulut, D; Bitiktas, S; Tan, B; Kavraal, S; İnal, A; Suer, C

    2015-12-01

    Since neurotoxicity of aluminium (Al) resembles the progressive neurodegeneration observed in Alzheimer Disease (AD), Al administration in several ways has been used to produce AD model. Intraperitoneal (ip) low dose (4.2 mg/ kg) Al injection in rats for long periods is the preferred method by some researchers. In this paper, the efficiency of this method for producing an AD model was evaluated. In this study, we looked at the neuropathology of Al and the characteristic lesions of AD by histological and immunohistochemical techniques and determined oxidative stress markers in the brains of Al-treated and control rats. We also made electrophysiological recordings at the hippocampus and evaluated possible behavioural changes by Morris water maze test. However, no pathologic changes occurred in the animals except for an impairment in long-term potentiation (LTP) in the hippocampus (e.g. the LTPs of population spike (PS) amplitude at 15 min post-tetanus were measured as 217±27% in Al-treated rats and as 240±42% in sham-treated rats, of baseline PS amplitude). According to the findings of the present study, low dose of ip Al in rats is not sufficient to produce a good AD model. Higher doses (≥10 mg/kg) should be used.

  11. Comparison of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin or carboplatin for diffuse malignant peritoneal mesothelioma.

    Science.gov (United States)

    Shetty, Shreya J; Bathla, Lokesh; Govindarajan, Venkatesh; Thomas, Peter; Loggie, Brian W

    2014-04-01

    Diffuse malignant peritoneal mesothelioma is a rare, aggressive disease. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have improved outcomes where systemic chemotherapy has not succeeded. In this study, we compare outcomes of patients treated with mitomycin or carboplatin as perfusate. In this retrospective study, 47 procedures (CRS + HIPEC) were conducted on 44 patients between March 2003 and August 2010 with either mitomycin or carboplatin. χ(2) and Student's t test were used for comparison of clinicopathological variables and Kaplan-Meier curves and log rank test were used to compare overall survival. Median survival of the mitomycin group was 18 months with 1- and 5-year survivals of 72.3 and 27.3 per cent, respectively. Median survival of the carboplatin group was not reached and 1- and 5-year survivals were 89.7 and 62.5 per cent, respectively (P = 0.014). Mean hospital and intensive care unit length of stay was 18.9 and 8.7 days in the mitomycin group and 12.5 and 2.3 days in the carboplatin group (P = 0.0069). Mean number of packed red blood cell units transfused was higher in the mitomycin group compared with the carboplatin group (3.54 vs 0.83, P mitomycin.

  12. In vitro assessment ofROS on motility of epididymal sperm of male rat exposed to intraperitoneal administration of nonylphenol

    Institute of Scientific and Technical Information of China (English)

    Ansoumane Kourouma; Duan Peng; Hady Keita; Aidogie Osamuyimen; Qi Suqin; Quan Chao; Yu Tingting; Yang Kedi

    2015-01-01

    Objective:To explore the mechanism by which nonylphenol (NP) interferes with male infertility through evaluation of its effects on epididymal sperm of adult male rats.Methods:Twenty four Sprague-Dawley (SD) rats were used as epididymal sperm donors. Previously rats were administrated with NP (0, 2, 10 and 50 mg/kg) body weight respectively in corn oil every forty-eight hours by intraperitoneal injection for 30 days. Computer assisted sperm analysis (CASA) was used to determine parameters of sperm. The sperm morphology examination was conducted with a high resolution microscope.Results:Results indicated that exposure to NP has no effect on body weight, while testes weights were significantly decreased. Computer assisted sperm analysis (CASA) showed significant decline in the percentage of motile spermatozoa (P<0.001), STR and LIN (P<0.01), significant increase in ALH (P<0.001), while significant decline in BCF (P<0.001) respectively. Plasma LDH was significantly increased while; plasmaγ-GT activity was significantly decreased. H2O2production and malondialdehyde (MDA) were significantly increased. The Plasma CAT, GSH-Px and SOD activities were significantly decreased.Conclusions:This concludes that NP leads oxidative stress in the epididymal sperm of rats. Moreover, NP can disrupt sperm motility and alterations in the sperm morphology.

  13. Tracer kinetics and actions of oral and intraperitoneal 1,25-dihydroxyvitamin D3 administration in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vieth, R.; Kooh, S.W.; Balfe, J.W.; Rawlins, M.; Tinmouth, W.W. (Univ. of Toronto, Ontario (Canada))

    1990-11-01

    Tracer kinetic parameters of ({sup 3}H)-1,25(OH)2D3 were calculated from data obtained following its acute oral (p.o.) or intraperitoneal (i.p.) administration. In normal rats studied after the tracer had distributed into the body, the slope and intercept of the log-serum ({sup 3}H)-1,25(OH)2D3 versus time relationship were not significantly influenced by the route of administration. Pretreatment with 1,25(OH)2D3 (0.2 micrograms/100 g/day) by the same route as the tracer resulted in the following changes: in p.o. rats the serum ({sup 3}H)-1,25(OH)2D3 intercept was much lower but the slope was not changed; in i.p. rats the intercept was not changed but the slope was increased. Both p.o. and i.p. treatment with 1,25(OH)2D3 lowered the weight gain and diet consumption, and increased serum calcium, kidney tissue calcium and urinary excretion of orally administered {sup 45}Ca. All the measures of bioactivity were greater in the i.p. dosed rats than in the p.o. dosed rats. We conclude that the p.o. 1,25(OH)2D3 was less potent because of diminished bioavailability due to self induction of its presystemic metabolism and inactivation.

  14. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis: initial experience in Oaxaca, Mexico.

    Science.gov (United States)

    García-Matus, Rolando; Hernández-Hernández, Carlos Alberto; Leyva-García, Omar; Vásquez-Ciriaco, Sergio; Flores-Ayala, Guillermo; Navarro-Hernández, Quetzalli; Pérez-Bustamante, Gerardo; Valencia-Mijares, Norma Miriam; Esquivel, Jesus

    2012-09-01

    Peritoneal carcinomatosis (PC) has been traditionally considered a terminal disease with median survivals reported in the literature of 6 to 12 months. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are playing an ever increasing role in the treatment of these patients. Excellent results have been achieved in well-selected patients but there is a very steep learning curve when starting a new program. A program for peritoneal surface malignancies in which patients with PC of gastrointestinal or gynecological origin were treated using multimodality therapy with combinations of systemic therapy, cytoreductive surgery (CRS), and HIPEC was initiated in December 2007 at "Hospital Regional de Alta Especialidad de Oaxaca," Mexico. We present the results of our initial experience. From December 2007 to February 2011, 26 patients were treated with CRS and HIPEC. There were 21 female patients. Most common indication (46%) was recurrent ovarian cancer. Mean duration of surgery was 260 minutes. Mean Peritoneal Cancer Index was 9. Twenty-three (88.5%) patients had a complete cytoreduction. Major morbidity and mortality rates were 19.5 and 3.8 per cent, respectively. Mean hospital stay was 8 days. At a mean follow-up of 20 months, median survival has not been reached. Rigorous preoperative workup, strict selection criteria, and mentoring from an experienced cytoreductive surgeon are mandatory and extremely important when starting a center for PC.

  15. In vivo toxicity and biodistribution of intraperitoneal and intravenous poly-L-lysine and poly-L-lysine/poly-L-glutamate in rats.

    Science.gov (United States)

    Isaksson, K; Akerberg, D; Posaric-Bauden, M; Andersson, R; Tingstedt, B

    2014-05-01

    The combination of two differently charged polypeptides, poly-L-lysine (PL) and poly-L-glutamate (PG), has shown excellent postsurgical antiadhesive properties. However, the high molecular, positively charged PL is toxic in high doses, proposed as lysis of red blood cells. This study aims to elucidate the in vivo toxicity and biodistribution of PL and complex bound PLPG comparing intravenous and intraperitoneal administration. Fifty-six Sprague-Dawley rats were used in a model with repeated blood samples within 30 min examining blood gases and blood smears. Similarly, FITC labelled PL were used to track bio distribution and clearance of PL, given as single dose and complex bound to PG after intravenous and intraperitoneal administration. Tissue for histology and immunohistochemistry was collected. Blood gases and blood smears as well as histology points to a toxic effect of high dose PL given intravenously but not after intraperitoneal administration. The toxic effect is exerted through endothelial disruption and subsequent bleeding in the lungs, provoking sanguineous lung edema. FITC-labelled PL experiments reveal a rapid clearance with differences between routes and complex binding. This study advocates a new theory of the toxic effects in vivo of high molecular PL. PLPG complex is safe to use as antiadhesive prevention based on this toxicity study given that PL is always intraperitoneally administered in combination with PG and that the dose is adequate.

  16. 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

  17. Pathogenic role of antiphospholipid antibodies

    NARCIS (Netherlands)

    Salmon, J. E.; de Groot, P. G.

    2008-01-01

    The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that AP

  18. Educational paper: Primary antibody deficiencies

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan); M. van der Burg (Mirjam)

    2011-01-01

    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies and are characterized by a defect in the production of normal amounts of antigen-specific antibodies. PADs represent a heterogeneous spectrum of conditions, ranging from often asymptomatic selective IgA a

  19. Targeting of Antibodies using Aptamers

    OpenAIRE

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  20. New engineered antibodies against prions

    Science.gov (United States)

    Škrlj, Nives; Dolinar, Marko

    2014-01-01

    A number of recently developed and approved therapeutic agents based on highly specific and potent antibodies have shown the potential of antibody therapy. As the next step, antibody-based therapeutics will be bioengineered in a way that they not only bind pathogenic targets but also address other issues, including drug targeting and delivery. For antibodies that are expected to act within brain tissue, like those that are directed against the pathogenic prion protein isoform, one of the major obstacles is the blood-brain barrier which prevents efficient transfer of the antibody, even of the engineered single-chain variants. We recently demonstrated that a specific prion-specific antibody construct which was injected into the murine tail vein can be efficiently transported into brain tissue. The novelty of the work was in that the cell penetrating peptide was used as a linker connecting both specificity-determining domains of the antibody peptide, thus eliminating the need for the standard flexible linker, composed of an arrangement of three consecutive (Gly4Ser) repeats. This paves the road toward improved bioengineered antibody variants that target brain antigens. PMID:23941991

  1. [Effects of Celosia argentea and Cucurbita moschata extracts on anti-DNP IgE antibody production in mice].

    Science.gov (United States)

    Imaoka, K; Ushijima, H; Inouye, S; Takahashi, T; Kojima, Y

    1994-05-01

    We have already reported that the Perilla frutescens extract (PFE) suppressed anti-DNA IgE antibody production in mice. In this study, we prepared extracts of Celosia argentea L. (CAE) and Cucurbita moschata Duch (CME), which are Chinese herbal medicines like Perilla frutescens, and examined the effects on anti-DNP antibody responses in mice. To examine the effects of CAE & CME on primary antibody responses, CAE & CME were intraperitoneally injected the day before primary immunization of DNP-ovalbumin. Anti-DNP antibody production was markedly suppressed. Then, we examined the effects on secondary antibody responses. CEA & CME were injected only the day before secondary immunization. Anti-DNP IgE production was markedly suppressed, but IgG responses were not affected. It was also found that mitogenic activity occurred in CAE & CME dose dependently in vitro. These effects of CAE & CME were superior to that of PFE. These results suggest that CAE & CME may be more useful than PFE for the suppression of IgE antibody in certain allergic disorders.

  2. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  3. Clearance of a monoclonal anti-DNA antibody following administration of DNA in normal and autoimmune mice

    Energy Technology Data Exchange (ETDEWEB)

    Jones, F.S.; Pisetsky, D.S.; Kurlander, R.J.

    1986-04-01

    To study the assembly of DNA-anti-DNA complexes in vivo, we have measured the clearance from blood and organ localization of a murine IgG2a monoclonal anti-DNA antibody, called 6/0, following the infusion of DNA intravenously or intraperitoneally. Intraperitoneal DNA caused a profound acceleration of 6/0 anti-DNA clearance that was dose dependent and demonstrable after the infusion of as little as 1.9 microgram per gram of body weight of single-stranded DNA. The antibody was cleared primarily in the liver without increased deposition in the kidney. Intraperitoneal infusions of DNA also accelerated the clearance of 6/0 in autoimmune MRL-lpr/lpr mice. In contrast, intravenous DNA given in comparable doses caused only a slight increase in 6/0 antibody clearance; this accelerated clearance was seen only at low antigen doses and only during the first 10 min following DNA infusion. Using double-radiolabeling techniques, 6/0 and Cl.18, an IgG2ak myeloma protein without anti-DNA activity, were found to disappear from blood at a comparable rate in both B6D2 mice and MRL-lpr/lpr mice. These results suggest that the DNA-anti-DNA immune complexes can form in vivo but that this process is profoundly affected by the manner in which DNA enters the circulation. In addition, the results suggest that DNA-dependent clearance is not a major pathway for anti-DNA metabolism in normal or at least one strain of autoimmune mice.

  4. Antibodies to Phospholipids and Liposomes: Binding of Antibodies to Cells

    Science.gov (United States)

    1987-01-01

    LIPOSOMES: BINDING OF ANTIBODIES TO CELLS 12. PERSONAL AUTHOR(S) W.E. FOGLER , G. M. SWARTZ, AND C.R. ALVING 13a TYPE OF REPORT 13b. TIME COVERED 14. DATE...Elsevier BBA 73693 Antibodies to phospholipids and liposomes: binding of antibodies to cells William E. Fogler *, Glenn M. Swartz, Jr. and Carl R. Alving...Immunol. 21. Research Associateship from the U.S. National 12863-86812Hall. T. and Esser, K. (1984) 3. Immunol. 132. 2059-2063 Research Council. 13 Fogler

  5. Simultaneous expression of displayed and secreted antibodies for antibody screen.

    Directory of Open Access Journals (Sweden)

    Yuanping Zhou

    Full Text Available The display of full-length antibody on the cell surface was achieved by fusing a transmembrane domain of the platelet-derived growth factor receptor (PDGFR to the C-terminus of the heavy chain constant region. We also incorporated a furin cleavage site between the constant region and PDGFR transmembrane domain to obtain secreted antibodies. As a result, antibodies can be expressed simultaneously on the cell surface in a membrane-anchored version for screening and selecting through fluorescence-activated cell sorting (FACS analysis, as well as in conditioned medium in a secreted version for function analysis.

  6. Estradiol-mediated increases in the anorexia induced by intraperitoneal injection of bacterial lipopolysaccharide in female rats.

    Science.gov (United States)

    Geary, Nori; Asarian, Lori; Sheahan, James; Langhans, Wolfgang

    2004-09-15

    Lipopolysaccharide (LPS) derived from the cell walls of gram-negative bacteria causes a robust acute phase response (APR) that includes fever, anorexia, and many other elements. Because immune system function, including some models of illness anorexia, is sexually differentiated, we investigated the sexual differentiation of the anorexia induced by intraperitoneal LPS injections in rats. Cycling female Long-Evans rats tested either during diestrus or estrus ate less following 6.25 microg/kg LPS than did intact males. Following 12.5 microg/kg LPS, females in estrus ate less than either females during diestrus or males. Similarly, a more pronounced anorexia occurred following 12.5, 25, and 50 microg/kg LPS in ovariectomized females that received cyclic estradiol treatment and were tested on the day modeling estrus than in untreated ovariectomized rats. LPS also increased the length of the rats' ovarian cycles, usually by a day, especially when injected during diestrus. As in male rats, when LPS injections were repeated in the same rats, both estradiol-treated and untreated rats failed to display any significant anorexia. The inhibitory effects of LPS on eating in intact and ovariectomized rats were expressed solely as decreases in spontaneous meal frequency, without significant alteration of spontaneous meal size. These data indicate that anorexia following peripheral LPS administration is sexually differentiated and that estradiol is sufficient to produce this response. The mechanism of the pathophysiological effect of estradiol on meal frequency appears to be different from the physiological effect of estradiol on food intake because the latter is expressed solely as a change in meal size.

  7. Intraperitoneal Injection of Ethanol Results in Drastic Changes in Bone Metabolism Not Observed When Ethanol is Administered by Oral Gavage

    Science.gov (United States)

    Iwaniec, Urszula T.; Turner, Russell T.

    2013-01-01

    Background Chronic alcohol abuse is associated with increased risk for osteoporosis while light to moderate alcohol intake correlates with reduced osteoporosis risk. Addition of alcohol to a liquid diet is often used to model chronic alcohol abuse. Methods to model intermittent drinking (including bindge drinking and light to moderate consumption) include 1) intragastric administration of alcohol by oral gavage or 2) intraperitoneal (ip) administration of alcohol by injection. However, it is unclear whether the latter two methods produce comparable results. The purpose of this investigation was to determine the skeletal response to alcohol delivered daily by oral gavage or ip injection. Materials and Methods Ethanol or vehicle was administered to 4-month-old female Sprague Dawley rats once daily at 1.2 g/kg body weight for 7 days. Following necropsy, bone formation and bone architecture were evaluated in tibial diaphysis (cortical bone) and proximal tibial metaphysis (cancellous bone) by histomorphometry. mRNA was measured for bone matrix proteins in distal femur metaphysis. Results Administration of alcohol by gavage had no significant effect on body weight gain or bone measurements. In contrast, administration of the same dose of alcohol by ip injection resulted in reduced body weight, total suppression of periosteal bone formation in tibial diaphysis, decreased cancellous bone formation in proximal tibial metaphysis, and decreased mRNA levels for bone matrix proteins in distal femur. Conclusions Our findings raise concerns regarding the use of ip injection of ethanol in rodents as a method for modeling the skeletal effects of intermittent exposure to alcohol in humans. This concern is based on a failure of the ip route to replicate the oral route of alcohol administration. PMID:23550821

  8. Tabhu: tools for antibody humanization

    DEFF Research Database (Denmark)

    Olimpieri, Pier Paolo; Marcatili, Paolo; Tramontano, Anna

    2015-01-01

    Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can...... elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity...

  9. A comparison of the results from intra-pleural and intra-peritoneal studies with those from inhalation and intratracheal tests for the assessment of pulmonary responses to inhalable dusts and fibres.

    Science.gov (United States)

    Drummond, Gail; Bevan, Ruth; Harrison, Paul

    2016-11-01

    The aim of this paper is to compare results from inhalation studies with those from intraperitoneal and intrapleural tests, where available, for a number of fibrous and particulate test materials. The objective is to determine how well intraperitoneal/intrapleural studies predict the pathological responses observed in more standard in vivo studies of pulmonary toxicity, with a particular focus on carcinogenicity. Published toxicity data was obtained for a number of materials including asbestos, wollastonite, MMVFs (including glass fibres, stone wools and RCF), silicon carbide whiskers, potassium octatitanate, quartz, kevlar, polypropylene and titanium dioxide. For some of the fibrous material reviewed, there is conformity between the results of intraperitoneal and inhalation tests such that they are either consistently positive or consistently negative. For the remaining fibrous materials reviewed, intraperitoneal and inhalation tests give different results, with positive results in the intraperitoneal test not being reflected by positive inhalation results. It is suggested that the intraperitoneal test can be used to exonerate a dust or fibre (because if negative in the intraperitoneal test it is extremely unlikely to be positive in either inhalation or intratracheal tests) but should not be used to positively determine that a dust or fibre is carcinogenic by inhalation. We would argue against the use of intraperitoneal tests for human health risk assessment except perhaps for the purpose of exoneration of a material from classification as a carcinogen.

  10. DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody

    Science.gov (United States)

    2016-03-01

    ECBC-TR-1356 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR ANTIBODY CHARACTERIZATION...From - To) Oct 2010 – Sep 2012 4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization...Arlington, VA 22203-2114 10. SPONSOR/MONITOR’S ACRONYM(S) DARPA 11. SPONSOR/MONITOR’S REPORT NUMBER(S) 12. DISTRIBUTION / AVAILABILITY STATEMENT

  11. Patient with perforation caused by emphysematous cholecystitis who showed flare on the skin of the right dorsal lumbar region and intraperitoneal free gas.

    Science.gov (United States)

    Kanehiro, Tetsuya; Tsumura, Hiroaki; Ichikawa, Toru; Hino, Yuji; Murakami, Yoshiaki; Sueda, Taijiro

    2008-01-01

    We report an 84-year-old man with perforation caused by emphysematous cholecystitis who showed flare on the skin of the right dorsal lumbar region and intraperitoneal free gas. The patient was admitted for abdominal pain, abdominal swelling, and consciousness disorder 18 days after the onset. Abdominal computed tomography (CT) revealed emphysema in the gallbladder and a small amount of intraperitoneal free gas. Intraoperative findings suggested gangrenous cholecystitis. The gallbladder wall was perforated, and an abscess involving the right subphrenic region, the periphery of the liver and gallbladder, and the right paracolonic groove, was detected. The flare on the body surface may have reflected abscess formation in the right abdominal cavity. Emphysematous cholecystitis induces necrosis and perforation in many patients, and immediate strategies such as emergency surgery are important.

  12. Addition of rapamycin to anti-CD3 antibody improves long-term glycaemia control in diabetic NOD mice.

    Directory of Open Access Journals (Sweden)

    Shira Perl

    Full Text Available AIMS/HYPOTHESIS: Non-Fc-binding Anti CD3 antibody has proven successful in reverting diabetes in the non-obese diabetes mouse model of type 1 diabetes and limited efficacy has been observed in human clinical trials. We hypothesized that addition of rapamycin, an mTOR inhibitor capable of inducing operational tolerance in allogeneic bone marrow transplantation, would result in improved diabetes reversal rates and overall glycemia. METHODS: Seventy hyperglycemic non-obese diabetic mice were randomized to either a single injection of anti CD3 alone or a single injection of anti CD3 followed by 14 days of intra-peritoneal rapamycin. Mice were monitored for hyperglycemia and metabolic control. RESULTS: Mice treated with the combination of anti CD3 and rapamycin had similar rates of diabetes reversal compared to anti CD3 alone (25/35 vs. 22/35. Mice treated with anti CD3 plus rapamycin had a significant improvement in glycemia control as exhibited by lower blood glucose levels in response to an intra-peritoneal glucose challenge; average peak blood glucose levels 30 min post intra-peritoneal injection of 2 gr/kg glucose were 6.9 mmol/L in the anti CD3 plus rapamycin group vs. 10 mmo/L in the anti CD3 alone (P<0.05. CONCLUSIONS/INTERPRETATION: The addition of rapamycin to anti CD3 results in significant improvement in glycaemia control in diabetic NOD mice.

  13. Evolution of antiphospholipid antibody syndrome.

    Science.gov (United States)

    Baviskar, Rutuja R; Amonkar, Gayathri P; Chaudhary, Vinod A; Balasubramanian, Meenakshi; Mohite, Shailesh C; Puranik, Gururaj V

    2012-12-01

    Antiphospholipid antibody syndrome is a very important cause of cerebral infarction, myocardial infarction, and repeated pregnancy losses in women. We present an extremely rare case of a 44-year-old man with antiphospholipid syndrome who collapsed and died suddenly. At autopsy, he was found to have both cerebral and myocardial infarction. In all young patients with cerebral infarction, myocardial infarction, pulmonary embolism, recurrent miscarriages, and unexplained low platelet count, one must consider the strong possibility of antiphospholipid antibody syndrome.

  14. Antibodies to watch in 2016

    OpenAIRE

    Reichert, Janice M

    2015-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, ar...

  15. Evaluation of the Lethal Potency of Scorpion and Snake Venoms and Comparison between Intraperitoneal and Intravenous Injection Routes

    Directory of Open Access Journals (Sweden)

    Naoual Oukkache

    2014-06-01

    Full Text Available Scorpion stings and snake bites are major health hazards that lead to suffering of victims and high mortality. Thousands of injuries associated with such stings and bites of venomous animals occur every year worldwide. In North Africa, more than 100,000 scorpion stings and snake bites are reported annually. An appropriate determination of the 50% lethal doses (LD50 of scorpion and snake venoms appears to be an important step to assess (and compare venom toxic activity. Such LD50 values are also commonly used to evaluate the neutralizing capacity of specific anti-venom batches. In the present work, we determined experimentally the LD50 values of reference scorpion and snake venoms in Swiss mice, and evaluated the influence of two main venom injection routes (i.e., intraperitoneal (IP versus intravenous (IV. The analysis of experimental LD50 values obtained with three collected scorpion venoms indicates that Androctonus mauretanicus (Am is intrinsically more toxic than Androctonus australis hector (Aah species, whereas the latter is more toxic than Buthus occitanus (Bo. Similar analysis of three representative snake venoms of the Viperidae family shows that Cerastes cerastes (Cc is more toxic than either Bitis arietans (Ba or Macrovipera lebetina (Ml species. Interestingly, the venom of Elapidae cobra snake Naja haje (Nh is far more toxic than viper venoms Cc, Ml and Ba, in agreement with the known severity of cobra-related envenomation. Also, our data showed that viper venoms are about three-times less toxic when injected IP as compared to IV, distinct from cobra venom Nh which exhibited a similar toxicity when injected IP or IV. Overall, this study clearly highlights the usefulness of procedure standardization, especially regarding the administration route, for evaluating the relative toxicity of individual animal venoms. It also evidenced a marked difference in lethal activity between venoms of cobra and vipers, which, apart from the nature of

  16. A moderate increase in ambient temperature modulates the Atlantic cod (Gadus morhua spleen transcriptome response to intraperitoneal viral mimic injection

    Directory of Open Access Journals (Sweden)

    Hori Tiago S

    2012-08-01

    Full Text Available Abstract Background Atlantic cod (Gadus morhua reared in sea-cages can experience large variations in temperature, and these have been shown to affect their immune function. We used the new 20K Atlantic cod microarray to investigate how a water temperature change which, simulates that seen in Newfoundland during the spring-summer (i.e. from 10°C to 16°C, 1°C increase every 5 days impacted the cod spleen transcriptome response to the intraperitoneal injection of a viral mimic (polyriboinosinic polyribocytidylic acid, pIC. Results The temperature regime alone did not cause any significant increases in plasma cortisol levels and only minor changes in spleen gene transcription. However, it had a considerable impact on the fish spleen transcriptome response to pIC [290 and 339 significantly differentially expressed genes between 16°C and 10°C at 6 and 24 hours post-injection (HPI, respectively]. Seventeen microarray-identified transcripts were selected for QPCR validation based on immune-relevant functional annotations. Fifteen of these transcripts (i.e. 88%, including DHX58, STAT1, IRF7, ISG15, RSAD2 and IκBα, were shown by QPCR to be significantly induced by pIC. Conclusions The temperature increase appeared to accelerate the spleen immune transcriptome response to pIC. We found 41 and 999 genes differentially expressed between fish injected with PBS vs. pIC at 10°C and sampled at 6HPI and 24HPI, respectively. In contrast, there were 656 and 246 genes differentially expressed between fish injected with PBS vs. pIC at 16°C and sampled at 6HPI and 24HPI, respectively. Our results indicate that the modulation of mRNA expression of genes belonging to the NF-κB and type I interferon signal transduction pathways may play a role in controlling temperature-induced changes in the spleen’s transcript expression response to pIC. Moreover, interferon effector genes such as ISG15 and RSAD2 were differentially expressed between fish injected with

  17. Preventing prolonged post-operative ileus in gastric cancer patients undergoing gastrectomy and intra-peritoneal chemotherapy

    Institute of Scientific and Technical Information of China (English)

    De-Chuan Chan; Kuo-Liang Shen; Yao-Chi Liu; Cheng-Jueng Chen; Jyh-Cherng Yu; Heng-Cheng Chu; Fa-Chang Chen; Teng-Wei Chen; Huan-Fa Hsieh; Tzu-Ming Chang

    2005-01-01

    AIM: To assess the efficacy of metoclopramide (Met) for prevention of prolonged post-operative ileus in advanced gastric cancer patients undergoing D2 gastrectomy and intra-peritoneal chemotherapy (IPC).METHODS: Thirty-two advanced gastric cancer patients undergoing D2 gastrectomy and IPC were allocated to two groups. Sixteen patients received Met immediately after operation (group A), and 16 did not (group B). Another 16 patients who underwent D2 gastrectomy without IPC were enrolled as the control group (group C). All patients had received epidural pain control. The primary endpoints were time to first post-operative flatus and time until oral feeding with a soft diet without discomfort. Secondary endpoints were early complications during hospitalization.RESULTS: Gender, the type of resection, operating time,blood loss, tumor status and amount of narcotics were connparable in the three groups. However, the group C patients were older than those in groups A and B (67.5±17.7 vs 56.8±13.2, 57.5±11.7 years, P= 0.048). First bowel flatus occurred after 4.35±0.93 d in group A, 4.94±1.37 d in group B, and 4.71±1.22 d in group C (P>0.05). Oral feeding of a soft diet was tolerated 7.21±1.92 d after operation in group A, 10.15±2.17 d in group B, and 7.53±1.35 d in group C(groups A and C vsgroup B, P<0.05). There was no significant difference in respect to the first flatus among the three groups. However, the time of tolerating oral intake with soft food in groups A and C patients was significantly shorter than that in group B patients. Levels of C-reactive protein (CRP) were significantly lower in group C and there was a more prominent and prolonged response in CRP level in patients undergoing IPC. The incidence of post-operative complications was similar in the three groups except for prolonged post-operative ileus. There was no increased risk of anastomotic leakage in patients receiving Met.CONCLUSION: The results suggest that a combination of intravenous

  18. Early results on the use of biomaterials as adjuvant to abdominal wall closure following cytoreduction and hyperthermic intraperitoneal chemotherapy

    Directory of Open Access Journals (Sweden)

    Boutros Cherif

    2010-08-01

    Full Text Available Abstract Background Hyperthermic chemotherapy applies thermal energy to both abdominal wall as well as the intra-abdominal viscera. The combination of the hyperthemia, chemotherapy and cytoreductive surgery (CRS is associated with a defined risk of abdominal wall and intestinal morbidity reported to be as high as 15%, respectively to date, no studies have evaluated the use of biomaterial mesh as adjuvant to abdominal wall closure in this group of patients. In the present report, we hypothesized that post HIPEC closure with a biomaterial can reduce abdominal wall morbidity after CRS and hyperthermic intraperitoneal chemotherapy. Materials and methods All patients treated with HIPEC in a tertiary care center over 12 months (2008-2009 period were included. Eight patients received cytoreductive surgery followed by HIPEC for 90 minutes using Mitomycin C (15 mg q 45 minutes × 2. Abdominal wall closure was performed using Surgisis (Cook Biotech. mesh in an underlay position with 3 cm fascial overlap-closure. Operative time, hospital length of stay (LOS as well as postoperative outcome with special attention to abdominal wall and bowel morbidity were assessed. Results Eight patients, mean age 59.7 ys (36-80 were treated according to the above protocol. The primary pathology was appendiceal mucinous adenocarcinoma (n = 3 colorectal cancer (n = 3, and ovarian cancer (n = 2. Four patients (50% presented initially with abdominal wall morbidity including incisional ventral hernia (n = 3 and excessive abdominal wall metastatic implants (n = 1. The mean peritoneal cancer index (PCI was 8.75. Twenty eight CRS were performed (3.5 CRS/patient. The mean operating time was 6 hours. Seven patients had no abdominal wall or bowel morbidity, the mean LOS for these patients was 8 days. During the follow up period (mean 6.3 months, one patient required exploratory laparotomy 2 weeks after surgery and subsequently developed an incisional hernia and enterocutaneous

  19. Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats

    Directory of Open Access Journals (Sweden)

    Costa E.L.

    2005-01-01

    Full Text Available The present study evaluated the acute effect of the intraperitoneal (ip administration of a whey protein hydrolysate (WPH on systolic arterial blood pressure (SBP and renal sodium handling by conscious spontaneously hypertensive rats (SHR. The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 176.6 ± 4.9 mmHg, N = 8, P = 0.001 and 1.0 g/kg (0.15 M NaCl: 188.5 ± 9.3 mmHg vs WPH: 163.8 ± 5.9 mmHg, N = 8, P = 0.0018. Creatinine clearance decreased significantly (P = 0.0084 in the WPH-treated group (326 ± 67 µL min-1 100 g body weight-1 compared to 0.15 M NaCl-treated (890 ± 26 µL min-1 100 g body weight-1 and captopril-treated (903 ± 72 µL min-1 100 g body weight-1 rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 ± 0.019% compared to 0.126 ± 0.041 and 0.66 ± 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033. Similarly, the fractional potassium excretion in WPH-treated rats (0.25 ± 0.05% was significantly lower (P = 0.0063 than in control (0.91 ± 0.15% and captopril-treated rats (1.24 ± 0.30%, respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE-inhibiting in vitro activity (IC50 = 0.68 mg/mL. The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

  20. Effect of intraperitoneally administered hydrolyzed whey protein on blood pressure and renal sodium handling in awake spontaneously hypertensive rats.

    Science.gov (United States)

    Costa, E L; Almeida, A R; Netto, F M; Gontijo, J A R

    2005-12-01

    The present study evaluated the acute effect of the intraperitoneal (ip) administration of a whey protein hydrolysate (WPH) on systolic arterial blood pressure (SBP) and renal sodium handling by conscious spontaneously hypertensive rats (SHR). The ip administration of WPH in a volume of 1 ml dose-dependently lowered the SBP in SHR 2 h after administration at doses of 0.5 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 176.6 +/- 4.9 mmHg, N = 8, P = 0.001) and 1.0 g/kg (0.15 M NaCl: 188.5 +/- 9.3 mmHg vs WPH: 163.8 +/- 5.9 mmHg, N = 8, P = 0.0018). Creatinine clearance decreased significantly (P = 0.0084) in the WPH-treated group (326 +/- 67 microL min-1 100 g body weight-1) compared to 0.15 M NaCl-treated (890 +/- 26 microL min-1 100 g body weight-1) and captopril-treated (903 +/- 72 microL min-1 100 g body weight-1) rats. The ip administration of 1.0 g WPH/kg also decreased fractional sodium excretion to 0.021 +/- 0.019% compared to 0.126 +/- 0.041 and 0.66 +/- 0.015% in 0.15 M NaCl and captopril-treated rats, respectively (P = 0.033). Similarly, the fractional potassium excretion in WPH-treated rats (0.25 +/- 0.05%) was significantly lower (P = 0.0063) than in control (0.91 +/- 0.15%) and captopril-treated rats (1.24 +/- 0.30%), respectively. The present study shows a decreased SBP in SHR after the administration of WPH associated with a rise in tubule sodium reabsorption despite an angiotensin I-converting enzyme (ACE)-inhibiting in vitro activity (IC50 = 0.68 mg/mL). The present findings suggest a pathway involving ACE inhibition but measurements of plasma ACE activity and angiotensin II levels are needed to support this suggestion.

  1. Intraperitoneal Infusion of Neutral-pH Superoxidized Solution in Rats: Evaluation of Toxicity and Complications on Peritoneal Surface and Liver

    Science.gov (United States)

    Aras, Abbas; Karaman, Erbil; Yıldırım, Serkan; Yılmaz, Özkan; Kızıltan, Remzi; Karaman, Kamuran

    2017-01-01

    Background Superoxidized water (SOW) is known to be a potent disinfectant. The aim of this study was to evaluate the toxicity and complications on the peritoneal surface and liver after infusion of pH-neutral SOW into the peritoneal cavity of rats. Material/Methods Thirty Wistar-Albino rats weighing 250–300 g were randomly divided into 3 groups (10 rats/group). Group1 (control group) rats received single dose of 10 mg/kg saline solution intraperitoneally. Group 2 (single-dose group) rats received a single dose of 10 mg/kg pH-neutral SOW intraperitoneally. Group 3 (multiple-doses group) rats received multiple doses of 10 mg/kg pH-neutral SOW intraperitoneally on days 1, 3, and 5. All animals were killed at 1 week after infusion. Blood specimens were taken to the laboratory and macroscopic and microscopic examinations were performed on each rat. Results All 30 rats survived after the infusion. The gross-macroscopic examinations revealed no pathologic findings in any of the 3 groups. The microscopic examination of peritoneum and liver showed no signs of toxicity or complications in any of the 3 groups. There were no statistically significant differences among the 3 groups with regards to the blood biochemistry, including hemoglobin, hematocrit, platelets, aspartate aminotransferase, alanine aminotransferase, urea, or creatinine levels (p>0.05). However, the leucocyte counts were lower in group 3 than in groups 1 and 2, but this was not statistically significant (p=0.189). Conclusions Intraperitoneal infusion of pH-neutral SOW does not result in any significant toxicity or complications on the liver and peritoneal surface. However, multiple infusions lead to low leucocyte counts and future studies with longer follow-up times are needed. PMID:28224975

  2. Tabhu: tools for antibody humanization.

    KAUST Repository

    Olimpieri, Pier Paolo

    2014-10-09

    SUMMARY: Antibodies are rapidly becoming essential tools in the clinical practice, given their ability to recognize their cognate antigens with high specificity and affinity, and a high yield at reasonable costs in model animals. Unfortunately, when administered to human patients, xenogeneic antibodies can elicit unwanted and dangerous immunogenic responses. Antibody humanization methods are designed to produce molecules with a better safety profile still maintaining their ability to bind the antigen. This can be accomplished by grafting the non-human regions determining the antigen specificity into a suitable human template. Unfortunately, this procedure may results in a partial or complete loss of affinity of the grafted molecule that can be restored by back-mutating some of the residues of human origin to the corresponding murine ones. This trial-and-error procedure is hard and involves expensive and time-consuming experiments. Here we present tools for antibody humanization (Tabhu) a web server for antibody humanization. Tabhu includes tools for human template selection, grafting, back-mutation evaluation, antibody modelling and structural analysis, helping the user in all the critical steps of the humanization experiment protocol. AVAILABILITY: http://www.biocomputing.it/tabhu CONTACT: anna.tramontano@uniroma1.it, pierpaolo.olimpieri@uniroma1.it SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

  3. Avian Diagnostic and Therapeutic Antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Bradley, David Sherman [UND SMHS

    2012-12-31

    A number of infectious agents have the potential of causing significant clinical symptomology and even death, but dispite this, the number of incidence remain below the level that supports producing a vaccine. Therapeutic antibodies provide a viable treatment option for many of these diseases. We proposed that antibodies derived from West Nile Virus (WNV) immunized geese would be able to treat WNV infection in mammals and potential humans. We demonstrated that WNV specific goose antibodies are indeed successful in treating WNV infection both prophylactically and therapeutically in a golden hamster model. We demonstrated that the goose derived antibodies are non-reactogenic, i.e. do not cause an inflammatory response with multiple exposures in mammals. We also developed both a specific pathogen free facility to house the geese during the antibody production phase and a patent-pending purification process to purify the antibodies to greater than 99% purity. Therefore, the success of these study will allow a cost effective rapidly producible therapeutic toward clinical testing with the necessary infrastructure and processes developed and in place.

  4. In an animal model nephrogenic systemic fibrosis cannot be induced by intraperitoneal injection of high-dose gadolinium based contrast agents

    Energy Technology Data Exchange (ETDEWEB)

    Langer, R.D., E-mail: rlanger@uaeu.ac.ae [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Lorke, D.E. [Florida International University, Miami, FL (United States); Neidl van Gorkom, K.F. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Petroianu, G. [Florida International University, Miami, FL (United States); Azimullah, S.; Nurulain, S.M.; Singh, S. [Faculty of Medicine and Health Sciences (FMHS), United Arab Emirates University, Al Ain (United Arab Emirates); Fuchsjäger, M. [Al Ain Hospital, MUV-VAMED, Al Ain (United Arab Emirates)

    2012-10-15

    Aim and objective: Nephrogenic systemic fibrosis (NSF) has been reported in humans to be most likely induced by gadolinium based contrast agents (GBCA), namely by gadodiamide, gadopentetate dimeglumine, and gadoversetamide, rarely by other GBCA. The pathogenesis of NSF remains unclear; different hypotheses are under discussion. The objective of the study is to assess if in the animal model human-like NSF changes can be induced by high-dose, intraperitoneal GBCA injections over four weeks. Materials and methods: After approval by the institutional animal ethics committee, six rats each were randomly assigned to groups, and treated with seven different GBCA. Intraperitoneal (IP) injections – proven in the animal model to be effective – were chosen to prolong the animals’ exposure to the respective GBCA. GBCA doses of previous intravenous (IV) animal studies were applied. After five weeks all rats were sacrificed. Sham controls were treated with IP saline injections, employing the same regimen. Results: No findings comparable with human NSF were observed in all animals after IP treatment with all seven GBCA at daily doses of 2.5 and 5.0 mmol/kg body weight (BW). No histopathological abnormalities of all examined organs were noted. Weight loss was stated in weeks three and four with GBCA injections at doses of 5.0 mmol/kg BW, but rats regained weight after cessation of GBCA treatment. Conclusions: NSF-comparable pathological findings could not be induced by high dose intraperitoneal injection of seven GBCA.

  5. Preparation of Anti—Cardiac Troponin I Monoclonal Antibodies and Their Characterization with Surface Plasmon Resonance Biosensor

    Institute of Scientific and Technical Information of China (English)

    WEIJing-yan; LIUXia; SONGDa-qian; BULi-sha; HUXing; MUYing

    2003-01-01

    Cardiac troponin I(cTuI)was separated and purified from human left ventricular tissue by affinity chromatographic method and used to immunize Balb/c mice by intraperitoneal injection and four hybridoma cell lines,which secreted monoclonal antibody(mAb)against buman cTnI,were obtained by cell fusion,identification and cloning twice.Three mAbs(9F5,2F11,8C12)were produced from the ascites of Balb/c mice injected intraperitoneally the hybridoma cells and characterized by means of a surface plasmon resonance(SPR) biosensor.An optimal and specific sensing membrane for troponin I was prepared with staphylococcal protein A(SPA) as the intermediate layer and mAb against human cTnI as the capture antibody.On the basis of the sensing membrane,two modes of operation of the SPR biosensor were developed,i.e..a direct detection of antigen-antibody affinity and a sandwich assay.In the sandwich assay deteciton mode,the mAbs competition was measured by monitoring whether the secondary antibody had been attached to the cTnI alresdy captured by the first antibody on the sensor surface.The SPR biosensor was shown to be able to directly daptured by the first antibody on the sensor surface.The SPR biosensor was shown to be abloe to directly detect the antigen-antibody affinity and the order of the affinity was found to be 9F5>2F11>8C12.In the sandwich detection mode,it was found that the different epitopes on the cTnI molecules were recognized by the three mAbs respectively,but the asymmetrical competition was shown between 2F11 and 8C12 and no competition was found between 9F5 and 2F11 or 8c12.Based on these results,a double monoclonal sandwich immunoassay for cTnI was developed by using the optmal antibody pair of 9F5 and 2F11 and the SPR biosensor with SPA substrate membrane,which showed an excellent sensitivity of 0.8μg/L for both the buffer and the serum samples compared with the direct detection of cTnI for the buffer with the lowest detection limit of 4μg/L and conventional

  6. Antibody and splenocyte proliferation response to whole inactivated Streptococcus pneumoniae serotype 1, 3 and 6B in mice.

    Science.gov (United States)

    Pană, Marina; Orhan, Rasid; Bănică, Leontina; Iancu, Adina Daniela; Stăvaru, Crina

    2011-01-01

    Animal models of infection and protection on the topic of the Streptococcus pneumoniae (S. pneumoniae) have encountered many difficulties generated by low immunogenicity, a characteristic of polysaccharide capsular bacteria and difference of virulence between serotypes and strains. We have explored the immune response after immunization with heat inactivated S. pneumoniae serotype 1, 3 and 6B in C57BL/6 mice by IgM and IgG detection, and by splenocyte in vitro 5-ethynyl-2'-deoxyuridine (EdU) incorporation after antigen specific stimulation, as a proposed method of cellular immune response evaluation. Antibody titer persistence after immunization was not lengthy while antigen specific proliferation response detected by EdU assay was remnant. Intraperitoneal (i.p.) challenge with serotype 6B S. pneumoniae proved that antibody titers and the detected specific cellular immune response do not cover seroprotective necessity and do not confer improved immunologic memory in comparison to non-immunized mice, which show natural resistance.

  7. Validating Antibodies to the Cannabinoid CB2 Receptor: Antibody Sensitivity Is Not Evidence of Antibody Specificity.

    Science.gov (United States)

    Marchalant, Yannick; Brownjohn, Philip W; Bonnet, Amandine; Kleffmann, Torsten; Ashton, John C

    2014-06-01

    Antibody-based methods for the detection and quantification of membrane integral proteins, in particular, the G protein-coupled receptors (GPCRs), have been plagued with issues of primary antibody specificity. In this report, we investigate one of the most commonly utilized commercial antibodies for the cannabinoid CB2 receptor, a GPCR, using immunoblotting in combination with mass spectrometry. In this way, we were able to develop powerful negative and novel positive controls. By doing this, we are able to demonstrate that it is possible for an antibody to be sensitive for a protein of interest-in this case CB2-but still cross-react with other proteins and therefore lack specificity. Specifically, we were able to use western blotting combined with mass spectrometry to unequivocally identify CB2 protein in over-expressing cell lines. This shows that a common practice of validating antibodies with positive controls only is insufficient to ensure antibody reliability. In addition, our work is the first to develop a label-free method of protein detection using mass spectrometry that, with further refinement, could provide unequivocal identification of CB2 receptor protein in native tissues.

  8. Effect of α7n-Acetylcholine Receptor Activation and Antibodies to TNF-α on Mortality of Mice and Concentration of Proinflammatory Cytokines During Early Stage of Sepsis.

    Science.gov (United States)

    Zabrodskii, P F; Gromov, M S; Maslyakov, V V

    2015-10-01

    Experiments on random-bred albino mice showed that activation α7n-acetylcholine receptors with anabasine (0.5 LD50) and the use of antibodies to TNF-α (1 mg/kg) 2 h before sepsis modeling significantly reduces mortality of mice from experimental sepsis (intraperitoneal injection of E. coli) due to a decrease in the blood concentration of proinflammatory cytokines TNF-α, IL-1β, and IL-6. After combined administration of anti-TNF-α antibodies and anabasine, an additive effect was observed.

  9. Production and Purification of Polyclonal Antibodies.

    Science.gov (United States)

    Nakazawa, Masami; Mukumoto, Mari; Miyatake, Kazutaka

    2016-01-01

    Polyclonal antibodies consist of a mixture of antibodies produced by multiple B-cell clones that have differentiated into antibody-producing plasma cells in response to an immunogen. Polyclonal antibodies raised against an antigen recognize multiple epitopes on a target molecule, which results in a signal amplification in indirect immunoassays including immune-electron microscopy. In this chapter, we present a basic procedure to generate polyclonal antibodies in rabbits.

  10. Antibodies to watch in 2016.

    Science.gov (United States)

    Reichert, Janice M

    2016-01-01

    The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016. As evidenced by the antibody therapeutics discussed in this perspective, the biopharmaceutical industry has a highly active late-stage clinical pipeline that may deliver numerous new products to the global market in the near future. *See Note added in proof for updates through December 31, 2015.

  11. Cross neutralizing antibodies in hamsters vaccinated with leptospiral bacterins produced with three serovars of serogroup Sejroe

    Directory of Open Access Journals (Sweden)

    Rosana Tabata

    2002-09-01

    Full Text Available Three leptospiral bacterins, produced with different serovars of Serogroup Sejroe, namely the hardjo (bacterin A, wolffi (bacterin B and guaricura (bacterin C, were evaluated in male hamsters (Mesocricetus auratus by comparing the agglutinating and neutralizing antibodies titers using microscopic agglutination (MAT and in vitro growth inhibition (GIT tests. The immunization schedule was based on two 1.0 mL doses of non-diluted formalininactivated whole culture bacterin given through subcutaneous route with 10-day interval. The challenge was performed ten days after the second vaccine dose, when the animals were inoculated with 0.2 mL of non-inactivated cultures of each serovar through intraperitoneal route. On the 21st post-challenge day (PCD, all animals were bled and their sera were joined in pools (n=8 and tested by MAT and GIT. All vaccinated and control animals presented no clinical signs of leptospirosis after the challenge, but the serovar guaricura was isolated from the kidneys of control animals on the 21st PCD. The MAT results showed cross agglutinins between serovars hardjo and wolffi, and between wolffi and guaricura. The GIT results revealed the presence of cross neutralizing antibodies between serovars wolffi or guaricura against hardjo, wolffi and guaricura. It was found that the tested strain of serovar hardjo did not produce detectable levels of neutralizing antibodies, indicating its poor immunogenicity.

  12. Effects of Monoclonal Antibody Against Adipocyte-Specific Membrane Protein on Lipid Metabolism in Pigs

    Institute of Scientific and Technical Information of China (English)

    GAO Shi-zheng; LIU Ling-yun; ZHAO Su-mei; HU Hong-mei; GE Chang-rong; LIU Yong-gang; ZHANG Xi

    2008-01-01

    This study was to investigate the regulation of monoclonal antibodies against adipocyte membrane proteins(McAb)on lipid metabolism in pigs.Forty Landrace x Saba pigs were randomly divided into eight groups;the control group was given 10 mL saline and the treat groups were given monoclonal antibody against adipocyte-specific membrane protein with 0.10 0.5,and 1.0 mg kg-1 body weight at 15 and 60 kg body weight,respectively,by intraperitoneal injection.The results showed that McAb could increase,significantly,serum lipoprotein lipase activity and reduce serum nonesterified fatty acid(NEFA)content.Meanwhile,McAb increased content of serum lipid,triglyceride(TG),cholesterol(CHO),high density lipoprotein(HDL),and low density lipoprotein(LDL) both at 15 and 60 kg body weight.However,McAb affected more significantly the lipid metabolism at 15 kg body weight than at 60 kg body weight.Moreover,this effect of McAb on lipid metabolism exhibited dose-dependent effect.These results suggested that this monoclonal antibody increased lipase activity,promoted lipolysis,and utilization of lipid so that McAb could be applied to restrain excessive fat deposition in porcine production through the regulation of fat metabolism.

  13. Production and characterization of monoclonal antibody specific to recombinant dengue multi-epitope protein.

    Science.gov (United States)

    Abhyankar, Ajay Vinayak; Bhargava, Rakesh; Jana, Asha Mukul; Sahni, Ajay Kumar; Rao, P V Lakshmana

    2008-06-01

    Monoclonal antibodies against novel dengue recombinant protein were produced following immunization of Balb/c mice with recombinant dengue multi-epitope protein (r-DMEP) expressed in Escherichia coli vector and purified in a single-step chromatography system. Antigenicity of r-DMEP was evaluated by dot enzyme immunoassay. Mice were immunized intraperitoneally with five doses each of 100 microg of this novel antigen at 1-week intervals and a final intravenous booster dose prior to the fusion. Hybridomas resulted from fusion of myeloma cells and splenocytes using PEG-1500 as an additive. Selection of the hybrids was done using HAT medium, and the hybrids thus selected were finally screened qualitatively and quantitatively by dot and plate immunoassays, respectively. Five antibody secretory hybrid clones exhibited specific reactivity against r-DMEP by dot-ELISA, whereas a lone clone was found to be cross-reactive with Japanese encephalitis virus (JEV). Monoclonal antibodies (MAbs) specific to r-DME protein recognized the envelope and non-structural epitopes by Western blot analysis. These MAbs were further checked for their diagnostic efficacy using dengue suspected clinical samples and found overall sensitivity and specificity for DRDE dipstick ELISA. MAb-based dipstick ELISA results were 85%, 75% and 85%, 90%, respectively.

  14. Antibodies to watch in 2013

    Science.gov (United States)

    Reichert, Janice M

    2013-01-01

    The transitions of antibody therapeutics to late-stage clinical development, regulatory review and the market are proceeding at a rapid pace in 2013. Since late 2012, two monoclonal antibody (mAb) therapeutics (itolizumab, trastuzumab emtansine) received their first approvals, first marketing applications for three mAbs (vedolizumab, ramucirumab, obinutuzumab) were submitted to regulatory agencies, and five mAbs (brodalumab, MABp1, moxetumomab pasudotox, tildrakizumab, rilotumumab) entered their first Phase 3 studies. The current total of commercially-sponsored antibody therapeutics undergoing evaluation in late-stage studies is 30. Recently announced study results for farletuzumab, naptumomab estafenatox, and tabalumab indicate that clinical endpoints were not met in some Phase 3 studies of these product candidates. PMID:23727858

  15. Epigenetics of the antibody response.

    Science.gov (United States)

    Li, Guideng; Zan, Hong; Xu, Zhenming; Casali, Paolo

    2013-09-01

    Epigenetic marks, such as DNA methylation, histone post-translational modifications and miRNAs, are induced in B cells by the same stimuli that drive the antibody response. They play major roles in regulating somatic hypermutation (SHM), class switch DNA recombination (CSR), and differentiation to plasma cells or long-lived memory B cells. Histone modifications target the CSR and, possibly, SHM machinery to the immunoglobulin locus; they together with DNA methylation and miRNAs modulate the expression of critical elements of that machinery, such as activation-induced cytidine deaminase (AID), as well as factors central to plasma cell differentiation, such as B lymphocyte-induced maturation protein-1 (Blimp-1). These inducible B cell-intrinsic epigenetic marks instruct the maturation of antibody responses. Their dysregulation plays an important role in aberrant antibody responses to foreign antigens, such as those of microbial pathogens, and self-antigens, such as those targeted in autoimmunity, and B cell neoplasia.

  16. Autologous antibodies that bind neuroblastoma cells.

    Science.gov (United States)

    Sun, Yujing; Sholler, Giselle S; Shukla, Girja S; Pero, Stephanie C; Carman, Chelsea L; Zhao, Ping; Krag, David N

    2015-11-01

    Antibody therapy of neuroblastoma is promising and our goal is to derive antibodies from patients with neuroblastoma for developing new therapeutic antibodies. The feasibility of using residual bone marrow obtained for clinical indications as a source of tumor cells and a source of antibodies was assessed. From marrow samples, neuroblastoma cells were recovered, grown in cell culture and also implanted into mice to create xenografts. Mononuclear cells from the marrow were used as a source to generate phage display antibody libraries and also hybridomas. Growth of neuroblastoma patient cells was possible both in vitro and as xenografts. Antibodies from the phage libraries and from the monoclonal hybridomas bound autologous neuroblastoma cells with some selectivity. It appears feasible to recover neuroblastoma cells from residual marrow specimens and to generate human antibodies that bind autologous neuroblastoma cells. Expansion of this approach is underway to collect more specimens, optimize methods to generate antibodies, and to evaluate the bioactivity of neuroblastoma-binding antibodies.

  17. Uses of monoclonal antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2013-04-09

    This invention provides a composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a suitable carrier. This invention provides a pharmaceutical composition comprising an effective amount of monoclonal antibody 8H9 or a derivative thereof and a pharmaceutically acceptable carrier. This invention also provides an antibody other than the monoclonal antibody 8H9 comprising the complementary determining regions of monoclonal antibody 8H9 or a derivative thereof, capable of binding to the same antigen as the monoclonal antibody 8H9. This invention provides a substance capable of competitively inhibiting the binding of monoclonal antibody 8H9. This invention also provides an isolated scFv of monoclonal antibody 8H9 or a derivative thereof. This invention also provides the 8H9 antigen. This invention also provides different uses of the monoclonal antibody 8H9 or its derivative.

  18. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  19. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  20. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2017-03-28

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  1. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  2. Preparation of Anti-cardiac Troponin I Monoclonal Antibodies and Their Characterization with Surface Plasmon Resonance Biosensor

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    Cardiac troponin I(cTnI) was separated and purified from human left ventricular tissue by affinity chromatographic method and used to immunize Balb/c mice by intraperitoneal injection and four hybridoma cell lines, which secreted monoclonal antibody(mAb) against human cTnI, were obtained by cell fusion, identification and cloning twice. Three mAbs(9F5, 2F11, 8C12) were produced from the ascites of Balb/c mice injected intraperitoneally the hybridoma cells and characterized by means of a surface plasmon resonance(SPR) biosensor. An optimal and specific sensing membrane for troponin I was prepared with staphylococcal protein A(SPA) as the intermediate layer and mAb against human cTnI as the capture antibody. On the basis of the sensing membrane, two modes of operation of the SPR biosensor were developed, i.e., a direct detection of antigen-antibody affinity and a sandwich assay. In the sandwich assay detection mode, the mAbs competition was measured by monitoring whether the secondary antibody had been attached to the cTnI already captured by the first antibody on the sensor surface. The SPR biosensor was shown to be able to directly detect the antigen-antibody affinity and the order of the affinity was found to be 9F5>2F11>8C12. In the sandwich detection mode, it was found that the different epitopes on the cTnI molecules were recognized by the three mAbs respectively, but the asymmetrical competition was shown between 2F11 and 8C12 and no competition was found between 9F5 and 2F11 or 8c12. Based on these results, a double monoclonal sandwich immunoassay for cTnI was developed by using the optimal antibody pair of 9F5 and 2F11 and the SPR biosensor with SPA substrate membrane, which showed an excellent sensitivity of 0.8 μg/L for both the buffer and the serum samples compared with the direct detection of cTnI for the buffer with the lowest detection limit of 4 μg/L and conventional ELISA with the sensitivity of 1.9 μg/L.

  3. A novel mouse monoclonal antibody targeting ErbB2 suppresses breast cancer growth

    Energy Technology Data Exchange (ETDEWEB)

    Kawa, Seiji [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan); Matsushita, Hirohisa; Ohbayashi, Hirokazu [Department of Research and Development, Nichirei Biosciences Inc., Tokyo 104-8402 (Japan); Semba, Kentaro [Department of Life Science and Medical Bio-Science, School of Science and Engineering, Waseda University, Tokyo 169-8555 (Japan); Yamamoto, Tadashi, E-mail: tyamamot@ims.u-tokyo.ac.jp [Division of Oncology, Institute of Medical Science, University of Tokyo, Shirokanedai 4-6-1, Minato-ku, Tokyo 108-8639 (Japan)

    2009-07-03

    Overexpression of ErbB2 in breast cancer is associated with increased recurrence and worse prognosis. Accumulating evidences suggest that molecular targeted therapy is a promising anticancer strategy. In this study, we produced a novel anti-ErbB2 monoclonal antibody, 6G10, that recognized an epitope distinct from the trastuzumab binding site. 6G10 induced aggregation of BT474 breast cancer cells and inhibited proliferation of various breast cancer cell lines including BT474. A growth inhibition assay showed that 6G10 had EC{sub 50} values comparable to trastuzumab, indicating that the drugs have a similar level of potency. Furthermore, intraperitoneal administration of 6G10 completely inhibited the growth of xenografted tumors derived from BT474 and SK-BR-3 cells. These data suggested that 6G10 has great therapeutic potential and could be administered to patients alternatively, or synergistically, with trastuzumab.

  4. Generation of a murine monoclonal antibody to capsular polysaccharide Vi from Salmonella Typhi

    Directory of Open Access Journals (Sweden)

    Fátima Reyes-López

    2015-11-01

    Full Text Available The conventional hybridoma technology has enabled the development of monoclonal antibodies (Mabs against many antigens. Mabs have several applications in the field of basic research, diagnosis, immunotherapy and vaccine manufacturing processes. Mabs-producing hybridomas against the capsular polysaccharide from Salmonella Typhi were obtained, after intraperitoneal immunization of BALB/c mice with 10 µg of capsular polysaccharide Vi conjugated to diphtheria toxoid, and subsequent fusion of lymphocytes isolated of the spleen and myeloma cells SP2/O. A Mab was selected, partially characterized, and named as 4G3E11. The isotype of this Mab was IgG1. It was proved by means of a sandwich ELISA that the 4G3E11 Mab reacts with different concentrations of polysaccharide in samples of the vax-TyVi® vaccine. The Mab obtained in this research could be useful as reagent for the detection and quantitation of polysaccharide Vi in typhoid vaccines.

  5. Antiphospholipid antibody syndrome and autoimmune diseases.

    Science.gov (United States)

    Ostrowski, Rochella A; Robinson, John A

    2008-02-01

    The arbitrary division between antiphospholipid antibody syndrome and secondary antiphospholipid antibody syndrome has not proven useful. Antiphospholipid antibodies in the absence of antiphospholipid antibody syndrome often occur as epiphenomena in many autoimmune diseases. They are very common in systemic lupus erythematosus. Antiphospholipid antibody syndrome is a significant comorbidity in lupus but is uncommon in Sjögren's syndrome, rheumatoid arthritis, scleroderma, and systemic vasculitis. Evidence is growing that antiphospholipid antibodies may have a pathogenic role in pulmonary hypertension and accelerated atherosclerosis of autoimmune diseases.

  6. Curcumin blocks autophagy and activates apoptosis of malignant mesothelioma cell lines and increases the survival of mice intraperitoneally transplanted with a malignant mesothelioma cell line.

    Science.gov (United States)

    Masuelli, Laura; Benvenuto, Monica; Di Stefano, Enrica; Mattera, Rosanna; Fantini, Massimo; De Feudis, Giuseppina; De Smaele, Enrico; Tresoldi, Ilaria; Giganti, Maria Gabriella; Modesti, Andrea; Bei, Roberto

    2017-01-30

    Malignant mesothelioma (MM) is a primary tumor arising from the serous membranes. The resistance of MM patients to conventional therapies, and the poor patients' survival, encouraged the identification of molecular targets for MM treatment. Curcumin (CUR) is a "multifunctional drug". We explored the in vitro effects of CUR on cell proliferation, cell cycle regulation, pro-survival signaling pathways, apoptosis, autophagy of human (MM-B1, H-Meso-1, MM-F1), and mouse (#40a) MM cells. In addition, we evaluated the in vivo anti-tumor activities of CUR in C57BL/6 mice intraperitoneally transplanted with #40a cells forming ascites.CUR in vitro inhibited MM cells survival in a dose- and time-dependent manner and increased reactive oxygen species'intracellular production and induced DNA damage. CUR triggered autophagic flux, but the process was then blocked and was coincident with caspase 8 activation which activates apoptosis. CUR-mediated apoptosis was supported by the increase of Bax/Bcl-2 ratio, increase of p53 expression, activation of caspase 9, cleavage of PARP-1, increase of the percentage of cells in the sub G1 phase which was reduced (MM-F1 and #40a) or abolished (MM-B1 and H-Meso-1) after MM cells incubation with the apoptosis inhibitor Z-VAD-FMK. CUR treatment stimulated the phosphorylation of ERK1/2 and p38 MAPK, inhibited that of p54 JNK and AKT, increased c-Jun expression and phosphorylation and prevented NF-κB nuclear translocation. Intraperitoneal administration of CUR increased the median survival of C57BL/6 mice intraperitoneally transplanted with #40a cells and reduced the risk of developing tumors. Our findings may have important implications for the design of MM treatment using CUR.

  7. Effect of cytoreductive surgery-assisted postoperative intraperitoneal hyperthermic perfusion chemotherapy combined with intravenous chemotherapy on serum malignant biological indicators of ovarian cancer patients

    Institute of Scientific and Technical Information of China (English)

    Xian-Lian Liu; Lei Yang

    2015-01-01

    Objective: To study the effect of cytoreductive surgery-assisted postoperative intraperitoneal hyperthermic perfusion chemotherapy combined with intravenous chemotherapy on serum malignant biological indicators of ovarian cancer patients.Methods:Advanced ovarian cancer patients who received cytoreductive surgery in our hospital from June 2010 to August 2014 were selected for study. Based on different postoperative chemotherapy schemes, patients undergoing intraperitoneal hyperthermic perfusion chemotherapy combined with intravenous chemotherapy were screened and enrolled in combination chemotherapy group; patients undergoing routine intravenous chemotherapy were screened and enrolled in intravenous chemotherapy group. Then contents of serum markers, proliferative genes and signaling pathway molecules of both groups were detected.Results:(1) Cell cycles: G0/G1 and S phase percentages in ovarian cancer biopsy tissues of combination chemotherapy group were lower than those of intravenous chemotherapy group; G2/M phase percentage was higher than that of intravenous chemotherapy group; (2) Tumor markers: after 1, 2, 3, 4, 5 and 6 chemotherapy cycles, compared with intravenous chemotherapy group, serum HE4 and sTWEAK contents of combination chemotherapy group trended to decrease significantly; (3) Proliferative genes: compared with intravenous chemotherapy group, mRNA contents of mortalin, CIP2A, GILZ and Ki-67 in serum of combination chemotherapy group trended to decrease significantly; (4) Signaling pathway molecules: mRNA contents of Crk, Dock180, Rac1 and YAP in serum of combination chemotherapy group showed a decreasing trend; mRNA contents of C3G, Rap1 and Hippo showed an increasing trend.Conclusion:Intraperitoneal hyperthermic perfusion chemotherapy combined with intravenous chemotherapy is helpful to kill ovarian cancer cells, inhibit expressions of proliferative genes and regulate functions of signaling pathways; it is an ideal chemotherapy scheme for ovarian

  8. Intraperitoneal delivery of a novel liposome-encapsulated paclitaxel redirects metabolic reprogramming and effectively inhibits cancer stem cells in Taxol(®)-resistant ovarian cancer.

    Science.gov (United States)

    Shen, Yao-An; Li, Wai-Hou; Chen, Po-Hung; He, Chun-Lin; Chang, Yen-Hou; Chuang, Chi-Mu

    2015-01-01

    Taxol(®) remained as the mainstay therapeutic agent in the treatment of ovarian cancer, however recurrence rate is still high. Cancer stem cells (CSCs) represent a subset of cells in the bulk of tumors and play a central role in inducing drug resistance and recurrence. Furthermore, cancer metabolism has been an area under intensive investigation, since accumulating evidence has shown that CSCs and cancer metabolism are closely linked, an effect named as metabolic reprogramming. In this work, we aimed to investigate the impacts of a novel liposome-encapsulated paclitaxel (Nano-Taxol) on the stemness phenotype and metabolic reprogramming. A paclitaxel-resistant cell line (TR) was established at first. Tumor growth was induced in the mice peritoneal cavity by inoculation of TR cells. A 2x2 factorial experiment was designed to test the therapeutic efficacy in which factor 1 represented the comparison of drugs (Taxol(®) versus Nano-Taxol), while factor 2 represented the delivery route (intravenous versus intraperitoneal delivery). In this work, we found that intraperitoneal delivery of Nano-Taxol redirects metabolic reprogramming, from glycolysis to oxidative phosphorylation, and effectively suppresses cancer stem cells. Also, intraperitoneal delivery of Nano-Taxol led to a significantly better control of tumor growth compared with intravenous delivery of Taxol(®) (current standard treatment). This translational research may serve as a novel pathway for the drug development of nanomedicine. In the future, this treatment modality may be extended to treat several relevant cancers that have been proved to be suitable for the loco-regional delivery of therapeutic agents, including colon cancer, gastric cancer, and pancreatic cancer.

  9. Effects of the GABA(B) receptor agonist baclofen administered orally on normal food intake and intraperitoneally on fat intake in non-deprived rats.

    Science.gov (United States)

    Bains, Rasneer S; Ebenezer, Ivor S

    2013-01-01

    It has been previously reported that the GABA(B) receptor agonist baclofen decreases food intake after oral administration and fat intake after intraperitoneal administration. The aim of the study was to investigate the effects of baclofen (1-4 mg/ kg) administered orally (Experiment 1) on food intake in non-deprived rats (n=6) and intraperitoneally (Experiment 2) on fat intake in non-deprived rats (n=8) that were naïve to baclofen (1st set of trials) and in the same group of rats after they were sub-chronically exposed to baclofen (2nd set of trials). The results from Experiment 1 show that baclofen had no effects on food intake during the 1st set of trials, but the 2 and 4 mg/kg doses significantly increased food consumption during the 2nd set of trials. Baclofen produced sedation during the 1st set of trials, but tolerance occurred to this effect and was not apparent during the 2nd set of trials. These observations suggest that the motor effects may have competed with the hyperphagic effects of baclofen during the 1st set of trials. The data from Experiment 2 show that baclofen had no effects on fat intake during either the 1st or 2nd set of trials. The results of the study thus indicate that orally administrated baclofen increases food intake and intraperitoneal administration has no effect on fat intake in non-deprived rats under the conditions used in this study. These findings may have important implications for research on the use of baclofen in studies concerned with ingestive behaviours.

  10. Rotura vesical intraperitoneal y reparación laparoscópica: ¿Es éste el nuevo gold standard?

    OpenAIRE

    Troncoso C,Pablo; Saavedra Z.,Álvaro; Sarras J,Miguel; Rojas R,Francisco

    2012-01-01

    Introducción: Actualmente la laparoscopia es el nuevo paradigma en muchos tratamientos quirúrgicos, pero su rol en trauma urológico es incipiente. Nuestro objetivo es mostrar una técnica factible y segura de cistorrafia laparoscópica por ruptura vesical intraperitoneal contusa. Caso: Un hombre de 28 años consulta por 6 horas de dolor hipogástrico, retención y globo vesical, después de una transgresión alcohólica. Ingresa con creatininemia y parámetros inflamatorios elevados. A pesar de un son...

  11. Absorbed Doses and Risk Estimates of (211)At-MX35 F(ab')2 in Intraperitoneal Therapy of Ovarian Cancer Patients

    DEFF Research Database (Denmark)

    Cederkrantz, Elin; Andersson, Håkan; Bernhardt, Peter

    2015-01-01

    dose associated with i.p. administration of (211)At-MX35 F(ab')2. METHODS AND MATERIALS: Patients in clinical remission after salvage chemotherapy for peritoneal recurrence of ovarian cancer underwent i.p. infusion of (211)At-MX35 F(ab')2. Potassium perchlorate was given to block unwanted accumulation...... 100 MBq/L, organ equivalent doses were less than 10% of the estimated tolerance dose. CONCLUSION: Intraperitoneal (211)At-MX35 F(ab')2 treatment is potentially a well-tolerated therapy for locally confined microscopic ovarian cancer. Absorbed doses to normal organs are low, but because the effective...

  12. DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 Human IgG Antibody Produced by AnaptysBio, Inc.

    Science.gov (United States)

    2016-02-01

    ECBC-TR-1339 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR ANTIBODY...CHARACTERIZATION: CHARACTERIZATION OF AN MS2 HUMAN IGG ANTIBODY PRODUCED BY ANAPTYSBIO, INC. DARPA ATP Standardized Test Bed for Antibody...Characterization: Characterization of an MS2 human IgG antibody produced by AnaptysBio DARPA ATP Standardized Test Bed for Antibody

  13. Polyclonal and monoclonal antibodies in clinic.

    Science.gov (United States)

    Wootla, Bharath; Denic, Aleksandar; Rodriguez, Moses

    2014-01-01

    Immunoglobulins (Ig) or antibodies are heavy plasma proteins, with sugar chains added to amino-acid residues by N-linked glycosylation and occasionally by O-linked glycosylation. The versatility of antibodies is demonstrated by the various functions that they mediate such as neutralization, agglutination, fixation with activation of complement and activation of effector cells. Naturally occurring antibodies protect the organism against harmful pathogens, viruses and infections. In addition, almost any organic chemical induces antibody production of antibodies that would bind specifically to the chemical. These antibodies are often produced from multiple B cell clones and referred to as polyclonal antibodies. In recent years, scientists have exploited the highly evolved machinery of the immune system to produce structurally and functionally complex molecules such as antibodies from a single B clone, heralding the era of monoclonal antibodies. Most of the antibodies currently in the clinic, target components of the immune system, are not curative and seek to alleviate symptoms rather than cure disease. Our group used a novel strategy to identify reparative human monoclonal antibodies distinct from conventional antibodies. In this chapter, we discuss the therapeutic relevance of both polyclonal and monoclonal antibodies in clinic.

  14. Antibody Engineering for Pursuing a Healthier Future

    Science.gov (United States)

    Saeed, Abdullah F. U. H.; Wang, Rongzhi; Ling, Sumei; Wang, Shihua

    2017-01-01

    Since the development of antibody-production techniques, a number of immunoglobulins have been developed on a large scale using conventional methods. Hybridoma technology opened a new horizon in the production of antibodies against target antigens of infectious pathogens, malignant diseases including autoimmune disorders, and numerous potent toxins. However, these clinical humanized or chimeric murine antibodies have several limitations and complexities. Therefore, to overcome these difficulties, recent advances in genetic engineering techniques and phage display technique have allowed the production of highly specific recombinant antibodies. These engineered antibodies have been constructed in the hunt for novel therapeutic drugs equipped with enhanced immunoprotective abilities, such as engaging immune effector functions, effective development of fusion proteins, efficient tumor and tissue penetration, and high-affinity antibodies directed against conserved targets. Advanced antibody engineering techniques have extensive applications in the fields of immunology, biotechnology, diagnostics, and therapeutic medicines. However, there is limited knowledge regarding dynamic antibody development approaches. Therefore, this review extends beyond our understanding of conventional polyclonal and monoclonal antibodies. Furthermore, recent advances in antibody engineering techniques together with antibody fragments, display technologies, immunomodulation, and broad applications of antibodies are discussed to enhance innovative antibody production in pursuit of a healthier future for humans.

  15. Pharmacokinetics interactions of monoclonal antibodies.

    Science.gov (United States)

    Ferri, Nicola; Bellosta, Stefano; Baldessin, Ludovico; Boccia, Donatella; Racagni, Giorgi; Corsini, Alberto

    2016-09-01

    The clearance of therapeutic monoclonal antibodies (mAbs) typically does not involve cytochrome P450 (CYP450)-mediated metabolism or interaction with cell membrane transporters, therefore the pharmacokinetics interactions of mAbs and small molecule drugs are limited. However, a drug may affect the clearance of mAbs through the modulation of immune response (e.g., methotrexate reduces the clearance of infliximab, adalimumab, and golimumab, possibly due to methotrexate's inhibitory effect on the formation of antibodies against the mAbs). In addition, mAbs that are cytokine modulators may modify the metabolism of drugs through their effects on P450 enzymes expression. For example, cytokine modulators such as tocilizumab (anti-IL-6 receptor antibody) may reverse the "inhibitory" effect of IL-6 on CYP substrates, resulting in a "normalization" of CYP activities. Finally, a drug may alter the clearance of mAbs by either increasing or reducing the levels of expression of targets of mAbs on the cell surface. For instance, statins and fibrates induce PCSK9 expression and therefore increase cellular uptake and clearance of alirocumab and evolocumab, anti-PCSK9 antibodies. In the present review, we will provide an overview on the pharmacokinetics properties of mAbs as related to the most relevant examples of mAbs-small molecule drug interaction.

  16. Monoclonal antibodies to Treponema Pallidum.

    NARCIS (Netherlands)

    H.J.M. van de Donk; J.D.A. van Embden; M.F. van Olderen; A.D.M.E. Osterhaus (Albert); J.C. de Jong (Jan)

    1984-01-01

    textabstractThree successive fusions of mouse myeloma cells and spleen lymphocytes of a mouse immunized with Treponema Pallidum resulted in one hybridoma producing anti T. pallidum antibodies for each fusion. The mice were immunized with live pallidum cells respectively 1, 3 and 5 months before fusi

  17. Antibody Isotype Switching in Vertebrates.

    Science.gov (United States)

    Senger, Kate; Hackney, Jason; Payandeh, Jian; Zarrin, Ali A

    2015-01-01

    The humoral or antibody-mediated immune response in vertebrates has evolved to respond to diverse antigenic challenges in various anatomical locations. Diversification of the immunoglobulin heavy chain (IgH) constant region via isotype switching allows for remarkable plasticity in the immune response, including versatile tissue distribution, Fc receptor binding, and complement fixation. This enables antibody molecules to exert various biological functions while maintaining antigen-binding specificity. Different immunoglobulin (Ig) classes include IgM, IgD, IgG, IgE, and IgA, which exist as surface-bound and secreted forms. High-affinity autoantibodies are associated with various autoimmune diseases such as lupus and arthritis, while defects in components of isotype switching are associated with infections. A major route of infection used by a large number of pathogens is invasion of mucosal surfaces within the respiratory, digestive, or urinary tract. Most infections of this nature are initially limited by effector mechanisms such as secretory IgA antibodies. Mucosal surfaces have been proposed as a major site for the genesis of adaptive immune responses, not just in fighting infections but also in tolerating commensals and constant dietary antigens. We will discuss the evolution of isotype switching in various species and provide an overview of the function of various isotypes with a focus on IgA, which is universally important in gut homeostasis as well as pathogen clearance. Finally, we will discuss the utility of antibodies as therapeutic modalities.

  18. Development of Antibody Against Sulfamethazine

    Institute of Scientific and Technical Information of China (English)

    LIZi-ying; XUWen-ge; LIUYi-bing; ZHANGLi-ling; GUOWei-zheng; HANShi-quan

    2003-01-01

    Polyclonal antibodies(PcAbs) against sulfamethazine(SMT) are obtained by immunizing rabbits with SMT-conjugated bovine serum albumin(BSA). The affinity constants (Ka) of the PcAbs are higher than 1×108 and the cross-reactivities with sulfadiazine(SD), sulfaquinoxaline (SQX) are lower than 0.05% (R/A).

  19. Detection of Campylobacter species using monoclonal antibodies

    Science.gov (United States)

    Young, Colin R.; Lee, Alice; Stanker, Larry H.

    1999-01-01

    A panel of species specific monoclonal antibodies were raised to Campylobacter coli, Campylobacter jejuni and Campylobacter lari. The isotypes, and cross-reactivity profiles of each monoclonal antibody against an extensive panel of micro- organisms, were determined.

  20. [Neuroimmunological diseases associated with VGKC complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-05-01

    Antibodies to voltage-gated potassium channels(VGKC) were first identified by radioimmunoassay of radioisotope labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were found only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in Morvan's syndrome and in a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins(for example LGI-1, Caspr-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now usually known as VGKC-complex antibodies. In general, LGI-1 antibodies are most common in limbic encephalitis with SIADH. Caspr-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability.

  1. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2014-07-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  2. Platelet antigens and antibodies. Literature review

    Directory of Open Access Journals (Sweden)

    N. V. Mineeva

    2013-01-01

    Full Text Available Platelet antigens structure, role of platelet antibodies in the pathogenesis of various clinical conditions, characteristic of modern antibodies detection methods are presented in this article.

  3. Chemical engineering of cell penetrating antibodies.

    Science.gov (United States)

    Zhao, Y; Lou, D; Burkett, J; Kohler, H

    2001-08-01

    Antibodies, being exquisitely specific tools in biology, are routinely used to detect and identify intra-cellular structures. However, current intra-cellular application of antibodies requires that the membrane be rendered leaky, resulting in the death of cells. Here, we present a novel method to allow antibodies to penetrate the cellular membrane of living cells without affecting cell viability. A peptide (MTS, membrane transport sequence) that facilitates transport across membranes has been site-specifically attached to antibodies. MTS-antibodies enter the living cells in culture and can be detected by immunofluorescence and ELISA after extraction. Cellular structures are visualized in living cells using a specific MTS-antibody. Antibodies with membrane penetrating properties can become an important tool for the study of intra-cellular processes in living cells. Furthermore, such membrane penetrating antibodies can be used to selectively stimulate or suppress functions of the cellular machinery.

  4. Characterization of serum and mucosal antibody responses in white sturgeon (Acipenser transmontanus Richardson) following immunization with WSIV and a protein hapten antigen.

    Science.gov (United States)

    Drennan, John D; Lapatra, Scott E; Swan, Christine M; Ireland, Sue; Cain, Kenneth D

    2007-09-01

    Serum and cutaneous mucus antibodies were monitored in white sturgeon for 15 weeks following intraperitoneal immunization. Ten fish were immunized (50 microg) with white sturgeon iridovirus (WSIV) or white sturgeon gonad (WSGO) tissue culture cells emulsified with or without FCA. An additional group was immunized with FITC:KLH+FCA. Fish were booster immunized at 6 weeks. Fish immunized with FITC:KLH+FCA produced significant serum antibodies to FITC by 6 weeks and this response peaked at 12 weeks (average titer 31,000). Mucosal antibodies to FITC were first detected at 12 weeks and significantly elevated by 15 weeks (average titer 18). Anti-WSIV antibody titers were detected in the serum by 9 weeks in fish immunized with WSIV and WSIV+FCA, but only a small number responded to immunization. At 15 weeks, four fish immunized with WSIV produced serum antibodies (average titer 838) and one fish immunized with WSIV+FCA had a serum titer of 1600. Mucosal anti-WSIV antibody titers of 8 and 16 were observed in two fish from the WSIV group at 12 weeks while four different fish from this group responded at 15 weeks (average titer 4). Western Blot using a monoclonal antibody confirmed immunoglobulin in mucus, and specificity to WSIV was further demonstrated by immunocytochemistry using serum from fish immunized with WSIV. Specific antibody was not detected in mucus of fish immunized with WSIV+FCA, WSGO, or WSGO+FCA. Collectively, these experiments demonstrate that white sturgeon can generate a specific antibody response following immunization, and is the first report showing mucosal immunoglobulin is present in this species.

  5. [Inhibition of morphine intake by antibodies to serotonin-modulating anticonsolidation protein in model of self-administration in rats].

    Science.gov (United States)

    Mekhtiev, A A; Rashidova, A M; Muslimov, I A

    2014-01-01

    The article concerns study of effects of polyclonal antibodies to serotonin-modulating anticonsolidation protein (SMAP) being in direct dependence on serotonin level and providing intracellular transduction of serotonergic signal, on positive reinforcement effect of morphine in rats. The task was formed in Wistar male rats in the model of morphine self-administration as a result of pressing of one of two levers attached to the wall, joined to the pump delivering each time 100 μg of morphine directly into the vena jugularis. In the 1st series of studies brain cingulate cortex and hypothalamus were taken from the rats achieved stable level of morphine intake and SMAP level was measured with indirect immune-enzyme assay. It was shown that in the morphine-self-injected rats SMAP level in the cingulate cortex is significantly upregulated (p = 0.01), while in the hypothalamus it was left unchanged. In the 2nd series of studies the rats with stable level of morphine intake were administered intraperitoneally with anti-SMAP rabbit polyclonal antibodies (experimental group) or non-immune γ-globulins (control group). Soon after antibodies administration the animals of the experimental group demonstrated manifold decrease of morphine intake lasted for 8 days (p positive reinforcement effect of morphine. Blockade of SMAP activity with anti-SMAP antibodies in the nerve cells induced sharp decrease of morphine intake due to disturbances of transduction through intracellular serotonin's signal channels.

  6. Engineered single chain antibody fragments for radioimmunotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Huhalov, A.; Chester, K. A. [Cancer Research UK Imaging and Targeting Group Royal Free, London (United Kingdom). Department of Oncology; University College Medical School Royal Free Campus, London (United Kingdom)

    2004-12-01

    An ideal molecule to deliver radioimmunotherapy (RIT) would be target specific and have prolonged residence time at high concentrations in the tumour with rapid clearance from normal tissues. It would also be non-immunogenic. These features can be rationally introduced into recombinant antibody-based proteins using antibody engineering techniques. This reviews focuses on the use of antibody engineering in the design and development of RIT molecules which have single chain Fv (scFv) antibody fragments as building blocks.

  7. Recombinant bispecific antibodies for cancer therapy

    Institute of Scientific and Technical Information of China (English)

    Roland E KONTERMANN

    2005-01-01

    Bispecific antibodies can serve as mediators to retarget effector mechanisms to disease-associated sites. Studies over the past two decades have revealed the potentials but also the limitations of conventional bispecific antibodies. The development of recombinant antibody formats has opened up the possibility of generating bispecific molecules with improved properties. This review summarizes recent developments in the field of recombinant bispecific antibodies and discusses further requirements for clinical development.

  8. Production and Screening of Monoclonal Peptide Antibodies.

    Science.gov (United States)

    Trier, Nicole Hartwig; Mortensen, Anne; Schiolborg, Annette; Friis, Tina

    2015-01-01

    Hybridoma technology is a remarkable and indispensable tool for generating high-quality monoclonal antibodies. Hybridoma-derived monoclonal antibodies not only serve as powerful research and diagnostic reagents, but have also emerged as the most rapidly expanding class of therapeutic biologicals. In this chapter, an overview of hybridoma technology and the laboratory procedures used routinely for hybridoma production and antibody screening are presented, including characterization of peptide antibodies.

  9. Anti-DNA antibodies in SLE

    Energy Technology Data Exchange (ETDEWEB)

    Voss, E.W.

    1988-01-01

    This book contains 8 chapters. Some of the titles are: Anti-DNA Antibodies in SLE: Historical Perspective; Specificity of Anti-DNA Antibodies in Systemic Lupus Erythematosus; Monoclonial Autoimmune Anti-DNA Antibodies; and Structure--Function Analyses of Anti-DNA Autoantibodies.

  10. Nanoparticles for the delivery of therapeutic antibodies

    DEFF Research Database (Denmark)

    Sousa, Flávia; Castro, Pedro; Fonte, Pedro;

    2016-01-01

    INTRODUCTION: Over the past two decades, therapeutic antibodies have demonstrated promising results in the treatment of a wide array of diseases. However, the application of antibody-based therapy implies multiple administrations and a high cost of antibody production, resulting in costly therapy...

  11. Antibodies to staphylococcal enterotoxin in laboratory personnel.

    OpenAIRE

    Jozefczyk, Z; Robbins, R N; Spitz, J M; Bergdoll, M S

    1980-01-01

    Eighty-five percent of laboratory personnel working with staphylococcal enterotoxin had antibodies to enterotoxin in their sera, whereas only 23% of the control group had antibodies specific for enterotoxin. Two persons who carried enterotoxin B-producing staphylococci in their noses, throats, or both, had antibodies to enterotoxin B in their sera.

  12. Humanization and characterization of an anti-ricin neutralization monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Wei-Gang Hu

    Full Text Available Ricin is regarded as a high terrorist risk for the public due to its high toxicity and ease of production. Currently, there is no therapeutic or vaccine available against ricin. D9, a murine monoclonal antibody developed previously in our laboratory, can strongly neutralize ricin and is therefore a good candidate for humanization. Humanization of D9 variable regions was achieved by a complementarity-determining region grafting approach. The humanized D9 (hD9 variable regions were further grafted onto human heavy and light chain constant regions to assemble the complete antibody gene. A foot-and-mouth-disease virus-derived 2A self-processing sequence was introduced between heavy and light chain DNA sequences to cleave the recombinant protein into a functional full-length antibody molecule from a single open reading frame driven by a single promoter in an adenoviral vector. After expression in mammalian cells and purification, the hD9 was demonstrated to have equimolar expression of the full-length antibody heavy and light chains. More importantly, the hD9 exhibited high affinity to ricin with K(D of 1.63 nM, comparable to its parental murine D9 (2.55 nM. In a mouse model, intraperitoneal (i.p. administration of hD9, at a low dose of 5 µg per mouse, 4 hours after the i.p. challenge with 5×LD50 ricin was found to rescue 100% of the mice. In addition, administered 6 hours post-challenge, hD9 could still rescue 50% of the mice. The hD9 has the potential to be used for prophylactic or therapeutic purposes against ricin poisoning.

  13. Phenotypic screening: the future of antibody discovery.

    Science.gov (United States)

    Gonzalez-Munoz, Andrea L; Minter, Ralph R; Rust, Steven J

    2016-01-01

    Most antibody therapeutics have been isolated from high throughput target-based screening. However, as the number of validated targets diminishes and the target space becomes increasingly competitive, alternative strategies, such as phenotypic screening, are gaining momentum. Here, we review successful phenotypic screens, including those used to isolate antibodies against cancer and infectious agents. We also consider exciting advances in the expression and phenotypic screening of antibody repertoires in single cell autocrine systems. As technologies continue to develop, we believe that antibody phenotypic screening will increase further in popularity and has the potential to provide the next generation of therapeutic antibodies.

  14. Serum Antibody Biomarkers for ASD

    Science.gov (United States)

    2015-10-01

    their mothers in many studies (e.g., Ashwood & Van deWater, 2004; Jyonouchi et al., 2005; Molloy et al., 2006; Braunschweig et al., 2013). Systemic...against brain and CNS proteins. For example, both abnormalities in serum antibody concentrations and T cells have been reported for ASD compared to...Accomplishments: - Nearly all serum samples have been obtained and processed. - Two unique peptoid libraries have been synthesized and validated. - The peptoid

  15. Bovine milk antibodies for health.

    Science.gov (United States)

    Korhonen, H; Marnila, P; Gill, H S

    2000-11-01

    The immunoglobulins of bovine colostrum provide the major antimicrobial protection against microbial infections and confer a passive immunity to the newborn calf until its own immune system matures. The concentration in colostrum of specific antibodies against pathogens can be raised by immunising cows with these pathogens or their antigens. Immune milk products are preparations made of such hyperimmune colostrum or antibodies enriched from it. These preparations can be used to give effective specific protection against different enteric diseases in calves and suckling pigs. Colostral immunoglobulin supplements designed for farm animals are commercially available in many countries. Also, some immune milk products containing specific antibodies against certain pathogens have been launched on the market. A number of clinical studies are currently in progress to evaluate the efficacy of immune milks in the prevention and treatment of various human infections, including those caused by antibiotic resistant bacteria. Bovine colostrum-based immune milk products have proven effective in prophylaxis against various infectious diseases in humans. Good results have been obtained with products targeted against rotavirus, Shigella flexneri, Escherichia coli, Clostridium difficile, Streptococcus mutans, Cryptosporidium parvum and Helicobacter pylori. Some successful attempts have been made to use immune milk in balancing gastrointestinal microbial flora. Immune milk products are promising examples of health-promoting functional foods, or nutraceuticals. This review summarises the recent progress in the development of these products and evaluates their potential as dietary supplements and in clinical nutrition.

  16. Broadly Neutralizing Antibodies for HIV Eradication.

    Science.gov (United States)

    Stephenson, Kathryn E; Barouch, Dan H

    2016-02-01

    Passive transfer of antibodies has long been considered a potential treatment modality for infectious diseases, including HIV. Early efforts to use antibodies to suppress HIV replication, however, were largely unsuccessful, as the antibodies that were studied neutralized only a relatively narrow spectrum of viral strains and were not very potent. Recent advances have led to the discovery of a large portfolio of human monoclonal antibodies that are broadly neutralizing across many HIV-1 subtypes and are also substantially more potent. These antibodies target multiple different epitopes on the HIV envelope, thus allowing for the development of antibody combinations. In this review, we discuss the application of broadly neutralizing antibodies (bNAbs) for HIV treatment and HIV eradication strategies. We highlight bNAbs that target key epitopes, such as the CD4 binding site and the V2/V3-glycan-dependent sites, and we discuss several bNAbs that are currently in the clinical development pipeline.

  17. 9 CFR 113.452 - Erysipelothrix Rhusiopathiae Antibody.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Erysipelothrix Rhusiopathiae Antibody... REQUIREMENTS Antibody Products § 113.452 Erysipelothrix Rhusiopathiae Antibody. Erysipelothrix Rhusiopathiae Antibody is a specific antibody product containing antibodies directed against one or more somatic...

  18. Advances in monoclonal antibody application in myocarditis

    Institute of Scientific and Technical Information of China (English)

    Li-na HAN; Shuang HE; Yu-tang WANG; Li-ming YANG; Si-yu LIU; Ting ZHANG

    2013-01-01

    Monoclonal antibodies have become a part of daily preparation technologies in many laboratories.Attempts have been made to apply monoclonal antibodies to open a new train of thought for clinical treatments of autoimmune diseases,inflammatory diseases,cancer,and other immune-associated diseases.This paper is a prospective review to anticipate that monoclonal antibody application in the treatment of myocarditis,an inflammatory disease of the heart,could be a novel approach in the future.In order to better understand the current state of the art in monoclonal antibody techniques and advance applications in myocarditis,we,through a significant amount of literature research both domestic and abroad,developed a systematic elaboration of monoclonal antibodies,pathogenesis of myocarditis,and application of monoclonal antibodies in myocarditis.This paper presents review of the literature of some therapeutic aspects of monoclonal antibodies in myocarditis and dilated cardiomyopathy to demonstrate the advance of monoclonal antibody application in myocarditis and a strong anticipation that monoclonal antibody application may supply an effective therapeutic approach to relieve the severity of myocarditis in the future.Under conventional therapy,myocarditis is typically associated with congestive heart failure as a progressive outcome,indicating the need for alternative therapeutic strategies to improve long-term results.Reviewing some therapeutic aspects of monoclonal antibodies in myocarditis,we recently found that monoclonal antibodies with high purity and strong specificity can accurately act on target and achieve definite progress in the treatment of viral myocarditis in rat model and may meet the need above.However,several issues remain.The technology on howto make a higher homologous and weak immunogenic humanized or human source antibody and the treatment mechanism of monoclonal antibodies may provide solutions for these open issues.If we are to further stimulate

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

    Directory of Open Access Journals (Sweden)

    Mozhgan Torabi

    2014-06-01

    Full Text Available Objective: 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. Materials and Methods: 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 naloxone (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. Results: 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 anxiolytic 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. Conclusion: It seems that the opioidergic system activity involved in the anxiolytic effect of nano and conventional ZnO may operate through shared and unshared pathways.

  20. Monoclonal antibodies to intermediate filament proteins of human cells: unique and cross-reacting antibodies.

    Science.gov (United States)

    Gown, A M; Vogel, A M

    1982-11-01

    Monoclonal antibodies were generated against the intermediate filament proteins of different human cells. The reactivity of these antibodies with the different classes of intermediate filament proteins was determined by indirect immunofluorescence on cultured cells, immunologic indentification on SDS polyacrylamide gels ("wester blot" experiments), and immunoperoxidase assays on intact tissues. The following four antibodies are described: (a) an antivimentin antibody generated against human fibroblast cytoskeleton; (b), (c) two antibodies that recognize a 54-kdalton protein in human hepatocellular carcinoma cells; and (d) an antikeratin antibody made to stratum corneum that recognizes proteins of molecular weight 66 kdaltons and 57 kdaltons. The antivimentin antibody reacts with vimentin (58 kdaltons), glial fibrillary acidic protein (GFAP), and keratins from stratum corneum, but does not recognize hepatoma intermediate filaments. In immunofluorescence assays, the antibody reacts with mesenchymal cells and cultured epithelial cells that express vimentin. This antibody decorates the media of blood vessels in tissue sections. One antihepatoma filament antibody reacts only with the 54 kdalton protein of these cells and, in immunofluorescence and immunoperoxidase assays, only recognizes epithelial cells. It reacts with almost all nonsquamous epithelium. The other antihepatoma filament antibody is much less selective, reacting with vimentin, GFAP, and keratin from stratum corneum. This antibody decorates intermediate filaments of both mesenchymal and epithelial cells. The antikeratin antibody recognizes 66-kdalton and 57-kdalton proteins in extracts of stratum corneum and also identifies proteins of similar molecular weights in all cells tested. However, by immunofluorescence, this antibody decorates only the intermediate filaments of epidermoid carcinoma cells. When assayed on tissue sections, the antibody reacts with squamous epithelium and some, but not all

  1. Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

    Directory of Open Access Journals (Sweden)

    Yağmur Derman

    2016-09-01

    Full Text Available Botulinum neurotoxins (BoNTs cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential use as bioweapons. To counter bio-threat and naturally-occurring botulism cases, well-tolerated antibodies by humans that neutralize BoNTs are relevant. In our previous work, we showed the neutralizing potential of macaque (Macaca fascicularis-derived scFv-Fc (scFv-Fc ELC18 by in vitro endopeptidase immunoassay and ex vivo mouse phrenic nerve-hemidiaphragm assay by targeting the light chain of the botulinum neurotoxin type E (BoNT/E. In the present study, we germline-humanized scFv-Fc ELC18 into a full IgG hu8ELC18 to increase its immunotolerance by humans. We demonstrated the protection and prophylaxis capacity of hu8ELC18 against BoNT/E in a mouse model. A concentration of 2.5 ng/mouse of hu8ELC18 protected against 5 mouse lethal dose (MLD in a mouse protection assay and complete neutralization of 1 LD50 of pure BoNT/E toxin was achieved with 8 ng of hu8ELC18 in mouse paralysis assay. Furthermore, hu8ELC18 protected mice from 5 MLD if injected up to 14 days prior to intraperitoneal BoNT/E administration. This newly-developed humanized IgG is expected to have high tolerance in humans.

  2. Neutralization of Botulinum Neurotoxin Type E by a Humanized Antibody

    Science.gov (United States)

    Derman, Yağmur; Selby, Katja; Miethe, Sebastian; Frenzel, André; Liu, Yvonne; Rasetti-Escargueil, Christine; Avril, Arnaud; Pelat, Thibaut; Urbain, Remi; Fontayne, Alexandre; Thullier, Philippe; Sesardic, Dorothea; Lindström, Miia; Hust, Michael; Korkeala, Hannu

    2016-01-01

    Botulinum neurotoxins (BoNTs) cause botulism and are the deadliest naturally-occurring substances known to humans. BoNTs have been classified as one of the category A agents by the Centers for Disease Control and Prevention, indicating their potential use as bioweapons. To counter bio-threat and naturally-occurring botulism cases, well-tolerated antibodies by humans that neutralize BoNTs are relevant. In our previous work, we showed the neutralizing potential of macaque (Macaca fascicularis)-derived scFv-Fc (scFv-Fc ELC18) by in vitro endopeptidase immunoassay and ex vivo mouse phrenic nerve-hemidiaphragm assay by targeting the light chain of the botulinum neurotoxin type E (BoNT/E). In the present study, we germline-humanized scFv-Fc ELC18 into a full IgG hu8ELC18 to increase its immunotolerance by humans. We demonstrated the protection and prophylaxis capacity of hu8ELC18 against BoNT/E in a mouse model. A concentration of 2.5 ng/mouse of hu8ELC18 protected against 5 mouse lethal dose (MLD) in a mouse protection assay and complete neutralization of 1 LD50 of pure BoNT/E toxin was achieved with 8 ng of hu8ELC18 in mouse paralysis assay. Furthermore, hu8ELC18 protected mice from 5 MLD if injected up to 14 days prior to intraperitoneal BoNT/E administration. This newly-developed humanized IgG is expected to have high tolerance in humans. PMID:27626446

  3. Generation of monospecific antibodies based on affinity capture of polyclonal antibodies.

    Science.gov (United States)

    Hjelm, Barbara; Forsström, Björn; Igel, Ulrika; Johannesson, Henrik; Stadler, Charlotte; Lundberg, Emma; Ponten, Fredrik; Sjöberg, Anna; Rockberg, Johan; Schwenk, Jochen M; Nilsson, Peter; Johansson, Christine; Uhlén, Mathias

    2011-11-01

    A method is described to generate and validate antibodies based on mapping the linear epitopes of a polyclonal antibody followed by sequential epitope-specific capture using synthetic peptides. Polyclonal antibodies directed towards four proteins RBM3, SATB2, ANLN, and CNDP1, potentially involved in human cancers, were selected and antibodies to several non-overlapping epitopes were generated and subsequently validated by Western blot, immunohistochemistry, and immunofluorescence. For all four proteins, a dramatic difference in functionality could be observed for these monospecific antibodies directed to the different epitopes. In each case, at least one antibody was obtained with full functionality across all applications, while other epitope-specific fractions showed no or little functionality. These results present a path forward to use the mapped binding sites of polyclonal antibodies to generate epitope-specific antibodies, providing an attractive approach for large-scale efforts to characterize the human proteome by antibodies.

  4. The tissue distribution of diazinon and the inhibition of blood cholinesterase activities in rats and mice receiving a single intraperitoneal dose of diazinon.

    Science.gov (United States)

    Tomokuni, K; Hasegawa, T; Hirai, Y; Koga, N

    1985-10-01

    The tissue distribution of diazinon and the inhibition of cholinesterase (ChE) activities in plasma, erythrocyte and brain were investigated using male rats and mice which received a single intraperitoneal (i.p.) dose of diazinon (20 or 100 mg/kg body wt) in olive oil. The blood diazinon level was estimated to reach a maximum at 1-2 h after the i.p. administration. It was demonstrated that the diazinon residue levels are the highest in the kidney, when comparing the distribution of diazinon among liver, kidney and brain in the animals after dosing. It was indicated that the ChE inhibition by diazinon exposure is greater in the plasma than in the erythrocytes for male mice, while its inhibition is greater in the erythrocytes for male rats. Brain ChE activity was also inhibited markedly in the mice after dosing.

  5. Surface activity of a monoclonal antibody.

    Science.gov (United States)

    Mahler, Hanns-Christian; Senner, Frank; Maeder, Karsten; Mueller, Robert

    2009-12-01

    The development of high concentration antibody formulations presents a major challenge for the formulation scientist, as physical characteristics and stability behavior change compared to low concentration protein formulations. The aim of this study was to investigate the potential correlation between surface activity and shaking stress stability of a model antibody-polysorbate 20 formulation. The surface activities of pure antibody and polysorbate 20 were compared, followed by a study on the influence of a model antibody on the apparent critical micelle concentration (CMC) of polysorbate 20 over a protein concentration range from 10 to 150 mg/mL. In a shaking stress experiment, the stability of 10, 75, and 150 mg/mL antibody formulations was investigated containing different concentrations of polysorbate 20, both below and above the CMC. The antibody increased significantly the apparent CMC of antibody-polysorbate 20 mixtures in comparison to the protein-free buffer. However, the concentration of polysorbate required for stabilization of the model antibody in a shaking stress experiment did not show dependence on the CMC. A polysorbate 20 level of 0.005% was found sufficient to stabilize both at low and high antibody concentration against antibody aggregation and precipitation.

  6. The Anatomic Pathology Evaluation of Liver with Diethylinitrosamine Treated via Intraperitoneal Injection Singly and Peros for 90 Days Carcinogenicity Study in F344 Rats

    Institute of Scientific and Technical Information of China (English)

    LI Shan-shan; KANEKO Toyozo; XING Rui-chang; WANG Xiu-wen; LI Bo; ZHANG Lin; LI Bao-wen; LANG Shu-hui; YANG Yan-wei; ZHANG Di; ZHANG Yang; NARAMA Isao; KAWAYI Zeshow

    2008-01-01

    Objective:To establish the integrity experiment method of short(medium)-term carcinogenicity test pursuant to GLP, make into relative SOP and improve the safeguard in the center.Methods:Diethylinitrosamine(DEN) is known as carcinogenic agent,whose target organ is liver. Using the two-stage carcinogenesis test method, DEN was treated to F344 rats via intraperitoneal injection singly(200 mg/kg), and peros administrated for 90 days(10 ppm). The liver in any group rat will be examined by light microscopy.Results:In pathologic examination, no liver cell tumor was shown in the livers of the rats that were singly treated with a carcinogenic chemical-DEN.Foci of cellular alteration were observed in the livers of these rats. The proliferation lesions of liver from slight to seveity(foci of cellular alteration-hepatocelluar adenoma-hepatocellular carcinoma)were observed in the livers of the rats which exposed peros to a low dose of DEN for 90 days after initiation by a single intraperitoneal injection. The incidence of hepatocelluar tumor was 35% in male animal,which was not shown in the liver of female rat.Conclusion:For current results, it may be possible that low-dose DEN acts as a promotor of hepatocelluar tumor if it was exposed in a population for a long time. It is considered that male hormone has a synergistic effect on hepatocelluar tumor development of DEN. This two-stage carcinogenesis test might be a new model for the study of drug induced and promoted carcinogenesis,which could be used to evaluate the carcinogenesis of chemical compound fast.

  7. Effect of S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion treatment on malignant molecule expression in gastric cancer patients with ascites as well as side effect assessment

    Institute of Scientific and Technical Information of China (English)

    Shuo Jian

    2016-01-01

    Objective:To study the effect of S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion on malignant molecule expression in gastric cancer patients with ascites as well as the related side effect.Methods: Gastric cancer patients with ascites who were treated in our hospital from February 2012 to July 2015 were selected as research subjects and randomly divided into perfusion chemotherapy group and routine chemotherapy group, and then overall chemotherapy conditions, ascites FGF molecule content, peripheral blood immune function indexes and the degree of side effect were compared between two groups. Results:Average treatment cycles of perfusion chemotherapy group were more than those of routine chemotherapy group, and ascites drainage volume within two cycles of chemotherapy was significantly less than that of routine chemotherapy group; after two cycles of chemotherapy, bFGF, FGF-2, FGF19 and FGFR4 content in ascites of perfusion chemotherapy group were significantly lower than those of routine chemotherapy group, CD3+CD4+, CD3+CD56+ and CD3-CD56+ cell content in peripheral blood were higher than those of routine chemotherapy group, and CD3+CD8+ cell content was lower than that of routine chemotherapy group; during chemotherapy, the number of cases with decreased numeration of leukocyte, abnormal liver function, abnormal kidney function and diarrhea of perfusion chemotherapy group were significantly lower than those of routine chemotherapy group.Conclusions: S-1 combined with cisplatin intraperitoneal circulatory hyperthermia perfusion chemotherapy can more effectively improve treatment compliance, suppress ascites, kill gastric cancer cells and improve immune function. It has fewer side effect and is the ideal way to treat gastric cancer with ascites.

  8. Unresectable gastric cancer with gastric outlet obstruction and distant metastasis responding to intraperitoneal and folfox chemotherapy after palliative laparoscopic gastrojejunostomy: report of a case

    Directory of Open Access Journals (Sweden)

    Park Joong-Min

    2010-12-01

    Full Text Available Abstract Background Gastric outlet obstruction (GOO caused by unresectable gastric cancer is a challenging aspect of patient care. There have been no reports involving patients with obstructing gastric cancer and several incurable factors curatively treated by multimodal treatments. Case presentation We report a case of 55-year-old man who was diagnosed with a poorly differentiated adenocarcinoma in the pre-pyloric antrum with GOO by gastroscopy. An abdominal computed tomography (CT scan revealed thickening of the gastric wall and adjacent fat infiltration, and a large amount of food in the stomach suggesting a passage disturbance, enlarged lymph nodes along the common hepatic and left gastric arteries, and multiple hepatic metastases. The serum carcinoembryonic antigen (CEA level was 343 ng/ml and the carbohydrate antigen (CA 19-9 level was within normal limits. The patient underwent a laparoscopic gastrojejunostomy for palliation of the GOO. On the 3rd and 12th days after surgery, he received intraperitoneal chemotherapy with 40 mg of docetaxel and 150 mg of carboplatin. Simultaneously, combined chemotherapy with 85 mg/m2 of oxaliplatin for the 1st day and 600 mg/m2 of 5-FU for 2 days (FOLFOX regimen was administered from the 8th post-operative day. After completion of nine courses of FOLFOX, the patient achieved a complete response (CR with complete disappearance of the primary tumor and the metastatic foci. He underwent a radical subtotal gastrectomy with D3 lymph node dissection 4 months after the initial palliative surgery. The pathologic results revealed no residual primary tumor and no lymph node metastasis in 43 dissected lymph nodes. He has maintained a CR for 18 months since the last operation. Conclusion Combination chemotherapy with systemic and intraperitoneal chemotherapy following laparoscopic bypass surgery showed marked efficacy in the treatment for unresectable advanced gastric cancer with GOO.

  9. Neonatal intraperitoneal or intravenous injections of recombinant adeno-associated virus type 8 transduce dorsal root ganglia and lower motor neurons.

    Science.gov (United States)

    Foust, Kevin D; Poirier, Amy; Pacak, Christina A; Mandel, Ronald J; Flotte, Terence R

    2008-01-01

    Targeting lower motor neurons (LMNs) for gene delivery could be useful for disorders such as spinal muscular atrophy and amyotrophic lateral sclerosis. LMNs reside in the ventral gray matter of the spinal cord and send axonal projections to innervate skeletal muscle. Studies have used intramuscular injections of adeno-associated virus type 2 (AAV2) to deliver viral vectors to LMNs via retrograde transport. However, treating large areas of the spinal cord in a human would require numerous intramuscular injections, thereby increasing viral titer and risk of immune response. New AAV serotypes, such as AAV8, have a dispersed transduction pattern after intravenous or intraperitoneal injection in neonatal mice, and may transduce LMNs by retrograde transport or through entry into the nervous system. To test LMN transduction after systemic injection, we administered recombinant AAV8 (rAAV8) carrying the green fluorescent protein (GFP) gene by intravenous or intraperitoneal injection to neonatal mice on postnatal day 1. Tissues were harvested 5 and 14 days postinjection and analyzed by real-time polymerase chain reaction and GFP immunohistochemistry to assess the presence of AAV genomes and GFP expression, respectively. Spinal cords were positive for AAV genomes at both time points. GFP immunohistochemistry revealed infrequent labeling of LMNs across all time points and injection routes. Somewhat surprisingly, there was extensive labeling of fibers in the dorsal horns and columns, indicating dorsal root ganglion transduction across all time points and injection routes. Our data suggest that systemic injection of rAAV8 is not an effective delivery route to target lower motor neurons, but could be useful for targeting sensory pathways in chronic pain.

  10. An antibody of TNF-alpha did not prevent thioacetamide-induced hepatotoxicity in rats.

    Science.gov (United States)

    Demirel, Ulvi; Harputluoglu, Murat M M; Seckin, Yuksel; Ciralik, Harun; Temel, Ismail; Ozyalin, Fatma; Otlu, Baris; Yilmaz, Bilgic; Dincturk, Mehmet Sarp; Aladag, Hulya

    2011-07-01

    Tumor necrosis factor (TNF)-α antibodies have been shown to reduce liver damage in different models. We investigated the effects of infliximab (a TNF-α antibody) on liver damage in thioacetamide (TAA)-induced hepatotoxicity in rats. Group 1 (n = 8) was the control group. In group 2 (n = 8), the TAA group, the rats received 300 mg/kg intraperitoneal (ip) TAA daily for 2 days. In group 3 (n = 8), the TAA + Infliximab (INF) group, infliximab (5 mg/kg ip daily) was administered 48 hours before the first dose of TAA daily for 2 days and was maintained for 4 consecutive days. In group 4 (n = 8), the INF group, the rats received only ip infliximab (5 mg/kg) daily. Livers were excised for histopathological and biochemical tests (thiobarbituric-acid-reactive substances [TBARS], and myeloperoxidase [MPO]). Serum ammonia, aspartate transaminase (AST), alanine transaminase (ALT), TNF-α, liver TBARS and MPO levels, and liver necrosis and inflammation scores in the TAA group were significantly higher than in the control and INF groups (all p induced hepatotoxicity, and infliximab does not improve oxidative liver damage.

  11. Conformation-Dependent High-Affinity Potent Ricin-Neutralizing Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Wei-Gang Hu

    2013-01-01

    Full Text Available Ricin is a potential biothreat agent with no approved antidote available for ricin poisoning. The aim of this study was to develop potent antibody-based antiricin antidotes. Four strong ricin resistant hybridoma clones secreting antiricin monoclonal antibodies (mAbs were developed. All four mAbs are bound to conformational epitopes of ricin toxin B (RTB with high affinity (KD values from 2.55 to 36.27 nM. RTB not only triggers cellular uptake of ricin, but also facilitates transport of the ricin toxin A (RTA from the endoplasmic reticulum to the cytosol, where RTA exerts its toxic activity. The four mAbs were found to have potent ricin-neutralizing capacities and synergistic effects among them as determined by an in vitro neutralization assay. In vivo protection assay demonstrated that all four mAbs had strong efficacy against ricin challenges. D9 was found to be exceptionally effective. Intraperitoneal (i.p. administration of D9, at a dose of 5 μg, 6 weeks before or 6 hours after an i.p. challenge with 5 × LD50 of ricin was able to protect or rescue 100% of the mice, indicating that mAb D9 is an excellent candidate to be developed as a potent antidote against ricin poisoning for both prophylactic and therapeutic purposes.

  12. Effects of the Sheep Polyclonal Antibodies Against the Porcine Adipocyte Plasma Membrane Proteins on Porcine Carcass Composition and Meat Quality

    Institute of Scientific and Technical Information of China (English)

    GAO Shi-zheng; HU Hong-mei; LIU Ling-yun; ZHANG Xi; LIU Yong-gang; GE Chang-rong

    2007-01-01

    To detect the effects of the polyclonal antibodies raised in sheep against porcine adipocyte plasma membranes on the porcine carcass composition and meat quality, 30 pigs assigned into 6 treatment groups were given intraperitoneal injections of sheep antipig adipocyte plasma membrane immunoglobulin (ASIg) or sheep nonimmune serum immunoglobulin (NSIg). At the end of the experiment, the pigs were slaughtered at 90 kg body weight, and carcasses and meat quality were evaluated. The results showed that when pigs intraperitoneally immunized with 20 or 30 mg ASIg at 15 kg body weight, 20 mg purified ASIg twice at 15 and 60 kg body weight, or 20 mg purified ASIg at 60 kg body weight, respectively, their lean meat percentage, fat meat percentage, backfat thickness, loin eye area leaf fat weight, caul fat weight, heart weight, liver weight, and kidney weight were significantly affected. However, the kidney weight, lung weight, dressing percentage,and spleen weight did not remarkably change. Our results indicated that pigs intraperitoneally immunized with 20 or 30 mg ASIg at 15 kg body weight, and 20 mg ASIg twice at 15 and 60 kg body weight, have significantly different drip loss rate,cooked meat ratio, tenderness, storage loss rate, muscle fiber diameter, moisture content, dry matter content, crude protein content, and crude fat content from the control group that received 20 mg NSIg at 15 kg body weight. However, meat pH,meat color value, meat marbling score, inosinate, and myohemoglobin were not significantly affected. Our results indicated ASIg could not significantly affect the content of most muscular amino acids and intramuscular fatty acids.

  13. Controlled delivery of antibodies from injectable hydrogels.

    Science.gov (United States)

    Fletcher, Nathan A; Babcock, Lyndsey R; Murray, Ellen A; Krebs, Melissa D

    2016-02-01

    Therapeutic antibodies are currently used for the treatment of various diseases, but large doses delivered systemically are typically required. Localized controlled delivery techniques would afford major benefits such as decreasing side effects and required doses. Injectable biopolymer systems are an attractive solution due to their minimally invasive potential for controlled release in a localized area. Here, alginate-chitosan hydrogels are demonstrated to provide controlled delivery of IgG model antibodies and also of Fab antibody fragments. Also, an alternate delivery system comprised of poly(lactic-co-glycolic acid) (PLGA) microspheres loaded with antibodies and encapsulated in alginate was shown to successfully provide another level of control over release. These biopolymer systems that offer controlled delivery for antibodies and antibody fragments will be promising for many applications in drug delivery and regenerative medicine.

  14. Antibody response to measles immunization in India*

    OpenAIRE

    Job, J. S.; John, T J; Joseph, A.

    1984-01-01

    Antibody response to measles vaccine was measured in 238 subjects aged 6-15 months. Seroconversion rates ranged from 74% at 6 months of age to 100% at 13-15 months; the differences in age-specific rates were not statistically significant. The postimmunization antibody titres increased with increasing age of the vaccinee. Seroconversion rates and antibody titres in 49 subjects with grades I and II malnutrition were not significantly different from those in the 189 normal subjects.

  15. Antiphospholipid Antibodies and Systemic Scleroderma

    Directory of Open Access Journals (Sweden)

    Awa Oumar Touré

    2013-03-01

    Full Text Available Objective: Antiphospholipid antibodies (APLs could be associated with an increased risk of vascular pathologies in systemic scleroderma. The aim of our study was to search for APLs in patients affected by systemic scleroderma and to evaluate their involvement in the clinical manifestations of this disease. Materials and Methods: We conducted a cross-sectional descriptive study, from January 2009 until August 2010, with patients received at the Department of Dermatology (Dakar, Senegal. Blood samples were taken at the hematology laboratory and were analyzed for the presence of APLs. Results: Forty patients were recruited. Various types of either isolated or associated APLs were found in 23 patients, i.e. 57.5% of the study population. The most frequently encountered antibody was IgG anti-β2 GPI (37.5% of the patients, followed by anticardiolipins (17.5% and lupus anticoagulants (5%. No statistically significant association of positive antiphospholipid-related tests to any of the scleroderma complications could be demonstrated. Conclusion: A high proportion of patients showing association of systemic scleroderma and APLs suggests the presence of a morbid correlation between these 2 pathologies. It would be useful to follow a cohort of patients affected by systemic scleroderma in order to monitor vascular complications following confirmation of the presence of antiphospholipid syndrome.

  16. Antibody engineering and therapeutics, The Annual Meeting of the Antibody Society: December 8-12, 2013, Huntington Beach, CA.

    Science.gov (United States)

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul W H I; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates.

  17. 6th Annual European Antibody Congress 2010

    Science.gov (United States)

    2011-01-01

    The 6th European Antibody Congress (EAC), organized by Terrapinn Ltd., was held in Geneva, Switzerland, which was also the location of the 4th and 5th EAC.1,2 As was the case in 2008 and 2009, the EAC was again the largest antibody congress held in Europe, drawing nearly 250 delegates in 2010. Numerous pharmaceutical and biopharmaceutical companies active in the field of therapeutic antibody development were represented, as were start-up and academic organizations and representatives from the US Food and Drug Administration (FDA). The global trends in antibody research and development were discussed, including success stories of recent marketing authorizations of golimumab (Simponi®) and canakinumab (Ilaris®) by Johnson & Johnson and Novartis, respectively, updates on antibodies in late clinical development (obinutuzumab/GA101, farletuzumab/MORAb-003 and itolizumab/T1 h, by Glycart/Roche, Morphotek and Biocon, respectively) and success rates for this fast-expanding class of therapeutics (Tufts Center for the Study of Drug Development). Case studies covering clinical progress of girentuximab (Wilex), evaluation of panobacumab (Kenta Biotech), characterization of therapeutic antibody candidates by protein microarrays (Protagen), antibody-drug conjugates (sanofi-aventis, ImmunoGen, Seattle Genetics, Wyeth/Pfizer), radio-immunoconjugates (Bayer Schering Pharma, Université de Nantes) and new scaffolds (Ablynx, AdAlta, Domantis/GlaxoSmithKline, Fresenius, Molecular Partners, Pieris, Scil Proteins, Pfizer, University of Zurich) were presented. Major antibody structural improvements were showcased, including the latest selection engineering of the best isotypes (Abbott, Pfizer, Pierre Fabre), hinge domain (Pierre Fabre), dual antibodies (Abbott), IgG-like bispecific antibodies (Biogen Idec), antibody epitope mapping case studies (Eli Lilly), insights in FcγRII receptor (University of Cambridge), as well as novel tools for antibody fragmentation (Genovis). Improvements

  18. Isoimmunization with anti-U antibody.

    Science.gov (United States)

    Turner, R J; Holder, W T; McCord, D L

    1984-03-01

    Isoimmunization with anti-U antibody is a rare but significant cause of hemolytic disease in black newborns. In this case report, an lgG antibody stimulated by fetomaternal transfusion produced a positive direct Coombs' test on cord blood but not neonatal hyperbilirubinemia. A review of the literature suggests the pathophysiology is similar to Rh isoimmunization. The anti-U antibody may develop as a result of pregnancy or blood transfusion in the 1.2 percent of American blacks who are at risk for developing the antibody. The principles of treatment employed in Rh isoimmunization can be successfully used in isoimmunization due to anti-U.

  19. Exceptional Antibodies Produced by Successive Immunizations.

    Directory of Open Access Journals (Sweden)

    Patricia J Gearhart

    2015-12-01

    Full Text Available Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.

  20. Single-domain antibodies for biomedical applications.

    Science.gov (United States)

    Krah, Simon; Schröter, Christian; Zielonka, Stefan; Empting, Martin; Valldorf, Bernhard; Kolmar, Harald

    2016-01-01

    Single-domain antibodies are the smallest antigen-binding units of antibodies, consisting either only of one variable domain or one engineered constant domain that solely facilitates target binding. This class of antibody derivatives comprises naturally occurring variable domains derived from camelids and sharks as well as engineered human variable or constant antibody domains of the heavy or light chain. Because of their high affinity and specificity as well as stability, small size and benefit of multiple re-formatting opportunities, those molecules emerged as promising candidates for biomedical applications and some of these entities have already proven to be successful in clinical development.

  1. Exacerbation of Acanthamoeba keratitis in animals treated with anti-macrophage inflammatory protein 2 or antineutrophil antibodies.

    Science.gov (United States)

    Hurt, M; Apte, S; Leher, H; Howard, K; Niederkorn, J; Alizadeh, H

    2001-05-01

    Neutrophils are thought to be involved in many infectious diseases and have been found in high numbers in the corneas of patients with Acanthamoeba keratitis. Using a Chinese hamster model of keratitis, conjunctival neutrophil migration was manipulated to determine the importance of neutrophils in this disease. Inhibition of neutrophil recruitment was achieved by subconjunctival injection with an antibody against macrophage inflammatory protein 2 (MIP-2), a powerful chemotactic factor for neutrophils which is secreted by the cornea. In other experiments, neutrophils were depleted by intraperitoneal injection of anti-Chinese hamster neutrophil antibody. The inhibition of neutrophils to the cornea resulted in an earlier onset and more severe infection compared to controls. Anti-MIP-2 antibody treatment produced an almost 35% reduction of myeloperoxidase activity in the cornea 6 days postinfection, while levels of endogenous MIP-2 secretion increased significantly. Recruitment of neutrophils into the cornea via intrastromal injections of recombinant MIP-2 generated an initially intense inflammation that resulted in the rapid resolution of the corneal infection. The profound exacerbation of Acanthamoeba keratitis seen when neutrophil migration was inhibited, combined with the rapid clearing of the disease in the presence of increased neutrophils, strongly suggests that neutrophils play an important role in combating Acanthamoeba infections in the cornea.

  2. Monoclonal Antibody Targeting Staphylococcus aureus Surface Protein A (SasA) Protect Against Staphylococcus aureus Sepsis and Peritonitis in Mice.

    Science.gov (United States)

    Yang, Yilong; Qian, Mengying; Yi, Shaoqiong; Liu, Shuling; Li, Bing; Yu, Rui; Guo, Qiang; Zhang, Xiaopeng; Yu, Changming; Li, Jianmin; Xu, Junjie; Chen, Wei

    2016-01-01

    Epidemic methicillin-resistant Staphylococcus aureus (MRSA) imposes an increasing impact on public health. Due to multi-antibiotics resistance in MRSA strains, there is an urgent need to develop novel therapeutics such as effective monoclonal antibodies (mAbs) against MRSA infections. Staphylococcus aureus surface protein A (SasA), a large surface-located protein (~240 kDa), is one of MSCRAMMs (microbial surface components recognizing adhesive matrix molecules) and a potential target for immunotherapeutic approaches against S. aureus infections. In the present study, we analyzed the sequence of SasA with bioinformatics tools and generated a protective monoclonal antibody (2H7) targeting the conserved domain of SasA. 2H7 was shown to recognize wild-type S. aureus and promote opsonophagocytic killing of S. aureus. In both sepsis and peritoneal infection models, prophylactic administration of 2H7 improved the survival of BALB/c mice challenged by S. aureus strain USA300 and ST239 (prevalent MRSA clones in North America and Asian countries, respectively) and enhanced bacterial clearance in kidneys. Additionally, 2H7 prophylaxis prevented the formation of intraperitoneal abscess in a murine model of peritoneal infection and therapeutic administration of 2H7 showed protective efficacy in a murine sepsis model. Our results presented here provide supporting evidences that an anti-SasA mAb might be a potential component in an antibody-based immunotherapeutic treatment of MRSA infections.

  3. An efficient method for isolating antibody fragments against small peptides by antibody phage display

    DEFF Research Database (Denmark)

    Duan, Zhi; Siegumfeldt, Henrik

    2010-01-01

    We generated monoclonal scFv (single chain variable fragment) antibodies from an antibody phage display library towards three small synthetic peptides derived from the sequence of s1-casein. Key difficulties for selection of scFv-phages against small peptides were addressed. Small peptides do....... The scFvs were sequenced and characterized, and specificity was characterized by ELISA. The methods developed in this study are universally applicable for antibody phage display to efficiently produce antibody fragments against small peptides....

  4. The time-course of hindbrain neuronal activity varies according to location during either intraperitoneal or subcutaneous tumor growth in rats: single Fos and dual Fos/dopamine β-hydroxylase immunohistochemistry.

    Science.gov (United States)

    Lackovicova, Lubica; Gaykema, Ronald P; Banovska, Lucia; Kiss, Alexander; Goehler, Lisa E; Mravec, Boris

    2013-07-15

    Neuronal activity in the nucleus of the solitary tract, ventrolateral medulla, area postrema, and parabrachial nucleus was studied in rats with intraperitoneal or subcutaneous tumors on the 7th, 14th, 21st, and 28th day after injection of fibrosarcoma tumor cells. We found that the number of Fos and dopamine β-hydroxylase immunopositive neurons differs between animals with intraperitoneal and subcutaneous tumors and also between tumor-bearing rats at different times following injection. Our data indicate that responses of the brainstem structures to peripheral tumor growth depend on the localization as well as the stage of the tumor growth.

  5. The production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi

    NARCIS (Netherlands)

    Joosten, V.; Lokman, C.; Hondel, C.A.M.J.J. van den; Punt, P.J.

    2003-01-01

    In this review we will focus on the current status and views concerning the production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi. We will focus on single-chain antibody fragment production (scFv and VHH) by these lower eukaryotes and the possible applications

  6. Effects of the Monoclonal Antibody against Porcine 40 kDa Adipocyte-specific Plasma Membrane Protein on Adipocytes and Carcass Composition

    Institute of Scientific and Technical Information of China (English)

    Shizheng GAO; Changrong GE; Xi ZHANG; Yonggang LIU

    2007-01-01

    The effects of the mouse monoclonal antibody against 40 kDa adipocyte-specific plasma membrane protein on porcine adipocytes and carcass composition were investigated in vitro and in vivo.Results revealed that the in vitro complement-mediated cytotoxicity of this monoclonal antibody can lead to adipocyte lysis, remarkable reduction of adipocyte lipid accumulation (P<0.01), and significant decrease of well-differentiated fat cells (P<0.01). Treatment of adipocytes with this antibody alone in vitro did not induce cell lysis, but could lead to noticeable reduction of well-differentiated cells and lipid accumulation (P<0.05) at the pre-adipocyte stage. In vivo, pigs injected with 0.5 mg/kg or 1.0 mg/kg of antibody showed smaller adipocyte sizes (P<0.01) and reduced lipid accumulation of adipocytes (P<0.01). Our results also indicated that pigs intraperitoneally or subcutaneously immunized with 0.5 mg/kg of monoclonal antibody at 15 kg or 1.0 mg/kg antibody at 60 kg had a higher lean meat percentage (P<0.05), larger loin eye area (P<0.05), lower fat meat percentage (P<0.05), less backfat thickness (P<0.05) and smaller leaf fat weight (P<0.05) than the control pigs, but other carcass traits such as caul fat weight, heart weight, liver weight, spleen weight,kidney weight, lung weight, and dressing percentage were not significantly affected. These results suggested that this monoclonal antibody could be applied to restrain excessive fat deposition in porcine production.

  7. Immunological characteristics of outer membrane protein omp31 of goat Brucella and its monoclonal antibody.

    Science.gov (United States)

    Zheng, W Y; Wang, Y; Zhang, Z C; Yan, F

    2015-10-05

    We examined the immunological characteristics of outer membrane protein omp31 of goat Brucella and its monoclonal antibody. Genomic DNA from the M5 strain of goat Brucella was amplified by polymerase chain reaction and cloned into the prokaryotic expression vector pGEX-4T-1. The expression and immunological characteristics of the fusion protein GST-omp31 were subjected to preliminary western blot detection with goat Brucella rabbit immune serum. The Brucella immunized BALB/c mouse serum was detected using purified protein. The high-potency mouse splenocytes and myeloma Sp2/0 cells were fused. Positive clones were screened by enzyme-linked immunosorbent assay to establish a hybridoma cell line. Mice were inoculated intraperitoneally with hybridoma cells to prepare ascites. The mAb was purified using the n-caprylic acid-ammonium sulfate method. The characteristics of mAb were examined using western blotting and enzyme-linked immunosorbent assay. A 680-base pair band was observed after polymerase chain reaction. Enzyme digestion identification and sequencing showed that the pGEX-4T-1-omp31 prokaryotic expression vector was successfully established; a target band of approximately 57 kDa with an apparent molecular weight consistent with the size of the target fusion protein. At 25°C, the expression of soluble expression increased significantly; the fusion protein GST-omp31 was detected by western blotting. Anti-omp31 protein mAb was obtained from 2 strains of Brucella. The antibody showed strong specificity and sensitivity and did not cross-react with Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Mycobacterium tuberculosis, or Bacillus pyocyaneus. The pGEX-4T-1-omp31 prokaryotic expression vector was successfully established and showed good immunogenicity. The antibody also showed strong specificity and good sensitivity.

  8. Aktivitas polisakarida krestin dari ekstrak Coriolus versicolor terhadap peningkatan antibodi Mus musculus akibat paparan Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Sri Puji Astuti Wahyuningsih

    2013-03-01

    Full Text Available This research aimed to know the bioactivity of polysaccharide krestin (PSK with a different timing on formation of mice antibodyexposed by Mycobacterium tuberculosis. Mycobacterium tuberculosis was used as infection agent that had an abilitiy to be imunogenicand to lead immune system responsses decreased. Polysaccharides krestin was used as immunopotentiator which had a role to activatemacrophage and stimulate B cell in order to produce antibody. This research involved 30 adult female mice of Mus musculus strain Balb/C in the age of 8 €“10 weeks and in the weight between of 30 €“40 g. Mice were divided into six groups, as follows: group K asa control, was added only aquades; group K+ as positive control, was added only PSK; group K- as negative control, was exposedby M. tuberculosis only; group P1 was added PSK before being exposed by M. tuberculosis; group P2 was added PSK after beingexposed by M. tuberculosis; group P3 was added PSK before and after being exposed by M. tuberculosis. Polysaccharides krestin wasadded by gavage with single dose of 500 μg and M. tuberculosis was exposed intraperitoneally with concentration of 5x108 bacteryper ml. The bioactivity of PSK was observed by formation antibody using indirect ELISA test. The results of research were the averageof OD value of K group was 0,590 ± 0,042, K+ group was 0.641 ± 0.025, K- group was 1.044 ± 0.054, P1 group was 1.032 ± 0.125,P2 group was 1.127 ± 0.042, P3 group was 1.230 ± 0.097. The conclusion of this research showed that the adding of PSK increasedmice formation antibody. The time of adding before and after being exposed M. tuberculosis was the most potential to raise antibodyproduction on mice.

  9. The Anti—tumor Effects of an Anti—CD71 Chimeric Antibody in Vitro and Its Distribution in a Tumor Xenograft Model

    Institute of Scientific and Technical Information of China (English)

    YANGDaofeng; WANGShuo; 等

    2002-01-01

    Objective To investigate the anti-tumor effects in vitro and in vivo distribution of the human/murine chimeric antibody (D2C).Methods The CD71 positive target cells(K562,CEM and SMMC7721) and the effector cells ,freshly isolated human PBMC,with the ratio of target cells to effector cells 1:50,were incubated in various dilutions of D2C antibody(Ab).Antibody dependent cytotoxicity(AD-CC) was tested by using an LDH-release assay.Instead of effector cells,complement was added to the target cells (CEM,SMMC-7721) with various dilutions of D2C Ab.A method of counting death cells was used in complement dependent cytotoxicity(CDC) assay.Tumor localization and distribution of the chimeric antibody(D2C) were observed by labeling the chimeric Ab with radioiodine(131I) and injecting in into nude mice(Balb/c nu/nu) transplanted with human hepatocellular carcinoma cells (SMMC-7721).Results A significant ADCC was observed with the increased concentration of the D2C Ab.Cytolysis of CD71-positive target cells by the D2C Ab was found in the presence of fresh rabbit complement.Labeled D2C administered by intraperitoneal as well as tumor regional in-jection,was visualized by SPECT. The distribution of D2C Ab in murine organs and tissues showed that non-specific binding was lower fol-lowing tumor regional administration than when the antibody was administered by an intraperitoneal injection.The human/murine chimeric antibody(D2C) has in vitro anti-tumor effects and can exert its effects in specific tumor localization.Its distribution and local effects in vi-vo can be detected by radioimmunoimaging. Conclusion CD71 human/murine chimeric antibody showed marked killing of tumor cells in vitro,and specific recognition and high affinity binding to tumor tissue in vivo.

  10. Antibodies to watch in 2017.

    Science.gov (United States)

    Reichert, Janice M

    Over 50 investigational monoclonal antibody (mAb) therapeutics are currently undergoing evaluation in late-stage clinical studies, which is expected to drive a trend toward first marketing approvals of at least 6-9 mAbs per year in the near-term. In the United States (US), a total of 6 and 9 mAbs were granted first approvals during 2014 and 2015, respectively; all these products are also approved in the European Union (EU). As of December 1, 2016, 6 mAbs (atezolizumab, olaratumab, reslizumab, ixekizumab, bezlotoxumab, oblitoxaximab) had been granted first approvals during 2016 in either the EU or US. Brodalumab, was granted a first approval in Japan in July 2016. Regulatory actions on marketing applications for brodalumab in the EU and US are not expected until 2017. In 2017, first EU or US approvals may also be granted for at least nine mAbs (ocrelizumab, avelumab, Xilonix, inotuzumab ozogamicin, dupilumab, sirukumab, sarilumab, guselkumab, romosozumab) that are not yet approved in any country. Based on announcements of company plans for regulatory submissions and the estimated completion dates for late-stage clinical studies, and assuming the study results are positive, marketing applications for at least 6 antibody therapeutics (benralizumab, tildrakizumab, emicizumab, galcanezumab, ibalizumab, PRO-140) that are now being evaluated in late-stage clinical studies may be submitted during December 2016* or 2017. Other 'antibodies to watch' in 2017 include 20 mAbs are undergoing evaluation in pivotal studies that have estimated primary completion dates in late 2016 or during 2017. Of these, 5 mAbs are for cancer (durvalumab, JNJ-56022473, ublituximab, anetumab ravtansine, glembatumumab vedotin) and 15 mAbs are for non-cancer indications (caplacizumab, lanadelumab, roledumab, tralokinumab, risankizumab, SA237, emapalumab, suptavumab, erenumab, eptinezumab, fremanezumab, fasinumab, tanezumab, lampalizumab, brolucizumab). Positive results from these studies may

  11. 21 CFR 866.3290 - Gonococcal antibody test (GAT).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Gonococcal antibody test (GAT). 866.3290 Section... antibody test (GAT). (a) Identification. A gonococcal antibody test (GAT) is an in vitro device that..., indirect fluorescent antibody, or radioimmunoassay, antibodies to Neisseria gonorrhoeae in sera...

  12. Determination of lethal doses 50 and 100 of propofol in lipid emulsion nor nanoemulsion intraperitoneally in miceDeterminação das doses letal 50 e 100 do propofol em nanoemulsão ou em emulsão lipídica pela via intraperitoneal em camundongos

    Directory of Open Access Journals (Sweden)

    Martielo Ivan Gehrcke

    2012-10-01

    Full Text Available The formulation of a drug can interfere with its absorption into the circulatory system and may result in changes in the dose required to achieve that particular effect. The aim of this study was to determine the lethal dose 50 (LD 50 and 100 (LD100 of a nanoemulsion of propofol and the lipid emulsion in mice intraperitoneally. One hundred sixty animals weighing 36.47±4.6g, which were distributed randomly into two groups: NANO and EMU who received propofol 1% in the nanoemulsion and lipid emulsion, respectively, intraperitoneally. Began with a dose of 250mg/kg (n=10 and from this isdecreased or increased the dose until achieving 0 and 100% of deaths in each group thus formed were seven subgroups in NANO (each subgroup n = 10 at doses 200, 250, 325, 350, 400, 425 and 475 mg/kg and in EMU eight subgroups (n= 10 each subset 250, 325, 350, 400, 425, 475, 525 and 575 mg/kg. In the CONTROL group (n=10 animals received saline in the largest volume used in the other groups to rule out death by the volume injected. Analysis of LD 50 and LD 100 were obtained by linear regression. The LD 50 was 320, 95 mg / kg and 4243, 51mg / kg and the LD 100 was445.99 mg / kg and 595.31 mg / kg to groups NANO and EMU, respectively. It follows that nanoemulsion is propofol in 25% more potent compared to the lipid emulsionintraperitoneally. A formulação de um fármaco pode interferir na sua absorção para o sistema circulatório, podendo resultar em alterações da dose necessária para que se consiga determinado efeito. O objetivo deste estudo foi determinar as doses letais 50 (DL 50 e 100 (DL100 do propofol em nanoemulsão e emulsão lipídica em camundongos pela via intraperitoneal. Foram utilizados 160 animais pesando 36,47 ± 4,6g, os quais foram distribuídos aleatoriamente em dois grupos: NANO e EMU que receberam propofol à 1% em nanoemulsão e em emulsão lipídica, respectivamente, pela via intraperitoneal. Iniciou-se com a dose de 250mg/kg (n=10 e a partir

  13. Photonic crystal fiber based antibody detection

    DEFF Research Database (Denmark)

    Duval, A; Lhoutellier, M; Jensen, J B

    2004-01-01

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy...

  14. Monoclonal antibodies reactive with hairy cell leukemia

    NARCIS (Netherlands)

    Visser, L; Shaw, A; Slupsky, J; Vos, H; Poppema, S

    1989-01-01

    Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibod

  15. Anti-influenza M2e antibody

    Energy Technology Data Exchange (ETDEWEB)

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  16. Methods for Selecting Phage Display Antibody Libraries.

    Science.gov (United States)

    Jara-Acevedo, Ricardo; Diez, Paula; Gonzalez-Gonzalez, Maria; Degano, Rosa Maria; Ibarrola, Nieves; Gongora, Rafael; Orfao, Alberto; Fuentes, Manuel

    2016-01-01

    The selection process aims sequential enrichment of phage antibody display library in clones that recognize the target of interest or antigen as the library undergoes successive rounds of selection. In this review, selection methods most commonly used for phage display antibody libraries have been comprehensively described.

  17. Receptor antibodies as novel therapeutics for diabetes

    DEFF Research Database (Denmark)

    Ussar, Siegfried; Vienberg, Sara Gry; Kahn, C Ronald

    2011-01-01

    Antibodies to receptors can block or mimic hormone action. Taking advantage of receptor isoforms, co-receptors, and other receptor modulating proteins, antibodies and other designer ligands can enhance tissue specificity and provide new approaches to the therapy of diabetes and other diseases....

  18. Antibody-drug conjugates: Intellectual property considerations.

    Science.gov (United States)

    Storz, Ulrich

    2015-01-01

    Antibody-drug conjugates are highly complex entities that combine an antibody, a linker and a toxin. This complexity makes them demanding both technically and from a regulatory point of view, and difficult to deal with in their patent aspects. This article discusses different issues of patent protection and freedom to operate with regard to this promising new class of drugs.

  19. Photonic crystal fiber based antibody detection

    OpenAIRE

    Duval, A.; Lhoutellier, M; Jensen, J. B.; Hoiby, P E; Missier, V; Pedersen, L. H.; Hansen, Theis Peter; Bjarklev, Anders Overgaard; Bang, Ole

    2004-01-01

    An original approach for detecting labeled antibodies based on strong penetration photonic crystal fibers is introduced. The target antibody is immobilized inside the air-holes of a photonic crystal fiber and the detection is realized by the means of evanescent-wave fluorescence spectroscopy and the use of a transversal illumination setup.

  20. Monoclonal Antibody Therapy for Advanced Neuroblastoma

    Science.gov (United States)

    NCI is sponsoring two clinical trials of a monoclonal antibody called ch14.18, in combination with other drugs, to see if the antibody may be helpful for children or young adults (up to age 21) with relapsed or refractory neuroblastoma.

  1. Anti-influenza M2e antibody

    Science.gov (United States)

    Bradbury, Andrew M.

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  2. Bioconjugation of antibodies to horseradish peroxidase (hrp)

    Science.gov (United States)

    The bioconjugation of an antibody to an enzymatic reporter such as horseradish peroxidase (HRP) affords an effective mechanism by which immunoassay detection of a target antigen can be achieved. The use of heterobifunctional cross—linkers to covalently link antibodies to HRP provides a simple and c...

  3. "Unconventional" Neutralizing Activity of Antibodies Against HIV

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Neutralizing antibodies are recognized to be one of the essential elements of the adaptive immune response that must be induced by an effective vaccine against HIV. However, only a limited number of antibodies have been identified to neutralize a broad range of primary isolates of HIV-1 and attempts to induce such antibodies by immunization were unsuccessful. The difficulties to generate such antibodies are mainly due to intrinsic properties of HIV-1 envelope spikes, such as high sequence diversity, heavy glycosylation, and inducible and transient nature of certain epitopes. In vitro neutralizing antibodies are identified using "conventional" neutralization assay which uses phytohemagglutinin (PHA)-stimulated human PBMCs as target cells. Thus, in essence the assay evaluates HIV-1 replication in CD4+ T cells. Recently, several laboratories including us demonstrated that some monoclonal antibodies and HIV-1-specific polyclonal IgG purified from patient sera, although they do not have neutralizing activity when tested by the "conventional" neutralization assay, do exhibit potent and broad neutralizing activity in "unconventional" ways. The neutralizing activity of these antibodies and IgG fractions is acquired through post-translational modifications, through opsonization of virus particles into macrophages and immature dendritic cells (iDCs), or through expression of antibodies on the surface of HIV-1-susceptible cells. This review will focus on recent findings of this area and point out their potential applications in the development of preventive strategies against HIV.

  4. Anti-miroestrol polyclonal antibodies: a comparison of immunogen preparations used to obtain desired antibody properties.

    Science.gov (United States)

    Kitisripanya, Tharita; Jutathis, Kamonthip; Inyai, Chadathorn; Komaikul, Jukrapun; Udomsin, Orapin; Yusakul, Gorawit; Tanaka, Hiroyuki; Putalun, Waraporn

    2016-04-01

    Immunogen quality is one important factor that contributes to desirable antibody characteristics. Highly specific antibodies against miroestrol can be used to develop a quality control immunoassay for Pueraria candollei products. In this study, we investigated how various immunogen preparations affect antibody properties. The results show that immunogen prepared using the Mannich reaction provides antibodies with higher specificity and sensitivity against miroestrol than immunogen prepared with the periodate reaction. The results suggest the Mannich reaction maintains the original structure of miroestrol and generates useful antibodies for developing immunoassays.

  5. Monoclonal antibodies in chronic lymphocytic leukemia.

    Science.gov (United States)

    Ferrajoli, Alessandra; Faderl, Stefan; Keating, Michael J

    2006-09-01

    Multiple options are now available for the treatment of chronic lymphocytic leukemia. Over the last 10 years, monoclonal antibodies have become an integral part of the management of this disease. Alemtuzumab has received approval for use in patients with fludarabine-refractory chronic lymphocytic leukemia. Rituximab has been investigated extensively in chronic lymphocytic leukemia both as a single agent and in combination with chemotherapy and other monoclonal antibodies. Epratuzumab and lumiliximab are newer monoclonal antibodies in the early phase of clinical development. This article will review the monoclonal antibodies more commonly used to treat chronic lymphocytic leukemia, the results obtained with monoclonal antibodies as single agents and in combination with chemotherapy, and other biological agents and newer compounds undergoing clinical trials.

  6. Production and characterization of peptide antibodies

    DEFF Research Database (Denmark)

    Trier, Nicole Hartwig; Hansen, Paul Robert; Houen, Gunnar

    2012-01-01

    Proteins are effective immunogens for generation of antibodies. However, occasionally the native protein is known but not available for antibody production. In such cases synthetic peptides derived from the native protein are good alternatives for antibody production. These peptide antibodies...... are powerful tools in experimental biology and are easily produced to any peptide of choice. A widely used approach for production of peptide antibodies is to immunize animals with a synthetic peptide coupled to a carrier protein. Very important is the selection of the synthetic peptide, where factors...... such as structure, accessibility and amino acid composition are crucial. Since small peptides tend not to be immunogenic, it may be necessary to conjugate them to carrier proteins in order to enhance immune presentation. Several strategies for conjugation of peptide-carriers applied for immunization exist...

  7. Antiphospholipid antibody: laboratory, pathogenesis and clinical manifestations

    Directory of Open Access Journals (Sweden)

    T. Ziglioli

    2011-06-01

    Full Text Available Antiphospholipid antibodies (aPL represent a heterogeneous group of antibodies that recognize various antigenic targets including beta2 glycoprotein I (β2GPI, prothrombin (PT, activated protein C, tissue plasminogen activator, plasmin and annexin A2. The most commonly used tests to detect aPL are: lupus anticoagulant (LAC, a functional coagulation assay, anticardiolipin antibody (aCL and anti-β2GPI antibody (anti-β2GPI, which are enzyme-linked immunoassay (ELISA. Clinically aPL are associated with thrombosis and/or with pregnancy morbidity. Apparently aPL alone are unable to induce thrombotic manifestations, but they increase the risk of vascular events that can occur in the presence of another thrombophilic condition; on the other hand obstetrical manifestations were shown to be associated not only to thrombosis but mainly to a direct antibody effect on the trophoblast.

  8. Antibody-based resistance to plant pathogens.

    Science.gov (United States)

    Schillberg, S; Zimmermann, S; Zhang, M Y; Fischer, R

    2001-01-01

    Plant diseases are a major threat to the world food supply, as up to 15% of production is lost to pathogens. In the past, disease control and the generation of resistant plant lines protected against viral, bacterial or fungal pathogens, was achieved using conventional breeding based on crossings, mutant screenings and backcrossing. Many approaches in this field have failed or the resistance obtained has been rapidly broken by the pathogens. Recent advances in molecular biotechnology have made it possible to obtain and to modify genes that are useful for generating disease resistant crops. Several strategies, including expression of pathogen-derived sequences or anti-pathogenic agents, have been developed to engineer improved pathogen resistance in transgenic plants. Antibody-based resistance is a novel strategy for generating transgenic plants resistant to pathogens. Decades ago it was shown that polyclonal and monoclonal antibodies can neutralize viruses, bacteria and selected fungi. This approach has been improved recently by the development of recombinant antibodies (rAbs). Crop resistance can be engineered by the expression of pathogen-specific antibodies, antibody fragments or antibody fusion proteins. The advantages of this approach are that rAbs can be engineered against almost any target molecule, and it has been demonstrated that expression of functional pathogen-specific rAbs in plants confers effective pathogen protection. The efficacy of antibody-based resistance was first shown for plant viruses and its application to other plant pathogens is becoming more established. However, successful use of antibodies to generate plant pathogen resistance relies on appropriate target selection, careful antibody design, efficient antibody expression, stability and targeting to appropriate cellular compartments.

  9. Intraperitoneal injection of neuropeptide Y (NPY) alters neurotrophin rat hypothalamic levels: Implications for NPY potential role in stress-related disorders.

    Science.gov (United States)

    Gelfo, Francesca; De Bartolo, Paola; Tirassa, Paola; Croce, Nicoletta; Caltagirone, Carlo; Petrosini, Laura; Angelucci, Francesco

    2011-06-01

    Neuropeptide Y (NPY) is a 36-amino acid peptide which exerts several regulatory actions within peripheral and central nervous systems. Among NPY actions preclinical and clinical data have suggested that the anxiolytic and antidepressant actions of NPY may be related to its antagonist action on the hypothalamic-pituitary-adrenal (HPA) axis. The neurotrophins brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) are proteins involved in the growth, survival and function of neurons. In addition to this, a possible role of neurotrophins, particularly BDNF, in HPA axis hyperactivation has been proposed. To characterize the effect of NPY on the production of neurotrophins in the hypothalamus we exposed young adult rats to NPY intraperitoneal administration for three consecutive days and then evaluated BDNF and NGF synthesis in this brain region. We found that NPY treatment decreased BDNF and increased NGF production in the hypothalamus. Given the role of neurotrophins in the hypothalamus, these findings, although preliminary, provide evidence for a role of NPY as inhibitor of HPA axis and support the idea that NPY might be involved in pathologies characterized by HPA axis dysfunctions.

  10. Effect of sub-chronic intraperitoneal administration of aminoguanidine on the memory and hippocampal apoptosis-related genes in diabetic rats.

    Science.gov (United States)

    Alipour, M; Amini, B; Adineh, F; Feizi, H; Jafari, M R

    Memory impairment is a common disorder in diabetes mellitus which is associated with hippocampal neuronal apoptosis. The present study was conducted to examine the effect of one-week intraperitoneal (ip), administration of aminoguanidine (AG) on passive avoidance learning (PAL) and Bcl-2 family gene expression in the hippocampus of rats. Sixty male rats were divided into ten groups: non-diabetic/diabetic animals with/without AG (50, 100, 200 and 400 mg/kg, ip) treatment for one week. PAL and Bcl-2 family genes were examined. AG (100 and 200 mg/kg) improved both memory and Bax, Bak, Bcl-2 and Bcl-xl deficiency significantly in diabetic rats. AG treatment also ameliorated the diabetes-induced changes in (Bcl-2+Bcl-xl)/(Bak+Bax) ratios considerably. These results propose that one-week ip administration of AG may recover the deficit cognition in diabetic rats via enhancing (Bcl-2+Bcl-xl)/(Bak+Bax) proportions (Tab. 2, Fig. 4, Ref. 55).

  11. Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

    Science.gov (United States)

    Cacabelos, R; Yamatodani, A; Fukui, H; Niigawa, H; Miyake, A; Watanabe, T; Nishimura, T; Wada, H

    1987-04-01

    Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.

  12. A comparative analysis of intraperitoneal versus intracerebroventricular administration of bromodeoxyuridine for the study of cell proliferation in the adult rat brain.

    Science.gov (United States)

    Cifuentes, M; Pérez-Martín, M; Grondona, J M; López-Ávalos, M D; Inagaki, N; Granados-Durán, P; Rivera, P; Fernández-Llebrez, P

    2011-10-15

    Bromodeoxyuridine (BrdU) is the most widely used marker to detect proliferative cells in the adult brain. Here we analyse whether the route of administration of the tracer influences the number of labelled cells. For the intraperitoneal (ip) administration of BrdU, we performed two daily injections during 7 days, and for an intracerebroventricular (icv) delivery, it was continuously infused into one lateral ventricle for a 7 days period as well. After ip administration, cells labelled with BrdU were seen in the subventricular zone of the striatal wall of the lateral ventricle, the hippocampus and the neurohemal circumventricular organs. Also, the habenula and large myelinated tracts, such as the fornix and the corpus callosum, showed many BrdU-positive nuclei. Labelled nuclei were scarce in the parenchymal regions of the rest of the brain. In contrast, a significant increase in the number of BrdU-positive nuclei was observed in the parenchyma of the periventricular zones after icv administration of the marker, thus showing a greater availability of the tracer when it was administered directly into the ventricular cerebrospinal fluid. We suggest that the availability of BrdU in the vicinity of proliferating cells may depend on the permeability of the brain vessels to nucleosides in each location. By using double immunocytochemistry we found that neurons, astrocytes, oligodendrocytes, tanycytes and microglia had incorporated the tracer, demonstrating their proliferation capacity.

  13. A comparison of intravenous plus intraperitoneal chemotherapy with intravenous chemotherapy alone for the treatment of gastric cancer:a Meta-analysis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Objective:We aimed to evaluate the effectiveness and safety of intravenous (IV) plus intraperitoneal (IP) chemotherapy compared to IV chemotherapy alone for patients with gastric cancer.Methods: Electronic databases were searched up to June 2013. Two authors independently assessed the quality of included studies. hTe GARDE System was adopted to rate the level of evidence. Of 392 citations, ifve RCTs involving 1, 072 patients were included.Results:Overall, a signiifcant improvement in in 1- and 3- and 5-year survival rate was observed in the IV plus IP chemotherapy group (3 RCTs,n=360, RR=1.10, 95% CI, 1.04~1.17), (5 RCTs,n=953, RR=1.22, 95% CI, 1.11~1.35) and (3 RCTs, n=347, RR=1.42, 95% CI, 1.12~1.80), respectively. Results supported a signiifcant decrease in the rate of metastases (1 RCT,n=85, RR=0.41 95% CI, 0.19~0.89) and peritoneal recurrence (2 RCTs,n=297, RR=0.41, 95% CI, 0.26~0.62) in the IV plus IP chemotherapy group, however, the incidence of adverse events was increased.Conclusion:For patients with gastric cancer, IV plus IP chemotherapy can improve the overall survival rate and prevent the distant or peritoneal metastases. An increased risk of neutropenia, peripheral edema and neuropathy was observed.

  14. Pulmonary influences on early post-operative recovery in patients after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy treatment: a retrospective study

    Directory of Open Access Journals (Sweden)

    Arakelian Erebouni

    2012-11-01

    Full Text Available Abstract Background The combination of cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC is a curative treatment option for peritoneal carcinomatosis (PC. There have been few studies on the pulmonary adverse events (AEs affecting patient recovery after this treatment, thus this study investigated these factors. Methods Between January 2005 and December 2006, clinical data on all pulmonary AEs and the recovery progress were reviewed for 76 patients with after CRS and HIPEC. Patients with pulmonary interventions (thoracocenthesis and chest tubes were compared with the non-intervention patients. Two senior radiologists, blinded to the post-operative clinical course, separately graded the occurrence of pulmonary AEs. Results Of the 76 patients, 6 had needed thoracocentesis and another 6 needed chest tubes. There were no differences in post-operative recovery between the intervention and non-intervention groups. The total number of days on mechanical ventilation, the length of stay in the intensive care unit, total length of hospital stay, tumor burden, and an American Society of Anesthesiologists (ASA grade of greater than 2 were correlated with the occurrence of atelectasis and pleural effusion. Extensive atelectasis (grade 3 or higher was seen in six patients, major pleural effusion (grade 3 in seven patients, and signs of heart failure (grade 1–2 in nine patients. Conclusions Clinical and radiological post-operative pulmonary AEs are common after CRS and HIPEC. However, most of the pulmonary AEs did not affect post-operative recovery.

  15. Analysis of Two Complementary Single-Gene Deletion Mutant Libraries of Salmonella Typhimurium in Intraperitoneal Infection of BALB/c Mice

    Science.gov (United States)

    Silva-Valenzuela, Cecilia A.; Molina-Quiroz, Roberto C.; Desai, Prerak; Valenzuela, Camila; Porwollik, Steffen; Zhao, Ming; Hoffman, Robert M.; Andrews-Polymenis, Helene; Contreras, Inés; Santiviago, Carlos A.; McClelland, Michael

    2016-01-01

    Two pools of individual single gene deletion (SGD) mutants of S. Typhimurium 14028s encompassing deletions of 3,923 annotated non-essential ORFs and sRNAs were screened by intraperitoneal (IP) injection in BALB/c mice followed by recovery from spleen and liver 2 days post infection. The relative abundance of each mutant was measured by microarray hybridization. The two mutant libraries differed in the orientation of the antibiotic resistance cassettes (either sense-oriented KanR, SGD-K, or antisense-oriented CamR, SGD-C). Consistent systemic colonization defects were observed in both libraries and both organs for hundreds of mutants of genes previously reported to be important after IP injection in this animal model, and for about 100 new candidate genes required for systemic colonization. Four mutants with a range of apparent fitness defects were confirmed using competitive infections with the wild-type parental strain: ΔSTM0286, ΔSTM0551, ΔSTM2363, and ΔSTM3356. Two mutants, ΔSTM0286 and ΔSTM2363, were then complemented in trans with a plasmid encoding an intact copy of the corresponding wild-type gene, and regained the ability to fully colonize BALB/c mice systemically. These results suggest the presence of many more undiscovered Salmonella genes with phenotypes in IP infection of BALB/c mice, and validate the libraries for application to other systems. PMID:26779130

  16. [A case of peritonitis carcinomatosa from goblet cell carcinoid of the appendix treated by intraperitoneal paclitaxel and systemic S-1 chemotherapy].

    Science.gov (United States)

    Nakamura, Shingen; Kimura, Shigeaki; Kashima, Masahiro; Shichijo, Kana; Yoshida, Sumiko; Harada, Eiji; Matsushita, Takaya; Oshima, Yasushi; Tamaki, Yasutami; Horiuchi, Noriaki; Takeichi, Toshiaki; Fujimoto, Hiroshi; Masuda, Kazuhiko; Iwasaka, Naohito; Shinomiya, Sadao

    2008-12-01

    Goblet cell carcinoid of the appendix is a rare neoplasm and clinically tends to take a malignant course. Most cases are young and early stage, and the surgical strategy is available. But appropriate chemotherapy for inoperable cases with peritoneal dissemination is not established. A 77-year-old woman with a past history of appendectomy was admitted to our hospital complaining of abdominal fullness. Abdominal computed tomography showed massive ascites and slight contrast enhancement of appendix. A tumor was found by colonoscopic examination at the orifice of vermiform and was diagnosed pathologically as goblet cell carcinoid of the appendix. Laparoscopy showed multiple peritoneal dissemination. We performed intraperitoneal paclitaxel(PTX)administration at 70 mg/m(2) week without any resection of the tumor. Ascites were reduced immediately, but drug-induced interstitial pneumonia occurred due to PTX. After steroid therapy, we switched to systemic S-1 therapy. For about one year, her tumor was controlled but became worse thirteen months after diagnosis and died. It is thought that intraabdominal paclitaxel administration and systemic S-1 therapy can be one of appropriate forms of chemotherapy for inoperable peritoneal carcinomatosis from goblet cell carcinoid of appendix.

  17. Report of a 7 year case-control study of continuous intraperitoneal insulin infusion and subcutaneous insulin therapy among patients with poorly controlled type 1 diabetes mellitus : Favourable effects on hypoglycaemic episodes

    NARCIS (Netherlands)

    van Dijk, P. R.; Logtenberg, S. J. J.; Groenier, K. H.; Gans, R. O. B.; Bilo, H. J. G.; Kleefstra, N.

    2014-01-01

    Aims: Continuous intraperitoneal insulin infusion (CIPII) is a last-resort treatment option for patients with type 1 diabetes mellitus (T1DM) who fail to reach adequate glycaemic control with subcutaneous (SC) insulin therapy. Aim was to compare the long-term effects of CIPII and SC insulin therapy

  18. 腹腔镜腹腔内还纳腹膜外修补术治疗嵌顿性股疝%Laparoscopic intraperitoneal apothesis and extraperitoneal prosthesis in treatment of strangulated femoral hernia

    Institute of Scientific and Technical Information of China (English)

    郭志刚; 周仕海; 王尧; 陈宏

    2014-01-01

    目的:探讨腹腔镜腹膜外修补术治疗嵌顿性股疝的应用价值。方法回顾性分析本院收治的嵌顿性股疝患者21例,均行腹腔镜腹腔内还纳腹膜外修补术。结果随访2个月以上,全组患者无伤口及补片感染,无血管和器官损伤,无一例复发。结论腹腔镜腹腔内还纳腹膜外修补术治疗嵌顿性股疝效果良好,复发率及术后并发症发生率低。%Objective To investigate the application value of laparoscopic intraperitoneal apothesis and extraperitoneal prosthesis in treatment of strangulated femoral hernia.Methods The clinical data of twenty-one cases of strangulated femoral hernia undergoing laparoscopic intraperitoneal apothesis and extraperitoneal prosthesis were retrospectively analyzed in our hospital.Results All the 21 patients were successfully subjected to laparoscopic intraperitoneal apothesis and extraperitoneal prosthesis. There was no wound and patch infection, vascular and organs injury, and recurrent cases during the follow-up. Conclusion Laparoscopic intraperitoneal apothesis and extraperitoneal prosthesis is a safe and efficient choice for strangulated femoral hernia with the low recurrence and less postoperative complications.

  19. Radiohalogenated half-antibodies and maleimide intermediate therefor

    Science.gov (United States)

    Kassis, A.I.; Khawli, L.A.

    1991-02-19

    N-(m-radiohalophenyl) maleimide can be conjugated with a reduced antibody having a mercapto group to provide a radiolabeled half-antibody having immunological specific binding characteristics of whole antibody. No Drawings

  20. Production of a monoclonal antibody specific for high molecular weight glutenin subunits (HMW-GS) in wheat and its antigenic determinant

    Institute of Scientific and Technical Information of China (English)

    WANG Hanqian; ZHANG Xueyong; WANG Hongmei; PANG Binshuang

    2005-01-01

    Wheat high molecular weight glutenin subunits (HMW-GS) 1Bx14 and 1By15 isolated by preparative SDS-PAGE are used as antigen to immunize BALB/c mice. Subcutaneous inoculation of the antigen is performed. The intra-peritoneal injection is completed 3 days before fusion with myeloma cell (SP2/0) via PEG-1500. The fusion cells are selected by indirect enzyme-linked immuno-sorbent assay (ELISA). Positive hybrid cells are further verified three times by limit dilution of the culture cells. A hybridoma cell line is successfully obtained. The monoclonal antibody belongs to IgG1 subclass. In immunoblotting, the antibody binds to all HMW-GS of T.aestivum cultivars, but does not bind to other storage proteins in seeds of wheat. This result is consisting with the high homology in amino acid sequences among the HMW glutenin subunits in wheat. The antibody also binds to HMW-GS storage proteins in Aegilops squarrosa and T. durum (durum wheat). Furthermore, it also binds to HMW storage proteins in Secale cereale (rye),Hordeum vulgare (barley). However, it never binds seed storage proteins in other cereals such as maize, oat, rice, foxtail millet, sorghum etc. The antigen determinant recognized by the antibody has been located within hexapeptide [PGQGQQ] or / and nonapeptide [GYYPTSPQQ] in the central repetitive region of HMW-GS.

  1. Antibody Engineering & Therapeutics, the annual meeting of The Antibody Society December 7-10, 2015, San Diego, CA, USA.

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M; Lund-Johansen, Fridtjof; Bradbury, Andrew R M; Carter, Paul J; Melis, Joost P M

    2016-01-01

    The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6-10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on "Antibodies to watch" in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries.

  2. Antiphospholipid Antibodies in Lupus Nephritis.

    Directory of Open Access Journals (Sweden)

    Ioannis Parodis

    Full Text Available Lupus nephritis (LN is a major manifestation of systemic lupus erythematosus (SLE. It remains unclear whether antiphospholipid antibodies (aPL alter the course of LN. We thus investigated the impact of aPL on short-term and long-term renal outcomes in patients with LN. We assessed levels of aPL cross-sectionally in SLE patients diagnosed with (n = 204 or without (n = 294 LN, and prospectively in 64 patients with active biopsy-proven LN (52 proliferative, 12 membranous, before and after induction treatment (short-term outcomes. Long-term renal outcome in the prospective LN cohort was determined by the estimated glomerular filtration rate (eGFR and the Chronic Kidney Disease (CKD stage, after a median follow-up of 11.3 years (range: 3.3-18.8. Cross-sectional analysis revealed no association between LN and IgG/IgM anticardiolipin or anti-β2-glycoprotein I antibodies, or lupus anticoagulant. Both aPL positivity and levels were similar in patients with active LN and non-renal SLE. Following induction treatment for LN, serum IgG/IgM aPL levels decreased in responders (p<0.005 for all, but not in non-responders. Both at active LN and post-treatment, patients with IgG, but not IgM, aPL had higher creatinine levels compared with patients without IgG aPL. Neither aPL positivity nor levels were associated with changes in eGFR from either baseline or post-treatment through long-term follow-up. Moreover, aPL positivity and levels both at baseline and post-treatment were similar in patients with a CKD stage ≥3 versus 1-2 at the last follow-up. In conclusion, neither aPL positivity nor levels were found to be associated with the occurrence of LN in SLE patients. However, IgG aPL positivity in LN patients was associated with a short-term impairment of the renal function while no effect on long-term renal outcome was observed. Furthermore, IgG and IgM aPL levels decreased following induction treatment only in responders, indicating that aPL levels are

  3. Combinatorial antibody libraries: new advances, new immunological insights.

    Science.gov (United States)

    Lerner, Richard A

    2016-08-01

    Immunochemists have become quite proficient in engineering existing antibody molecules to control their pharmacological properties. However, in terms of generating new antibodies, the combinatorial antibody library has become a central feature of modern immunochemistry. These libraries are essentially an immune system in a test tube and enable the selection of antibodies without the constraints of whole animal or cell-based systems. This Review provides an overview of how antibody libraries are constructed and discusses what can be learnt from these synthetic systems. In particular, the Review focuses on new biological insights from antibody libraries - such as the concept of 'SOS antibodies' - and the growing use of intracellular antibodies to perturb cellular functions.

  4. Structure Based Antibody-Like Peptidomimetics

    Directory of Open Access Journals (Sweden)

    Mark I. Greene

    2012-02-01

    Full Text Available Biologics such as monoclonal antibodies (mAb and soluble receptors represent new classes of therapeutic agents for treatment of several diseases. High affinity and high specificity biologics can be utilized for variety of clinical purposes. Monoclonal antibodies have been used as diagnostic agents when coupled with radionuclide, immune modulatory agents or in the treatment of cancers. Among other limitations of using large molecules for therapy the actual cost of biologics has become an issue. There is an effort among chemists and biologists to reduce the size of biologics which includes monoclonal antibodies and receptors without a reduction of biological efficacy. Single chain antibody, camel antibodies, Fv fragments are examples of this type of deconstructive process. Small high-affinity peptides have been identified using phage screening. Our laboratory used a structure-based approach to develop small-size peptidomimetics from the three-dimensional structure of proteins with immunoglobulin folds as exemplified by CD4 and antibodies. Peptides derived either from the receptor or their cognate ligand mimics the functions of the parental macromolecule. These constrained peptides not only provide a platform for developing small molecule drugs, but also provide insight into the atomic features of protein-protein interactions. A general overview of the reduction of monoclonal antibodies to small exocyclic peptide and its prospects as a useful diagnostic and as a drug in the treatment of cancer are discussed.

  5. Glycosylation profiles of therapeutic antibody pharmaceuticals.

    Science.gov (United States)

    Wacker, Christoph; Berger, Christoph N; Girard, Philippe; Meier, Roger

    2011-11-01

    Recombinant antibodies specific for human targets are often used as therapeutics and represent a major class of drug products. Their therapeutic efficacy depends on the formation of antibody complexes resulting in the elimination of a target molecule or the modulation of specific signalling pathways. The physiological effects of antibody therapeutics are known to depend on the structural characteristics of the antibody molecule, specifically on the glycosylation which is the result of posttranslational modifications. Hence, production of therapeutic antibodies with a defined and consistent glycoform profile is needed which still remains a considerable challenge to the biopharmaceutical industry. To provide an insight into the industries capability to control their manufacturing process and to provide antibodies of highest quality, we conducted a market surveillance study and compared major oligosaccharide profiles of a number of monoclonal antibody pharmaceuticals sampled on the Swiss market. Product lot-to-lot variability was found to be generally low, suggesting that a majority of manufacturers have implemented high quality standards in their production processes. However, proportions of G0, G1 and G2 core-fucosylated chains derived from different products varied considerably and showed a bias towards the immature agalactosidated G0 form. Interestingly, differences in glycosylation caused by the production cell type seem to be of less importance compared with process related parameters such as cell growth.

  6. Baculovirus display of functional antibody Fab fragments.

    Science.gov (United States)

    Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

    2015-08-01

    The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

  7. Next generation of antibody therapy for cancer

    Institute of Scientific and Technical Information of China (English)

    Zhenping Zhu; Li Yan

    2011-01-01

    Monoclonal antibodies (mAbs) have become a major class of therapeutic agents providing effective altematives to treating various human diseases. To date, 15 mAbs have been approved by regulatory agencies in the world for clinical use in oncology indications. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the host immune system differentiate these biologics from traditional small molecule anticancer drugs. mAb-basod regimens have brought clinical benefits, including improvements in overall survival, to patients with a variety of cancers. Many challenges still remain, however, to fully realize the potential of these new medicines. With our further understanding of cancer biology, mechanism of antibody action, and advancement of antibody engineering technologies, many novel antibody formats or antibody-derived molecules are emerging as promising new generation therapeutics. Carefully designed and engineered, they retain the advantage of specificity and selectivity of original antibodies, but in the meantime acquire additional special features such as improved pharmacokinetics, increased selectivity, and enhanced anticancer efficacy. Promising clinical results are being generated with these newly improved antibody-based therapeutics.

  8. HIV-1 resistance to neutralizing antibodies: Determination of antibody concentrations leading to escape mutant evolution.

    Science.gov (United States)

    Magnus, Carsten; Reh, Lucia; Trkola, Alexandra

    2016-06-15

    Broadly neutralizing antibodies against human immunodeficiency virus type 1 (HIV-1) are considered vital components of novel therapeutics and blueprints for vaccine research. Yet escape to even the most potent of these antibodies is imminent in natural infection. Measures to define antibody efficacy and prevent mutant selection are thus urgently needed. Here, we derive a mathematical framework to predict the concentration ranges for which antibody escape variants can outcompete their viral ancestors, referred to as mutant selection window (MSW). When determining the MSW, we focus on the differential efficacy of neutralizing antibodies against HIV-1 in two canonical infection routes, free-virus infection and cell-cell transmission. The latter has proven highly effective in vitro suggesting its importance for both in vivo spread as well as for escaping targeted intervention strategies. We observed a range of MSW patterns that highlight the potential of mutants to arise in both transmission pathways and over wide concentration ranges. Most importantly, we found that only when the arising mutant has both, residual sensitivity to the neutralizing antibody and reduced infectivity compared to the parental virus, antibody dosing outside of the MSW to restrict mutant selection is possible. Emergence of mutants that provide complete escape and have no considerable fitness loss cannot be prevented by adjusting antibody doses. The latter may in part explain the ubiquitous resistance to neutralizing antibodies observed in natural infection and antibody treatment. Based on our findings, combinations of antibodies targeting different epitopes should be favored for antibody-based interventions as this may render complete resistance less likely to occur and also increase chances that multiple escapes result in severe fitness loss of the virus making longer-term antibody treatment more feasible.

  9. Studies on Purification of Methamidophos Monoclonal Antibodies and Comoarative Immunoactivity of Purified Antibodies

    Institute of Scientific and Technical Information of China (English)

    SU-QING ZHAO; YUAN-MING SUN; CHUN-YAN ZHANG; XIAO-YU HUANG; HOU-RUI ZHANG; ZHEN-YU ZHU

    2003-01-01

    Objective To purify Methamidophos (Met) monoclonal antibodies with two methods andcompare immune activity of purified antibodies. Method Caprylic acid ammonium sulphateprecipition (CAASP) method and Sepharose protein-A (SPA) affinity chromatography method wereused to purify Met monoclonal antibodies, UV spectrum scanning was used to determine proteincontent and recovery of purified antibodies, sodium dodecylsulphate polyacrylamide gelelectrophoresis (SDS-PAGE) was used to analyze the purity of purified antibodies, and enzyme-linkedimmunosorbent assay (ELISA) was used to determine immune activity of purified antibodies.Results Antibody protein content and recovery rate with CAASP method were 7.62 mg/mL and8.05% respectively, antibody protein content and recovery rate with SPA method were 6.45 mg/mLand 5.52% respectively. Purity of antibodies purified by SPA method was higher than that by CAASPmethod. The half-maximal inhibition concentration (IC50) of antibodies purified by SPA to Met was181.26 μg/mL, and the linear working range and the limit of quantification (LOD) were 2.43-3896.01μg/mL and 1.03 μg/mL, respectively. The IC50 of antibodies purified by CAASP to Met was 352.82μg/mL, and the linear working range and LOD were 10.91-11412.29 ug/mL and 3.42 μg/mL,respectively. Conclusion Antibodies purified by SPA method are better than those by CAASPmethod, and Met monoclonal antibodies purified by SPA method can be used to prepare gold-labelledtesting paper for analyzing Met residue in vegetable and drink water.

  10. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  11. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  12. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  13. Immunocytochemical and Immunohistochemical Staining with Peptide Antibodies.

    Science.gov (United States)

    Friis, Tina; Pedersen, Klaus Boberg; Hougaard, David; Houen, Gunnar

    2015-01-01

    Peptide antibodies are particularly useful for immunocytochemistry (ICC) and immunohistochemistry (IHC), where antigens may denature due to fixation of tissues and cells. Peptide antibodies can be made to any defined sequence, including unknown putative proteins and posttranslationally modified sequences. Moreover, the availability of large amounts of the antigen (peptide) allows inhibition/adsorption controls, which are important in ICC/IHC, due to the many possibilities for false-positive reactions caused by immunoglobulin Fc receptors, nonspecific reactions, and cross-reactivity of primary and secondary antibodies with other antigens and endogenous immunoglobulins, respectively. Here, simple protocols for ICC and IHC are described together with recommendations for appropriate controls.

  14. Preparation, Characterization, and Application of Antiharpinxoo Antibody

    Institute of Scientific and Technical Information of China (English)

    SHAO Min; LI Ming; PAN Xiao-mei; WANG Jin-sheng

    2006-01-01

    Polyclonal antiharpinxoo rabbit antibody has been prepared successfully using purified harpinxoo protein as an immunogen.The ELISA titer of the antiserum against harpinxoo was about 1:2 000. Western blot analysis showed that the antiserum could bind to the expression harpinxoo protein in particular. hrf1, encoding harpinxoo, is an expression in transgenic rice,detected by antiharpinxoo rabbit antibody. The rabbit antibody against harpinxoo can be used to study further about the biological function, harpinxoo localization, and hrf1 gene expression in other plants.

  15. Uses of monoclonial antibody 8H9

    Science.gov (United States)

    Cheung, Nai-Kong V.

    2015-06-23

    This invention provides an antibody that binds the same antigen as that of monoclonal antibody 8H9, wherein the heavy chain CDR (Complementary Determining Region)1 comprises NYDIN, heavy chain CDR2 comprises WIFPGDGSTQY, heavy chain CDR3 comprises QTTATWFAY, and the light chain CDR1 comprises RASQSISDYLH, light chain CDR2 comprises YASQSIS, and light chain CDR3 comprises QNGHSFPLT. In another embodiment, there is provided a polypeptide that binds the same antigen as that of monoclonal antibody 8H9, wherein the polypeptide comprises NYDIN, WIFPGDGSTQY, QTTATWFAY, RASQSISDYLH, YASQSIS, and QNGHSFPLT.

  16. Advances in recombinant antibody manufacturing.

    Science.gov (United States)

    Kunert, Renate; Reinhart, David

    2016-04-01

    Since the first use of Chinese hamster ovary (CHO) cells for recombinant protein expression, production processes have steadily improved through numerous advances. In this review, we have highlighted several key milestones that have contributed to the success of CHO cells from the beginning of their use for monoclonal antibody (mAb) expression until today. The main factors influencing the yield of a production process are the time to accumulate a desired amount of biomass, the process duration, and the specific productivity. By comparing maximum cell densities and specific growth rates of various expression systems, we have emphasized the limiting parameters of different cellular systems and comprehensively described scientific approaches and techniques to improve host cell lines. Besides the quantitative evaluation of current systems, the quality-determining properties of a host cell line, namely post-translational modifications, were analyzed and compared to naturally occurring polyclonal immunoglobulin fractions from human plasma. In summary, numerous different expression systems for mAbs are available and also under scientific investigation. However, CHO cells are the most frequently investigated cell lines and remain the workhorse for mAb production until today.

  17. Correlation of protection against Japanese encephalitis virus and JE vaccine (IXIARO(®)) induced neutralizing antibody titers.

    Science.gov (United States)

    Van Gessel, Yvonne; Klade, Christoph S; Putnak, Robert; Formica, Alessandra; Krasaesub, Somporn; Spruth, Martin; Cena, Bruno; Tungtaeng, Anchalee; Gettayacamin, Montip; Dewasthaly, Shailesh

    2011-08-11

    Immune sera from volunteers vaccinated in a blinded Phase 3 clinical trial with JE-VAX(®) and a new Japanese encephalitis virus (JEV) vaccine (IC51 or IXIARO), were tested for the ability to protect mice against lethal JEV challenge. Sera from IXIARO vaccinated subjects were pooled into four batches based on neutralizing antibody measured by plaque reduction neutralization test (PRNT(50) titer): high (∼200), medium (∼40-50), low (∼20) and negative (<10). Pooled sera from JE-VAX(®) vaccinated subjects (PRNT(50) titer∼55) and pooled JEV antibody negative pre-vaccination sera were used as controls. Groups of ten 6- to 7-week-old female ICR mice were injected intraperitoneally with 0.5 ml of each serum pool diluted 1:2 or 1:10, challenged approximately 18 h later with a lethal dose of either JEV strain SA14 (genotype III) or strain KE-093 (genotype I) and observed for 21 days. All mice in the non-immune serum groups developed clinical signs consistent with JEV infection or died, whereas high titer sera from both IXIARO and JE-VAX(®) sera protected 90-100% of the animals. Statistical tests showed similar protection against both JEV strains SA14 and KE-093 and protection correlated with the anti-JEV antibody titer of IXIARO sera as measured by PRNT(50). Ex vivo neutralizing antibody titers showed that almost all mice with a titer of 10 or greater were fully protected. In a separate study, analysis of geometric mean titers (GMTs) of the groups of mice vaccinated with different doses of IXIARO and challenged with JEV SA14 provided additional evidence that titers≥10 were protective.

  18. Intraperitoneal tension-free repair of a small midline ventral abdominal wall hernia: randomized study with a mean follow-up of 3 years.

    Science.gov (United States)

    Bensaadi, Hocine; Paolino, Luca; Valenti, Antonio; Polliand, Claude; Barrat, Christophe; Champault, Gérard

    2014-01-01

    Funding received from Cousin Biotech, Wervicq Sud, France, and CR Bard Inc., Cranston, RI. The aim of this prospective randomized study was to determine the long-term recurrence and complication rates after small abdominal wall hernia repair with two different bilayer prostheses. Hernia repair using prosthetic mesh material has become the preferred method of repair, because the recurrence rates are much lower than with conventional repair techniques. The use of a hernia bilayer patch, composite expanded polytetrafluoroethylene (ePTFE)-polypropylene, with intraperitoneal placement behind the hernia defect, through a small incision, may be efficient, safe, and cost-effective. This study is a randomized, single-institution trial, including 83 selected consecutive patients with primary (umbilical, epigastric) or incisional anterior abdominal wall defects from 2 to 5 cm. Hernia repair was performed by direct local access in ambulatory surgery; the prosthesis used was a circular bilayer with an inner face in ePTFE to avoid bowel adhesion. One group was treated with a Ventralex® Hernia Patch (Bard USA). The second group was treated with a Cabs'Air® Composite (Cousin Biotech France), which was delivered with two to four fixation sutures and a balloon to properly deploy the mesh intraperitoneally. Patients' characteristics and operative and postoperative data were prospectively collected. The primary outcome was late recurrence. Secondary outcomes included, pain, discomfort and quality of life before and after (3 months) surgery using the SF-12 questionnaire, patient-surgeon satisfaction, and early and late complications. Among 98 patients, 83 were included in the study protocol between January 2007 and August 2011. The two groups were comparable according to pre- and intraoperative data. According to surgeon experience, placement of the Cabs'Air® device was significantly faster (P = 0.01) and easier. At 3 months, there was significantly less pain and less discomfort for

  19. Impact of Pressurized Intraperitoneal Aerosol Chemotherapy on Quality of Life and Symptoms in Patients with Peritoneal Carcinomatosis: A Retrospective Cohort Study

    Science.gov (United States)

    Grass, Fabian; Kefleyesus, Amaniel; Achtari, Chahin; Romain, Benoit; Montemurro, Michael

    2017-01-01

    Background. Peritoneal cancer treatment aims to prolong survival, but preserving Quality of Life (QoL) under treatment is also a priority. Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) is a novel minimally invasive repeatable treatment modality. The aim of the present study was to assess QoL in our cohort of PIPAC patients. Methods. Analysis of all consecutive patients included from the start of PIPAC program (January 2015). QoL (0–100: optimal) and symptoms (no symptom: 0–100) were measured prospectively before and after every PIPAC procedure using EORTC QLQ-C30. Results. Forty-two patients (M : F = 8 : 34, median age 66 (59–73) years) had 91 PIPAC procedures in total (1 : 4x, 17 : 3x, 12 : 2x, and 12 : 1x). Before first PIPAC, baseline QoL was measured as median of 66 ± 2.64. Prominent complaints were fatigue (32 ± 4.3) and digestive symptoms as diarrhea (17 ± 3.75), constipation (17 ± 4.13), and nausea (7 ± 2.54). Overall Quality of Life was 64 ± 3.75 after PIPAC#1 (p = 0.57), 61 ± 4.76 after PIPAC#2 (p = 0.89), and 70 ± 6.67 after PIPAC#3 (p = 0.58). Fatigue symptom score was 44 ± 4.86 after PIPAC#1 and 47 ± 6.69 and 34 ± 7.85 after second and third applications, respectively (p = 0.40). Diarrhea (p = 0.31), constipation (p = 0.76), and nausea (p = 0.66) did not change significantly under PIPAC treatment. Conclusion. PIPAC treatment of peritoneal carcinomatosis had no negative impact on patients' overall QoL and its components or on main symptoms. This study was registered online on Research Registry (UIN: 1608).

  20. Hyperthermic intraperitoneal chemotherapy with mitomycin C and 5-fluorouracil in patients at high risk of peritoneal metastasis from colorectal cancer: A preliminary clinical study.

    Science.gov (United States)

    Shimizu, Tomoharu; Murata, Satoshi; Sonoda, Hiromichi; Mekata, Eiji; Ohta, Hiroyuki; Takebayashi, Katsushi; Miyake, Tohru; Tani, Tohru

    2014-05-01

    Although hyperthermic intraperitoneal chemotherapy (HIPEC) has been extensively used to treat patients with peritoneal metastases (PM) from colorectal cancer (CRC), a standard protocol has not yet been established. The aim of this preliminary clinical study was to confirm in vitro the efficacy of mitomycin C combined with 5-fluorouracil (MMC-5FU) under hyperthermic conditions in CRC and investigate the pharmacokinetics and feasibility of HIPEC with MMC-5FU for patients at high risk of PM from CRC. To simulate HIPEC in vitro, we used the collagen gel droplet-embedded culture drug sensitivity test with the HCT166 colorectal cell line to assess the antitumor efficacy of MMC and 5FU as single-agent and combination treatments following incubation with HCT116 cells for 30 min at either 37 or 42°C. In addition, five patients at high risk of PM from CRC underwent surgical tumor resection followed by HIPEC with MMC-5FU. Our results demonstrated that the combined administration of MMC-5FU suppressed tumor cell proliferation more efficiently compared to either agent used alone. In addition, hyperthermia at 42°C significantly enhanced drug sensitivity. During the clinical application of HIPEC with MMC-5FU, no grade 4 hematological toxicities or surgical adverse events were recorded. In addition, there was no evidence of peritoneal recurrence during a median observational period of 38 months. Of note, two patients with positive intraoperative peritoneal cytology at the first surgery developed no peritoneal recurrence and exhibited negative peritoneal cytology at the second surgery. In conclusion, HIPEC using MMC-5FU was shown to be a feasible therapeutic option, with an acceptable toxicity profile, for patients at high risk of PM from CRC. Therefore, HIPEC with MMC-5FU may be a promising novel therapeutic option for such patients, which merits further verification of its safety and efficacy in large-scale clinical trials.

  1. Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Park Sook-Eun

    2011-12-01

    Full Text Available Abstract Centrally administered insulin-like growth factor (IGF-I has anti-depressant activity in several rodent models, including lipopolysaccharide (LPS-induced depression. In this study we tested the ability of IGF-I and GPE (the N-terminal tri-peptide derived from IGF-I to alter depression-like behavior induced by intraperitoneal (i.p. administration of LPS in a preventive and curative manner. In the first case, IGF-I (1 μg or GPE (5 μg was administered i.c.v. to CD-1 mice followed 30 min later by 330 μg/kg body weight i.p. LPS. In the second case, 830 μg/kg body weight LPS was given 24 h prior to either IGF-I or GPE. When administered i.p., LPS induced full-blown sickness assessed as a loss of body weight, decrease in food intake and sickness behavior. None of these indices were affected by IGF-I or GPE. LPS also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. When administered before or after LPS, IGF-I and GPE abrogated the LPS response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. Similar to previous work with IGF-I, GPE decreased brain expression of cytokines in response to LPS although unlike IGF-I, GPE did not induce the expression of brain-derived neurotrophic factor (BDNF. LPS induced expression of tryptophan dioxygenases, IDO1, IDO2 and TDO2, but expression of these enzymes was not altered by GPE. Thus, both IGF-I and GPE elicit specific improvement in depression-like behavior independent of sickness, an action that could be due to their anti-inflammatory properties.

  2. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy improves survival for patients with peritoneal carcinomatosis from colorectal cancer: a phase II study from a Chinese center.

    Directory of Open Access Journals (Sweden)

    Chao-Qun Huang

    Full Text Available Peritoneal carcinomatosis (PC is a difficult clinical challenge in colorectal cancer (CRC because conventional treatment modalities could not produce significant survival benefit, which highlights the acute need for new treatment strategies. Our previous case-control study demonstrated the potential survival advantage of cytoreductive surgery (CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC over CRS alone. This phase II study was to further investigate the efficacy and adverse events of CRS+HIPEC for Chinese patients with CRC PC.A total of 60 consecutive CRC PC patients underwent 63 procedures consisting of CRS+HIPEC and postoperative chemotherapy, all by a designated team focusing on this combined treatment modality. All the clinico-pathological information was systematically integrated into a prospective database. The primary end point was disease-specific overall survival (OS, and the secondary end points were perioperative safety profiles.By the most recent database update, the median follow-up was 29.9 (range 3.5-108.9 months. The peritoneal cancer index (PCI ≤20 was in 47.0% of patients, complete cytoreductive surgery (CC0-1 was performed in 53.0% of patients. The median OS was 16.0 (95% confidence interval [CI] 12.2-19.8 months, and the 1-, 2-, 3-, and 5-year survival rates were 70.5%, 34.2%, 22.0% and 22.0%, respectively. Mortality and grades 3 to 5 morbidity rates in postoperative 30 days were 0.0% and 30.2%, respectively. Univariate analysis identified 3 parameters with significant effects on OS: PCI ≤20, CC0-1 and adjuvant chemotherapy over 6 cycles. On multivariate analysis, however, only CC0-1 and adjuvant chemotherapy ≥6 cycles were found to be independent factors for OS benefit.CRS+HIPEC at a specialized treatment center could improve OS for selected CRC PC patients from China, with acceptable perioperative safety.

  3. 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.

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

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    Bossù Paola

    2012-05-01

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

  5. Cytoreductive Surgery plus Hyperthermic Intraperitoneal Chemotherapy to Treat Advanced/Recurrent Epithelial Ovarian Cancer: Results from a Retrospective Study on Prospectively Established Database

    Directory of Open Access Journals (Sweden)

    Jian-Hua Sun

    2016-04-01

    Full Text Available BACKGROUND: Despite the best standard treatment, optimal cytoreductive surgery (CRS and platinum/taxane-based chemotherapy, prognosis of advanced epithelial ovarian carcinoma (EOC remains poor. Recently, CRS plus hyperthermic intraperitoneal chemotherapy (HIPEC has been developed to treat peritoneal carcinomatosis (PC. This study was to evaluate the efficacy and safety of CRS+HIPEC to treat PC from advanced/recurrent EOC. METHODS: Forty-six PC patients from advanced EOC (group A or recurrent EOC (group B were treated by 50 CRS+HIPEC procedures. The primary endpoints were progression-free survival (PFS and overall survival (OS; the secondary endpoints were safety profiles. RESULTS: The median OS was 74.0 months [95% confidence interval (CI 8.5-139.5] for group A versus 57.5 months (95% CI 29.8-85.2 for group B (P = .68. The median PFS was not reached for group A versus 8.5 months (95% CI 0-17.5 for group B (P = .034. Better median OS correlated with peritoneal cancer index (PCI 20 group, P = .01, complete cyroreduction (residual disease ≤ 2.5 mm [79.5 months for completeness of cytoreduction (CC score 0-1 vs 24.3 months for CC 2-3, P = .00], and sensitivity to platinum (65.3 months for platinum-sensitive group vs 20.0 for platinum-resistant group, P = .05. Serious adverse events occurred in five patients (10.0%. Multivariate analysis identified CC score as the only independent factor for better survival. CONCLUSION: For advanced/recurrent EOC, CRS+HIPEC could improve OS with acceptable safety.

  6. Development of a new model for the induction of chronic kidney disease via intraperitoneal adenine administration, and the effect of treatment with gum acacia thereon.

    Science.gov (United States)

    Al Za'abi, Mohammed; Al Busaidi, Mahfouda; Yasin, Javid; Schupp, Nicole; Nemmar, Abderrahim; Ali, Badreldin H

    2015-01-01

    Oral adenine (0.75% w/w in feed), is an established model for human chronic kidney disease (CKD). Gum acacia (GA) has been shown to be a nephroprotective agent in this model. Here we aimed at developing a new adenine-induced CKD model in rats via a systemic route (intraperitoneal, i.p.) and to test it with GA to obviate the possibility of a physical interaction between GA and adenine in the gut. Adenine was injected i.p. (50 or 100 mg/Kg for four weeks), and GA was given concomitantly in drinking water at a concentration of 15%, w/v. Several plasma and urinary biomarkers of oxidative stress were measured and the renal damage was assessed histopathologically. Adenine, at the two given i.p. doses, significantly reduced body weight, and increased relative kidney weight, water intake and urine output. It dose-dependently increased plasma and urinary inflammatory and oxidative stress biomarkers, and caused morphological and histological damage resembling that which has been reported with oral adenine. Concomitant treatment with GA significantly mitigated almost all the above measured indices. Administration of adenine i.p. induced CKD signs very similar to those induced by oral adenine. Therefore, this new model is quicker, more practical and accurate than the original (oral) model. GA ameliorates the CKD effects caused by adenine given i.p. suggesting that the antioxidant and anti-inflammatory properties possessed by oral GA are the main mechanism for its salutary action in adenine-induced CKD, an action that is independent of its possible interaction with adenine in the gut.

  7. Patient-Derived Antibody Targets Tumor Cells

    Science.gov (United States)

    An NCI Cancer Currents blog on an antibody derived from patients that killed tumor cells in cell lines of several cancer types and slowed tumor growth in mouse models of brain and lung cancer without evidence of side effects.

  8. Synthesis of bifunctional antibodies for immunoassays.

    Science.gov (United States)

    DeSilva, B S; Wilson, G S

    2000-09-01

    The synthesis of bifunctional antibodies using the principle of solid-phase synthesis is described. Two Fab' fragments were chemically linked together via a bismaleimide crosslinking reagent. The F(ab')(2) fragments from intact immunoglobulin G (IgG) were prepared using an immobilized pepsin column. Goat, mouse, and human antibodies were digested completely within 4 h. The F(ab')(2) fragments thus produced did not contain any IgG impurities. Fab' fragments were produced by reducing the heavy interchain disulfide bonds using 2-mercaptoethylamine. Use of the solid-phase reactor in the preparation of the bifunctional antibodies eliminated many of the time-consuming separation steps between the fragmentation and conjugation steps. This procedure facilitates the automation of bifunctional antibody preparation and the rapid optimization of reaction conditions.

  9. Solid phase synthesis of bifunctional antibodies.

    Science.gov (United States)

    DeSilva, B S; Wilson, G S

    1995-12-15

    Bifunctional antibodies were prepared using the principle of solid-phase synthesis. The two Fab' fragments were chemically linked together via a bismaleimide crosslinking reagent. The F(ab')2 fragments from intact IgG were prepared using an immobilized pepsin column. Goat, mouse and human antibodies were digested completely within 4 h. The F(ab')2 fragments thus produced did not contain any IgG impurities. The Fab' fragments were produced by reducing the inter-heavy chain disulfide bonds using 2-mercaptoethylamine. The use of the solid-phase reactor in the preparation of the bifunctional antibodies eliminated many of the time-consuming separation steps between the fragmentation and conjugation steps. This procedure facilitates the automation of the bifunctional antibody preparation and the rapid optimization of reaction conditions.

  10. Characterization of methylsulfinylalkyl glucosinolate specific polyclonal antibodies

    DEFF Research Database (Denmark)

    Mirza, Nadia Muhammad Akram; Schulz, Alexander; Halkier, Barbara Ann

    2016-01-01

    Antibodies towards small molecules, like plant specialized metabolites, are valuable tools for developing quantitative and qualitative analytical techniques. Glucosinolates are the specialized metabolites characteristic of the Brassicales order. Here we describe the characterization of polyclonal...... rabbit antibodies raised against the 4-methylsulfinylbutyl glucosinolate, glucoraphanin that is one of the major glucosinolates in the model plant Arabidopsis thaliana (hereafter Arabidopsis). Analysis of the cross-reactivity of the antibodies against a number of glucosinolates demonstrated...... that it was highly selective for methionine-derived aliphatic glucosinolates with a methyl-sulfinyl group in the side chain. Use of crude plant extracts from Arabidopsis mutants with different glucosinolate profiles showed that the antibodies recognized aliphatic glucosinolates in a plant extract and did not cross...

  11. Primary Antiphospholipid Antibody Syndrome: A Case Report.

    Science.gov (United States)

    Kadeli, Deepak K; Hanjagi, Siddaraya Y

    2015-10-01

    Primary Antiphospholipid antibody syndrome is a rare disease associated with thromboembolic events which may affect either the arterial or the venous vasculature. It presents with an increased risk of thrombosis in pregnant woman leading to repeated fetal losses. We present here a case of primary antiphospholipid antibody syndrome in young women who had previous event of gangrene of toes leading to their amputation and repeated fetal losses.

  12. Neutralizing antibodies to Haemophilus ducreyi cytotoxin.

    OpenAIRE

    Lagergård, T; Purvén, M

    1993-01-01

    Neutralizing antibodies against cytotoxin produced by Haemophilus ducreyi bacteria were studied in rabbits by an assay employing HEp-2 cells and diluted crude cytotoxin preparations from the organism. Antisera to 12 different H. ducreyi strains were prepared by immunization of rabbits with bacterial sonicates combined with Freund's adjuvant. The antibody response during infection with H. ducreyi was studied in two groups of rabbits which were infected with five live strains by either single o...

  13. Mepanipyrim haptens and antibodies with nanomolar affinity

    OpenAIRE

    Esteve Turrillas, Francesc Albert; Mercader Badia, Josep Vicent; Agulló, Consuelo; Abad Somovilla, Antonio; Abad Fuentes, Antonio

    2013-01-01

    Mepanipyrim is an anilinopyrimidine fungicide used worldwide for crop protection. With the aim of developing useful immunoreagents for mepanipyrim immunoanalysis, two new functionalized derivatives were prepared and antibodies were generated. Affinity and specificity were assessed by direct and indirect competitive ELISA using homologous and heterologous conjugates. Although all antibodies were selective for the target analyte, the immunizing hapten structure was revealed as a determinant for...

  14. Autoimmune encephalitis: Clinical diagnosis versus antibody confirmation

    Directory of Open Access Journals (Sweden)

    Asha Caroline Cyril

    2015-01-01

    Full Text Available Context: Autoimmune encephalitis is a heterogeneous disorder which is being diagnosed with increasing frequency. The diagnosis of these disorders is based on the detection of autoantibodies and characteristic clinical profiles. Aims: We aimed to study the antibody profile in encephalitis patients with suspected autoimmune etiology presenting to a tertiary care center. Settings and Design: The subjects were selected by screening all patients with clinical profile suggesting autoimmune encephalitis admitted in the neuromedical intensive care unit (ICU of a tertiary care center in South India. Materials and Methods: Patients who fulfilled modified Zuliani et al.′s, criteria for autoimmune encephalitis were identified during the period December 2009-June 2013. Blood samples from these subjects were screened for six neuronal antibodies. Statistical analysis used: Chi-square test was applied to compare the antibody positive and negative patients. Results: Out of 1,227 patients screened, 39 subjects (14 males: 25 females were identified with a mean age of 15.95 years and 19 cases were assessed in the acute and 20 in the convalescent phase of the illness. Seizure (87.8 % was the most common presenting symptom; status epilepticus occurred in 23 (60.5% patients during the course of the illness. Fourteen (35.9% patients were N-methyl-D-aspartate receptor (NMDAR antibody-positive and all were negative for the other antibodies tested. Conclusions: One-third of patients presenting with acute noninfective encephalitis would be positive for NMDAR antibodies with the remaining two-thirds with clinically suspected autoimmune encephalitis being antibody-negative. There are few markers in the clinical and investigative profiles to distinguish antibody-positive and -negative patients.

  15. Structure and specificity of lamprey monoclonal antibodies

    OpenAIRE

    Herrin, Brantley R.; Alder, Matthew N; Roux, Kenneth H.; Sina, Christina; Ehrhardt, Götz R. A.; Boydston, Jeremy A.; Turnbough, Charles L.; Cooper, Max D.

    2008-01-01

    Adaptive immunity in jawless vertebrates (lamprey and hagfish) is mediated by lymphocytes that undergo combinatorial assembly of leucine-rich repeat (LRR) gene segments to create a diverse repertoire of variable lymphocyte receptor (VLR) genes. Immunization with particulate antigens induces VLR-B-bearing lymphocytes to secrete antigen-specific VLR-B antibodies. Here, we describe the production of recombinant VLR-B antibodies specific for BclA, a major coat protein of Bacillus anthracis spores...

  16. Therapeutic monoclonal antibody for Sporotrichosis

    Directory of Open Access Journals (Sweden)

    Sandro eAlmeida

    2012-11-01

    Full Text Available Sporotrichosis is a chronic subcutaneous mycosis that affects either humans or animals and occurs worldwide. This subcutaneous mycosis had been attributed to a single etiological agent, Sporothrix schenckii. S. schenckii exhibits a considerable genetic variability, where recently, was suggesting that this taxon consists of a complex of species. Sporotrichosis is caused by traumatic inoculation of the fungus, which is a ubiquitous environmental saprophyte that can be isolated from soil and plant debris. The infection is limited to the cutaneous forms but, recently, occurrences of more severe clinical forms of this mycosis were described, especially among immunocompromized individuals. The immunological mechanisms involved in prevention and control of sporotrichosis are still not very well understood. Some works suggest that cell-mediated immunity plays an important role in protecting the host against S. schenckii. In contrast, the role of the humoral immune response in protection against this fungus have not been studied in detail. In a previous study, we showed that antigens secreted by S. schenckii induce a specific humoral response in infected animals, mainly against the 70-kDa molecules, indicating a possible participation of specific antibodies to this molecule in infection control. In an other work of the our group, we produced a mAb against a 70-kDa glycoprotein of S. schenckii in order to better understand the effect of passive immunization of mice infected with S. schenckii. Results showed a significant reduction in the number of CFU in organs of mice when the mAb was injected before and during S. schenckii infection. Similar results were observed when T-cell deficient mice were used. Drugs of choice in the treatment of sporothrichosis require long periods and frequently relapses are observed, mainly in immunocompromized patients. The strong protection induced by mAb against a 70-kDa glycoprotein makes it a strong candidate for a

  17. IMPORTANCE OF RESEARCH HLA ANTIBODIES CLASS I AND II, AND MICA ANTIBODIES IN KIDNEY TRANSPLANTATION

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutia

    2011-01-01

    Full Text Available The purpose of this study was to investigate the occurrence of HLA and MICA antibodies in patients from the waiting list for kidney transplantation and their influence on the course of post-transplant period. Determination of HLA antibodies class I and II, and MICA antibodies was performed on a platform of Luminex (xMAP-tech- nology using sets LABScreen ONE LAMBDA (U.S.. A total of 156 patients from the waiting list for kidney transplantation. Revealed the presence of HLA and MICA antibodies in the serum of 31.4% of patients. Regraf- ted patients increased the content of antibodies to the antigens of HLA system was noted in 88.2% of cases, 47% met the combination of antibodies to the I, II classes and MICA. In patients awaiting first kidney transplantation, HLA and MICA antibodies were determined in 23.7% of cases. The presence of pretransplant HLA and MICA antibodies had a significant influence on the course of post-transplant period. Patients with the presence of HLA and MICA in 50% of cases delayed graft function. Sessions of plasmapheresis can reduce the concentration of HLA and MICA antibodies on average by 61.1%. 

  18. Construction of human antibody gene libraries and selection of antibodies by phage display.

    Science.gov (United States)

    Frenzel, André; Kügler, Jonas; Wilke, Sonja; Schirrmann, Thomas; Hust, Michael

    2014-01-01

    Antibody phage display is the most commonly used in vitro selection technology and has yielded thousands of useful antibodies for research, diagnostics, and therapy.The prerequisite for successful generation and development of human recombinant antibodies using phage display is the construction of a high-quality antibody gene library. Here, we describe the methods for the construction of human immune and naive scFv gene libraries.The success also depends on the panning strategy for the selection of binders from these libraries. In this article, we describe a panning strategy that is high-throughput compatible and allows parallel selection in microtiter plates.

  19. Generation of HER2 monoclonal antibodies using epitopes of a rabbit polyclonal antibody.

    Science.gov (United States)

    Hu, Francis Jingxin; Uhlen, Mathias; Rockberg, Johan

    2014-01-25

    One of the issues in using polyclonal antibodies is the limited amount of reagent available from an immunisation, leading to batch-to-batch variation and difficulties in obtaining the same antibody performance when the same antigen is re-immunised into several separate animals. This led to the development of hybridoma technology allowing, at least theoretically, for an unlimited production of a specific binder. Nevertheless, polyclonal antibodies are widely used in research and diagnostics and there exists a need for robust methods to convert a polyclonal antibody with good binding performance into a renewable monoclonal with identical or similar binding specificity. Here we have used precise information regarding the functional recognition sequence (epitope) of a rabbit polyclonal antibody with attractive binding characteristics as the basis for generation of a renewable mouse monoclonal antibody. First, the original protein fragment antigen was used for immunisation and generation of mouse hybridoma, without obtaining binders to the same epitope region. Instead a peptide designed using the functional epitope and structural information was synthesised and used for hybridoma production. Several of the monoclonal antibodies generated were found to have similar binding characteristics to those of the original polyclonal antibody. These monoclonal antibodies detected native HER2 on cell lines and were also able to stain HER2 in immunohistochemistry using xenografted mice, as well as human normal and cancer tissues.

  20. Antibody-mediated resistance against plant pathogens.

    Science.gov (United States)

    Safarnejad, Mohammad Reza; Jouzani, Gholamreza Salehi; Tabatabaei, Meisam; Tabatabaie, Meisam; Twyman, Richard M; Schillberg, Stefan

    2011-01-01

    Plant diseases have a significant impact on the yield and quality of crops. Many strategies have been developed to combat plant diseases, including the transfer of resistance genes to crops by conventional breeding. However, resistance genes can only be introgressed from sexually-compatible species, so breeders need alternative measures to introduce resistance traits from more distant sources. In this context, genetic engineering provides an opportunity to exploit diverse and novel forms of resistance, e.g. the use of recombinant antibodies targeting plant pathogens. Native antibodies, as a part of the vertebrate adaptive immune system, can bind to foreign antigens and eliminate them from the body. The ectopic expression of antibodies in plants can also interfere with pathogen activity to confer disease resistance. With sufficient knowledge of the pathogen life cycle, it is possible to counter any disease by designing expression constructs so that pathogen-specific antibodies accumulate at high levels in appropriate sub-cellular compartments. Although first developed to tackle plant viruses and still used predominantly for this purpose, antibodies have been targeted against a diverse range of pathogens as well as proteins involved in plant-pathogen interactions. Here we comprehensively review the development and implementation of antibody-mediated disease resistance in plants.

  1. Standardization of anti-DNA antibody assays.

    Science.gov (United States)

    Pisetsky, David S

    2013-07-01

    Antibodies to DNA (anti-DNA) are the serological hallmark of systemic lupus erythematosus and represent important biomarkers for clinical and research purposes. These antibodies are part of a family of antibodies to nucleosomes and bind to conserved sites widely present on DNA. While the value of anti-DNA as a biomarker is well established, the assay for these antibodies has involved a variety of DNA sources and systems to detect DNA-anti-DNA interactions. The influence of these variations on antibody detection has complicated assay standardization. As an antigen, DNA has unique features since it is a highly charged polymer that has structural heterogeneity. This heterogeneity can affect antigenicity which can vary on the basis of DNA origin, size, conformation and mobility. In addition, as a polymer, DNA can promote patterns of antibody binding based on monogamous or bivalent interaction which require an extended polynucleotide structure. Understanding the nature of DNA as an antigen can facilitate interpretation of serological tests and underpin efforts at better standardization.

  2. Discovery of functional antibodies targeting ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I; Gardener, Matthew J; Williams, Wendy A

    2015-04-01

    Ion channels play critical roles in physiology and disease by modulation of cellular functions such as electrical excitability, secretion, cell migration, and gene transcription. Ion channels represent an important target class for drug discovery that has been largely addressed, to date, using small-molecule approaches. A significant opportunity exists to target these channels with antibodies and alternative formats of biologics. Antibodies display high specificity and affinity for their target antigen, and they have the potential to target ion channels very selectively. Nevertheless, isolating antibodies to this target class is challenging due to the difficulties in expression and purification of ion channels in a format suitable for antibody drug discovery in addition to the complexity of screening for function. In this article, we will review the current state of ion channel biologics discovery and the progress that has been made. We will also highlight the challenges in isolating functional antibodies to these targets and how these challenges may be addressed. Finally, we also illustrate successful approaches to isolating functional monoclonal antibodies targeting ion channels by way of a number of case studies drawn from recent publications.

  3. Antiphospholipid Antibody Syndrome Presenting with Unilateral Adrenal Hemmorhage.

    Science.gov (United States)

    Ullah, Kifayat; Butt, Ghias; Neopane, Sippy; Arshi, Shahana

    2016-06-01

    The antiphospholipid antibody syndrome presents with vascular thrombosis which involve both arterial and venous systems. The clinical presentation of antiphospholipid antibody syndrome includes obstetric complications leading to recurrent abortions, presence of circulating antibodies against phospholipids, and multi-organ thromboembolisms. We report a case of a patient who presented with unilateral adrenal hemorrhage and subsequently found to have antiphospholipid antibody syndrome and lupus nephritis.

  4. Avian Diagnostic and Therapeutic Antibodies to Viral Emerging Pathogens

    Energy Technology Data Exchange (ETDEWEB)

    David Bradley

    2011-03-31

    During the current period the following key objectives were achieved: demonstration of high titer antibody production by geese following immunization with inactived H1N1 virus; completion of the epitope mapping of West Nile Virus-specific goose antibodies and initiation of epitope mapping of H1N1 flu-specific goose antibodies; advancement in scalable purification of goose antibodies.

  5. Antibody to a 145-kilodalton outer membrane protein has bactericidal activity and protective activity against experimental bacteremia caused by a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius. The Brazilian Purpuric Fever Study Group.

    Science.gov (United States)

    Rubin, L G; Rizvi, A

    1991-12-01

    The immunologic basis for protection against Brazilian purpuric fever, a septicemic infection associated with Haemophilus influenzae biogroup aegyptius bacteremia, is unknown. Passive immunization of infant rats with antiserum to whole bacterial cells of the homologous strain protects them from experimental bacteremia following bacterial challenge. In immunoblotting, antibody to a 145-kDa protein (P145) was present in protective antisera but not in nonprotective antisera. As judged by analysis of the antibodies eluted from whole bacterial cells and the agglutination of bacteria by antisera to P145, this protein is surface exposed. We prepared monospecific rat antisera to this protein by three methods: (i) immunization with whole bacterial cells and absorption with a Brazilian purpuric fever strain not expressing P145, (ii) immunization with gel-purified P145, and (iii) immunization with a P145-expressing transformant of a laboratory H. influenzae strain expressing this protein and absorption of the antiserum with the laboratory H. influenzae strain. These antisera had low antilipooligosaccharide antibody titers, were reactive only with P145, and had bactericidal activity in vitro. Following passive immunization, these antisera partially protected infant rats from bacteremia resulting from intraperitoneal challenge with bacteria. As assessed by immunoblotting, pooled adult human sera contained antibodies reactive with P145. Antibody to P145 may contribute to protection against Brazilian purpuric fever.

  6. Coming-of-Age of Antibodies in Cancer Therapeutics.

    Science.gov (United States)

    Ayyar, B Vijayalakshmi; Arora, Sushrut; O'Kennedy, Richard

    2016-12-01

    Antibody-based therapies have garnered considerable success in recent years. This is due to the availability of strategies to successfully engineer antibodies into humanized forms, better understanding of the biological processes involved in cancer development, the availability of novel recombinant antibody formats, better antibody selection platforms, and improved antibody conjugation methodologies. Such achievements have led to an explosion in the generation of antibodies and antibody-associated constructs for the treatment of cancer and other diseases. In this review, we critically assess recent trends in the development and applications of bispecific antibodies (bsAbs), antibody-drug conjugates (ADCs), and immune checkpoint inhibitors (ICIs) as cancer therapeutics. We also highlight recent US FDA approvals and clinical trials of antibody-based cancer therapies.

  7. [Advances in the study of natural small molecular antibody].

    Science.gov (United States)

    Zhu, Lei; Zhang, Da-peng

    2012-10-01

    Small molecule antibodies are naturally existed and well functioned but not structurally related to the conventional antibodies. They are only composed of heavy protein chains or light chains, much smaller than common antibody. The first small molecule antibody, called Nanobody was engineered from heavy-chain antibodies found in camelids. Cartilaginous fishes also have heavy-chain antibodies (IgNAR, "immunoglobulin new antigen receptor"), from which single-domain antibodies called Vnar fragments can be obtained. In addition, free light chain (FLC) antibodies in human bodies are being developed as therapeutic and diagnostic agents. Comparing to intact antibodies, common advantages of small molecule antibodies are with better solubility, tissue penetration, stability towards heat and enzymes, and comparatively low production costs. This article reviews the structural characteristics and mechanism of action of the Nanobody, IgNAR and FLC.

  8. Brain delivery of AAV9 expressing an anti-PrP monovalent antibody delays prion disease in mice.

    Science.gov (United States)

    Moda, Fabio; Vimercati, Chiara; Campagnani, Ilaria; Ruggerone, Margherita; Giaccone, Giorgio; Morbin, Michela; Zentilin, Lorena; Giacca, Mauro; Zucca, Ileana; Legname, Giuseppe; Tagliavini, Fabrizio

    2012-01-01

    Prion diseases are caused by a conformational modification of the cellular prion protein (PrP (C)) into disease-specific forms, termed PrP (Sc), that have the ability to interact with PrP (C) promoting its conversion to PrP (Sc). In vitro studies demonstrated that anti-PrP antibodies inhibit this process. In particular, the single chain variable fragment D18 antibody (scFvD18) showed high efficiency in curing chronically prion-infected cells. This molecule binds the PrP (C) region involved in the interaction with PrP (Sc) thus halting further prion formation. These findings prompted us to test the efficiency of scFvD18 in vivo. A recombinant Adeno-Associated Viral vector serotype 9 was used to deliver scFvD18 to the brain of mice that were subsequently infected by intraperitoneal route with the mouse-adapted scrapie strain RML. We found that the treatment was safe, prolonged the incubation time of scrapie-infected animals and decreased the burden of total proteinase-resistant PrP (Sc) in the brain, suggesting that scFvD18 interferes with prion replication in vivo. This approach is relevant for designing new therapeutic strategies for prion diseases and other disorders characterized by protein misfolding.

  9. Neuropathogenesis of Zika Virus in a Highly Susceptible Immunocompetent Mouse Model after Antibody Blockade of Type I Interferon

    Science.gov (United States)

    Smith, Darci R.; Hollidge, Bradley; Daye, Sharon; Zeng, Xiankun; Blancett, Candace; Kuszpit, Kyle; Bocan, Thomas; Koehler, Jeff W.; Coyne, Susan; Minogue, Tim; Kenny, Tara; Chi, Xiaoli; Yim, Soojin; Miller, Lynn; Schmaljohn, Connie; Bavari, Sina; Golden, Joseph W.

    2017-01-01

    Animal models are needed to better understand the pathogenic mechanisms of Zika virus (ZIKV) and to evaluate candidate medical countermeasures. Adult mice infected with ZIKV develop a transient viremia, but do not demonstrate signs of morbidity or mortality. Mice deficient in type I or a combination of type I and type II interferon (IFN) responses are highly susceptible to ZIKV infection; however, the absence of a competent immune system limits their usefulness for studying medical countermeasures. Here we employ a murine model for ZIKV using wild-type C57BL/6 mice treated with an antibody to disrupt type I IFN signaling to study ZIKV pathogenesis. We observed 40% mortality in antibody treated mice exposed to ZIKV subcutaneously whereas mice exposed by intraperitoneal inoculation were highly susceptible incurring 100% mortality. Mice infected by both exposure routes experienced weight loss, high viremia, and severe neuropathologic changes. The most significant histopathological findings occurred in the central nervous system where lesions represent an acute to subacute encephalitis/encephalomyelitis that is characterized by neuronal death, astrogliosis, microgliosis, scattered necrotic cellular debris, and inflammatory cell infiltrates. This model of ZIKV pathogenesis will be valuable for evaluating medical countermeasures and the pathogenic mechanisms of ZIKV because it allows immune responses to be elicited in immunologically competent mice with IFN I blockade only induced at the time of infection. PMID:28068342

  10. Intranasal Immunization of Mice to Avoid Interference of Maternal Antibody against H5N1 Infection.

    Directory of Open Access Journals (Sweden)

    Fenghua Zhang

    Full Text Available Maternally-derived antibodies (MDAs can protect offspring against influenza virus infection but may also inhibit active immune responses. To overcome MDA- mediated inhibition, active immunization of offspring with an inactivated H5N1 whole-virion vaccine under the influence of MDAs was explored in mice. Female mice were vaccinated twice via the intraperitoneal (IP or intranasal (IN route with the vaccine prior to mating. One week after birth, the offspring were immunized twice via the IP or IN route with the same vaccine and then challenged with a lethal dose of a highly homologous virus strain. The results showed that, no matter which immunization route (IP or IN was used for mothers, the presence of MDAs severely interfered with the active immune response of the offspring when the offspring were immunized via the IP route. Only via the IN immunization route did the offspring overcome the MDA interference. These results suggest that intranasal immunization could be a suitable inoculation route for offspring to overcome MDA interference in the defense against highly pathogenic H5N1 virus infection. This study may provide references for human and animal vaccination to overcome MDA-induced inhibition.

  11. Cross-reactive broadly neutralizing antibodies: timing is everything

    OpenAIRE

    Euler, Zelda; Schuitemaker, Hanneke

    2012-01-01

    The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology. In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection. We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

  12. Cross-reactive broadly neutralizing antibodies: timing is everything.

    Science.gov (United States)

    Euler, Zelda; Schuitemaker, Hanneke

    2012-01-01

    The recent surge of research into new broadly neutralizing antibodies in HIV-1 infection has recharged the field of HIV-1 vaccinology. In this review we discuss the currently known broadly neutralizing antibodies and focus on factors that may shape these antibodies in natural infection. We further discuss the role of these antibodies in the clinical course of the infection and consider immunological obstacles in inducing broadly neutralizing antibodies with a vaccine.

  13. Relevance of anti-myelin antibodies in Multiple Sclerosis

    OpenAIRE

    2005-01-01

    Antibodies directed against myelin antigens have been described in multiple sclerosis (MS). Although anti-myelin antibodies have been implicated in central nervous system (CNS) demyelination, it is unclear to what extent anti-myelin antibodies contribute to MS pathogenesis. In this dissertation, the role of antibodies in MS and in the animal model experimental allergic encephalomyelitis (EAE) is addressed in eight chapters: Chapter 1: A review on antibodies, complement and Fc receptors in MS ...

  14. Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose-response curves in mice.

    Science.gov (United States)

    Salama, Raghda A M; El Gayar, Nesreen H; Georgy, Sonia S; Hamza, May

    2016-01-01

    Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose-response curves. This study aims at identifying the equivalent intraperitoneal (i.p.) doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose-response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.). The dose-response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents), the area under the 'change in mechanical threshold'-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

  15. Pautas de protección frente al riesgo de exposición a citostáticos en quimioterapia intraperitoneal hipertérmica

    Directory of Open Access Journals (Sweden)

    Carolina Miraz-Novas

    Full Text Available Objetivo: El objetivo del trabajo realizado es identificar las tareas de riesgo asociadas a la manipulación de citostáticos, detectadas en la aplicación de Quimioterapia Intraperitoneal con Hipertermia (HIPEC aplicada según la técnica de Sugarbaker y las diferentes soluciones llevadas a cabo para su control. Método: La detección y evaluación de los riesgos existentes, así como la propuesta y selección de las diferentes medidas de prevención implantadas se realizaron siguiendo las pautas de: entrevista y estudio de la actividad con el personal especialista implicado, estudio bibliográfico, identificación de requerimientos legales y normativos aplicables, para finalizar estableciendo las medidas de control. Por último se comprobó mediante consulta a las partes involucradas el grado de satisfacción con las medidas adoptadas (adherencia a las medidas y la eficacia de las medidas adoptadas (número de accidentes e incidentes. Resultados: Se identificaron las tareas de mayor riesgo y las principales vías de exposición. Se determinaron medidas de control de la exposición por vía inhalatoria y dérmica, acordes a los requisitos establecidos para la protección de los trabajadores y para uso en campo quirúrgico, minimizando el disconfor que pudieran provocar al personal. Conclusiones: Se pone de manifiesto la posibilidad de conjugar protección del personal, cumplimiento normativo, preservación del campo quirúrgico y confort del personal. A través de acciones formativas e informativas y el trabajo cooperativo de los diferentes servicios participantes, se consiguió un elevado grado de aceptación por parte del personal involucrado de las medidas de prevención establecidas. Se minimizó la inquietud del personal frente a los riesgos laborales afrontados en HIPEC. Como cierre de la acción preventiva, se considera recomendable la comprobación de la eficacia de las medidas adoptadas a través de evaluación cuantitativa.

  16. Equivalent intraperitoneal doses of ibuprofen supplemented in drinking water or in diet: a behavioral and biochemical assay using antinociceptive and thromboxane inhibitory dose–response curves in mice

    Directory of Open Access Journals (Sweden)

    Raghda A.M. Salama

    2016-07-01

    Full Text Available Background. Ibuprofen is used chronically in different animal models of inflammation by administration in drinking water or in diet due to its short half-life. Though this practice has been used for years, ibuprofen doses were never assayed against parenteral dose–response curves. This study aims at identifying the equivalent intraperitoneal (i.p. doses of ibuprofen, when it is administered in drinking water or in diet. Methods. Bioassays were performed using formalin test and incisional pain model for antinociceptive efficacy and serum TXB2 for eicosanoid inhibitory activity. The dose–response curve of i.p. administered ibuprofen was constructed for each test using 50, 75, 100 and 200 mg/kg body weight (b.w.. The dose–response curves were constructed of phase 2a of the formalin test (the most sensitive phase to COX inhibitory agents, the area under the ‘change in mechanical threshold’-time curve in the incisional pain model and serum TXB2 levels. The assayed ibuprofen concentrations administered in drinking water were 0.2, 0.35, 0.6 mg/ml and those administered in diet were 82, 263, 375 mg/kg diet. Results. The 3 concentrations applied in drinking water lay between 73.6 and 85.5 mg/kg b.w., i.p., in case of the formalin test; between 58.9 and 77.8 mg/kg b.w., i.p., in case of the incisional pain model; and between 71.8 and 125.8 mg/kg b.w., i.p., in case of serum TXB2 levels. The 3 concentrations administered in diet lay between 67.6 and 83.8 mg/kg b.w., i.p., in case of the formalin test; between 52.7 and 68.6 mg/kg b.w., i.p., in case of the incisional pain model; and between 63.6 and 92.5 mg/kg b.w., i.p., in case of serum TXB2 levels. Discussion. The increment in pharmacological effects of different doses of continuously administered ibuprofen in drinking water or diet do not parallel those of i.p. administered ibuprofen. It is therefore difficult to assume the equivalent parenteral daily doses based on mathematical calculations.

  17. Higher cytotoxicity of divalent antibody-toxins than monovalent antibody-toxins

    Energy Technology Data Exchange (ETDEWEB)

    Won, JaeSeon; Nam, PilWon; Lee, YongChan [College of Life Sciences and Graduate School of Biotechnology, Korea University, 5-ga Anam-dong, Sungbuk-gu, Seoul 136-701 (Korea, Republic of); Choe, MuHyeon, E-mail: choemh@korea.ac.kr [College of Life Sciences and Graduate School of Biotechnology, Korea University, 5-ga Anam-dong, Sungbuk-gu, Seoul 136-701 (Korea, Republic of)

    2009-04-24

    Recombinant antibody-toxins are constructed via the fusion of a 'carcinoma-specific' antibody fragment to a toxin. Due to the high affinity and high selectivity of the antibody fragments, antibody-toxins can bind to surface antigens on cancer cells and kill them without harming normal cells [L.H. Pai, J.K. Batra, D.J. FitzGerald, M.C. Willingham, I. Pastan, Anti-tumor activities of immunotoxins made of monoclonal antibody B3 and various forms of Pseudomonas exotoxin, Proc. Natl. Acad. Sci. USA 88 (1991) 3358-3362]. In this study, we constructed the antibody-toxin, Fab-SWn-PE38, with SWn (n = 3, 6, 9) sequences containing n-time repeated (G{sub 4}S) between the Fab fragment and PE38 (38 kDa truncated form of Pseudomonas exotoxin A). The SWn sequence also harbored one cysteine residue that could form a disulfide bridge between two Fab-SWn-PE38 monomers. We assessed the cytotoxicity of the monovalent (Fab-SWn-PE38), and divalent ([Fab-SWn-PE38]{sub 2}) antibody-toxins. The cytotoxicity of the dimer against the CRL1739 cell line was approximately 18.8-fold higher than that of the monomer on the ng/ml scale, which was approximately 37.6-fold higher on the pM scale. These results strongly indicate that divalency provides higher cytotoxicity for an antibody-toxin.

  18. Presence of non-maternal antibodies in newborns of mothers with antibody deficiencies.

    NARCIS (Netherlands)

    M. Hahn-Zoric; B. Carlsson; J. Bjö rkander; A.D.M.E. Osterhaus (Albert); L. Mellander; L.A. Hanson

    1992-01-01

    textabstractTo explain the mechanism for induction and production of specific antibodies found in the newborn already at birth, without previous known exposure to the antigen, we chose a model that presumably excluded the possibility of specific antibodies being transferred from the mother to the fe

  19. A recombinant, fully human monoclonal antibody with antitumor activity constructed from phage-displayed antibody fragments

    NARCIS (Netherlands)

    Huls, GA; Heijnen, IAFM; Cuomo, ME; Koningsberger, JC; Boel, E; de Vries, ARV; Loyson, SAJ; Helfrich, W; Henegouwen, GPV; van Meijer, M; de Kruif, J; Logtenberg, T

    1999-01-01

    A single-chain Fv antibody fragment specific for the tumor-associated Ep-CAM molecule was isolated from a semisynthetic phage display library and converted into an intact, fully human IgG1 monoclonal antibody (huMab), The purified huMab had an affinity of 5 nM and effectively mediated tumor cell kil

  20. Discovery of diverse and functional antibodies from large human repertoire antibody libraries.

    Science.gov (United States)

    Schwimmer, Lauren J; Huang, Betty; Giang, Hoa; Cotter, Robyn L; Chemla-Vogel, David S; Dy, Francis V; Tam, Eric M; Zhang, Fangjiu; Toy, Pamela; Bohmann, David J; Watson, Susan R; Beaber, John W; Reddy, Nithin; Kuan, Hua-Feng; Bedinger, Daniel H; Rondon, Isaac J

    2013-05-31

    Phage display antibody libraries have a proven track record for the discovery of therapeutic human antibodies, increasing the demand for large and diverse phage antibody libraries for the discovery of new therapeutics. We have constructed naïve antibody phage display libraries in both Fab and scFv formats, with each library having more than 250 billion clones that encompass the human antibody repertoire. These libraries show high fidelity in open reading frame and expression percentages, and their V-gene family distribution, VH-CDR3 length and amino acid usage mirror the natural diversity of human antibodies. Both the Fab and scFv libraries show robust sequence diversity in target-specific binders and differential V-gene usage for each target tested, supporting the use of libraries that utilize multiple display formats and V-gene utilization to maximize antibody-binding diversity. For each of the targets, clones with picomolar affinities were identified from at least one of the libraries and for the two targets assessed for activity, functional antibodies were identified from both libraries.

  1. A study on associations between antiprothrombin antibodies, antiplasminogen antibodies and thrombosis

    NARCIS (Netherlands)

    Simmelink, MJA; De Groot, PG; Derksen, RHWM

    2003-01-01

    Anti-prothrombin antibodies area frequent cause of lupus anticoagulant (LAC), a thrombotic risk factor. Prothrombin shares structural homology with plasminogen, a kringle protein with an important role in fibrinolysis. Cross-reactivity between antiprothrombin antibodies and plasminogen has been desc

  2. Thermodynamics of antibody-antigen interaction revealed by mutation analysis of antibody variable regions.

    Science.gov (United States)

    Akiba, Hiroki; Tsumoto, Kouhei

    2015-07-01

    Antibodies (immunoglobulins) bind specific molecules (i.e. antigens) with high affinity and specificity. In order to understand their mechanisms of recognition, interaction analysis based on thermodynamic and kinetic parameters, as well as structure determination is crucial. In this review, we focus on mutational analysis which gives information about the role of each amino acid residue in antibody-antigen interaction. Taking anti-hen egg lysozyme antibodies and several anti-small molecule antibodies, the energetic contribution of hot-spot and non-hot-spot residues is discussed in terms of thermodynamics. Here, thermodynamics of the contribution from aromatic, charged and hydrogen bond-forming amino acids are discussed, and their different characteristics have been elucidated. The information gives fundamental understanding of the antibody-antigen interaction. Furthermore, the consequences of antibody engineering are analysed from thermodynamic viewpoints: humanization to reduce immunogenicity and rational design to improve affinity. Amino acid residues outside hot-spots in the interface play important roles in these cases, and thus thermodynamic and kinetic parameters give much information about the antigen recognition. Thermodynamic analysis of mutant antibodies thus should lead to advanced strategies to design and select antibodies with high affinity.

  3. The antibody mining toolbox: an open source tool for the rapid analysis of antibody repertoires.

    Science.gov (United States)

    D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D; Shen, Xiaohong; Bradbury, Andrew R M; Kiss, Csaba

    2014-01-01

    In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput screening methods such as enzyme-linked immunosorbant assay. The high cost and the need for bioinformatics experts and powerful computer clusters, however, have limited the general use of deep sequencing in antibody selections. Here, we describe the AbMining ToolBox, an open source software package for the straightforward analysis of antibody libraries sequenced by the three main next generation sequencing platforms (454, Ion Torrent, MiSeq). The ToolBox is able to identify heavy chain CDR3s as effectively as more computationally intense software, and can be easily adapted to analyze other portions of antibody variable genes, as well as the selection outputs of libraries based on different scaffolds. The software runs on all common operating systems (Microsoft Windows, Mac OS X, Linux), on standard personal computers, and sequence analysis of 1-2 million reads can be accomplished in 10-15 min, a fraction of the time of competing software. Use of the ToolBox will allow the average researcher to incorporate deep sequence analysis into routine selections from antibody display libraries.

  4. Antibody-Mediated Internalization of Infectious HIV-1 Virions Differs among Antibody Isotypes and Subclasses.

    Science.gov (United States)

    Tay, Matthew Zirui; Liu, Pinghuang; Williams, LaTonya D; McRaven, Michael D; Sawant, Sheetal; Gurley, Thaddeus C; Xu, Thomas T; Dennison, S Moses; Liao, Hua-Xin; Chenine, Agnès-Laurence; Alam, S Munir; Moody, M Anthony; Hope, Thomas J; Haynes, Barton F; Tomaras, Georgia D

    2016-08-01

    Emerging data support a role for antibody Fc-mediated antiviral activity in vaccine efficacy and in the control of HIV-1 replication by broadly neutralizing antibodies. Antibody-mediated virus internalization is an Fc-mediated function that may act at the portal of entry whereby effector cells may be triggered by pre-existing antibodies to prevent HIV-1 acquisition. Understanding the capacity of HIV-1 antibodies in mediating internalization of HIV-1 virions by primary monocytes is critical to understanding their full antiviral potency. Antibody isotypes/subclasses differ in functional profile, with consequences for their antiviral activity. For instance, in the RV144 vaccine trial that achieved partial efficacy, Env IgA correlated with increased risk of HIV-1 infection (i.e. decreased vaccine efficacy), whereas V1-V2 IgG3 correlated with decreased risk of HIV-1 infection (i.e. increased vaccine efficacy). Thus, understanding the different functional attributes of HIV-1 specific IgG1, IgG3 and IgA antibodies will help define the mechanisms of immune protection. Here, we utilized an in vitro flow cytometric method utilizing primary monocytes as phagocytes and infectious HIV-1 virions as targets to determine the capacity of Env IgA (IgA1, IgA2), IgG1 and IgG3 antibodies to mediate HIV-1 infectious virion internalization. Importantly, both broadly neutralizing antibodies (i.e. PG9, 2G12, CH31, VRC01 IgG) and non-broadly neutralizing antibodies (i.e. 7B2 mAb, mucosal HIV-1+ IgG) mediated internalization of HIV-1 virions. Furthermore, we found that Env IgG3 of multiple specificities (i.e. CD4bs, V1-V2 and gp41) mediated increased infectious virion internalization over Env IgG1 of the same specificity, while Env IgA mediated decreased infectious virion internalization compared to IgG1. These data demonstrate that antibody-mediated internalization of HIV-1 virions depends on antibody specificity and isotype. Evaluation of the phagocytic potency of vaccine

  5. Metabolic engineering of monoclonal antibody carbohydrates for antibody-drug conjugation.

    Science.gov (United States)

    Okeley, Nicole M; Toki, Brian E; Zhang, Xinqun; Jeffrey, Scott C; Burke, Patrick J; Alley, Stephen C; Senter, Peter D

    2013-10-16

    The role that carbohydrates play in antibody function and pharmacokinetics has made them important targets for modification. The terminal fucose of the N-linked glycan structure, which has been shown to be involved in modulation of antibody-directed cellular cytotoxicity, is a particularly interesting location for potential modification through incorporation of alternative sugar structures. A library of fucose analogues was evaluated for their ability to incorporate into antibody carbohydrates in place of the native fucose. A number of efficiently incorporated molecules were identified, demonstrating the ability of fucosyltransferase VIII to utilize a variety of non-natural sugars as substrates. Among these structures was a thiolated analogue, 6-thiofucose, which was incorporated into the antibody carbohydrate with good efficiency. This unnatural thio-sugar could then be used for conjugation using maleimide chemistry to produce antibody-drug conjugates with pronounced cytotoxic activities and improved homogeneity compared to drug attachment through hinge disulfides.

  6. Antibody engineering using phage display with a coiled-coil heterodimeric Fv antibody fragment.

    Directory of Open Access Journals (Sweden)

    Xinwei Wang

    Full Text Available A Fab-like antibody binding unit, ccFv, in which a pair of heterodimeric coiled-coil domains was fused to V(H and V(L for Fv stabilization, was constructed for an anti-VEGF antibody. The anti-VEGF ccFv showed the same binding affinity as scFv but significantly improved stability and phage display level. Furthermore, phage display libraries in the ccFv format were constructed for humanization and affinity maturation of the anti-VEGF antibody. A panel of V(H frameworks and V(H-CDR3 variants, with a significant improvement in affinity and expressibility in both E. coli and yeast systems, was isolated from the ccFv phage libraries. These results demonstrate the potential application of the ccFv antibody format in antibody engineering.

  7. Antibody Fragments as Probe in Biosensor Development

    Directory of Open Access Journals (Sweden)

    Serge Muyldermans

    2008-08-01

    Full Text Available Today’s proteomic analyses are generating increasing numbers of biomarkers, making it essential to possess highly specific probes able to recognize those targets. Antibodies are considered to be the first choice as molecular recognition units due to their target specificity and affinity, which make them excellent probes in biosensor development. However several problems such as difficult directional immobilization, unstable behavior, loss of specificity and steric hindrance, may arise from using these large molecules. Luckily, protein engineering techniques offer designed antibody formats suitable for biomarker analysis. Minimization strategies of antibodies into Fab fragments, scFv or even single-domain antibody fragments like VH, VL or VHHs are reviewed. Not only the size of the probe but also other issues like choice of immobilization tag, type of solid support and probe stability are of critical importance in assay development for biosensing. In this respect, multiple approaches to specifically orient and couple antibody fragments in a generic one-step procedure directly on a biosensor substrate are discussed.

  8. Monoclonal antibody disulfide reduction during manufacturing

    Science.gov (United States)

    Hutterer, Katariina M.; Hong, Robert W.; Lull, Jonathon; Zhao, Xiaoyang; Wang, Tian; Pei, Rex; Le, M. Eleanor; Borisov, Oleg; Piper, Rob; Liu, Yaoqing Diana; Petty, Krista; Apostol, Izydor; Flynn, Gregory C.

    2013-01-01

    Manufacturing-induced disulfide reduction has recently been reported for monoclonal human immunoglobulin gamma (IgG) antibodies, a widely used modality in the biopharmaceutical industry. This effect has been tied to components of the intracellular thioredoxin reduction system that are released upon cell breakage. Here, we describe the effect of process parameters and intrinsic molecule properties on the extent of reduction. Material taken from cell cultures at the end of production displayed large variations in the extent of antibody reduction between different products, including no reduction, when subjected to the same reduction-promoting harvest conditions. Additionally, in a reconstituted model in which process variables could be isolated from product properties, we found that antibody reduction was dependent on the cell line (clone) and cell culture process. A bench-scale model using a thioredoxin/thioredoxin reductase regeneration system revealed that reduction susceptibility depended on not only antibody class but also light chain type; the model further demonstrates that the trend in reducibility was identical to DTT reduction sensitivity following the order IgG1λ > IgG1κ > IgG2λ > IgG2κ. Thus, both product attributes and process parameters contribute to the extent of antibody reduction during production. PMID:23751615

  9. Recombinant shark natural antibodies to thyroglobulin.

    Science.gov (United States)

    Schluter, Samuel F; Jensen, Ingvill; Ramsland, Paul A; Marchalonis, John J

    2005-01-01

    As cartilaginous fish are the vertebrates most distal from man to produce antibodies, fundamental information regarding conservation and variation of the antigen binding site should be gained by comparing the properties of antibodies directed against the same antigen from the two species. Since monoclonal cell lines cannot be generated using shark B cells, we isolated antigen binding recombinant single chain Fv antibodies (scFv) comprising of the complete variable regions from shark light and heavy chains. Thyroglobulin was used as the selecting antigen as both sharks and humans express natural antibodies to mammalian thyroglobulin in the absence of purposeful immunization. We report that recombinant sandbar shark (Carcharhinus plumbeus) scFvs that bind bovine thyroglobulin consist of heavy chain variable regions (VH) homologous to those of the human VHIII subset and light chain variable regions (VL) homologous to those of the human Vlambda6 subgroup. The homology within the frameworks is sufficient to enable the building of three-dimensional models of the shark VH/VL structure using established human structures as templates. In natural antibodies of both species, the major variability lies in the third complementarity determining region (CDR3) of both VH and VL.

  10. 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

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O efeito analgésico de infusões intraperitoneais de anestésicos locais após colecistectomia videolaparoscópica é controverso e os resultados descritos vão de alívio considerável à pequena redução da dor. O objetivo deste estudo foi avaliar a eficácia da administração intraperitoneal da mistura com excesso enantiomérico de 50% de bupivacaína (S75-R25 para o alívio da dor no pós-operatório de colecistectomia videolaparoscópica. MÉTODO: Estudo aleatório, placebo-controlado e duplamente encoberto com 40 pacientes submetidos à colecistectomia videolaparoscópica divididos em dois grupos: GI (n = 20 que recebeu 80 mL de solução de bupivacaína S75-R25 a 0,125% intraperitoneal no fim da operação; GII (n = 20 que recebeu 80 mL de solução fisiológica a 0,9%. Ambos os grupos receberam 40 mg de tenoxicam e 30 mg.kg-1 de dipirona, por via venosa, pouco antes do fim da operação. A analgesia no pós-operatório (PO foi feita com tramadol. Foram avaliados os escores de dor em repouso, ao sentar e à manobra de Valsalva, segundo a escala numérica ao despertar e 2, 4, 8, 12 e 24 horas no PO; a presença de dor no ombro; o tempo para a primeira solicitação do analgésico; e o seu consumo cumulativo. RESULTADOS: Houve diferença estatística significativa entre os escores de dor às 12 horas no PO com o paciente em repouso (GI JUSTIFICATIVA Y OBJETIVOS: El efecto analgésico de infusiones intraperitoneales de anestésicos locales después colecistectomía videolaparoscópica es controvertido y los resultados descritos van desde el alivio considerable a la pequeña reducción del dolor. El objetivo de este estudio fue evaluar la eficacia de la administración intraperitoneal de la mezcla con exceso enantiomérico de 50% de bupivacaína (S75-R25 para el alivio del dolor en el postoperatorio de colecistectomía videolaparoscópica. MÉTODO: Estudio aleatorio, placebo-controlado y doblemente encubierto con

  11. DARPA Antibody Technology Program. Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv Antibody Produced by Illumina

    Science.gov (United States)

    2016-08-01

    ECBC-TR-1395 DARPA ANTIBODY TECHNOLOGY PROGRAM STANDARDIZED TEST BED FOR...Thompson James Carney RESEARCH AND TECHNOLOGY DIRECTORATE Candice Warner Melody Zacharko EXCET, INC. Springfield, VA 22151-2110...4. TITLE AND SUBTITLE DARPA Antibody Technology Program Standardized Test Bed for Antibody Characterization: Characterization of an MS2 ScFv

  12. Limbic encephalitis associated with elevated antithyroid antibodies.

    Science.gov (United States)

    Hacohen, Yael; Joseph, Sonia; Kneen, Rachel; Eunson, Paul; Lin, Jean-Pierre; Vincent, Angela; Lim, Ming

    2014-06-01

    Immune-mediated limbic encephalitis affects both adults and children. Patients typically present with seizures, memory problems, and imaging changes in the medial temporal lobes. Both paraneoplastic and nonparaneoplastic forms have been described in which the antibody to the voltage-gated potassium channel-complex associated protein, leucine-rich glioma-inactivated 1, is most commonly reported. Elevated antithyroid antibodies have also been reported in a range of neurological syndromes with encephalopathy, such as limbic encephalitis, often collectively termed Hashimoto encephalopathy, a condition whereby corticosteroids responsiveness with a complete recovery is commonly observed. Here we describe 3 children presenting with limbic encephalitis with elevated thyroid antibodies that did not respond to corticosteroids alone and required more aggressive immunotherapy, mirroring the slower treatment response that is more frequently seen in other immune-mediated forms of limbic encephalitis.

  13. Calciphylaxis in catastrophic antiphospholipid antibody syndrome.

    Science.gov (United States)

    Shah, Surbhi; Larson, Andrew; Datta, Yvonne

    2015-06-01

    Antiphospholipid antibody syndrome (APS) is a multisystem disorder characterized by vascular thrombosis and presence of circulating autoantibodies. The presence of APS can predispose to macrovascular as well as microvascular thrombotic events. Renal involvement is a common occurrence especially in the background of systemic lupus erythematosus. Skin appears to be another frequent target organ and a significant proportion of patients may present with skin lesions at the time of diagnosis. We present the case of a patient who presented with skin necrosis secondary to antiphospholipid antibody syndrome despite being on therapeutic anticoagulation and then developed dystrophic calcification secondary to her renal insufficiency. This complex skin condition eventually leads to her demise, as she was not a candidate for surgical management of these lesions. Why is this important? This case brings to our attention the need to consider calciphylaxis as a cause of ecchymotic-appearing skin lesions in dialysis patients on warfarin in patients with antiphospholipid antibody syndrome.

  14. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  15. Adsorption of monoclonal antibodies to glass microparticles.

    Science.gov (United States)

    Hoehne, Matthew; Samuel, Fauna; Dong, Aichun; Wurth, Christine; Mahler, Hanns-Christian; Carpenter, John F; Randolph, Theodore W

    2011-01-01

    Microparticulate glass represents a potential contamination to protein formulations that may occur as a result of processing conditions or glass types. The effect of added microparticulate glass to formulations of three humanized antibodies was tested. Under the three formulation conditions tested, all three antibodies adsorbed irreversibly at near monolayer surface coverages to the glass microparticles. Analysis of the secondary structure of the adsorbed antibodies by infrared spectroscopy reveal only minor perturbations as a result of adsorption. Likewise, front-face fluorescence quenching measurements reflected minimal tertiary structural changes upon adsorption. In contrast to the minimal effects on protein structure, adsorption of protein to suspensions of glass microparticles induced significant colloidal destabilization and flocculation of the suspension.

  16. Imaging spectrum of primary antiphospholipid antibody syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Kwon Ha; Won, Jong Jin [Wonkwang University Hospital, Iksan (Korea, Republic of); Ha, Hyun Kwon; Kim, Jung Hoon; Kim, Jeong Gon; Ki, Won Woo; Kim, Pyo Nyun; Lee, Moon Gyu; Auh, Yong Ho [Asan Medical Center, Seoul (Korea, Republic of)

    1998-04-01

    Antiphospholipid antibody syndrome is recognized as one of the most important causes of hypercoagulability. It can be clinically diagnosed if patients have experienced unexplained recurrent venous or arterial thrombosis, recurrent fetal loss, or thrombocytopenia in the presence of circulating autoantibodies to phospholipids, such as anticardiolipin antibody or lupus anticoagulant. Approximately half of all patients with this syndrome do not have associated systemic disease, and their condition is described as primary antiphospholipid antibody syndrome (PAPS). In the remainder, the syndrome is accompanied by systemic lupus erythematosus or other connective tissue diseases, and is known as secondary antiphospholipid syndrome (1). The purpose of this paper is to illustrate the systemic manifestation of PAPS, focusing on the radiological findings of CT, MR and angiography in clinically proven patients. (author). 8 refs., 10 figs.

  17. Non-antibody protein-based biosensors

    Science.gov (United States)

    2016-01-01

    Biosensors that depend on a physical or chemical measurement can be adversely affected by non-specific interactions. For example, a biosensor designed to measure specifically the levels of a rare analyte can give false positive results if there is even a small amount of interaction with a highly abundant but irrelevant molecule. To overcome this limitation, the biosensor community has frequently turned to antibody molecules as recognition elements because they are renowned for their exquisite specificity. Unfortunately antibodies can often fail when immobilised on inorganic surfaces, and alternative biological recognition elements are needed. This article reviews the available non-antibody-binding proteins that have been successfully used in electrical and micro-mechanical biosensor platforms. PMID:27365032

  18. Sensitive neutralization test for rubella antibody.

    Science.gov (United States)

    Sato, H; Albrecht, P; Krugman, S; Ennis, F A

    1979-01-01

    A modified rubella virus plaque neutralization test for measuring rubella antibody was developed based on the potentiation of the virus-antibody complex by heterologous anti-immunoglobulin. The test is highly sensitive, yielding titers on the average 50 to 100 times higher than the haemagglutination inhibition test or the conventional plaque neutralization test. The sensitivity of this enhanced neutralization test is somewhat limited by the existence of a prozone phenomenon which precludes testing of low-titered sera below a dilution of 1:16. No prozone effect was observed with cerebrospinal fluids. The specificity of the enhanced neutralization test was determined by seroconversion of individuals receiving rubella vaccine. Although the rubella hemagglutination inhibition test remains the test of choice in routine diagnostic and surveillance work, the enhanced rubella neutralization test is particularly useful in monitoring low-level antibody in the cerebrospinal fluid in patients with neurological disorders and in certain instances of vaccine failure. PMID:107192

  19. Antibody-based biological toxin detection

    Energy Technology Data Exchange (ETDEWEB)

    Menking, D.E.; Goode, M.T. [Army Edgewood Research, Development and Engineering Center, Aberdeen Proving Ground, MD (United States)

    1995-12-01

    Fiber optic evanescent fluorosensors are under investigation in our laboratory for the study of drug-receptor interactions for detection of threat agents and antibody-antigen interactions for detection of biological toxins. In a direct competition assay, antibodies against Cholera toxin, Staphylococcus Enterotoxin B or ricin were noncovalently immobilized on quartz fibers and probed with fluorescein isothiocyanate (FITC) - labeled toxins. In the indirect competition assay, Cholera toxin or Botulinum toxoid A was immobilized onto the fiber, followed by incubation in an antiserum or partially purified anti-toxin IgG. These were then probed with FITC-anti-IgG antibodies. Unlabeled toxins competed with labeled toxins or anti-toxin IgG in a dose dependent manner and the detection of the toxins was in the nanomolar range.

  20. Anti-DNA antibodies--quintessential biomarkers of SLE.

    Science.gov (United States)

    Pisetsky, David S

    2016-02-01

    Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

  1. Antibody engineering & therapeutics, the annual meeting of the antibody society December 7–10, 2015, San Diego, CA, USA

    Science.gov (United States)

    Pauthner, Matthias; Yeung, Jenny; Ullman, Chris; Bakker, Joost; Wurch, Thierry; Reichert, Janice M.; Lund-Johansen, Fridtjof; Bradbury, Andrew R.M.; Carter, Paul J.; Melis, Joost P.M.

    2016-01-01

    ABSTRACT The 26th Antibody Engineering & Therapeutics meeting, the annual meeting of The Antibody Society united over 800 participants from all over the world in San Diego from 6–10 December 2015. The latest innovations and advances in antibody research and development were discussed, covering a myriad of antibody-related topics by more than 100 speakers, who were carefully selected by The Antibody Society. As a prelude, attendees could join the pre-conference training course focusing, among others, on the engineering and enhancement of antibodies and antibody-like scaffolds, bispecific antibody engineering and adaptation to generate chimeric antigen receptor constructs. The main event covered 4 d of scientific sessions that included antibody effector functions, reproducibility of research and diagnostic antibodies, new developments in antibody-drug conjugates (ADCs), preclinical and clinical ADC data, new technologies and applications for bispecific antibodies, antibody therapeutics for non-cancer and orphan indications, antibodies to harness the cellular immune system, building comprehensive IgVH-gene repertoires through discovering, confirming and cataloging new germline IgVH genes, and overcoming resistance to clinical immunotherapy. The Antibody Society's special session focused on “Antibodies to watch” in 2016. Another special session put the spotlight on the limitations of the new definitions for the assignment of antibody international nonproprietary names introduced by the World Health Organization. The convention concluded with workshops on computational antibody design and on the promise and challenges of using next-generation sequencing for antibody discovery and engineering from synthetic and in vivo libraries. PMID:26909869

  2. Immunosuppressive activity of Semen Persicae ethanol extract on specific antibody and cellular response to ovalbumin in mice.

    Science.gov (United States)

    Zhang, Yi-Bin; Qin, Feng; Sun, Hong-Xiang

    2006-09-01

    The immunosuppressive activity of the ethanol extract of Semen Persicae (EESP) was studied with respect to specific antibody and cellular response to ovalbumin (OVA) in mice. The effects of EESP on mice splenocyte proliferation in vitro were measured. EESP significantly suppressed concanavalin A (ConA)- and lipopolysaccharide (LPS)-stimulated splenocyte proliferation in vitro in a concentration-dependent manner. Furthermore, the effects of EESP at three dose levels on the humoral and cellular immune responses in the OVA-immunized mice were examined. ICR Mice were immunized subcutaneously with OVA on day 0 and 14. Starting on the day of immunization, the mice were administered intraperitoneally with EESP at a single dose of 0.25, 0.5, and 1.0 mg, and cyclosporin A (CsA, positive drug) at a single dose of 0.1 mg at intervals of 7 days. On day 28, mitogen- and OVA-induced splenocyte proliferation and OVA-specific antibody level in serum were measured. EESP significantly decreased ConA-, LPS-, and OVA-induced splenocyte proliferation in the OVA-immunized mice at the dose of 1.0 mg. Meanwhile, the OVA-specific serum IgG, IgG1, and IgG2b antibody levels in the OVA-immunized mice were markedly reduced by EESP in a dose-dependent manner. The results suggest that EESP could suppress the cellular and humoral immune response in mice, and deserve further research to be developed as immunosuppressant.

  3. Investigation of Antiphosphatidyl-Serine Antibody and Antiphosphatidyl-Inositol Antibody in Ischemic Stroke Patients

    Directory of Open Access Journals (Sweden)

    Hirohisa Okuma

    2010-01-01

    Full Text Available Antiphospholipid syndrome is characterized by arterial or venous thrombosis and the presence of antiphospholipid antibodies (aPL. We measured β2-GPI aCL, IgGaCL, LA, antiphosphatidyl-serine antibody (PS, and antiphosphatidyl-inositol antibody (PI in each patient at one month after the onset of stroke. In addition, carotid artery echography was performed in patients positive for PI or PS. Among the 250 patients, 13.6% (34/250 were positive for either PI or PS, and 6.8% (17/250 were positive for both. Carotid artery echography performed on these 34 patients showed that the frequencies of increased intimal-medial thickness (IMT of 1.1 mm or more, plaque, and carotid artery stenosis of 50% or more were all significantly higher in patients positive for antinuclear antibody than those negative for the antibody (P<.05. PI and PS are associated with antinuclear antibody and precipitation of atherosclerosis. Ischemic stroke patients with SLE frequently showed a variety of antiphospholipid-protein antibodies.

  4. Mouse x pig chimeric antibodies expressed in Baculovirus retain the same properties of their parent antibodies.

    Science.gov (United States)

    Jar, Ana M; Osorio, Fernando A; López, Osvaldo J

    2009-01-01

    The development of hybridoma and recombinant DNA technologies has made it possible to use antibodies against cancer, autoimmune disorders, and infectious diseases in humans. These advances in therapy, as well as immunoprophylaxis, could also make it possible to use these technologies in agricultural species of economic importance such as pigs. Porcine reproductive and respiratory syndrome virus (PRRSV) is an arterivirus causing very important economic losses to the industry. Passive transfer of antibodies obtained by biotechnology could be used in the future to complement or replace vaccination against this and other pig pathogens. To this end, we constructed and studied the properties of chimeric mouse x pig anti-PRRSV antibodies. We cloned the constant regions of gamma-1 and gamma-2 heavy chains and the lambda light chain of pig antibodies in frame with the variable regions of heavy and light chains of mouse monoclonal antibody ISU25C1, which has neutralizing activity against PRRSV. The coding regions for chimeric IgG1 and IgG2 were expressed in a baculovirus expression system. Both chimeric antibodies recognized PRRSV in ELISA as well as in a Western-blot format and, more importantly, were able to neutralize PRRSV in the same fashion as the parent mouse monoclonal antibody ISU25C1. In addition, we show that both pig IgG1 and IgG2 antibodies could bind complement component C1q, with IgG2 being more efficient than IgG1 in binding C1q. Expressing chimeric pig antibodies with protective capabilities offers a new alternative strategy for infectious disease control in domestic pigs.

  5. Antiphospholipid antibody syndrome presenting with hemichorea.

    Science.gov (United States)

    Ayalew, Yezenash; Khattak, Fazlihakim

    2012-01-01

    A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs) at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120) and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

  6. Pulmonary manifestations of the antiphospholipid antibody syndrome.

    Science.gov (United States)

    Ford, H James; Roubey, Robert A S

    2010-09-01

    A broad spectrum of pulmonary disease may occur in antiphospholipid antibody syndrome. The most common pulmonary manifestations are pulmonary thromboembolism and pulmonary hypertension. In this article the authors review these manifestations, as well as less common findings including acute respiratory distress syndrome, alveolar hemorrhage, and pulmonary capillaritis.

  7. The antiphospholipid antibody syndrome: a case report.

    Science.gov (United States)

    Luma, Henry Namme; Doualla, Marie-Solange; Temfack, Elvis; Bagnaka, Servais Albert Fiacre Eloumou; Mankaa, Emmanuella Wankie; Fofung, Dobgima

    2012-01-01

    Antiphospholipid antibody syndrome is defined by the presence of thromboembolic complications and/or pregnancy morbidity in the presence of persistently increased titers of antiphospholipid antibodies. Its clinical presentation can be diverse and any organ can be involved, with a current impact in most surgical and medical specialties. The authors present the case of a 43-year-old man who, over a 13-year period of follow-up, presented with thrombosis of the mesenteric vein, inferior vena cava, and axillary and subclavian veins in a setting where diagnostic and therapeutic options are limited and costly. Through this case report, the authors aim to describe the evolution of this complex pathology, which to date has not been described in the authors' milieu - probably because of its challenging diagnosis and the limited treatment options available. The authors conclude that clinicians need to have a high index of suspicion of APS in patients who present with a thrombotic episode - clinicians should investigate for the presence of antiphospholipid antibodies, as early diagnosis may influence the course of the disease. Furthermore, resources for the detection of antiphospholipid antibodies should be made readily available in resource-limited settings. Finally, patient education on the importance of drug compliance, periodic monitoring, and prevention of thrombosis is indispensable, especially as mortality could be associated with the effects of vascular thrombosis and/or the effects of bleeding due to anticoagulants.

  8. Pathophysiology of the antiphospholipid antibody syndrome.

    Science.gov (United States)

    Willis, Rohan; Pierangeli, Silvia S

    2011-11-01

    Antiphospholipid antibodies (aPL) are associated with the recurrent pregnancy loss and thrombosis that characterizes the antiphospholipid antibody syndrome (APS). Although the ontogeny of these pathogenic antibodies has not been fully elucidated, there is evidence that indicates the involvement of both genetic and environmental factors. The ability of aPL to induce a procoagulant phenotype in APS patients plays a central role in the development of arterial and venous thrombotic manifestations typical of the disease. Inflammation serves as a necessary link between this procoagulant phenotype and actual thrombus development and is an important mediator of the placental injury seen in APS patients with obstetric complications. Recent evidence has indicated a role for abnormal cellular proliferation and differentiation in the pathophysiology of APS, especially in those patients with pregnancy morbidity and other more atypical manifestations that have no identifiable thrombotic cause. The interplay of genetic and environmental factors responsible for aPL development and the mechanisms by which these antibodies produce disease in APS patients is the focus of this review.

  9. Antigen/Antibody Analyses in Leishmaniasis.

    Science.gov (United States)

    1983-09-01

    antibodies in human sera with antigens of protozoan parasites . It was found that enzyme substrate reactions had distinct advantages over typical...autoradiographic procedures. Analyses of various sera identified a number of antigens of protozoan parasites which may be useful in discriminating infections

  10. Neutralizing antibodies in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Mirjam B Zeisel; Samira Fafi-Kremer; Isabel Fofana; Heidi Barth; Fran(c)oise Stoll-Keller; Michel Doffo(e)l; Thomas F Baumert

    2007-01-01

    Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays,the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses.In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.(C) 2007 The WJG Press. All rights reserved.

  11. IgA Antibodies in Rett Syndrome

    Science.gov (United States)

    Reichelt, K. L.; Skjeldal, O.

    2006-01-01

    The level of IgA antibodies to gluten and gliadin proteins found in grains and to casein found in milk, as well as the level of IgG to gluten and gliadin, have been examined in 23 girls with Rett syndrome and 53 controls. Highly statistically significant increases were found for the Rett population compared to the controls. The reason for this…

  12. Coronavirus antibodies in African bat species.

    Science.gov (United States)

    Müller, Marcel A; Paweska, Janusz T; Leman, Patricia A; Drosten, Christian; Grywna, Klaus; Kemp, Alan; Braack, Leo; Sonnenberg, Karen; Niedrig, Matthias; Swanepoel, Robert

    2007-09-01

    Asian bats have been identified as potential reservoir hosts of coronaviruses associated with severe acute respiratory syndrome (SARS-CoV). We detected antibody reactive with SARS-CoV antigen in 47 (6.7%) of 705 bat serum specimens comprising 26 species collected in Africa; thus, African bats may harbor agents related to putative group 4 CoV.

  13. Antineutrophil cytoplasmic antibodies in juvenile chronic arthritis

    NARCIS (Netherlands)

    Mulder, L; Horst, G; Limburg, P; deGraeffMeeder, ER; Kuis, W; Kallenberg, C

    1997-01-01

    Objective, To evaluate the diagnostic significance of antineutrophil cytoplasmic antibodies (ANCA) by assessing the prevalence of ANCA in juvenile chronic arthritis (JCA) (n = 93) of either oligoarticular, polyarticular, or systemic onset. To investigate the prevalence of ANCA in other diseases of c

  14. Antiphospholipid Antibody Syndrome Presenting with Hemichorea

    Directory of Open Access Journals (Sweden)

    Yezenash Ayalew

    2012-01-01

    Full Text Available A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120 and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40 mg daily and aspirin 300 mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

  15. Monoclonal antibody technologies and rapid detection assays

    Science.gov (United States)

    Novel methodologies and screening strategies will be outlined on the use of hybridoma technology for the selection of antigen specific monoclonal antibodies. The development of immunoassays used for diagnostic detection of prions and bacterial toxins will be discussed and examples provided demonstr...

  16. IgA as therapeutic antibody

    NARCIS (Netherlands)

    Leusen, Jeanette H W

    2015-01-01

    This review is focused on the promises of IgA as a new therapeutic antibody. For more than 30 years IgG molecules have been used in the clinic in the fields of oncology, hematology, auto immune diseases and infections. However, IgA might be a good alternative, since it recruits different effector ce

  17. Developing recombinant antibodies for biomarker detection

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Cheryl L.; Fischer, Christopher J.; Pefaur, Noah B.; Miller, Keith D.; Kagen, Jacob; Srivastava, Sudhir; Rodland, Karin D.

    2010-10-01

    Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (eg, yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune libraries provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays.

  18. Pyridoxal-5'-phosphate-dependent catalytic antibodies.

    Science.gov (United States)

    Gramatikova, Svetlana; Mouratou, Barbara; Stetefeld, Jörg; Mehta, Perdeep K; Christen, Philipp

    2002-11-01

    Strategies for expanding the catalytic scope of antibodies include the incorporation of inorganic or organic cofactors into their binding sites. An obvious choice is pyridoxal-5'-phosphate (PLP), which is probably the most versatile organic cofactor of enzymes. Monoclonal antibodies against the hapten N(alpha)-(5'-phosphopyridoxyl)-L-lysine, a stable analog of the covalent coenzyme-substrate adducts were screened by a competition ELISA for binding of the PLP-amino acid Schiff base adduct. The Schiff base with its C4'-N alpha double bond is, in contrast to the hapten, a planar compound and is an obligatory intermediate in all PLP-dependent reactions of amino acids. This highly discriminating screening step eliminated all but 5 of 24 hapten-binding antibodies. The five remaining antibodies were tested for catalysis of the PLP-dependent alpha,beta-elimination reaction of beta-chloroalanine. Antibody 15A9 complied with this selection criterion and catalyzed in addition the cofactor-dependent transamination reaction of hydrophobic D-amino acids and oxo acids (k(cat)'=0.42 min(-1) with D-alanine at 25 degrees C). Homology modeling together with alanine scanning yielded a 3D model of Fab 15A9. The striking analogy between antibody 15A9 and PLP-dependent enzymes includes the following features: (1) The binding sites accommodate the planar coenzyme-amino acid adduct. (2) The bond at C alpha to be broken lies together with the C alpha-N bond in a plane orthogonal to the plane of coenzyme and imine bond. (3) The alpha-carboxylate group of the substrate is bound by an arginine residue. (4) The coenzyme-substrate adduct assumes a cisoid conformation. (5) PLP markedly contributes to catalytic efficiency, being a 10(4) times more efficient amino group acceptor than pyruvate. The protein moiety, however, ensures reaction as well as substrate specificity, and further accelerates the reaction (in 15A9 k(cat (Ab x PLP))'/k(cat (PLP))'=5 x 10(3)). The analogies of antibody 15A9 with

  19. Antibody-Mediated Rejection: A Review

    Science.gov (United States)

    Garces, Jorge Carlos; Giusti, Sixto; Staffeld-Coit, Catherine; Bohorquez, Humberto; Cohen, Ari J.; Loss, George E.

    2017-01-01

    Background: Chronic antibody injury is a serious threat to allograft outcomes and is therefore the center of active research. In the continuum of allograft rejection, the development of antibodies plays a critical role. In recent years, an increased recognition of molecular and histologic changes has provided a better understanding of antibody-mediated rejection (AMR), as well as potential therapeutic interventions. However, several pathways are still unknown, which accounts for the lack of efficacy of some of the currently available agents that are used to treat rejection. Methods: We review the current diagnostic criteria for AMR; AMR paradigms; and desensitization, treatment, and prevention strategies. Results: Chronic antibody-mediated endothelial injury results in transplant glomerulopathy, manifested as glomerular basement membrane duplication, double contouring, or splitting. Clinical manifestations of AMR include proteinuria and a rise in serum creatinine. Current strategies for the treatment of AMR include antibody depletion with plasmapheresis (PLEX), immunoadsorption (IA), immunomodulation with intravenous immunoglobulin (IVIG), and T cell– or B cell–depleting agents. Some treatment benefits have been found in using PLEX and IA, and some small nonrandomized trials have identified some benefits in using rituximab and the proteasome inhibitor-based therapy bortezomib. More recent histologic follow-ups of patients treated with bortezomib have not shown significant benefits in terms of allograft outcomes. Furthermore, no specific treatment approaches have been approved by the US Food and Drug Administration. Other agents used for more difficult rejections include bortezomib and eculizumab (an anti-C5 monoclonal antibody). Conclusion: AMR is a fascinating field with ample opportunities for research and progress in the future. Despite the use of advanced techniques for the detection of human leukocyte antigen (HLA) or non-HLA donor-specific antibodies

  20. The antiphospholipid antibody syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Luma HN

    2012-10-01

    Full Text Available Henry Namme Luma,1,2 Marie-Solange Doualla,1,2 Elvis Temfack,1 Servais Albert Fiacre Eloumou Bagnaka,1 Emmanuella Wankie Mankaa,3 Dobgima Fofung41Department of Internal Medicine, Douala General Hospital, Douala, Cameroon; 2Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon; 3Department of Radiology, Douala General Hospital Douala, Cameroon; 4Department of Abdominal Surgery, Daniel Muna Memorial Clinic, Douala, CameroonAbstract: Antiphospholipid antibody syndrome is defined by the presence of thromboembolic complications and/or pregnancy morbidity in the presence of persistently increased titers of antiphospholipid antibodies. Its clinical presentation can be diverse and any organ can be involved, with a current impact in most surgical and medical specialties. The authors present the case of a 43-year-old man who, over a 13-year period of follow-up, presented with thrombosis of the mesenteric vein, inferior vena cava, and axillary and subclavian veins in a setting where diagnostic and therapeutic options are limited and costly. Through this case report, the authors aim to describe the evolution of this complex pathology, which to date has not been described in the authors' milieu – probably because of its challenging diagnosis and the limited treatment options available. The authors conclude that clinicians need to have a high index of suspicion of APS in patients who present with a thrombotic episode – clinicians should investigate for the presence of antiphospholipid antibodies, as early diagnosis may influence the course of the disease. Furthermore, resources for the detection of antiphospholipid antibodies should be made readily available in resource-limited settings. Finally, patient education on the importance of drug compliance, periodic monitoring, and prevention of thrombosis is indispensable, especially as mortality could be associated with the effects of vascular thrombosis and/or the effects