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Sample records for intraperitoneal gentamicin dosing

  1. 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

  2. Dose-Dependent Amelioration of Gentamicin-Induced ...

    African Journals Online (AJOL)

    increase in serum urea and creatine while 3ml/kg of the same drug completely prevented the increase in serum urea and creatine in this model. Conclusion: Vitamin B-complex dose-dependently ameliorated gentamicin-induced nephrotoxicity in adult Swiss albino rats when given intramuscularly. This finding may have ...

  3. Changes in the avian cochlea after single high-dose gentamicin.

    Science.gov (United States)

    Girod, D A; Park, R H; Park, D L; Durham, D

    2000-01-01

    Define the time course of functional and anatomical damage and subsequent recovery (by regeneration) of hair cells in the chicken inner ear after a single high-dose of gentamicin. Broiler chicks were given a single intraperitoneal dose (200 mg/kg) of gentamicin (n = 39) or saline (n = 39). Functional status was evaluated with auditory brainstem response (ABR) thresholds before injection and before sacrifice at 2, 5, 9, 16, 21, 28, and 70 days postinjection. The cochleae were then examined with scanning electron microscopy (SEM) to assess the extent of damage along the cochlea and absolute hair cell numbers in the basal 15% of the cochlea (high-frequency region). Considerable variability between animals was seen for both ABR and SEM changes. Damage was maximal at 5 days postinjection with an average ABR threshold shift of 12 dB (range -10 to 50 dB) and basal cochlear damage of 28% (range 12%-57%). Hair cell counts were significantly decreased in the basal 15% of the cochlea at 5 days. Hair cell regeneration resulted in rapid anatomical and functional recovery, but evidence of hair cell disorganization persisted at 70 days despite improved thresholds. A single high dose of gentamicin produces a significant but variable anatomical and functional insult in the chick cochlea. Hair cell regeneration results in rapid but incomplete recovery.

  4. Adverse effects of a single dose of gentamicin in adults: a systematic review.

    Science.gov (United States)

    Hayward, Rachel S; Harding, Jan; Molloy, Rob; Land, Lucy; Longcroft-Neal, Kate; Moore, David; Ross, Jonathan D C

    2018-02-01

    To systematically review the frequency and type of adverse events associated with a single dose of intravenous or intramuscular gentamicin in adults, for any indication, in studies where a comparator was available. A review protocol was developed and registered (PROSPERO: CRD42013003229). Studies were eligible for review if they: recruited participants aged ≥16 years; used gentamicin intramuscularly or intravenously as a single one-off dose; compared gentamicin to another medication or placebo; and monitored adverse events. MEDLINE, EMBASE, Cochrane Library, trial registries, conference proceedings and other relevant databases were searched up to November 2016. Risk of bias was assessed on all included studies. In total, 15 522 records were identified. After removal of duplicates, screening of title/abstracts for relevance and independent selection of full texts by two reviewers, 36 studies were included. Across all the included studies, 24 107 participants received a single one-off dose of gentamicin (doses ranged from 1 mg kg -1 to 480 mg per dose). Acute kidney injury was described in 2520 participants receiving gentamicin. The large majority of cases were reversible. There were no cases of ototoxicity reported in patients receiving gentamicin. A meta-analysis was not performed due to study heterogeneity. A significant number of patients saw a transient rise in creatinine after a single dose of gentamicin at doses up to 480 mg. Persistent renal impairment and other adverse events were relatively rare. © 2017 The British Pharmacological Society.

  5. Dose-Dependent Amelioration of Gentamicin-Induced ...

    African Journals Online (AJOL)

    Erah

    Other attempts at controlling gentamicin toxicity, including the use of pyridoxal phosphate, ascorbic acid, calcium loading, calcium channel blocker,1 vitamin E 5 and acupuncture6 have shown either promising or inconsistent results in animals . Those that showed limited efficacy have been difficult to apply clinically due to.

  6. Eight years' experience of an extended-interval dosing protocol for gentamicin in neonates.

    Science.gov (United States)

    Begg, Evan J; Vella-Brincat, Jane W A; Robertshawe, Barbara; McMurtrie, Mark J; Kirkpatrick, Carl M J; Darlow, Brian

    2009-05-01

    Dosing of gentamicin in neonates in Christchurch has been carried out since 2000 using a locally developed extended-interval dosing protocol. All dosing data have been recorded in a database. The aims of this study were to analyse the database to determine what percentage of neonates achieved target values for C(max), C(min) and AUC, and to use the pharmacokinetic values of gentamicin to simulate new dosing protocols. C(max), C(min) and AUC were compared with target values. Clearance (CL), volume of distribution (V) and half-life (t(1/2)) were estimated, and used to produce new predictive dosing protocols that were tested and compared with the results of the original protocol. Gentamicin concentrations from 1461 individual doses were recorded in the database. Four hundred and eight were excluded. Of the remaining 1053, 84% achieved the target C(max) (>10 mg/L), 77% the target C(min) (<1 mg/L) and 63% the target AUC (within 80% to 125%). The number achieving target C(max) and C(min) values was improved markedly by prolonging the dosing intervals, but not by altering the predictive equations. Since the majority of the neonates only received a single dose of gentamicin, a new V-based model was also tested, and performed well. CL (L/kg) increased, while V (L/kg) and t(1/2) (h) both decreased with respect to weight. Extending the dose interval improved the success in achieving target C(max) and C(min), while revision of the dosing equation did not. A V-based model provides an alternative approach to the first dose of gentamicin in neonates.

  7. A pre–postintervention study to evaluate the impact of dose calculators on the accuracy of gentamicin and vancomycin initial doses

    Science.gov (United States)

    Hamad, Anas; Cavell, Gillian; Hinton, James; Wade, Paul; Whittlesea, Cate

    2015-01-01

    Objectives Gentamicin and vancomycin are narrow-therapeutic-index antibiotics with potential for high toxicity requiring dose individualisation and continuous monitoring. Clinical decision support (CDS) tools have been effective in reducing gentamicin and vancomycin dosing errors. Online dose calculators for these drugs were implemented in a London National Health Service hospital. This study aimed to evaluate the impact of these calculators on the accuracy of gentamicin and vancomycin initial doses. Methods The study used a pre–postintervention design. Data were collected using electronic patient records and paper notes. Random samples of gentamicin and vancomycin initial doses administered during the 8 months before implementation of the calculators were assessed retrospectively against hospital guidelines. Following implementation of the calculators, doses were assessed prospectively. Any gentamicin dose not within ±10% and any vancomycin dose not within ±20% of the guideline-recommended dose were considered incorrect. Results The intranet calculator pages were visited 721 times (gentamicin=333; vancomycin=388) during the 2-month period following the calculators’ implementation. Gentamicin dose errors fell from 61.5% (120/195) to 44.2% (95/215), pcalculator implementation, pcalculators significantly improved the prescribing of initial doses of these agents. Therefore, healthcare organisations should consider using such CDS tools to support the prescribing of these high-risk drugs. PMID:26044758

  8. A pre-postintervention study to evaluate the impact of dose calculators on the accuracy of gentamicin and vancomycin initial doses.

    Science.gov (United States)

    Hamad, Anas; Cavell, Gillian; Hinton, James; Wade, Paul; Whittlesea, Cate

    2015-06-04

    Gentamicin and vancomycin are narrow-therapeutic-index antibiotics with potential for high toxicity requiring dose individualisation and continuous monitoring. Clinical decision support (CDS) tools have been effective in reducing gentamicin and vancomycin dosing errors. Online dose calculators for these drugs were implemented in a London National Health Service hospital. This study aimed to evaluate the impact of these calculators on the accuracy of gentamicin and vancomycin initial doses. The study used a pre-postintervention design. Data were collected using electronic patient records and paper notes. Random samples of gentamicin and vancomycin initial doses administered during the 8 months before implementation of the calculators were assessed retrospectively against hospital guidelines. Following implementation of the calculators, doses were assessed prospectively. Any gentamicin dose not within ± 10% and any vancomycin dose not within ± 20% of the guideline-recommended dose were considered incorrect. The intranet calculator pages were visited 721 times (gentamicin=333; vancomycin=388) during the 2-month period following the calculators' implementation. Gentamicin dose errors fell from 61.5% (120/195) to 44.2% (95/215), pcalculator implementation, pcalculators significantly improved the prescribing of initial doses of these agents. Therefore, healthcare organisations should consider using such CDS tools to support the prescribing of these high-risk drugs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  9. Using Six Sigma to improve once daily gentamicin dosing and therapeutic drug monitoring performance.

    LENUS (Irish Health Repository)

    Egan, Sean

    2012-08-07

    BACKGROUND: Safe, effective therapy with the antimicrobial gentamicin requires good practice in dose selection and monitoring of serum levels. Suboptimal therapy occurs with breakdown in the process of drug dosing, serum blood sampling, laboratory processing and level interpretation. Unintentional underdosing may result. This improvement effort aimed to optimise this process in an academic teaching hospital using Six Sigma process improvement methodology. METHODS: A multidisciplinary project team was formed. Process measures considered critical to quality were defined, and baseline practice was examined through process mapping and audit. Root cause analysis informed improvement measures. These included a new dosing and monitoring schedule, and standardised assay sampling and drug administration timing which maximised local capabilities. Three iterations of the improvement cycle were conducted over a 24-month period. RESULTS: The attainment of serum level sampling in the required time window improved by 85% (p≤0.0001). A 66% improvement in accuracy of dosing was observed (p≤0.0001). Unnecessary dose omission while awaiting level results and inadvertent disruption to therapy due to dosing and monitoring process breakdown were eliminated. Average daily dose administered increased from 3.39 mg\\/kg to 4.78 mg\\/kg\\/day. CONCLUSIONS: Using Six Sigma methodology enhanced gentamicin usage process performance. Local process related factors may adversely affect adherence to practice guidelines for gentamicin, a drug which is complex to use. It is vital to adapt dosing guidance and monitoring requirements so that they are capable of being implemented in the clinical environment as a matter of routine. Improvement may be achieved through a structured localised approach with multidisciplinary stakeholder involvement.

  10. Comparing the effect of multiple-dose and once-daily regimens of gentamicin therapy on fraction excretion of magnesium

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    Hossein Khalili

    2006-05-01

    Full Text Available This study was designed to compare the influence of ordinary (multiple-dose and once-daily administration of gentamicin on tubular nephrotoxicity based on the urinary excretion of magnesium (Mg as an indicator for this type of side effect. Thirty-two hospitalized patients, who were assigned to receive at least 5-days treatment with gentamicin at the infectious disease ward of Imam Hospital in Tehran, were prospectively studied. Seventeen patients received multiple-doses of gentamicin per day and 15 patients received once-daily regimen. At the beginning and at the end of of gentamicin therapy, blood urea, serum creatinine (Cr and Mg levels were measured. Additionally 24-hour urine samples were collected for measurement of urinary volume, creatinine and Mg excretions. In both treatment groups serum Mg concentration was significantly lower and fraction excretion of (FEMg were considerably higher at the end of gentamicin therapy compared with the beginning of the treatment. However, the serum and urinary creatinine levels did not change significantly in the two groups

  11. Gentamicin pharmacokinetics in the chicken inner ear.

    Science.gov (United States)

    Bunting, Eric C; Park, Debra L; Durham, Dianne; Girod, Douglas A

    2004-06-01

    Avians have the unique ability to regenerate cochlear hair cells that are lost due to ototoxins or excessive noise. Many methodological techniques are available to damage the hair cells for subsequent scientific study. A recent method utilizes topical application of an ototoxic drug to the round window membrane. The current study examines the pharmacokinetics of gentamicin in the inner ear of chickens following topical application to the round window membrane or a single systemic high dose given intraperitoneally. Chickens were given gentamicin topically or systemically and survived for 1, 4, 12, 24, or 120 h (controls at 4 and 120 h). Serum and perilymph samples were obtained prior to sacrifice and measured for gentamicin levels. Results revealed higher levels of gentamicin in the perilymph of topically treated chickens than systemically treated chickens, with significant amounts of gentamicin still present in both at the latest survival time of 5 days. As expected, systemically treated chickens had much higher levels of gentamicin in the serum than topically treated chickens. Advantages and disadvantages to each method of drug administration are discussed.

  12. Determination of the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits: a comparative study

    International Nuclear Information System (INIS)

    Naeem, U.; Jamal, S.; Waheed, A.

    2015-01-01

    Objective: To determine the effects of levofloxacin on gentamicin induced nephrotoxicity in rabbits. Study Design: Comparative experimental study. Place and Duration of Study: The animal house of Army Medical College, Rawalpindi, and the pathology department of Army Medical College, Rawalpindi, from July 2009 to January 2010. Material and Methods: The effects of levofloxacin on gentamicin-induced nephrotoxicity were evaluated in rabbits. Twenty four rabbits were used in this study which were randomly divided into four groups (n= 6 in each group). Six animals were injected for 15 days with saline (NaCl; 0.9%), six with gentamicin alone at doses of 20 mg/kg of body weight/12 h (intramuscularly), six with combination of gentamicin (20 mg/kg/12 h) with low therapeutic doses of levofloxacin (30 mg/kg/24 h) and the last six were treated with gentamicin and high therapeutic doses of levofloxacin (50 mg/kg/24 h). Levofloxacin was given by intraperitoneal route. Results: Gentamicin induced nephrotoxicity was evaluated by histopathological and serum analysis. The extent of nephrotoxicity was significantly increased when gentamicin was given in combination with levofloxacin both in low and high doses. Conclusion: Levofloxacin enhances gentamicin induced nephrotoxicity and extent of this nephrotoxicity increased with increasing dose of levofloxacin. (author)

  13. A simple high-dose gentamicin regimen showed no side effects among neonates

    DEFF Research Database (Denmark)

    Blaabjerg, Anne Sofie; Kofoed, Poul-Erik; Dalegaard, Mette Correll

    2017-01-01

    INTRODUCTION: Treatment of infections in neonates with gentamicin is a balance between optimising bactericidal effect and minimising adverse effects. Previously, at the Neonatal Intensive Care Unit (NICU) at Kolding Hospital, Denmark, neonates suspected of having infections were treated daily...... infection. FUNDING: none. TRIAL REGISTRATION: Danish Data Protection Agency (2008-58-0035)....

  14. Carrot (Daucus carota L.): Nephroprotective against gentamicin-induced nephrotoxicity in rats

    Science.gov (United States)

    Sodimbaku, Vamsi; Pujari, Latha; Mullangi, Raviteja; Marri, Saisudheer

    2016-01-01

    Objectives: Daucus carota L.(DC) commonly known as carrot, folkorically used as ethnomedicine to treat nephrosis and other urinary disorders. Hence, the present study was aimed to investigate the nephroprotective effects of ethanolic root extract of DC against gentamicin-induced nephrotoxicity in Albino Wistar rats. Methods: Nephrotoxicity in rats was induced by intraperitoneal administration of gentamicin (100 mg/kg/day) for 8 days. Rats of either sex were divided into four groups (n = 6). Group 1 served as control that received normal saline (i.p.) whereas Group 2 (GM) was treated with gentamicin which served as gentamicin-intoxicated group. Group 3–4 (DC200, DC 400) were pretreated with DC at doses of 200 mg/kg and 400 mg/kg (p.o.), respectively, 1 h before the gentamicin intoxication. Following treatment, the nephroprotective effects of DC were evaluated by using serum levels of urea, blood urea nitrogen (BUN), uric acid, and creatinine levels; change in body weight and wet kidney weight along with the histological observations among the experimental groups. Results: Gentamicin intoxication induced elevated serum urea, BUN, uric acid, and creatinine levels which was found to be significantly (P < 0.01) decreased in a dose-dependent manner in groups received DC which was also evidenced by the histological observations. Conclusion: DC showed a significant nephroprotective effect in a dose-dependent manner by ameliorating the gentamicin-induced nephrotoxicity and thus authenticates its ethnomedicinal use. PMID:27127313

  15. Efficacy of single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Lyimo Fadhili M

    2012-06-01

    Full Text Available Abstract Background Caesarean section is a commonly performed operation worldwide. It has been found to increase rates of maternal infectious morbidities more than five times when compared to vaginal delivery. Provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to caesarean section has been found to reduce post-caesarean infection tremendously. Many centers recommend provision of a single dose of antibiotics, as repeated doses offer no benefit over a single dose. At Bugando Medical Centre post caesarean infection is among the top five causes of admission at the post-natal ward. Unfortunately, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are designated for caesarean section. Common practice and generally the clinician’s preference are to provide repeated dosages of antibiotic prophylaxis after caesarean section to most of the patients. This study aims to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post caesarean infection. Methods/Design The study is an interventional, open-label, two-armed, randomized, single-center study conducted at Bugando Medical Centre Mwanza, Tanzania. It is an ongoing trial for the period of seven months; 490 eligible candidates will be enrolled in the study. Study subjects will be randomly allocated into two study arms; “A” and “B”. Candidates in “A” will receive a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation and candidates in “B” will receive the same drugs prior to the operation and continue with gentamicin and metronidazole for 24 hours. The two groups will be followed up for a period of one month and assessed for signs and symptoms of surgical site infection. Data will be extracted from a case record form and entered into Epi data3.1 software before being transferred to SPSS

  16. Interferência do intervalo de administração da droga sobre a nefrotoxicidade da gentamicina em ratos Influence of the dose regimen on the gentamicin nephrotoxicity in rats

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    Verônica Cunha Rodrigues Oliveira

    2001-06-01

    Full Text Available A insuficiência renal aguda (IRA que apresenta índice de mortalidade em torno de 50%, pode ser definida como um abrupto declínio da filtração glomerular, resultante de isquemia ou toxicidade. A nefrotoxicidade por drogas é uma das etiologias mais freqüentes (27% e sugere-se que o intervalo de administração da droga pode interferir neste efeito colateral, entretanto o melhor regime de administração ainda não está bem estabelecido. Este conhecimento proporcionaria uma atuação mais direcionada de enfermagem na prevenção desta IRA hospitalar. Os resultados obtidos nesta pesquisa, indicam que a infusão única de gentamicina determina menor nefrotoxicidade, provavelmente devido à redução da sua concentração plasmática nas 24hs, diminuindo o acúmulo intracelular deste fármaco, um dos principais mecanismos celulares deste tipo de lesão. Este regime de tratamento mostra portanto vantagens quanto ao custo, efeito nefrotóxico e segurança quanto à eficácia terapêutica.The acute renal failure (ARF, that still presents a righ mortality rate (50% can be defined as an abrupt decline of the glomerular filtration, resultant of isquemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27% of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100mg/kg in one dose or in two doses (2x 50mg/kg,by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracelular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, showes advantages not only related

  17. Biomechanical evaluation of polymethyl methacrylate with the addition of various doses of cefazolin, vancomycin, gentamicin, and silver microparticles.

    Science.gov (United States)

    Ficklin, Michael G; Kunkel, Kevin A R; Suber, Jonathan T; Gerard, Patrick D; Kowaleski, Michael P

    2016-09-20

    Numerous studies have examined the biomechanics of polymethyl methacrylate (PMMA) with added antibiotics, but direct comparison between studies is difficult. Our purpose was to evaluate the effects of the addition of antibiotic drugs and silver on compressive and bending strength of PMMA. Our null hypothesis was that there would be no significant difference in the compressive strength or bending strength of PMMA with the addition of silver or varying amounts of antibiotic drugs. Polymethyl methacrylate was mixed with cefazolin, gentamicin, vancomycin, or silver; the control was PMMA alone. Antibiotic groups contained 20 g PMMA and 0.5 g, 1 g, 2 g, or 3 g of antibiotic. Silver groups had 0.25 g silver powder alone added to 20 g PMMA or silver with PMMA and 0, 0.5 g or 1 g of antibiotic. Samples underwent four-point bending and compression testing in air at room temperature and prevailing humidity. Pairwise comparisons between groups and to the ASTM and ISO standards were performed. Compression: All antibiotic and silver groups were weaker than the control. Samples with cefazolin tended to be stronger than other antibiotic groups with equivalent doses of antibiotic. All groups were above the ASTM standard, except 3 g vancomycin. Four-point bending: The addition of antibiotics did not significantly affect bending strength in groups with lower doses of antibiotics. The silver + PMMA group was weaker than the control. No groups were significantly below the ISO standard except the 3 g vancomycin group. The addition of antibiotic or silver decreased the biomechanical strength in all samples, but not below the ASTM or ISO standard for most groups. The addition of cefazolin appears to affect strength the least, while high doses of vancomycin alter strength the most.

  18. A histological study of the effect of exogenous melatonin on gentamicin induced structural alterations of proximal tubules in rats.

    Science.gov (United States)

    Kapić, Dina; Mornjaković, Zakira; Ćosović, Esad; Šahinović, Maida

    2014-02-01

    The aim of this research was to assess the reactive changes of rat proximal tubules caused by gentamicin and the effect of relatively low doses of melatonin. 48 adult male Wistar rats were distributed into six groups of equal size which all received one of the following daily intraperitoneal injections: vehicle (5% ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8 days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8 days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days (GM1, GM2) and two groups treated only with melatonin in two different doses (5 or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative and semi-quantitative light microscopy analysis of proximal tubules. Exogenous melatonin had no significant effect on the microstructure, independently of dosis. The changes of proximal tubules microstructure induced by gentamicin were expressed in the form of granulovacuolar degeneration, necrosis and desquamation. The grade of proximal tubular changes was smaller in animals who besides gentamicin received melatonin. Melatonin has a dose dependent protective effect on the structural alterations of proximal tubules of the kidney induced by gentamicin.

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  20. Cocleotoxicidade da gentamicina por doses habituais para neonatos - estudo funcional A functional study on gentamicin-related cochleotoxicity in its conventional dose in newborns

    Directory of Open Access Journals (Sweden)

    Carla Luiza Baggio

    2010-02-01

    product otoacoustic emissions, before and after the use of gentamicin. RESULTS: in all the assessments, the external hair cells functional status, studied by means of the distortion product otoacoustic emissions, proved preserved. CONCLUSION: In the present study, we did not notice changes in outer hair cell function in the albino guinea pigs treated with gentamicin in the doses of 4 mg/Kg/day and 2.5 mg/Kg/day every 12 hours for 10 and 14 days.

  1. Randomized controlled study of intraincisional infiltration versus intraperitoneal instillation of standardized dose of ropivacaine 0.2% in post-laparoscopic cholecystectomy pain: Do we really need high doses of local anesthetics-time to rethink!

    Science.gov (United States)

    Kaushal-Deep, Singh Mathuria; Anees, Afzal; Khan, Shehtaj; Khan, Mohammad Amanullah; Lodhi, Mehershree

    2018-01-16

    Earlier studies done to compare the efficacy of use of local anesthetics at intraperitoneal location versus intraincisional use had utilized equal amount of drugs at the two locations, usually 10-20 ml. Using this large amount of drug in the small space of intraincisional location as compared to similar amount of drug in large intraperitoneal space created an inadvertent bias in favor of patients receiving the drug intraincisionally so these patients naturally experienced less pain. To conduct a randomized, triple-blind, placebo-controlled study by standardizing dose of local anesthetic, to compare the effectiveness of intraperitoneal against intraincisional use of ropivacaine 0.2% for post-laparoscopic cholecystectomy pain relief. 294 patients underwent elective 4-port laparoscopic cholecystectomy. Patients were triple blindly randomized. All patients received ~ 23 ml of solution, of which 20 ml was given intraperitoneally (1 ml/cm; 16 ml along right hemi-dome and 4 ml in gall bladder fossa) and ~ 3 ml intraincisionally (1 ml/cm of length of incision). Solution was either normal saline or drug (0.2% ropivacaine) depending on the group [controls (n = 86), intraperitoneal group (n = 100), and intraincisional group (n = 108)]. 5 different pain scales were used for assessment of overall pain. Pain scores were assessed at 5 points of time. Patients in intraincisional group showed significantly less overall pain and rescue analgesia requirement (p  0.05); and shoulder pain was significantly less in intraperitoneal group (p < 0.05). The intraincisional use of injection ropivacaine at its minimum concentration of 0.2% in minimal doses of 1 ml/cm at the end of procedure provides significantly more post-operative analgesia as compared to intraperitoneal group and controls. However, for controlling shoulder pain, the use of intraperitoneal ropivacaine is desirable.

  2. Systemic Toxicity of Intraperitoneal Vancomycin

    OpenAIRE

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2017-01-01

    The relationship between the antigen dose and the quality of an immune response generated upon immunization is poorly understood. However, findings show that the immune system is indeed influenced by the antigen dose; hence underlining the importance of correctly determining which dose to use...... in order to generate a certain type of immune response. To investigate this area further, we used Göttingen minipigs asan animal model especially due to the similar body size and high degree of immunome similarity between humans and pigs. In this study, we show that both a humoral and a cell......-mediated immune (CMI) response can be generated following intraperitoneal immunization with tetanus toxoid (TT) formulated in the CAF09 liposomal adjuvant. Importantly, a low antigen dose induced more TT-specific polyfunctional T cells, whereas antigen-specific IgG production was observed upon high...

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-11-01

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

  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. Biodistribution of a High Dose of Diamond, Graphite, and Graphene Oxide Nanoparticles After Multiple Intraperitoneal Injections in Rats.

    Science.gov (United States)

    Kurantowicz, Natalia; Strojny, Barbara; Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Grodzik, Marta; Wierzbicki, Mateusz; Lipińska, Ludwika; Mitura, Katarzyna; Chwalibog, André

    2015-12-01

    Carbon nanoparticles have recently drawn intense attention in biomedical applications. Hence, there is a need for further in vivo investigations of their biocompatibility and biodistribution via various exposure routes. We hypothesized that intraperitoneally injected diamond, graphite, and graphene oxide nanoparticles may have different biodistribution and exert different effects on the intact organism. Forty Wistar rats were divided into four groups: the control and treated with nanoparticles by intraperitoneal injection (4 mg of nanoparticles/kg body weight) eight times during the 4-week period. Blood was collected for evaluation of blood morphology and biochemistry parameters. Photographs of the general appearance of each rat's interior were taken immediately after sacrifice. The organs were excised and their macroscopic structure was visualized using a stereomicroscope. The nanoparticles were retained in the body, mostly as agglomerates. The largest agglomerates (up to 10 mm in diameter) were seen in the proximity of the injection place in the stomach serous membrane, between the connective tissues of the abdominal skin, muscles, and peritoneum. Numerous smaller, spherical-shaped aggregates (diameter around 2 mm) were lodged among the mesentery. Moreover, in the connective and lipid tissue in the proximity of the liver and spleen serosa, small aggregates of graphite and graphene oxide nanoparticles were observed. However, all tested nanoparticles did not affect health and growth of rats. The nanoparticles had no toxic effects on blood parameters and growth of rats, suggesting their potential applicability as remedies or in drug delivery systems.

  7. Biodistribution of a High Dose of Diamond, Graphite, and Graphene Oxide Nanoparticles After Multiple Intraperitoneal Injections in Rats

    Science.gov (United States)

    Kurantowicz, Natalia; Strojny, Barbara; Sawosz, Ewa; Jaworski, Sławomir; Kutwin, Marta; Grodzik, Marta; Wierzbicki, Mateusz; Lipińska, Ludwika; Mitura, Katarzyna; Chwalibog, André

    2015-10-01

    Carbon nanoparticles have recently drawn intense attention in biomedical applications. Hence, there is a need for further in vivo investigations of their biocompatibility and biodistribution via various exposure routes. We hypothesized that intraperitoneally injected diamond, graphite, and graphene oxide nanoparticles may have different biodistribution and exert different effects on the intact organism. Forty Wistar rats were divided into four groups: the control and treated with nanoparticles by intraperitoneal injection (4 mg of nanoparticles/kg body weight) eight times during the 4-week period. Blood was collected for evaluation of blood morphology and biochemistry parameters. Photographs of the general appearance of each rat's interior were taken immediately after sacrifice. The organs were excised and their macroscopic structure was visualized using a stereomicroscope. The nanoparticles were retained in the body, mostly as agglomerates. The largest agglomerates (up to 10 mm in diameter) were seen in the proximity of the injection place in the stomach serous membrane, between the connective tissues of the abdominal skin, muscles, and peritoneum. Numerous smaller, spherical-shaped aggregates (diameter around 2 mm) were lodged among the mesentery. Moreover, in the connective and lipid tissue in the proximity of the liver and spleen serosa, small aggregates of graphite and graphene oxide nanoparticles were observed. However, all tested nanoparticles did not affect health and growth of rats. The nanoparticles had no toxic effects on blood parameters and growth of rats, suggesting their potential applicability as remedies or in drug delivery systems.

  8. 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

  9. Intraperitoneal immunoconjugates

    International Nuclear Information System (INIS)

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

    1990-01-01

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

  10. Gentamicin in Pseudomonas aeruginosa

    African Journals Online (AJOL)

    infections by Ps. aeruginosa is contra-indicated. In our study only 2,3 % of the Ps. aeruginosa strains were resistant to gentamicin (MIC 25 Ilg/ml). In view of the synergy reported for combined gentamicin and carbeni- cillin therapy," a combination of these two drugs may be recommended in the treatment of all Pseudomonas.

  11. SPIRULINA PLATENSIS PROTECTS AGAINST RENAL INJURY IN RATS WITH GENTAMICIN-INDUCED ACUTE TUBULAR NECROSIS

    Science.gov (United States)

    Avdagić, Nesina; Ćosović, Esad; Nakaš-Ićindić, Emina; Mornjaković, Zakira; Začiragić, Asija; Hadžović-Džuvo, Almira

    2008-01-01

    The present study was carried out to evaluate the renoprotective antioxidant effect of Spirulina platensis on gentamicin-induced acute tubular necrosis in rats. Albino-Wistar rats, (9male and 9 female), weighing approximately 250 g, were used for this study. Rats were randomly assigned to three equal groups. Control group received 0,9 % sodium chloride intraperitoneally for 7 days at the same volume as gentamicin group. Gentamicin group was treated intraperitoneally with gentamicin, 80mg/kg daily for 7 days. Gentamicin+spirulina group received Spirulina platensis 1000 mg/kg orally 2 days before and 7 days concurrently with gentamicin (80mg/kg i.p.). Nephrotoxicity was assessed by measuring plasma nitrite concentration, stabile metabolic product of nitric oxide with oxygen. Plasma nitrite concentration was determined by colorimetric method using Griess reaction. For histological analysis kidney specimens were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) stain. Plasma nitrite concentration and the level of kidney damage were significantly higher in gentamicin group in comparison both to the control and gentamicin+spirulina group. Spirulina platensis significantly lowered the plasma nitrite level and attenuated histomorphological changes related to renal injury caused by gentamicin. Thus, the results from present study suggest that Spirulina platensis has renoprotective potential in gentamicin-induced acute tubular necrosis possibly due to its antioxidant properties. PMID:19125703

  12. Gentamicin in Pseudomonas aeruginosa

    African Journals Online (AJOL)

    drug resistance in Ps. aeruginosa strains, isolated in our laboratory. Department of Microbiology, University of the ... The recipient was Escherichia coli Kl2 strain J53." RESULTS. Carbenicillin Resistance in ... gentamicin, Km = kanamycin, Su = sulphonamide, Srn = streptomycin, le = tetracyclint::. of resistance markers to ...

  13. Paraprotein interference with turbidimetric gentamicin assay.

    Science.gov (United States)

    Dimeski, Goce; Bassett, Kendra; Brown, Nigel

    2015-01-01

    Gentamicin due to its low level of resistance and rapid bactericidal activity is commonly used to treat gram-negative bacteria. However, due to its toxic effects it needs to be monitored. To date, no interference has been reported with gentamicin assays. A patient with leg cellulitis and sepsis received a single dose of gentamicin and a sample was sent for gentamicin analysis. The sample showed high blank absorbance readings on Beckman DxC800 and DC800 analysers with various dilutions. A second sample was received and analysed on a Roche Cobas system to obtain a result. A third sample was received 107 hours later with the same results and this sample was then analysed neat and post ethanol precipitation on all the turbidimetric assays available on the DxC800 analyser. The high blank absorbance was observed upon addition of the reactive reagents due to protein precipitation. Although not obvious from the patient protein results, it was shown the presence of high IgM paraprotein, 18.9 g/L (reference range 0.4-2.3 g/L) was the cause of precipitation, giving high blank readings. Of all the other turbidimetric assays, only vancomicin and valproate showed similar high blank absorbance readings. To be able to provide more rapid results it was shown ethanol could be used as a precipitant of proteins in both calibrators and patient samples with acceptable recovery. IgM paraprotein was identified as the cause of interference with the gentamicin, vancomicin and valproate assays. Protein interference in these assays can be overcome by precipitation with ethanol.

  14. Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome

    Directory of Open Access Journals (Sweden)

    Olufunsho Awodele

    2015-04-01

    Full Text Available Background: National Agency for Food and Drugs Administration and Control (NAFDAC, which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg of gentamicin on kidney using animal models. Methods: Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated. Results: Significant increase (p ≤ 0.001 in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001 elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed. Conclusion: Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.

  15. Gentamicin Nephrotoxicity in Subclinical Renal Disease.

    Science.gov (United States)

    Frazier, Donita L.

    The purpose of the present study was to examine the pharmacokinetic disposition of gentamicin and to define the mechanisms which predispose to nephrotoxicity in subclinical renal disease. Subtotally nephrectomized beagle dogs were used as a model for human beings with compromised renal function secondary to a reduced number of functional nephrons. Using ultrastructural morphometry, light microscopy and clinical chemistry data, the model was defined and the nephrotoxic responses of intact dogs administered recommended doses of drug were compared to the response of subtotally nephrectomized dogs administered reduced doses based on each animal's clearance of drug. Lysosomal and mitochondrial morphometric changes suggested mechanisms for increased sensitivity. To determine if increased sensitivity in this model was dependent on altered serum concentrations, variable rate infusions based on individual pharmacokinetic disposition of drug were administered using computer-driven infusion pumps. Identical serum concentration-time profiles were achieved in normal dogs and subtotally nephrectomized dogs, however, toxicity was significantly greater in nephrectomized dogs. The difference in the nephrotoxic response was characterized by administering supratherapeutic doses of drug to dogs. Nephrectomized dogs given a recommended dose of gentamicin became oliguric during the second week of treatment and increasingly uremic after withdrawal of drug. In contrast, intact dogs administered 2 times the recommended dose of gentamicin become only slightly polyuric during week 4 of treatment. The need to individualize dosage regimens based on drug clearance and not serum creatinine nor creatinine clearance alone was substantiated by describing the pharmacokinetic disposition of gentamicin in spontaneously occurring disease states. Four individualized dosage regimens with differing predicted efficacy were then administered to nephrectomized dogs to determine their relative nephrotoxic

  16. 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

    PURPOSE: Ovarian cancer is often diagnosed at an advanced stage with dissemination in the peritoneal cavity. Most patients achieve clinical remission after surgery and chemotherapy, but approximately 70% eventually experience recurrence, usually in the peritoneal cavity. To prevent recurrence...... 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...... of the infused therapy solution. RESULTS: The urinary bladder, thyroid, and kidneys (1.9, 1.8, and 1.7 mGy per MBq/L) received the 3 highest estimated absorbed doses. When the tissue-weighting factors were applied, the largest contributors to the effective dose were the lungs, stomach, and urinary bladder. Using...

  17. THE EFFECT OF FICUS CARICA L. (ANJIR) LEAF EXTRACT ON GENTAMICIN INDUCED NEPHROTOXICITY IN ADULT MALE ALBINO MICE.

    Science.gov (United States)

    Ghaffar, Ammara; Tahir, Mohammad; Lone, Khalid Pervez; Faisal, Bushra; Latif, Waqas

    2015-01-01

    Gentamicin is an aminoglycoside isolated from Micromonospora purpurea known for its nephrotoxicity. Ficus carica L is known to treat many ailments. This study was designed to investigate the effects of Ficus carica L. (Anjir) leaf extract on renal oxidative stress induced by gentamicin in albino mice. In this laboratory based experimental study 30 mice were divided into three groups, containing 10 mice each. Group A being the control; groups B and C were experimental and treated with gentamicin 200 mg/kg/day intraperitoneally and, Ficus carica L. leaf extract 400 mg/kg/day orally with gentamicin 200 mg/kg/day intraperitoneally respectively for a period of 8 days. Blood samples were taken 24 hours after completion of the experimental period by cardiac puncture under anesthesia and kidneys of each mouse were taken out for microscopic examination. Gentamicin treatment increased serum urea and creatinine levels (group B). Ficus carica L. leaf extract treated animals showed significant reduction in biochemical markers of kidney functions in group C. The histopathological examination of group A showed normal renal structure which was deranged in group B treated with only gentamicin, whereas, group C exhibited marked improvement in histological structure. Ficus carica L. leaf extract is effective in preventing gentamicin induced functional and structural changes in kidney of albino mice.

  18. Dry powder versus intravenous and nebulized gentamicin in cystic fibrosis and bronchiectasis. A pilot study.

    Science.gov (United States)

    Crowther Labiris, N R; Holbrook, A M; Chrystyn, H; Macleod, S M; Newhouse, M T

    1999-11-01

    Aminoglycosides are a mainstay of therapy for patients with cystic fibrosis (CF) or non-CF bronchiectasis who are infected with Pseudomonas aeruginosa (Psa). Traditionally, aerosolized antibiotics are delivered by liquid nebulization. The objective of this study was to determine whether a gentamicin dry powder inhaler (DPI) is as microbiologically active and potentially safe as gentamicin inhaled via a small-volume nebulizer (SVN) or given intravenously. The study was done according to a randomized, single-dose, and triple crossover protocol. Ten patients with CF or non-CF bronchiectasis and chronically infected with Psa were recruited. Patients received a single dose of either gentamicin 160 mg via DPI or SVN, or gentamicin at 5 mg/kg by intravenous infusion. In seven of the 10 patients, the minimum inhibitory concentration (MIC) was achieved in sputum after DPI and SVN, with mean (95% confidence interval) gentamicin concentrations at 2 h after administration of 13.1 microgram/g sputum (range: 2.2 to 23.9 microgram/g) and 97.2 microgram/g sputum (range: 0.3 to 194.2 microgram/g), respectively, whereas gentamicin levels in the sputum after intravenous administration failed to reach the MIC. Gentamicin given by DPI and SVN significantly decreased the sputum Psa density (p order of magnitude. No significant decline in bacterial counts was observed after intravenous gentamicin. When gentamicin was inhaled, blood concentrations were minimal, and were below concentrations known to cause systemic toxicity. For treatment of Psa infections susceptible to gentamicin, gentamicin administration by DPI appeared to be as efficient as by SVN, despite the delivery of a 7-fold lower dose to the airways.

  19. Protective effect of quercetin in gentamicin-induced oxidative stress in vitro and in vivo in blood cells. Effect on gentamicin antimicrobial activity.

    Science.gov (United States)

    Bustos, Pamela Soledad; Deza-Ponzio, Romina; Páez, Paulina Laura; Albesa, Ines; Cabrera, José Luis; Virgolini, Miriam Beatriz; Ortega, María Gabriela

    2016-12-01

    We have evaluated the effect of gentamicin and gentamicin plus quercetin on ROS production, endogenous antioxidant defenses (SOD and CAT) and lipid peroxidation in vitro on human leukocytes and in vivo on whole rat blood. Gentamicin generated ROS production in human leukocytes, produced a dual effect on both enzymes dosage-dependent and generated an increase in lipid peroxidation. Quercetin, in leukocytes stimulated by gentamicin, showed more inhibitory capacity in ROS production than the reference inhibitor (vitaminC) in mononuclear cells and a similar protective behavior at this inhibitor in polymorphonuclear cells. Quercetin, in both cellular systems, tend to level SOD and CAT activities, reaching basal values and could prevent lipidic peroxidation induced by gentamicin. The results in Wistar rats confirmed that therapeutic doses of gentamicin can induce oxidative stress in whole blood and that the gentamicin treatment plus quercetin can suppress ROS generation, collaborate with SOD and CAT and diminish lipid peroxidation. Finally, flavonoid and antibiotic association was evaluated on the antimicrobial activity in S. aureus and E. coli, showing that changes were not generated in the antibacterial activity of gentamicin against E. coli strains, while for strains of S. aureus a beneficial effect observes. Therefore, we have demonstrated that gentamicin could induce oxidative stress in human leukocytes and in whole blood of Wistar rats at therapeutic doses and that quercetin may to produce a protective effect on this oxidative stress generated without substantially modifying the antibacterial activity of gentamicin against E. coli strains, and it contributes to this activity against S. aureus strains. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Effects of Kangshen Oral Liquid on Gentamicin-induced Acute ...

    African Journals Online (AJOL)

    Purpose: To investigate the effects of Kangshen oral liquid (KSOL) on gentamicin sulfate (GS)-induced acute kidney injury (AKI) in rats. Methods: The rats were randomly divided into seven groups and treated with normal saline (NS), GS, furosemide, uremic clearance granule, or one of three different doses of KSOL. Several ...

  1. Partridge embryo pathology in relation to gentamicin-induced lesions

    Directory of Open Access Journals (Sweden)

    Hadi Tavakkoli

    2016-10-01

    Full Text Available Objective: To determine the macroscopic and microscopic lesions of various dosages of gentamicin in the partridge embryo. Methods: Fertile chukar partridge eggs were allocated into four groups. Group 1: salineinjected group whose individuals were administered by sterile physiological saline solution of 0.2 mL/egg inserted into yolk sac. Groups 2, 3 and 4 whose individuals were similarly administered by gentamicin sulfate at a dosage of 80 mg/kg egg-weight once, twice and three times, respectively. Results: Results showed that the embryos were congested and stunted in the gentamicininjected groups. Defects in feet, wings and feather development were accompanied by microscopic lesions in brain, meninges, heart, lungs, liver and kidneys. Histopathological lesions were noticed as edema, undeveloped tissues, necrosis and degeneration in the affected organs. Conclusions: Based on acquired results, it is concluded that gentamicin at above-described dosages causes toxicopathological effects to the partridge embryo in a dose dependent manner.

  2. In Vitro Adsorption of Gentamicin and Netilmicin by Polyacrylonitrile and Polyamide Hemofiltration Filters ▿

    Science.gov (United States)

    K.N. Lam, Philip; Tian, Qi; Ip, Margaret; Gomersall, Charles D.

    2010-01-01

    Adsorption of gentamicin and netilmicin by new polyacrylonitrile and polyamide hemofiltration filters was studied over 4 h, using a single-compartment in vitro continuous venovenous hemofiltration model. After the first dose (16.6 mg of gentamicin, 19.3 mg of netilmicin), 14.9 mg of gentamicin and 19.2 mg of netilmicin were adsorbed to polyacrylonitrile filters in vitro. Adsorption by polyacrylonitrile filters was rapid and irreversible and could be increased by repeated dosing. Adsorption by polyamide filters was substantially less. PMID:19949050

  3. In vitro adsorption of gentamicin and netilmicin by polyacrylonitrile and polyamide hemofiltration filters.

    Science.gov (United States)

    K N Lam, Philip; Tian, Qi; Ip, Margaret; Gomersall, Charles D

    2010-02-01

    Adsorption of gentamicin and netilmicin by new polyacrylonitrile and polyamide hemofiltration filters was studied over 4 h, using a single-compartment in vitro continuous venovenous hemofiltration model. After the first dose (16.6 mg of gentamicin, 19.3 mg of netilmicin), 14.9 mg of gentamicin and 19.2 mg of netilmicin were adsorbed to polyacrylonitrile filters in vitro. Adsorption by polyacrylonitrile filters was rapid and irreversible and could be increased by repeated dosing. Adsorption by polyamide filters was substantially less.

  4. on gentamicin nephrotoxicity in rats

    African Journals Online (AJOL)

    Admin

    Design: Experimental study using a pre-validated model. Subject: Adult Swiss albino rats weighing 140-214g, Generic gentamicin sulphate ... antibiotics to clinical medicine in 1944 (Gilbert, 1991) heralded an era of triumph over gram negative pathogens and, previously disastrous, sepsis. Nephrotoxicity and ototoxicity are ...

  5. Adequacy of a hospital-wide standard dose of 7mg/kg bodyweight gentamicin sufficient to achieve an adequate prophylactic maximum serum concentration (Cmax) in burn patients undergoing surgical burn wound treatment

    NARCIS (Netherlands)

    Borra, L.C.P.; Bosch, T.M.; Baar, M.E. van; Dokter, J.; Oen, I.M.; Ruijgrok, E.J.

    2016-01-01

    INTRODUCTION: Pharmacokinetics of drugs can be significantly altered in burn patients. The aim of our study was to validate if the current hospital-wide standard dosage of 7mg/kg total bodyweight gentamicin is sufficient to achieve an adequate prophylactic Cmax (Cmax>/=20mg/L). MATERIALS AND

  6. Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability.

    Science.gov (United States)

    Lee, Jeong-Han; Park, Channy; Kim, Se-Jin; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; So, Hong-Seob; Park, Raekil

    2013-03-08

    Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibitors, including gadolinium and ruthenium red, which resulted in markedly inhibited GTTR uptake and gentamicin-induced hair cell damage in rodent and zebrafish ototoxic model systems. These results indicate that the cytotoxic vulnerability of cochlear hair cells in the basal turn to gentamicin may depend on effective uptake of the drug, which was, in part, mediated by the TRPV1 and TRPV4 proteins.

  7. Protective role of ginseng against gentamicin induced changes in kidney of albino mice

    International Nuclear Information System (INIS)

    Hafeez, M.; Saeed, F.

    2011-01-01

    Background: Use of gentamicin is now limited due to its toxic effects, mainly on kidney and vestibular system. Herbal products including ginseng has been reported to possess protective effects against drugs induced nephrotoxicity in experimental animals. The current investigation was designed to evaluate the effects of ginseng on gentamicin induced nephrotoxicity. Methods: Eighteen male albino mice of 6-8 weeks age, were divided into 3 groups. Group-A served as control and was given normal mouse diet; Group-B was given 80 mg/Kg/day of gentamicin intraperitoneally dissolved in 1 ml of distilled water for fifteen days. Group-C was given 80 mg/Kg/day of gentamicin intraperitoneally dissolved in 1 ml of distilled water along with 100 mg/Kg/day of ginseng orally dissolved in 1 ml of distilled water, also for fifteen days. At the end of the experiment, blood was drawn from each animal by cardiac puncture for renal function tests. Each animal was then sacrificed and kidneys removed for routine histological studies. Results: In group B, weight of the animals and kidneys decreased and there was significant increase in mean serum urea, creatinine and intraluminal diameter (p<0.001) of proximal convoluted tubules as compared to the controls (group-A). Moderate to severe necrotic and degenerative changes in proximal convoluted tubules were seen in this group. When the Ginseng and gentamicin were given together (group-C), a statistically significant improvement in the mean body and kidney weight along with improvement in renal function tests and tubular diameter were seen (p<0.001). Conclusion: It appears that Ginseng has some protective role against gentamicin induced nephrotoxicity. (author)

  8. Cost evaluation of therapeutic drug monitoring of gentamicin at a teaching hospital in Malaysia

    Directory of Open Access Journals (Sweden)

    Ibrahim MI

    2014-03-01

    Full Text Available Background: Therapeutic drug monitoring (TDM makes use of serum drug concentrations as an adjunct to decision-making. Preliminary data in our hospital showed that approximately one-fifth of all drugs monitored by TDM service were gentamicin. Objective: In this study, we evaluated the costs associated with providing the service in patients with bronchopneumonia and treated with gentamicin. Methods: We retrospectively collected data from medical records of patients admitted to the Hospital Universiti Sains Malaysia over a 5-year period. These patients were diagnosed with bronchopneumonia and were on gentamicin as part of their treatment. Five hospitalisation costs were calculated; (i cost of laboratory and clinical investigations, (ii cost associated with each gentamicin dose, (iii fixed and operating costs of TDM service, (iv cost of providing medical care, and (v cost of hospital stay during gentamicin treatment. Results: There were 1920 patients admitted with bronchopneumonia of which 67 (3.5% had TDM service for gentamicin. Seventy-three percent (49/67 patients were eligible for final analysis. The duration of gentamicin therapy ranged from 3 to 15 days. The cost of providing one gentamicin assay was MYR25, and the average cost of TDM service for each patient was MYR104. The average total hospitalisation cost during gentamicin treatment for each patient was MYR442 (1EUR approx. MYR4.02. Conclusion: Based on the hospital perspective, in patients with bronchopneumonia and treated with gentamicin, the provision of TDM service contributes to less than 25% of the total cost of hospitalization.

  9. [Influence of dose regimen on gentamycin nephrotoxicity in rats].

    Science.gov (United States)

    Oliveira, V C; Tejos, C R; Hosaka, E M; Andrade, S C; Araújo, M; Vattimo, M F

    2001-06-01

    The acute renal failure (ARF), that still presents a right mortality rate (50%) can be defined as an abrupt decline of the glomerular filtration, resultant of ischemic or toxicity event. The drugs nephrotoxicity is one of the most frequent cause (27%) of ARF and it is suggested that the interval of administration of the drug can interfere in this side effect, however the best administration regimen is not very well established. This study evaluated the renal function of rats that received gentamicin (100 mg/kg) in one dose or in two doses (2 x 50 mg/kg), by intraperitoneal infusion. The results obtained in this research, indicated that the single infusion of gentamicin determined smaller nephrotoxicity by the reduction of serum concentration of this drug in 24 hours, decreasing the intracellular accumulation of this gentamicin, which is one of the main cellular mechanisms of this renal injury. The single dose treatment regime, otherwise, shows advantages not only related to the nephrotoxicity effect, but also it is relevant to the cost and safety, which can be rationable factors in the administration of this drug.

  10. Garlic-supplemented diet attenuates gentamicin-induced ototoxicity: an experimental study.

    Science.gov (United States)

    Uzun, Lokman; Balbaloglu, Evrim; Akinci, Harun

    2012-02-01

    Gentamicin sulfate is a potent aminoglycoside antibiotic associated with serious side effects, including ototoxicity. Garlic, with its intrinsic antioxidant activity, may prove beneficial in prevention of ototoxicity. In this study, we investigated the effect of a 4% garlic-supplemented diet on the ototoxicity induced by gentamicin in rats by using brain stem evoked response audiometry. Eighteen male Wistar rats with an intact Preyer's reflex and an initial weight of 220 to 260 g were randomly assigned to a group with gentamicin injection and garlic supplementation, a group with gentamicin injection without garlic supplementation, or a control group (6 rats each group). Gentamicin was given by intraperitoneal injection at 120 mg/kg body weight once daily for 16 days. The garlic-supplemented diet was prepared by adding pulverized whole garlic cloves to standard chow in a 4% proportion. After 21 days, hearing thresholds were evaluated by use of brain stem evoked response audiometry at 10 kHz. The mean (+/- SD) amplitudes of the auditory thresholds (sensation level) measured by use of brain stem evoked response audiometry for the group with garlic supplementation, the group without garlic, and the control group were 43.3 +/- 8.16, 78.0 +/- 4.47, and 16.7 +/- 5.16 dB sensation level, respectively. The differences were statistically significant (p garlic-supplemented diet seems to attenuate aminoglycoside-induced hearing loss.

  11. A suicide involving intraperitoneal injection of pentobarbital.

    Science.gov (United States)

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

    2016-09-01

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

  12. Immunological methods for gentamicin determination

    International Nuclear Information System (INIS)

    Krugers Dagneauz, P.G.L.C.; Olthuis, F.M.F.G.

    1979-01-01

    For immunoassay, an antibody against the substance to the determined, the pure substance itself, and a labelled form or derivative of the substance are required. The principles and problems of the preparation of antibodies are discussed, some methods for the preparation of derivatives labelled with radioactive tracers or enzymes are reviewed, and homologous enzyme-immunological determination of gentamicin is discussed in detail. A comparison is mae of three radio-immunological determination methods, and the most suitable radio-immunological method is compared with two microbiological techniques. The results are found to be comparable. (Auth.)

  13. A controlled and sustained local gentamicin delivery system for inner ear applications.

    Science.gov (United States)

    Xu, Lei; Heldrich, Jonna; Wang, Haibo; Yamashita, Taku; Miyamoto, Shunsuke; Li, Andrew; Uboh, Cornelius E; You, Youwen; Bigelow, Douglas; Ruckenstein, Michael; O'Malley, Bert; Li, Daqing

    2010-09-01

    Intratympanic gentamicin injection (ITGI) has gained acceptance worldwide for the treatment of Ménière's disease. Reports assessing the efficacy of ITGI suffer from high variability between patients. This variability may be due to ITGI, which does not permit a sustained diffusion of gentamicin across the round window membrane. The present study investigates the effectiveness of a sustained local hydrogel system on the delivery of gentamicin into the inner ear for the treatment of Ménière's disease. A matrix of hydrogel loaded with/without gentamicin was explored in vivo. Gentamicin was applied to the ear of mice either through ITGI or in the hydrogel system. Pharmacokinetics, hearing, and balance function were examined to study how the hydrogel system affected the gentamicin delivery and inner ear functions. The 2 gentamicin delivery methods yielded different kinetics curves. The hydrogel system achieved sustained release during a 7-day period, with a flat plateau phase from Day 1 to Day 3 and slow descent in the subsequent days. The ITGI curve dramatically declined after the peak concentration at Day 1 and was almost eliminated by Day 3. The hydrogel system yielded noticeable balance dysfunction with no significant hearing changes. In contrast, ITGI exhibited no significant influences on the inner ear functions after applying the same dose of 40 kg of gentamicin. The hydrogel system established in this research allows for more sustained and consistent and efficient drug release than traditional ITGI for the transport of gentamicin into the inner ear, offering a new and exciting treatment of Ménière's disease.

  14. Integrated transcriptomic and proteomic evaluation of gentamicin nephrotoxicity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Com, Emmanuelle, E-mail: emmanuelle.com@univ-rennes1.fr [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); INSERM U625, Proteomics Core Facility Biogenouest, Rennes (France); Boitier, Eric; Marchandeau, Jean-Pierre [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France); Brandenburg, Arnd [Genedata AG, Basel (Switzerland); Schroeder, Susanne [Nycomed GmbH, Barsbüttel (Germany); Hoffmann, Dana; Mally, Angela [University of Würzburg, Department of Toxicology, University of Würzburg, Würzburg (Germany); Gautier, Jean-Charles [sanofi-aventis R and D, Disposition Safety and Animal Research, Vitry-sur-Seine (France)

    2012-01-01

    Gentamicin is an aminoglycoside antibiotic, which induces renal tubular necrosis in rats. In the context of the European InnoMed PredTox project, transcriptomic and proteomic studies were performed to provide new insights into the molecular mechanisms of gentamicin-induced nephrotoxicity. Male Wistar rats were treated with 25 and 75 mg/kg/day subcutaneously for 1, 3 and 14 days. Histopathology observations showed mild tubular degeneration/necrosis and regeneration and moderate mononuclear cell infiltrate after long-term treatment. Transcriptomic data indicated a strong treatment-related gene expression modulation in kidney and blood cells at the high dose after 14 days of treatment, with the regulation of 463 and 3241 genes, respectively. Of note, the induction of NF-kappa B pathway via the p38 MAPK cascade in the kidney, together with the activation of T-cell receptor signaling in blood cells were suggestive of inflammatory processes in relation with the recruitment of mononuclear cells in the kidney. Proteomic results showed a regulation of 163 proteins in kidney at the high dose after 14 days of treatment. These protein modulations were suggestive of a mitochondrial dysfunction with impairment of cellular energy production, induction of oxidative stress, an effect on protein biosynthesis and on cellular assembly and organization. Proteomic results also provided clues for potential nephrotoxicity biomarkers such as AGAT and PRBP4 which were strongly modulated in the kidney. Transcriptomic and proteomic data turned out to be complementary and their integration gave a more comprehensive insight into the putative mode of nephrotoxicity of gentamicin which was in accordance with histopathological findings. -- Highlights: ► Gentamicin induces renal tubular necrosis in rats. ► The mechanisms of gentamicin nephrotoxicity remain still elusive. ► Transcriptomic and proteomic analyses were performed to study this toxicity in rats. ► Transcriptomic and proteomic

  15. A prospective study of gentamicin ototoxicity

    DEFF Research Database (Denmark)

    Winkel, O; Hansen, M M; Kaaber-Bühler, Søren

    2010-01-01

    of gentamicin did not rule out the possiblity of ototoxicity. These results urge the continuing of prospective studies and indicate that gentamicin should be used only as a link in the primary treatment of severe infection or in cases in which other, less toxic agents have failed....

  16. A prospective study of gentamicin ototoxicity

    DEFF Research Database (Denmark)

    Winkel, O; Hansen, M M; Kaaber-Bühler, Søren

    1978-01-01

    of gentamicin did not rule out the possiblity of ototoxicity. These results urge the continuing of prospective studies and indicate that gentamicin should be used only as a link in the primary treatment of severe infection or in cases in which other, less toxic agents have failed....

  17. Quantitative deposition of aerosolized gentamicin in cystic fibrosis

    International Nuclear Information System (INIS)

    Ilowite, J.S.; Gorvoy, J.D.; Smaldone, G.C.

    1987-01-01

    In cystic fibrosis (CF), the clinical effectiveness of aerosolized antibiotics is controversial. Previous investigators have not considered the type of nebulizer, droplet size, and dose to the lung in assessing the results of aerosol therapy. The present study tests the importance of these factors by standardizing an aerosol system for delivery of antibiotics and other agents to patients with CF. Particle size, distribution, and output from a commercially available nebulizer were measured. Thirteen patients with CF inhaled aerosol (MMAD = 1.1 micron) containing gentamicin (160 mg in nebulizer) and /sup 99m/Tc-labeled human serum albumin. Patients' sputum and serum were analyzed for gentamicin levels by immunoenzymatic assay. Using a gamma camera and suitable filters, central versus peripheral deposition (C/P ratio) and whole lung deposition were measured and related to sputum gentamicin levels. Gentamicin deposit averaged 12.3 mg +/- 5.9 (SD) or 7.69% of the original amount placed in the nebulizer. Peak sputum levels averaged 376.6 micrograms/ml +/- 275, whereas serum levels were undetectable in all patients. When peak sputum levels were normalized for the amount deposited, a close correlation with C/P ratio was obtained (r = 0.88, p less than 0.05). Furthermore, an inverse relationship was found between the C/P ratio and the %FEV1 (r = 0.76, p less than 0.05). Finally, a bell-shaped relationship between deposited dose and minute ventilation was seen in the patients (r = 0.88, p less than 0.05), i.e., an optimal minute ventilation was shown. These relationships may be important when designing future clinical studies

  18. Intraperitoneal explosion following gastric perforation

    OpenAIRE

    K. Mansfield, Scott; Roderick Borrowdale, Roderick Borrowdale

    2017-01-01

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

  19. Intraperitoneal explosion following gastric perforation.

    Science.gov (United States)

    Mansfield, Scott K; Borrowdale, Roderick

    2014-04-01

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

  20. Intraperitoneal explosion following gastric perforation

    Directory of Open Access Journals (Sweden)

    Scott K. Mansfield

    2014-04-01

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

  1. Persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis*

    Science.gov (United States)

    Tan, Xun; Jiang, Ye-wen; Huang, Yi-jun; Hu, Song-hua

    2009-01-01

    This study was designed to investigate persistence of gentamicin residues in milk after the intramammary treatment of lactating cows for mastitis. Milk samples were collected at a 1-d interval after the last administration from 34 individual cows that had received intramammary infusions of gentamicin. The doses and treatment times evaluated in this study represented those that have been applied by veterinarians in practice. The tetrazolium chloride assay was used to determine whether there were significant residues of the antibiotic in the samples. Persistence of detectable drug residues in milk from 33 cows (28 cows, ≤6 infusions at ≤0.7 g gentamicin; and 5 cows, 2 infusions at 0.8 g gentamicin) did not exceed 5 d; but 1 cow (5 infusions at 0.8 g gentamicin) had detectable residues in its milk for 9 d. Our results suggest that a 5-d milk withdrawal period might be insufficient to secure the clearance of the contamination of gentamicin, because treatment times and dosages contribute to the antibiotic clearance. A larger scale of samples are needed for further investigations. PMID:19353746

  2. Experimental gentamicin-induced nephrotoxicity in the sheep

    Directory of Open Access Journals (Sweden)

    Fartashvand Majid

    2014-12-01

    Full Text Available The aim of the study was to investigate the nephrotoxic effects of gentamicin in adult male sheep, and to identify the earliest signs of toxicity and the extent of clinical and biochemical changes. Twenty clinically healthy yearling male Iranian fattailed sheep were injected with gentamicin sulfate at a daily dose of 80 mg/kg for 9-10 d when nephrotoxicosis was induced. Blood samples were collected weekly before and after induction of nephrotoxicosis. Gentamicin-induced nephrotoxicity was characterised by increased creatinine and urea levels in serum, electrolyte imbalances, occurrence of albuminuria, and renal dysfunction. Significant elevation in respiratory and heart rates were observed one week after treatment (P < 0.05. There was a noticeable increase in water consumption, lethargy, and loss of appetite in treated sheep. There were significant correlations between serum creatinine and potassium (P = 0.004, r = 0.759, sodium (P = 0.017, r = 0.501, and urea (P = 0.021, r = 0.617 levels. Additionally, significant negative correlations between serum total protein and albumin and creatinine (P = 0.023, r = -0.484 and urea (P = 0.036, r = -0.381 were found. At necropsy, the kidneys were pale, swollen, and wet on the cut surface, especially perirenal tissues and ureters were oedematous. These findings confirmed the previous reports in other species.

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

    African Journals Online (AJOL)

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

  4. 21 CFR 529.1044b - Gentamicin sulfate solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate solution. 529.1044b Section 529... Gentamicin sulfate solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate... solution with a gentamicin concentration of 250 to 1,000 parts per million. A concentration of 500 parts...

  5. 21 CFR 524.1044a - Gentamicin ophthalmic solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin ophthalmic solution. 524.1044a Section... § 524.1044a Gentamicin ophthalmic solution. (a) Specifications. Each milliliter of sterile aqueous solution contains gentamicin sulfate equivalent to 3 milligrams of gentamicin. (b) Sponsor. See No. 000061...

  6. Evaluation of three gentamicin serum assay techniques

    International Nuclear Information System (INIS)

    Matzke, G.R.; Gwizdala, C.; Wery, J.; Ferry, D.; Starnes, R.

    1982-01-01

    This investigation was designed to compare the enzyme-modified immunoassay (Syva--EMIT) with a radioimmunoassay (New England Nuclear--RIA) and the radiometric assay (Johnston--BACTEC) to determine the optimal assay for use in our aminoglycoside dosing service. The serum concentration determinations obtained via the three assay methods were analyzed by linear regression analysis. Significant positive correlations were noted between the three assay techniques (p less than 0.005) during both sample collection phases. The coefficients of determination for EMIT vs BACTEC and RIA vs BACTEC were 0.73 and 0.83 during phase 1, respectively, and 0.65 and 0.68 during phase 2, respectively. The slope of the regression lines also varied markedly during the two phases; 0.49 and 0.42 for EMIT and for RIA vs BACTEC, respectively, during phase 1 compound with 1.12 and 0.77, respectively, during phase 2. The differences noted in these relationships during phase 1 and 2 may be related to the alteration of the pH of the control sera utilized in the BACTEC assay. In contrast, RIA vs EMIT regression analysis indicated that existence of a highly significant relationship (p less than 0.0005 and r2 . 0.90). The EMIT technique was the easiest and most accurate for determination of serum gentamicin concentrations, whereas the BACTEC method was judged unacceptable for clinical use

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

    Science.gov (United States)

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

    2018-01-06

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

  8. Protective effects of Zhibai Dihuang Wan on renal tubular cells affected with gentamicin-induced apoptosis.

    Science.gov (United States)

    Hsu, Yung-Ho; Chen, Tso-Hsiao; Wu, Mei-Yi; Lin, Yuh-Feng; Chen, Wen-Liang; Cheng, Tzu-Hurng; Chen, Cheng-Hsien

    2014-01-01

    Zhibai Dihuang Wan (ZDW) is an ancient traditional Chinese medicine composed of eight herbal ingredients and has been used to treat chronic kidney inflammation and diabetes for thousands of years. Nonetheless, the influence of ZDW on acute kidney injury is still unknown. We intended to identify the influence of ZDW on cell growth and gentamicin-induced apoptotic injury in renal tubular cells. We extracted ZDW with artificial intestinal fluid and treated rat renal tubular cells (NRK-52E) with various concentrations of the ZDW extraction. Cell proliferation and gentamicin-induced apoptosis of NRK-52E cells were evaluated using real-time proliferation monitoring and annexin V staining, respectively. Western blotting was used to evaluate the levels of Bcl-2 and caspase-3 expression. The effect of ZDW on gentamicin-induced kidney injury was also monitored in mice using the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) assay, and the measurement of serum creatinine and blood urea nitrogen. We found that 30 μg/ml of ZDW promoted cell proliferation of the rat renal tubular cells. ZDW also expressed a dose-dependent protective effect against gentamicin-induced apoptosis in the cells. Pretreatment with 3 μg/ml or 30 μg/ml of ZDW maximally increased Bcl-2 and decreased cleaved caspase-3 in the gentamicin-treated NRK-52E cells. Among the herbal ingredients of ZDW, only Phellodendron amurense Rupr., bark (Cortex Phellodendri), and Anemarrhena asphodeloides Bunge, rhizome inhibited both the gentamicin-induced Bcl-2 decrease and cleaved caspase-3 increase. Phellodendron amurense Rupr., bark and Anemarrhena asphodeloides Bunge, rhizome also inhibited gentamicin-induced apoptosis at particular concentrations; however, these two ingredients were less effective than ZDW. In the mouse model of gentamicin-induced nephropathy, the ZDW treatment significantly reduced apoptotic cells in the renal cortex and improved renal function. Our

  9. Aged garlic extract attenuates gentamicin induced renal damage and oxidative stress in rats.

    Science.gov (United States)

    Maldonado, Perla D; Barrera, Diana; Medina-Campos, Omar N; Hernández-Pando, Rogelio; Ibarra-Rubio, María E; Pedraza-Chaverrí, José

    2003-10-03

    Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Experimental evidences suggest a role of reactive oxygen species in GM-induced nephrotoxicity. Therefore, we investigated if aged garlic extract (AGE), an antioxidant, has a protective role in this experimental model. Four groups of male Wistar rats were studied: 1) Control (CT), injected subcutaneously (s.c.) and intraperitoneally (i.p.) with saline, 2) GM, treated s.c. with GM (70 mg/kg/12 hours/4 days), 3) AGE, treated i.p with AGE (1.2 mL/kg/12 hours/6 days), and 4) GM + AGE treated with GM and AGE. The treatment with AGE started two days before the first dose of GM (GM + AGE group) or saline (AGE group). Animals were sacrificed on day 5, and blood, urine, and kidneys were obtained. Nephrotoxicity was made evident by: 1) the increase in blood urea nitrogen and plasma creatinine, 2) the decrease in plasma glutathione peroxidase (GPx) activity and the urinary increase in N-acetyl-beta-D-glucosaminidase activity and total protein, and 3) necrosis of proximal tubular cells. These alterations were prevented or ameliorated by AGE treatment. Furthermore, AGE prevented the GM-induced increase in the renal levels of oxidative stress markers: nitrotyrosine and protein carbonyl groups and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities. The protective effect of AGE was associated with the decrease in the oxidative stress and the preservation of Mn-SOD, GPx, and GR activities in renal cortex. These data suggest that AGE may be a useful agent for the prevention of GM-nephrotoxicity.

  10. Intraperitoneal pressure in peritoneal dialysis

    Directory of Open Access Journals (Sweden)

    Vicente Pérez Díaz

    2017-11-01

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

  11. Comparison of amikacin and gentamicin.

    Science.gov (United States)

    Klastersky, J; Odio, W; Hensgens, C

    1975-03-01

    The sensitivity to gentamicin (G) and to amikacin (A) of 25 strains of Escherichia coli (EC), 25 Klebsiella sp. (K), 25 Proteus and Providence sp. (PP), and 25 Ps. aeruginosa (PA) were tested in vitro by the disc method, by the inocula-replicating method, and by a tube dilution technique using 10-5 microorganisms/ml. Bactericidal concentrations active on 50% and 90% of the strains were 1.5 and 4.5 mug/ml for EC, 3 and mug/ml for K, 1.5 and 3 mug/ml for PP, and 3 and 3 mug/ml for PA. Resistance to killing by 12 mug/ml of G was found for 16 strains (1 EC, 9 K, 4 PP, and 2 PA) but only 5 strains were also resistant to 12 mug/ml of A. Conversely, 4 strains (1 EC, 1 PP, and 2 PA) were resistant to 12 mug/ml of A but were killed by 6 mug/ml of G or even less. G (1.5 MG/KG) AND A (5 mg/kg) were administered to 5 bolunteers in a crossover fashion. The mean bactericidal activity of the sera obtained at 1 hr after the injection of G and A was, respectively, 1/4 and 1/4 for ED, 1/4 and 1/8 for K, 1/2 and 1/2 for PP, and 1/2 and 1/2 for PA. Sera obtained in A-treated patients killed at a dilution of 1/8, 8 strains of ED, 17 K, 1 PP, and O PA; at that dilution sera from G-treated patients killed 5 ED, 9 K, O P, and O PA. The main advantage of A over G might be the absence of cross-resistance between A and G for particular pathogens.

  12. An Antioxidant Screen Identifies Candidates for Protection of Cochlear Hair Cells from Gentamicin Toxicity

    Directory of Open Access Journals (Sweden)

    Volker Noack

    2017-08-01

    Full Text Available Reactive oxygen species are important elements in ototoxic damage to hair cells (HCs, appearing early in the damage process. Higher levels of natural antioxidants are positively correlated with resistance to ototoxins and many studies have shown that exogenous antioxidants can protect HCs from damage. While a very wide variety of antioxidants with different characteristics and intracellular targets exist, most ototoxicity studies have focused upon one or a few well-characterized compounds. Relatively little research has attempted to determine the comparative efficacy of large variety of different antioxidants. This has been in part due to the lack of translation between cell culture and in vivo measures of efficacy. To circumvent this limitation, we used an in vitro assay based on micro-explants from the basal and middle turns of the neonatal mouse organ of Corti to screen a commercial redox library of diverse antioxidant compounds for their ability to protect mammalian HCs from a high dose of the ototoxic antibiotic gentamicin. The library included several antioxidants that have previously been studied as potential treatments for HC damage, as well as many antioxidants that have never been applied to ototoxicity. The micro-explants were treated with 200 μM gentamicin alone, gentamicin plus one of three dosages of a redox compound, the highest dosage of compound alone, or were untreated. HC counts were determined before the gentamicin insult and at 1, 2, and 3 days afterward to evaluate the HC survival. From a total of 81 antioxidant compounds, 13 exhibited significant protection of HCs. These included members of a variety of antioxidant classes with several novel antioxidants, not previously tested on HCs, appearing to alleviate the damaging gentamicin effect. Some compounds previously shown to be protective of HCs were correspondingly protective in this in vitro screen, while others were not. Finally, one of the three pro-oxidant compounds

  13. Prevention of hepatorenal toxicity with Sonchus asper in gentamicin treated rats

    Directory of Open Access Journals (Sweden)

    Khan Muhammad R

    2011-11-01

    Full Text Available Abstract Background Sonchus asper possesses antioxidant capacity and is used in liver and kidney disorders. We have investigated the preventive effect of methanolic extract of Sonchus asper (SAME on the gentamicin induced alterations in biochemical and morphological parameters in liver and kidneys of Sprague-Dawley male rat. Methods Acute oral toxicity studies were performed for selecting the therapeutic dose of SAME. 30 Sprague-Dawley male rats were equally divided into five groups with 06 animals in each. Group I received saline (0.5 ml/kg bw; 0.9% NaCl while Group II administered with gentamicin 0.5 ml (100 mg/kg bw; i.p. for ten days. Animals of Group III and Group IV received gentamicin and SAME 0.5 ml at a dose of 100 mg/kg bw and 200 mg/kg bw, respectively while Group V received only SAME at a dose of 200 mg/kg bw. Biochemical parameters including aspartate transaminase (AST, alanine transaminase (ALT, alkaline phosphatase (ALP, lactate dehydrogenase (LDH, γ-glutamyltransferase (γ-GT, total cholesterol, triglycerides, total protein, albumin, creatinine, blood urea nitrogen (BUN, total bilirubin and direct bilirubin were determined in serum collected from various groups. Urinary out puts were measured in each group and also assessed for the level of protein and glucose. Lipid peroxides (TBARS, glutathione (GSH, DNA injuries and activities of antioxidant enzymes; catalase (CAT, peroxidase (POD and superoxide dismutase (SOD were determined in liver and renal samples. Histopathological studies of liver and kidneys were also carried out. Results On the basis of acute oral toxicity studies, 2000 mg/kg bw did not induce any toxicity in rats, 1/10th of the dose was selected for preventive treatment. Gentamicin increased the level of serum biomarkers; AST, ALT, ALP, LDH, γ-GT, total cholesterol, triglycerides, total protein, albumin, creatinine, BUN, total and direct bilirubin; as were the urinary level of protein, glucose, and urinary output

  14. 21 CFR 520.1044a - Gentamicin sulfate oral solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate oral solution. 520.1044a Section 520.1044a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Gentamicin sulfate oral solution. (a) Specifications. Each milliliter of aqueous solution contains gentamicin...

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

    Science.gov (United States)

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

    2014-01-01

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

  16. 21 CFR 522.1044 - Gentamicin.

    Science.gov (United States)

    2010-04-01

    ... old for treatment of porcine colibacillosis caused by strains of E. coli sensitive to gentamicin. (iii.... Administer intramuscularly or subcutaneously. If response is not noted after 7 days, the antibiotic... early mortality caused by Escherichia coli. Salmonella typhimurium, and Pseudomonas aeruginosa that are...

  17. Silica-Gentamicin Nanohybrids: Synthesis and Antimicrobial Action

    Directory of Open Access Journals (Sweden)

    Dina Ahmed Mosselhy

    2016-03-01

    Full Text Available Orthopedic applications commonly require the administration of systemic antibiotics. Gentamicin is one of the most commonly used aminoglycosides in the treatment and prophylaxis of infections associated with orthopedic applications, but gentamicin has a short half-life. However, silica nanoparticles (SiO2 NPs can be used as elegant carriers for antibiotics to prolong their release. Our goal is the preparation and characterization of SiO2-gentamicin nanohybrids for their potential antimicrobial administration in orthopedic applications. In vitro gentamicin release profile from the nanohybrids (gentamicin-conjugated SiO2 NPs prepared by the base-catalyzed precipitation exhibited fast release (21.4% during the first 24 h and further extension with 43.9% release during the five-day experiment. Antimicrobial studies of the SiO2-gentamicin nanohybrids versus native SiO2 NPs and free gentamicin were performed against Bacillus subtilis (B. subtilis, Pseudomonas fluorescens (P. fluorescens and Escherichia coli (E. coli. SiO2-gentamicin nanohybrids were most effective against B. subtilis. SiO2 NPs play no antimicrobial role. Parallel antimicrobial studies for the filter-sterilized gentamicin were performed to assess the effect of ultraviolet (UV-irradiation on gentamicin. In summary, the initial fast gentamicin release fits the need for high concentration of antibiotics after orthopedic surgical interventions. Moreover, the extended release justifies the promising antimicrobial administration of the nanohybrids in bone applications.

  18. Silica-Gentamicin Nanohybrids: Synthesis and Antimicrobial Action.

    Science.gov (United States)

    Mosselhy, Dina Ahmed; Ge, Yanling; Gasik, Michael; Nordström, Katrina; Natri, Olli; Hannula, Simo-Pekka

    2016-03-05

    Orthopedic applications commonly require the administration of systemic antibiotics. Gentamicin is one of the most commonly used aminoglycosides in the treatment and prophylaxis of infections associated with orthopedic applications, but gentamicin has a short half-life. However, silica nanoparticles (SiO₂ NPs) can be used as elegant carriers for antibiotics to prolong their release. Our goal is the preparation and characterization of SiO₂-gentamicin nanohybrids for their potential antimicrobial administration in orthopedic applications. In vitro gentamicin release profile from the nanohybrids (gentamicin-conjugated SiO₂ NPs) prepared by the base-catalyzed precipitation exhibited fast release (21.4%) during the first 24 h and further extension with 43.9% release during the five-day experiment. Antimicrobial studies of the SiO₂-gentamicin nanohybrids versus native SiO₂ NPs and free gentamicin were performed against Bacillus subtilis ( B. subtilis ), Pseudomonas fluorescens ( P. fluorescens ) and Escherichia coli ( E. coli ). SiO₂-gentamicin nanohybrids were most effective against B. subtilis . SiO₂ NPs play no antimicrobial role. Parallel antimicrobial studies for the filter-sterilized gentamicin were performed to assess the effect of ultraviolet (UV)-irradiation on gentamicin. In summary, the initial fast gentamicin release fits the need for high concentration of antibiotics after orthopedic surgical interventions. Moreover, the extended release justifies the promising antimicrobial administration of the nanohybrids in bone applications.

  19. Inhalational Gentamicin Treatment Is Effective Against Pneumonic Plague in a Mouse Model

    Directory of Open Access Journals (Sweden)

    David Gur

    2018-04-01

    Full Text Available Pneumonic plague is an infectious disease characterized by rapid and fulminant development of acute pneumonia and septicemia that results in death within days of exposure. The causative agent of pneumonic plague, Yersinia pestis (Y. pestis, is a Tier-1 bio-threat agent. Parenteral antibiotic treatment is effective when given within a narrow therapeutic window after symptom onset. However, the non-specific “flu-like” symptoms often lead to delayed diagnosis and therapy. In this study, we evaluated inhalational gentamicin therapy in an infected mouse model as a means to improve antibiotic treatment efficacy. Inhalation is an attractive route for treating lung infections. The advantages include directly dosing the main infection site, the relative accessibility for administration and the lack of extensive enzymatic drug degradation machinery. In this study, we show that inhalational gentamicin treatment administered 24 h post-infection, prior to the appearance of symptoms, protected against lethal intranasal challenge with the fully virulent Y. pestis Kimberley53 strain (Kim53. Similarly, a high survival rate was demonstrated in mice treated by inhalation with another aminoglycoside, tobramycin, for which an FDA-approved inhaled formulation is clinically available for cystic fibrosis patients. Inhalational treatment with gentamicin 48 h post-infection (to symptomatic mice was also successful against a Y. pestis challenge dose of 10 i.n.LD50. Whole-body imaging using IVIS technology demonstrated that adding inhalational gentamicin to parenteral therapy accelerated the clearance of Y. pestis from the lungs of infected animals. This may reduce disease severity and the risk of secondary infections. In conclusion, our data suggest that inhalational therapy with aerosolized gentamicin may be an effective prophylactic treatment against pneumonic plague. We also demonstrate the benefit of combining this treatment with a conventional parenteral

  20. Delineating the Biosynthesis of Gentamicin X2, the Common Precursor of the Gentamicin C Antibiotic Complex

    Science.gov (United States)

    Huang, Chuan; Huang, Fanglu; Moison, Eileen; Guo, Junhong; Jian, Xinyun; Duan, Xiaobo; Deng, Zixin; Leadlay, Peter F.; Sun, Yuhui

    2015-01-01

    Summary Gentamicin C complex is a mixture of aminoglycoside antibiotics used worldwide to treat severe Gram-negative bacterial infections. Despite its clinical importance, the enzymology of its biosynthetic pathway has remained obscure. We report here insights into the four enzyme-catalyzed steps that lead from the first-formed pseudotrisaccharide gentamicin A2 to gentamicin X2, the last common intermediate for all components of the C complex. We have used both targeted mutations of individual genes and reconstitution of portions of the pathway in vitro to show that the secondary alcohol function at C-3″ of A2 is first converted to an amine, catalyzed by the tandem operation of oxidoreductase GenD2 and transaminase GenS2. The amine is then specifically methylated by the S-adenosyl-l-methionine (SAM)-dependent N-methyltransferase GenN to form gentamicin A. Finally, C-methylation at C-4″ to form gentamicin X2 is catalyzed by the radical SAM-dependent and cobalamin-dependent enzyme GenD1. PMID:25641167

  1. Gentamicin Pharmacokinetics in the Chicken Inner Ear

    OpenAIRE

    Bunting, Eric C.; Park, Debra L.; Durham, Dianne; Girod, Douglas A.

    2004-01-01

    Avians have the unique ability to regenerate cochlear hair cells that are lost due to ototoxins or excessive noise. Many methodological techniques are available to damage the hair cells for subsequent scientific study. A recent method utilizes topical application of an ototoxic drug to the round window membrane. The current study examines the pharmacokinetics of gentamicin in the inner ear of chickens following topical application to the round window membrane or a single system...

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

    Science.gov (United States)

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

    1992-11-01

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

  3. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.

    Science.gov (United States)

    Lakhera, Abhijeet; Ganeshpurkar, Aditya; Bansal, Divya; Dubey, Nazneen

    2015-06-01

    Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (pCoriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.

  4. Donor corneoscleral rim contamination by gentamicin-resistant organisms

    Directory of Open Access Journals (Sweden)

    Gopinathan Usha

    1994-01-01

    Full Text Available Gentamicin is the most widely used antibiotic in the decontamination of donor cornea for penetrating keratoplasty. However, the incidence of resistance to gentamicin is on the rise. Bacterial isolates from 178 donor corneal rims were studied for gentamicin sensitivity. The overall rate of gentamicin resistance was 63.4%. At 86.2% the Pseudomonas. species had the highest rate of resistance, followed by Streptococci at 84.6%. The high rate of gentamicin resistance encountered by us and others suggest that either addition of a second antibiotic to corneal storage media or replacement of gentamicin by an antibiotic with a broader spectrum of activity may help reduce the risk of endophthalmitis following penetrating keratoplasty

  5. Evaluation of novel biomarkers of nephrotoxicity in Cynomolgus monkeys treated with gentamicin

    International Nuclear Information System (INIS)

    Gautier, Jean-Charles; Zhou, Xiaobing; Yang, Yi; Gury, Thierry; Qu, Zhe; Palazzi, Xavier; Léonard, Jean-François; Slaoui, Mohamed; Veeranagouda, Yaligara; Guizon, Isabelle; Boitier, Eric; Filali-Ansary, Aziz; Berg, Bart H.J. van den; Poetz, Oliver; Joos, Thomas; Zhang, Tianyi; Wang, Jufeng; Detilleux, Philippe; Li, Bo

    2016-01-01

    Most studies to evaluate kidney safety biomarkers have been performed in rats. This study was conducted in Cynomolgus monkeys in order to evaluate the potential usefulness of novel biomarkers of nephrotoxicity in this species. Groups of 3 males were given daily intramuscular injections of gentamicin, a nephrotoxic agent known to produce lesions in proximal tubules, at dose-levels of 10, 25, or 50 mg/kg/day for 10 days. Blood and 16-h urine samples were collected on Days − 7, − 3, 2, 4, 7, and at the end of the dosing period. Several novel kidney safety biomarkers were evaluated, with single- and multiplex immunoassays and in immunoprecipitation-LC/MS assays, in parallel to histopathology and conventional clinical pathology parameters. Treatment with gentamicin induced a dose-dependent increase in kidney tubular cell degeneration/necrosis, ranging from minimal to mild severity at 10 mg/kg/day, moderate at 25 mg/kg/day, and to severe at 50 mg/kg/day. The results showed that the novel urinary biomarkers, microalbumin, α1-microglobulin, clusterin, and osteopontin, together with the more traditional clinical pathology parameters, urinary total protein and N-acetyl-β-D-glucosaminidase (NAG), were more sensitive than blood urea nitrogen (BUN) and serum creatinine (sCr) to detect kidney injury in the monkeys given 10 mg/kg/day gentamicin for 10 days, a dose leading to an exposure which is slightly higher than the desired therapeutic exposure in clinics. Therefore, these urinary biomarkers represent non-invasive biomarkers of proximal tubule injury in Cynomolgus monkeys which may be potentially useful in humans. - Highlights: • Gentamicin induced kidney tubular cell degeneration/necrosis in Cynomolgus monkey • Urinary clusterin and osteopontin were sensitive biomarkers of kidney injury. • Microalbumin and α1-microglobulin in urine were also more sensitive than serum creatinine.

  6. Effects of Ashwagandha (Withania somnifera Root Extract On Some Serum Liver Marker Enzymes (AST, ALT In Gentamicin Intoxicated Rats

    Directory of Open Access Journals (Sweden)

    Nayma Sultana

    2012-06-01

    Full Text Available Background: Liver is an essential metabolic organ. It can be damaged due to prolonged use and higher doses of drugs, exposure to some chemicals, toxins, or infectious agents. Herbal plants as ashwagandha (Withania somnifera may have free radical scavenging activity thereby can be used for the prevention and treatment of liver damage.Objective: To observe the effect of ashwagandha (Withania somnifera root extract on gentamicin induced changes of some liver marker enzymes e,g serum aspartate amino transferase (AST and alanine amino transferase (ALT in Wistar albino rats.Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka from 1st July 2010 to 30th June 2011. A total number of 35 Wistar albino rats, aged 90 to 120 days, weighing between 150 to 200 grams were selected for the study. After acclimatization for 14 days, they were divided into control group (Group A and experimental group (Group B. Control group was again subdivided into group A1 (baseline control, consisted of 10 rats and group A2 (gentamicin treated control group, consisted of 10 rats. Again, experimental group (Group B-ashwagandha pretreated and gentamicin treated group consisted of 15 rats. All groups of animals received basal diet for 22 consecutive days. In addition to this, group A2 also received gentamicin subcutaneously (100mg /kg body weight/day for the last eight (15th to 22nd day consecutive days. Again, group B received ashwagandha root extract (500mg/kg body weight/day, orally for 22 consecutive days and gentamicin subcutaneously (100mg/kg body weight /day for last eight (15th to 22nd day days. All the animals were sacrificed on 23rd day. Then blood and liver samples were collected. For assessment of liver function, serum AST, ALT and bilirubin levels were estimated. All these tests were done by standard Laboratory technique. The statistical analysis was done by one way ANOVA and Bonferroni test as

  7. The Rapid Emergence of High Level Gentamicin Resistance in Enterococci

    Directory of Open Access Journals (Sweden)

    Kevin R Forward

    1990-01-01

    Full Text Available The proportion of enterococci isolated from blood and urine cultures that were highly resistant to gentamicin and streptomycin were determined. No blood or urine isolates highly resistant to gentamicin were seen in 1983, whereas by 1986–87 25% of blood and 17% of urine isolates were highly resistant. The rapid emergence of gentamicin resistance has serious implications for patients with life threatening enterococcal disease.

  8. Gentamicin pharmacokinetics in term newborn infants receiving high-frequency oscillatory ventilation or conventional mechanical ventilation: a case-controlled study.

    Science.gov (United States)

    Bhatt-Mehta, Varsha; Donn, Steven M

    2003-10-01

    To compare the pharmacokinetics of gentamicin in infants receiving high-frequency oscillatory ventilation (HFOV) with infants receiving conventional mechanical ventilation. A case-controlled study design was used to compare the pharmacokinetics of gentamicin in critically ill infants receiving HFOV and conventional mechanical ventilation. Medical records of all full-term newborn infants (> or =37 weeks gestational age) who received either high-frequency mechanical ventilation or conventional mechanical ventilation between 1991 and 2001 were reviewed and relevant patient demographics, renal function tests and gentamicin administration and plasma concentration data collected. Elimination rate constant, half-life, volume of distribution and clearance for both groups were calculated using standard kinetics equations. A tertiary care children's hospital. Newborn infants, > or =37 weeks gestational age, receiving gentamicin and high-frequency mechanical ventilation or conventional mechanical ventilation. In total, 18 patients were included in the conventional mechanical ventilation group and 15 in the HFOV group. The mean gentamicin dose for conventional mechanical ventilation and HFOV groups infants were 2.52+/-0.07 and 2.5+/-0.07 mg/kg/dose, respectively. Initial dosing interval was 12 hours in all of the conventional mechanical ventilation infants and 13 of the 15 HFOV infants. The dosing interval for the remaining two HFOV infants was 18 hours. No patient in either group demonstrated oliguria. Statistical analysis using the Student t-test for unequal variances yielded significant differences between the two groups with regard to elimination rate constant, half-life, volume of distribution and clearance, with a p value of mechanical ventilation group (13.4+2.23) (p>0.05). Infants receiving HFOV had reduced gentamicin clearance. Full-term infants receiving HFOV should be initiated at gentamicin dosing intervals of 18 hours rather than the traditional 12 hours

  9. 21 CFR 529.1044a - Gentamicin sulfate intrauterine solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate intrauterine solution. 529.1044a Section 529.1044a Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... § 529.1044a Gentamicin sulfate intrauterine solution. (a) Specifications. Each milliliter of solution...

  10. Enzymuria in neonates receiving continuous intravenous infusion of gentamicin

    DEFF Research Database (Denmark)

    Colding, H; Brygge, K; Brendstrup, L

    1992-01-01

    with non-treatment periods in the same newborn infant (33 infants). The same tendency applied to AAP. Newborn infants receiving continuous intravenous infusion of gentamicin were not found to be at greater risk of nephrotoxicity than those receiving intermittent gentamicin treatment, using NAG and AAP...

  11. Instrumental characterization of the smectite clay–gentamicin hybrids

    Indian Academy of Sciences (India)

    This paper focusses on the intercalation of clay mineral with gentamicin (an aminoglycoside antibiotic). The smectite clay–gentamicin hybrids were prepared by a solution intercalation at 60°C and the process was carried out on unmodified smectite clay and on smectite after Na+ ionic activation. The resulting ...

  12. Intraperitoneal stone migration during percutaneos nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Akif Diri

    2014-12-01

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

  13. Adjuvant Bidirectional Chemotherapy Using an Intraperitoneal Port

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Evon S. Ereifej

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

  16. Effect of Ashwagandha (Withania Somnifera Root Extract Against Gentamicin Induced Changes of Serum Urea and Creatinine Levels in Rats

    Directory of Open Access Journals (Sweden)

    Nayma Sultana

    2011-12-01

    Full Text Available AbstractBackground: Kidney is an important excretory organ. Its damage can be occurred due to prolonged use and higher doses of drugs, exposure to some chemicals, toxins, or infectious agents. Herbal plants as Ashwagandha (Withania somnifera may have free radical scavenging activity thereby can be used for the prevention and treatment of kidney damage.Objective: To observe the nephroprotective effect of Ashwagandha (Withania somnifera root against gentamicin induced nephrotoxicity in Wistar albino rats.Methods: This experimental study was carried out in the Department of Physiology, Sir Salimullah Medical College (SSMC, Dhaka from 1st July 2010 to 30th June 2011. A total number of 35 Wistar albino rats, age ranged from 90 to 120 days, weighing between 150 to 200 grams were included in this study. After acclimatization for 14 days, they were divided into control group (Group A and experimental group (Group B. Control group was again subdivided into group A1 (baseline control, consisted of 10 rats and group A2 (gentamicin treated control group, consisted of 10 rats. Again, experimental group (Group B- Ashwagandha pretreated and gentamicin treated group consisted of 15 rats. All groups of animals received basal diet for 22 consecutive days. In addition to this, group A2 also received gentamicin subcutaneously (100mg /kg body weight/day for the last eight (15th to 22nd day consecutive days. Again, group B received ashwagandha root extract (500mg/kg body weight/ day; orally for 22 consecutive days and gentamicin subcutaneously (100mg/kg body weight /day for last eight (15th to 22nd day days. All the animals were sacrificed on 23rd day. Then blood and kidney sample were collected. Estimation of serum urea, creatinine levels were done by using standard Laboratory kits. The statistical analysis was done by one way ANOVA and Bonferroni test as applicable.Results: The mean serum urea, creatinine levels were significantly (p<0.001 higher in gentamicin

  17. Effect of Taurine on the antimicrobial efficiency of Gentamicin

    Directory of Open Access Journals (Sweden)

    Islambulchilar Mina

    2011-12-01

    Full Text Available Context: Gentamicin is mainly used in severe infections caused by gram-negatives. However toxicity including nephrotoxicity and ototoxicity is one of the most important complications of its treatment. The production of free radicals seems to be involved in gentamicin toxicity mechanism. Taurine, a major intracellular free β-amino acid, is known to be an endogenous antioxidant. So potentially the co-therapy of taurine and gentamicin would reduce the adverse effects of the antibiotic. Objectives: In this study, we wished to know the effect of taurine on the antibiotic capacity of gentamicin. methods: strains of P. aeruginosa, E. coli, S. aureus and S. epidermidis were used as test organisms. Minimum inhibitory concentrations of gentamicin in the presence and absence of taurine at quantities from 40 to 2 mg/L were determined using macro-dilution method. Results: MICs were determined in the various concentrations of taurine for bacterial indicators. The MIC values of gentamicin for P. aeruginosa, S. aureus and E. coli remained unchanged in the values of 2.5, 5 and 20 μg/ml respectively in the absence and presences of different concentrations of taurine. The bactericidal activity of gentamicin against S. epidermidis was increased by addition of taurine in the concentrations higher than 6 mg/L. Conclusion: According to our study the antibacterial activity of gentamicin against the indicator microorganisms were not interfere with taurine at selected concentrations. Further in vivo studies are needed to establish if a combination of gentamicin and taurine would have the same effect.

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

    International Nuclear Information System (INIS)

    Kuna, P.

    1983-01-01

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

  19. A New Type of Biphasic Calcium Phosphate Cement as a Gentamicin Carrier for Osteomyelitis

    Directory of Open Access Journals (Sweden)

    Wen-Yu Su

    2013-01-01

    Full Text Available Osteomyelitis therapy is a long-term and inconvenient procedure for a patient. Antibiotic-loaded bone cements are both a complementary and alternative treatment option to intravenous antibiotic therapy for the treatment of osteomyelitis. In the current study, the biphasic calcium phosphate cement (CPC, called α-TCP/HAP (α-tricalcium phosphate/hydroxyapatite biphasic cement, was prepared as an antibiotics carrier for osteomyelitis. The developed biphasic cement with a microstructure of α-TCP surrounding the HAP has a fast setting time which will fulfill the clinical demand. The X-ray diffraction and Fourier transform infrared spectrometry analyses showed the final phase to be HAP, the basic bone mineral, after setting for a period of time. Scanning electron microscopy revealed a porous structure with particle sizes of a few micrometers. The addition of gentamicin in α-TCP/HAP would delay the transition of α-TCP but would not change the final-phase HAP. The gentamicin-loaded α-TCP/HAP supplies high doses of the antibiotic during the initial 24 hours when they are soaked in phosphate buffer solution (PBS. Thereafter, a slower drug release is produced, supplying minimum inhibitory concentration until the end of the experiment (30 days. Studies of growth inhibition of Staphylococcus aureus and Pseudomonas aeruginosa in culture indicated that gentamicin released after 30 days from α-TCP/HAP biphasic cement retained antibacterial activity.

  20. 21 CFR 520.1044b - Gentamicin sulfate pig pump oral solution.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Gentamicin sulfate pig pump oral solution. 520....1044b Gentamicin sulfate pig pump oral solution. (a) Specifications. Each milliliter of pig pump oral solution contains gentamicin sulfate equivalent to 4.35 milligrams of gentamicin. (b) Sponsor. See Nos...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  2. Incidence of high-level gentamicin resistance in enterococci at ...

    African Journals Online (AJOL)

    gentamicin resistance (HLGR) in enterococcal isolates at. Johannesburg Hospital. Design. Survey of laboratory isolates. Setting. Academic hospitals. Bacterial strains. Consecutive samples of enterococcaf isolates. ... that for severe infections, particularly endocarditis and meningitis, bactericidal antimicrobial therapy is ...

  3. Developmental pharmacokinetics of gentamicin in preterm and term neonates

    DEFF Research Database (Denmark)

    Nielsen, Elisabet I; Sandström, Marie; Honoré, Per Hartvig

    2009-01-01

    BACKGROUND AND OBJECTIVE: Preterm and term newborn infants show wide interindividual variability (IIV) in pharmacokinetic parameters of gentamicin. More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concen...

  4. Clinicopathological Studies on Gentamicin Toxicity in White Leghorn Commercial Layers

    Directory of Open Access Journals (Sweden)

    Najam Ul Islam, M. Zargham Khan1, M. Kashif Saleemi*1, Ahrar Khan1, Sheraz Ahmed Bhatti1, Muhammad Yousaf2 and Zahoor-ul-Hassan3

    2011-10-01

    Full Text Available Gentamicin is an effective and economical drug used to control infectious diseases in poultry but is highly toxic and had slow clearance from the body. This study aimed to report three cases of gentamicin toxicity in three White Leghorn (WLH layer flocks in different poultry producing areas of Pakistan. In first case, gentamicin was injected in a 9000 WLH layer flock @ 10 mg/kg body weight (BW for seven times during 9-15 weeks for age. In second case, gentamicin was injected in a flock of 7500 WLH layers @ 25 mg/kg BW for four times during 17-18 weeks of age. In third case, gentamicin was injected in flock of 16000 WLH layers @ 22.22 mg/kg BW three times in 20-21 weeks of age. Flock wise mortality was 8.69, 82.63 and 71.86%, respectively. Birds were dehydrated, emaciated and had prominent keel bone. Clinical signs included dehydration, decreased body weight leading to emaciation, decreased feed intake, increased water intake and watery diarrhea. Necropsy revealed prominent keal bone, shrunken muscles swollen kidneys bulging out from bony sockets. Petechial and echymotic hemorrhages were present on heart and skeletal muscles. Liver was enlarged with hemorrhagic streaks on its surface. Microscopically, hemorrhages and acute tubular necrosis was recorded in kidneys. Liver had hemorrhages, cellular infiltration and vacuolar (fatty degeneration of hepatocytes. From the results, it could be concluded that overdosing and repeated administration of gentamicin was highly toxic to birds.

  5. Correlation between apramycin and gentamicin use in pigs and an increasing reservoir of gentamicin-resistant Escherichia coli

    DEFF Research Database (Denmark)

    Jensen, Vibeke Frøkjær; Jakobsen, Lotte; Emborg, Hanne-Dorthe

    2006-01-01

    ), diagnostic submissions from pigs (clinical isolates) and pork were obtained from the national surveillance of antimicrobial resistance and from routine diagnostic laboratories. Antimicrobial consumption data were obtained from the Danish Medicines Agency (1997-2000) and from the VetStat database (2001...... and gentamicin resistance in Escherichia coli strains from pork, healthy pigs and diagnostic submissions from pigs and to investigate potential relationships to the use of apramycin and gentamicin at farm and national levels. Methods: Data on Danish E. coli isolates from healthy pigs (indicator bacteria......-2004). The genetic background for gentamicin resistance was investigated by PCR. Relationships between antimicrobial usage and resistance were analysed by chi(2) test and logistic regression. Results: At the farm level, the occurrence of apramycin/gentamicin cross-resistance was correlated to the use of apramycin (P...

  6. Patients’ safety: is there a systemic release of gentamicin by gentamicin-coated tibia nails in clinical use?

    Directory of Open Access Journals (Sweden)

    Moghaddam A

    2016-09-01

    Full Text Available Arash Moghaddam,1 Viola Graeser,1 Fabian Westhauser,1 Ulrike Dapunt,1 Till Kamradt,1 Stefan M Woerner,2 Gerhard Schmidmaier1 1HTRG – Heidelberg Traume Research Group Center for Orthopedics, Trauma and Spinal Cord Injury, University Hospital Heidelberg, Heidelberg, Germany; 2Department of Internal Medicine and Clinical Chemistry, University Hospital Heidelberg, Heidelberg, Germany Introduction: Osteitis is one of the most serious complications in orthopedic surgery. Expert Tibia Nail (ETN PROtect™ coated with a biodegradable layer of gentamicin-laden polymer was developed for prophylaxis of osteomyelitis. In systemic administration, gentamicin has only a small therapeutic index and serious side effects; it is potentially nephrotoxic as well as ototoxic. It is not yet known if relevant gentamicin concentrations are released into the systemic circulation after implantation of gentamicin-coated nails. In order to evaluate the patients’ risks profiles and increase patient safety, we measured gentamicin levels in pre- and postoperative serum samples of patients undergoing implantation of ETN PROtect.Methods: Twenty-five patients who received ETN PROtect between March 2012 and August 2014 were included in this study. Collection of blood samples occurred before the operation, at weeks 1–4, 3 and 6 months, and up to 1 year after the implantation. Measurement of gentamicin levels in serum samples was performed at the central laboratory of Heidelberg University Hospital. Additionally, laboratory parameters, C-reactive protein, leukocyte number, urea and creatinine concentrations were analyzed in routine controls before and after operating and assessed for systemic side effects.Results: Over the course of this prospective observational study, we were able to determine that gentamicin-coated nails do not release gentamicin into the systemic circulation above the lowest detectable level of 0.2 mg/dL. There were slight increases in the mean

  7. Tritium labeled Gentamicin C : II.- Bioradioactive products of Gentamicin by Catalytic H2O-3H exchange reaction

    International Nuclear Information System (INIS)

    Suarez, C.; Diaz, A.; Paz, D.; Jimeno, M.L.

    1992-01-01

    The main bioradioactive degradation products from catalytic hydrogen exchange of gentamicin C, (C1 + C2 + C1a) in basic form, are generated by N-dimethylations in 3 - N and 6'-N positions. Their structures were confirmed by HNMR and 13 CNMR. These derivatives were fractionated by chromatography on silica gel. Antibacterial activities were similar to those of the parent antibiotics. Tritium exchange, under vacuum or nitrogen, is highly increased (4:1) when gentamicina are in basic form. In contrast with gentamicin sulfate, hydrolytic subproducts as garamine, gentamicine, garosamine and purpurosamines are practically absent. To properly optimize the exchange process, the composition of the gentamicin C complex must be taken into account. The exchange decreases in the order C2 > C1 > C1a. Because of 6' -N-dimenthyl gentamicin C1 is C2, the radiochemical yield of C2 appears enhanced in the H 2 O- 3 H exchange of a mixture of them. Radioactivity distribution among the components and subunits of these three gentamicins were studied by stron and mild hydrolysis, and by methanolysis. (author)

  8. Tritium Labeled Gentamicin C: II.- Bioradiactive Degradation Products of Gentamicin by Catalytic H2O-3H Exchange Reaction

    International Nuclear Information System (INIS)

    Suarez, C.; Diaz, A.; Paz, D.; Jimeno, M. L.

    1992-01-01

    The main bio radioactive degradation products from catalytic hydrogen exchange of gentamicin C, (C1 + C2 + Cla) in basic form, are generated by N-demethylation in 3 - N and 6-N positions. Their structures were confirmed by 1HNMR and 13CNMR. These derivatives were fractionated by chromatography on silica gel. Antibacterial activities were similar to those of the parent antibiotics. Tritium exchange, under vacuum or nitrogen, is highly increased (4:1) when gentamicin are in basic form. In contrast with gentamicin sulfate, hydrolytic sub products as gramine, genta mines, garosamine and purpurosamines are practically absent. To properly optimize the exchange process, the composition of the gentamicin C complex must be taken into account. The exchange decreases in the order C2 > C1> Cla. Because of 6'-N-demethyl gentamicin C1 is C2, the radiochemical yield of C2 appears enhanced in the H2O-3H exchange of a mixture of them. Radioactivity distribution among the components and subunits of these three gentamicin were studied by strong and mild hydrolysis, and by methanolysis. (Author) 18 refs

  9. Impact of Gentamicin Coadministration along with High Fructose Feeding on Progression of Renal Failure and Metabolic Syndrome in Sprague-Dawley Rats

    Directory of Open Access Journals (Sweden)

    Zaid O. Ibraheem

    2014-01-01

    Full Text Available The current study evaluates the impact of high fructose feeding in rat model of gentamicin induced nephrotoxicity. Sprague-Dawley rats weighing 180–200 g were randomized into four groups; (C received standard rodents chow with free access to ad libitum drinking water for 8 weeks and was considered as control, (F received standard rodents chow with free access to drinking water supplemented with 20% (W/V fructose for the same abovementioned period, (FG was fed as group F and was given 80 mg/kg (body weight/day gentamicin sulphate intraperitoneally during the last 20 days of the feeding period, and (G was given gentamicin as above and fed as group C. Renal function was assessed at the end of the treatment period through measuring serum creatinine, uric acid and albumin, creatinine clearance, absolute and fractional excretion of both sodium and potassium, twenty-four-hour urinary excretion of albumin, and renal histology. For metabolic syndrome assessment, fasting plasma glucose and insulin were measured and oral glucose tolerance test was performed throughout the treatment period. Results showed that gentamicin enhances progression of fructose induced metabolic syndrome. On the other hand, fructose pretreatment before gentamicin injection produced a comparable degree of renal dysfunction to those which were given fructose-free water but the picture of nephrotoxicity was somewhat altered as it was characterized by higher extent of glomerular congestion and protein urea. Overall, more vigilance is required when nephrotoxic drugs are prescribed for patients with fructose induced metabolic syndrome.

  10. Electrolyte composition of renal tubular cells in gentamicin nephrotoxicity

    International Nuclear Information System (INIS)

    Matsuda, O.; Beck, F.X.; Doerge, A.T.; Thurau, K.

    1988-01-01

    The effect of long-term gentamicin administration on sodium, potassium, chloride and phosphorus concentrations was studied in individual rat renal tubular cells using electron microprobe analysis. Histological damage was apparent only in proximal tubular cells. The extent of damage was only mild after 7 days of gentamicin administration (60 mg/kg body wt/day) but much more pronounced after 10 days. GFR showed a progressive decline during gentamicin treatment. In non-necrotic proximal tubular cells, sodium was increased from 14.6 +/- 0.3 (mean +/- SEM) in controls to 20.6 +/- 0.4 after 7 and 22.0 +/- 0.8 mmol/kg wet wt after 10 days of gentamicin administration. Chloride concentration was higher only after 10 days (20.6 +/- 0.6 vs. 17.3 +/- 0.2 mmol/kg wet wt). Both cell potassium and phosphorus concentrations were diminished by 6 and 15, and by 8 and 25 mmol/kg wet wt after 7 and 10 days of treatment, respectively. In contrast, no major alterations in distal tubular cell electrolyte concentrations could be observed after either 7 or 10 days of gentamicin administration. As in proximal tubular cells, distal tubular cell phosphorus concentrations were, however, lowered by gentamicin treatment. These results clearly indicate that gentamicin exerts its main effect on proximal tubular cells. Decreased potassium and increased sodium and chloride concentrations were observed in proximal tubular cells exhibiting only mild histological damage prior to the onset of advanced tissue injury. Necrotic cells, on the other hand, showed widely variable intracellular electrolyte concentration patterns

  11. Studies of labelling conditions for gentamicin with sup(99m)Tc. Complexation with ruthexium. Establishment of pharmacokinetics parameters through compartmental analysis

    International Nuclear Information System (INIS)

    Carvalho, O.G. de.

    1988-01-01

    Gentamicin sulphate is an aminoglycoside antibiotic type specifically used for treatment of infections produced by Gram-negative bacterias but at the other hand it presents ototoxic reactions as a serious side effect. The main purpose of labelling gentamicin with sup(99m)Tc was to obtain a radioactive tracer to carry out biological studies and compartmental analysis of this antibiotic. The optimal labelling conditions of gentamicin sulphate with sup(99m)Tc, using sodium pertechnetate solution eluted from a sup(99)Mo- sup(99m)Tc generator, were stablished by testing different masses of antibiotic, and reduction agent (SnCl sub(2).2H sub(2)O), and also different reaction time and final labelling PH. The same labelling procedure was used with Re (amonium perrenate) in order to obtain some semi-quantitative approximations of the chemical structure of the complex formed, since Re and Tc present similar chemical characteristics. In this way it is possible to suggest the role that the groups NH2 and C-O bonding of the gentamicin play in the complexation process. From the studies of the biological uptake of sup(99m)Tc-gentamicin sulphate in rats, the kidneys showed the highest affinity for the antibiotic. The maximum uptake was observed in 180 to 240 minutes followed by a decrease of it afterwards. For the dose and time used, no significative uptake by the auricular region was detected. Curve of plasma decay of sup(99m)Tc-gentamicin was obtained, and from the exponentials of each beanch of this curve respective half-lives were calculated. Furthermore the apparent volume of distribution was determined, and with the residual radioactivity in the body, the biological half-life and total clearance were obtained. The distribution of sup(99m)Tc-gentamicin in rats was set in a bi-compartments in addition to a retention one for the 24 hours time interval studied. (author)

  12. Evaluation of protective effect of hydroalcoholic extract of Crocus sativus petals on preventing of gentamicin induced peliosis hepatis and hepatic telangiectasis in rats: short communication

    Directory of Open Access Journals (Sweden)

    Arash Omidi

    2013-02-01

    Full Text Available Peliosis hepatis is a rare liver disease characterized by blood-filled cavities scattered irregularly throughout the liver. Risk factors for peliosis include chronic illness such as AIDS, tuberculosis, cancer also use of some drugs such as anabolic steroids and azathioprine. The aim of the present study was to evaluate the curative properties of crocus sativus petals on induced peliosis hepatis in rats. Thirty two male Wistar rats (weight: 180-220 g were randomly divided into four equal groups: group 1 (healthy group received only IP normal saline, group2 received IP 80mg/kg.bw gentamicin, group3 IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract, and group 4 was given IP 80mg/kg.bw gentamicin+ 40mg/kg crocus sativus petal extract. At the end of the experiment, the rats were anesthetized and their blood samples were collected through cardiac puncture for AST and ALT measurement.Then, the livers of the subjects were excised and fixed in formalin. It was found that AST significantly increased in gentamicin group (P<0.05 compared to the healthy group and groups treated by means of crocus sativus petal extract .Moreover, there was no significant differences between the groups administered the extract and those given gentamicin. Histologically,heterogeneous multiple blood-filled cavities were observed in gentamicin group (2 and the treatment groups (3 and 4. The results of the present study show that doses of hydroalcoholic extract of crocus sativus do not effect on peliosis hepatic and telangiectasis due to gentamicin sulfate in rats

  13. CT evaluation of the intraperitoneal fluid distribution

    Energy Technology Data Exchange (ETDEWEB)

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

    1982-07-01

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

  14. Effect of platelet activating factor antagonist treatment on gentamicin nephrotoxicity

    Directory of Open Access Journals (Sweden)

    A. Rodriguez-Barbero

    1992-01-01

    Full Text Available To assess whether PAF could be involved in the gentamicin-induced nephrotoxicity, we have studied the effect of PAF antagonist BN-52021 on renal function in rats after gentamicin (GENTA treatment. Experiments were completed in 21 Wistar rats divided into three groups: group GENTA was injected with gentamicin 100 mg kg−1 body wt/day s.c. for 6 days. Group GENTA + BN received gentamicin and BN-52021 i.p. 5 mg kg−1 body wt/day. A third group served as control. Rats were placed in meta-bolic cages and plasma creatinine and creatinine clearance were measured daily. GENTA group showed a progressive increase in plasma creatinine, a drop in creatinine clearance and an increase in urinary excretion of N-acetyl-β-D-glucosaminidase and alkaline phosphatase. GENTA + BN group showed a lesser change in plasma creatinine and a creatinine clearance, but no difference with GENTA group in urinary excretion of NAG and AP were observed. Histological examination revealed a massive cortical tubular necrosis in rats treated with gentamicin, whereas in BN-52021 injected animals tubular damage was markedly attenuated. The present results suggest a role for PAF in the gentamicininduced nephro-toxicity.

  15. Effect of basic amino acids and aminoglycosides on 3H-gentamicin uptake in cortical slices of rat and human kindney

    International Nuclear Information System (INIS)

    Bennett, W.M.; Plamp, C.E.; Elliott, W.C.; Parker, R.A.; Porter, G.A.

    1982-01-01

    The uptake of 3 H-gentamicin was assessed in renal cortical slices of Fischer 344 male rats and four human cadaver kidneys not utilized for renal transplantation. In both species the uptake was maximal at 90 min and maintained a steady state therafter. The characteristics of the energy-dependent component of 3 H-gentamicin uptake were not altered by various basic amino acids, but competitive inhibition was induced by other aminoglycosides in a dose-dependent fashion. Thus aminoglycosides appear to share a transport process that is distinct from those of organic bases or other cationic substances. In addition, under the experimental conditions employed, the basolateral membranes of the tubular cell is capable of energy-dependent uptake of gentamicin. The role of this route of cellular uptake of aminoglycoside in clinical nephrotoxicity is speculative

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

    Science.gov (United States)

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

    2016-12-01

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

  17. Antibiotic disposition in experimental pneumonic pasteurellosis: gentamicin and tylosin.

    Science.gov (United States)

    Burrows, G E; Barto, P B; Martin, B

    1986-01-01

    The effects of severe respiratory disease on the disposition of antibiotics were evaluated using two drugs chosen because of their widely differing solubility characteristics. The experiments were carried out in series, using five calves for each drug. The drugs were given to seven week old calves before and after induction of pneumonia by bilateral intrapulmonary administration of 3 mL of 5 X 10(7) colony forming units of Pasteurella haemolytica. Following inoculation, the calves developed clinical signs of pneumonia and were given gentamicin (5 mg/kg) or tylosin (10 mg/kg) 48, 60 and 72 hours after Pasteurella administration. There was a statistically significant decrease in distribution rate but not elimination rate of gentamicin. For tylosin, there was a significant increase in elimination rate. These results indicate the kinetics of tylosin but not gentamicin are sufficiently altered as to support a need for increased frequency of administration with severe respiratory disease in calves. Images Fig. 2. PMID:3756673

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

    African Journals Online (AJOL)

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

  19. Effect of nettle (Urtica dioica extract on gentamicin induced nephrotoxicity in male rabbits

    Directory of Open Access Journals (Sweden)

    Nadia Abdulkarim Salih

    2015-09-01

    Conclusions: Therefore, it can be assumed that the nephroprotective effect shown by nettle in gentamicin-induced nephrotoxicity can reserve intracellular levels of biological pathways and supportively enhance excretion of toxic levels of gentamicin.

  20. Thymus morphometry of New Zealand White Rabbits treated with gentamicin

    Directory of Open Access Journals (Sweden)

    Matheus Henrique Magalhães Silva

    2010-09-01

    Full Text Available The aim of this study was to evaluate the morphometry of cortical and medullary thymic lobes individualized by determination of area (μm2, perimeter (μm, maximum and minimum diameter (μm and shape factor in New Zealand White rabbits. The spleens of ten rabbits treated with gentamicin and ten control rabbits (males and females were histologically processed. The gentamicin dosage and the time of administration of this aminoglicoside were according to therapeutic recommendation. This antibiotic did not cause any alteration in the morphometry of the spleen, and it seemed not to be an immunosuppressive drug.

  1. Thymus morphometry of New Zealand White Rabbits treated with gentamicin

    Directory of Open Access Journals (Sweden)

    Matheus Henrique Magalhães Silva

    2010-01-01

    Full Text Available The aim of this study was to evaluate the morphometry of cortical and medullary thymic lobes individualized by determination of area (µm2, perimeter (µm, maximum and minimum diameter (µm and shape factor in New Zealand White rabbits. The spleens of ten rabbits treated with gentamicin and ten control rabbits (males and females were histologically processed. The gentamicin dosage and the time of administration of this aminoglicoside were according to therapeutic recommendation. This antibiotic did not cause any alteration in the morphometry of the spleen, and it seemed not to be an immunosuppressive drug.

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

    Science.gov (United States)

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

    2016-08-06

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

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

    Science.gov (United States)

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

    2016-01-01

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

  4. Simvastatin protects auditory hair cells from gentamicin-induced toxicity and activates Akt signaling in vitro

    Directory of Open Access Journals (Sweden)

    Brand Yves

    2011-11-01

    Full Text Available Abstract Background Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, known as statins, are commonly used as cholesterol-lowering drugs. During the past decade, evidence has emerged that statins also have neuroprotective effects. Research in the retina has shown that simvastatin, a commonly used statin, increases Akt phosphorylation in vivo, indicating that the PI3K/Akt pathway contributes to the protective effects achieved. While research about neuroprotective effects have been conducted in several systems, the effects of statins on the inner ear are largely unknown. Results We evaluated whether the 3-hydroxy-3-methylglutaryl-coenzyme A reductase is present within the rat cochlea and whether simvastatin is able to protect auditory hair cells from gentamicin-induced apoptotic cell death in a in vitro mouse model. Furthermore, we evaluated whether simvastatin increases Akt phosphorylation in the organ of Corti. We detected 3-hydroxy-3-methylglutaryl-coenzyme A reductase mRNA in organ of Corti, spiral ganglion, and stria vascularis by reverse transcriptase-polymerase chain reaction (RT-PCR. Moreover, we observed a dose-dependent and significant reduction of hair cell loss in organs of Corti treated with simvastatin in addition to gentamicin, as compared to samples treated with gentamicin alone. The protective effect of simvastatin was reversed by addition of mevalonate, a downstream metabolite blocked by simvastatin, demonstrating the specificity of protection. Finally, Western blotting showed an increase in organ of Corti Akt phosphorylation after simvastatin treatment in vitro. Conclusion These results suggest a neuroprotective effect of statins in the inner ear, mediated by reduced 3-hydroxy-3-methylglutaryl-coenzyme A reductase metabolism and Akt activation.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

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

  6. Effect of gentamicin and levels of ambient sound on hearing screening outcomes in the neonatal intensive care unit: A pilot study.

    Science.gov (United States)

    Garinis, Angela C; Liao, Selena; Cross, Campbell P; Galati, Johnathan; Middaugh, Jessica L; Mace, Jess C; Wood, Anna-Marie; McEvoy, Lindsey; Moneta, Lauren; Lubianski, Troy; Coopersmith, Noe; Vigo, Nicholas; Hart, Christopher; Riddle, Artur; Ettinger, Olivia; Nold, Casey; Durham, Heather; MacArthur, Carol; McEvoy, Cynthia; Steyger, Peter S

    2017-06-01

    Hearing loss rates in infants admitted to neonatal intensive care units (NICU) run at 2-15%, compared to 0.3% in full-term births. The etiology of this difference remains poorly understood. We examined whether the level of ambient sound and/or cumulative gentamicin (an aminoglycoside) exposure affect NICU hearing screening results, as either exposure can cause acquired, permanent hearing loss. We hypothesized that higher levels of ambient sound in the NICU, and/or gentamicin dosing, increase the risk of referral on the distortion product otoacoustic emission (DPOAE) assessments and/or automated auditory brainstem response (AABR) screens. This was a prospective pilot outcomes study of 82 infants (sound pressure level dosimeter was used to collect daily sound exposure in the NICU for each neonate. Gentamicin dosing was also calculated for each infant, including the total daily dose based on body mass (mg/kg/day), as well as the total number of treatment days. DPOAE and AABR assessments were conducted prior to discharge to evaluate hearing status. Exclusion criteria included congenital infections associated with hearing loss, and congenital craniofacial or otologic abnormalities. The mean level of ambient sound was 62.9 dBA (range 51.8-70.6 dBA), greatly exceeding American Academy of Pediatrics (AAP) recommendation of 4172 Hz) was 44%. DPOAE referrals were significantly greater for infants receiving >2 days of gentamicin dosing compared to fewer doses (p = 0.004). The effect of sound exposure and gentamicin treatment on hearing could not be determined due to the low number of NICU infants without gentamicin exposure (for control comparisons). All infants were exposed to higher levels of ambient sound that substantially exceed AAP guidelines. More referrals were generated by DPOAE assessments than with AABR screens, with significantly more DPOAE referrals with a high-frequency F2 range, consistent with sound- and/or gentamicin-induced cochlear dysfunction. Adding

  7. Potential Renoprotective Effects of Rosemary and Thyme Against Gentamicin Toxicity in Rats.

    Science.gov (United States)

    Abdel-Azeem, Amal S; Hegazy, Amany M; Zeidan, Hala M; Ibrahim, Khadiga S; El-Sayed, Eman M

    2017-07-04

    Gentamicin (GM) is a drug used commonly against gram-negative bacteria. Its therapeutic use is mainly limited by its nephrotoxicity. This investigation was aimed at evaluating the nephroprotective effects of rosemary (RM; Rosmarinus officinalis) and thyme (TV; Thymus vulgaris) against GM toxicity. Rats were divided into four groups. Normal control group was treated intraperitoneally (i.p.) with saline; positive control group was administered GM 60 mg/kg/day i.p.; RM group was co-administered 8% RM aqueous extract, 10 mL/kg/day, orally with GM; and TV group was co-administered 8% TV aqueous extract orally, 10 mL/kg/day with GM. Both RM and TV groups extracted significantly ameliorated plasma kidney function biomarkers, and reduced malondialdhyde and glucose levels. Meanwhile, RM extract significantly modulated the electrolyte concentration and increased plasma insulin levels as compared with the GM group. However, the aqueous extract of RM showed more pronounced effects than TV extract. Our data were confirmed by histopathological examination and deoxyribonucleic acid (DNA) fragmentation analysis. Deleterious histopathological changes and increased DNA fragmentation induced by GM treatment were markedly controlled by the co-administration of RM and TV. Such renoprotective influence of RM and TV suggests their concurrent supplementation with GM therapy to limit GM toxicity.

  8. 77 FR 3598 - Ophthalmic and Topical Dosage Form New Animal Drugs; Gentamicin and Betamethasone Spray

    Science.gov (United States)

    2012-01-25

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration 21 CFR Part 524 [Docket No... veterinary prescription use of gentamicin sulfate and betamethasone valerate topical spray in dogs. DATES... prescription use of Gentamicin Topical Spray (gentamicin sulfate and betamethasone valerate) in dogs. Sparhawk...

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  10. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis.

    Science.gov (United States)

    González-Vázquez, Patricia; Larrañeta, Eneko; McCrudden, Maelíosa T C; Jarrahian, Courtney; Rein-Weston, Annie; Quintanar-Solares, Manjari; Zehrung, Darin; McCarthy, Helen; Courtenay, Aaron J; Donnelly, Ryan F

    2017-11-10

    Neonatal infections are a leading cause of childhood mortality in low-resource settings. World Health Organization guidelines for outpatient treatment of possible serious bacterial infection (PSBI) in neonates and young infants when referral for hospital treatment is not feasible include intramuscular gentamicin (GEN) and oral amoxicillin. GEN is supplied as an aqueous solution of gentamicin sulphate in vials or ampoules and requires health care workers to be trained in dose calculation or selection of an appropriate dose based on the patient's weight band and to have access to safe injection supplies and appropriate sharps disposal. A simplified formulation, packaging, and delivery method to treat PSBI in low-resource settings could decrease user error and expand access to lifesaving outpatient antibiotic treatment for infants with severe infection during the neonatal period. We developed dissolving polymeric microneedles (MN) arrays to deliver GEN transdermally. MN arrays were produced from aqueous blends containing 30% (w/w) of GEN and two polymers approved by the US Food and Drug Administration: sodium hyaluronate and poly(vinylpyrrolidone). The arrays (19×19 needles and 500μm height) were mechanically strong and were able to penetrate a skin simulant to a depth of 378μm. The MN arrays were tested in vitro using a Franz Cell setup delivering approximately 4.45mg of GEN over 6h. Finally, three different doses (low, medium, and high) of GEN delivered by MN arrays were tested in an animal model. Maximum plasma levels of GEN were dose-dependent and ranged between 2 and 5μg/mL. The time required to reach these levels post-MN array application ranged between 1 and 6h. This work demonstrated the potential of dissolving MN arrays to deliver GEN transdermally at therapeutic levels in vivo. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  11. Pharmacokinetic modeling of gentamicin in treatment of infective endocarditis: Model development and validation of existing models.

    Directory of Open Access Journals (Sweden)

    Anna Gomes

    Full Text Available Gentamicin shows large variations in half-life and volume of distribution (Vd within and between individuals. Thus, monitoring and accurately predicting serum levels are required to optimize effectiveness and minimize toxicity. Currently, two population pharmacokinetic models are applied for predicting gentamicin doses in adults. For endocarditis patients the optimal model is unknown. We aimed at: 1 creating an optimal model for endocarditis patients; and 2 assessing whether the endocarditis and existing models can accurately predict serum levels. We performed a retrospective observational two-cohort study: one cohort to parameterize the endocarditis model by iterative two-stage Bayesian analysis, and a second cohort to validate and compare all three models. The Akaike Information Criterion and the weighted sum of squares of the residuals divided by the degrees of freedom were used to select the endocarditis model. Median Prediction Error (MDPE and Median Absolute Prediction Error (MDAPE were used to test all models with the validation dataset. We built the endocarditis model based on data from the modeling cohort (65 patients with a fixed 0.277 L/h/70kg metabolic clearance, 0.698 (±0.358 renal clearance as fraction of creatinine clearance, and Vd 0.312 (±0.076 L/kg corrected lean body mass. External validation with data from 14 validation cohort patients showed a similar predictive power of the endocarditis model (MDPE -1.77%, MDAPE 4.68% as compared to the intensive-care (MDPE -1.33%, MDAPE 4.37% and standard (MDPE -0.90%, MDAPE 4.82% models. All models acceptably predicted pharmacokinetic parameters for gentamicin in endocarditis patients. However, these patients appear to have an increased Vd, similar to intensive care patients. Vd mainly determines the height of peak serum levels, which in turn correlate with bactericidal activity. In order to maintain simplicity, we advise to use the existing intensive-care model in clinical practice to

  12. Spirulina platensis protects against gentamicin-induced nephrotoxicity in rats.

    Science.gov (United States)

    Karadeniz, Ali; Yildirim, Abdulkadir; Simsek, Nejdet; Kalkan, Yildiray; Celebi, Fikret

    2008-11-01

    The present study aimed to investigate the protective effect of Spirulina platensis (SP) on gentamicin sulphate (GS)-induced changes in the levels of lipid peroxidation and endogenous antioxidants in the kidney of rats. Sprague-Dawley rats were treated in separate groups as follows for 7 consecutive days: control (C), gentamicin sulphate (100 mg/kg i.p.) (GS), Spirulina platensis (1000 mg/kg orally) (SP) and Spirulina platensis (1000 mg/kg orally) plus gentamicin sulphate (100 mg/kg i.p.) (SP + GS). The degree of protection was evaluated by determining the effects of Spirulina platensis on malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPX) and nitric oxide (NO), and plasma creatinine and urea levels were estimated in kidney homogenates to evaluate antioxidant activity, and the kidney was histologically examined as well. Spirulina platensis elicited significant nephroprotective activity by decreasing lipid peroxidation (MDA) and elevated the levels of GSH, SOD, GPX, NO, creatinine and urea. Furthermore, these biochemical observations were supplemented by histological examination of the rat kidneys. In conclusion, the present study indicates a very important role of reactive oxygen species (ROS) and the relation to renal dysfunction and point to the therapeutic potential of Spirulina platensis in gentamicin sulphate induced nephrotoxicity.

  13. Evaluation of Gentamicin-Entrapped Solid Lipid Microparticles ...

    African Journals Online (AJOL)

    Keywords: Solid lipid microparticles, Gentamicin, Capra hircus, Phospholipon® 90 G, Solidified reverse micellar solution. Tropical Journal of Pharmaceutical .... while batches D1–D3 are unloaded (zero- drug) SLMs; P90G = Phospholipon® 90G, GF = goat fat; each formulation was made up to 100 %w/w with distilled water ...

  14. Pharmacokinetics of gentamicin eluted from a regenerating bone graft substitute

    DEFF Research Database (Denmark)

    Stravinskas, M; Horstmann, P; Ferguson, J

    2016-01-01

    in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer's solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution...

  15. Developmental pharmacokinetics of gentamicin in preterm and term neonates

    DEFF Research Database (Denmark)

    Nielsen, Elisabet I; Sandström, Marie; Honoré, Per Hartvig

    2009-01-01

    as having a significant influence on the central volume of distribution, with a preterm neonate having a larger central volume of distribution per kilogram of bodyweight than a term neonate. Cystatin C and creatinine were not correlated with gentamicin clearance in this study population. The external...

  16. Instrumental characterization of the smectite clay–gentamicin hybrids

    Indian Academy of Sciences (India)

    The resulting structural/microstructural properties and the potential for introducing gentamicin between smectite clay layers were investigated by means of X-ray ... infrared spectroscopic techniques and transmission electron microscopy and scanning electron microscopy with energy-dispersive spectroscopy X-ray analysis.

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

    Directory of Open Access Journals (Sweden)

    Xinghong Yang

    2011-01-01

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

  18. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    Science.gov (United States)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; de, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-03-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis.

  19. Attenuation of Pseudomonas aeruginosa biofilm formation by Vitexin: A combinatorial study with azithromycin and gentamicin

    Science.gov (United States)

    Das, Manash C.; Sandhu, Padmani; Gupta, Priya; Rudrapaul, Prasenjit; De, Utpal C.; Tribedi, Prosun; Akhter, Yusuf; Bhattacharjee, Surajit

    2016-01-01

    Microbial biofilm are communities of surface-adhered cells enclosed in a matrix of extracellular polymeric substances. Extensive use of antibiotics to treat biofilm associated infections has led to the emergence of multiple drug resistant strains. Pseudomonas aeruginosa is recognised as a model biofilm forming pathogenic bacterium. Vitexin, a polyphenolic group of phytochemical with antimicrobial property, has been studied for its antibiofilm potential against Pseudomonas aeruginosa in combination with azithromycin and gentamicin. Vitexin shows minimum inhibitory concentration (MIC) at 260 μg/ml. It’s antibiofilm activity was evaluated by safranin staining, protein extraction, microscopy methods, quantification of EPS and in vivo models using several sub-MIC doses. Various quorum sensing (QS) mediated phenomenon such as swarming motility, azocasein degrading protease activity, pyoverdin and pyocyanin production, LasA and LasB activity of the bacteria were also evaluated. Results showed marked attenuation in biofilm formation and QS mediated phenotype of Pseudomonas aeruginosa in presence of 110 μg/ml vitexin in combination with azithromycin and gentamicin separately. Molecular docking of vitexin with QS associated LuxR, LasA, LasI and motility related proteins showed high and reasonable binding affinity respectively. The study explores the antibiofilm potential of vitexin against P. aeruginosa which can be used as a new antibiofilm agent against microbial biofilm associated pathogenesis. PMID:27000525

  20. Influence of the irradiation of rabbit meat on unbound ampicillin and gentamicin contents

    International Nuclear Information System (INIS)

    Pavlov, A.; Vashin, I.; Lashev, L.; Todorov, B.

    1993-01-01

    A most interesting fact is the tendency toward higher levels of unbound ampicillin in meat after the irradiation, especially at doses of 1 and 1.5 kGy. A probable explanation could be the release of protein-bound ampicillin. Such a release, however, is not a result from protein destruction, because according to data available, it could be achieved only when irradiation doses are above 5 kGy. First, change lipids, but proteins could be degradated when doses are up to 1500 kGy. Another evidence supporting this suggestion, is the fact that when irradiated with 2 kGy, the level of unbound antibiotic is only 1.22 mg/kg. So, with medium doses of irradiation, release of bound ampicillin is probably potentiated. Lower levels of free ampicillin in meat, irradiated with a dose of 2 kGy could be explained with the destruction of active substance at higher doses of radiation. In conclusion, it could be stated that both antibiotics have a different pattern of behaviour when irradiated with gamma rays and when stored at minus temperatures. If there are no gentamicin residues in irradiated and stored for a long time meat, it follows that there is no antibiotic in meat. For ampicillin this statement could be not true. (orig.)

  1. Evaluation of effects on the peritoneum after intraperitoneal α-radioimmunotherapy with (211)At

    DEFF Research Database (Denmark)

    Cederkrantz, Elin; Angenete, Eva; Bäck, Tom

    2012-01-01

    The introduction of the short-lived α-emitter (211)At to intraperitoneal radioimmunotherapy has raised the issue of the tolerance dose of the peritoneum. The short range of the α-particles (70 μm) and the short half-life (7.21 h) of the nuclide yield a dose distribution in which the peritoneum......-ethylenediamine tetraacetic acid, was measured for evaluation of the small solute transport capacity of the peritoneal membrane. The macroscopic status of the peritoneum and the mesenteric windows was documented when the mice were sacrificed. Biopsies of the peritoneum were taken for morphology and immunohistochemical...

  2. Antibacterial Efficacy of a New Gentamicin-Coating for Cementless Prostheses Compared to Gentamicin-Loaded Bone Cement

    NARCIS (Netherlands)

    Neut, Danielle; Dijkstra, Rene J. B.; Thompson, Jonathan I.; van der Mei, Henny C.; Busscher, Henk J.

    2011-01-01

    Cementless prostheses are increasingly popular but require alternative prophylactic measures than the use of antibiotic-loaded bone cements. Here, we determine the 24-h growth inhibition of gentamicin-releasing coatings from grit-blasted and porous-coated titanium alloys, and compare their

  3. Ameliorative effects of metformin on renal histologic and biochemical alterations of gentamicin-induced renal toxicity in Wistar rats

    Directory of Open Access Journals (Sweden)

    Fatemeh Ghaed Amini

    2012-01-01

    Full Text Available Background: The aim of this study was to test the potential properties of metformin (MF to protect the kidney from gentamicin (GM-induced renal toxicity. Materials and Methods: In this preclinical study, 50 male Wistar rats were randomly divided into five groups of 10 rats in each. In the first group (group I, they were kept in the same condition as others without receiving drugs for 10 days. In group II, the rats were injected intraperitoneally with 100 mg/kg/day of GM for 10 consecutive days. Group III rats received 100 mg/kg/day MF orally for 10 days. In group IV, the rats received GM (100 mg/kg; intraperitoneally for 10 days and 100 mg/kg/day MF orally for the next 10 days. In the last group (group V, the rats received a combination of GM 100 mg/kg/day intraperitoneally and MF 100 mg/kg/day orally for 10 days simultaneously. Serum blood urea nitrogen (BUN and creatinine (Cr values were measured and renal tissues of the animals were processed for light microscope examination. Results: The levels of BUN in groups II, IV, and V, and also the serum level of Cr in groups II and V were increased significantly after the experiment. Furthermore, post-treatment with MF or co-treatment with MF could prevent the elevation of serum BUN and Cr induced by GM and also attenuates the damage score (P < 0.05. Conclusions: MF may prevent or ameliorate GM-induced acute renal failure, and therefore it might be beneficial in patients under treatment with this medicine.

  4. Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities.

    Science.gov (United States)

    Alhariri, Moayad; Majrashi, Majed A; Bahkali, Ali H; Almajed, Faisal S; Azghani, Ali O; Khiyami, Mohammad A; Alyamani, Essam J; Aljohani, Sameera M; Halwani, Majed A

    2017-01-01

    We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca . The liposomal gentamicin formulations were prepared by the dehydration-rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from -0.22 to -31.7 mV. Gentamicin encapsulation efficiency inside the liposomal formulation ranged from 1.8% to 43.6%. The liposomes retained >60% of their gentamicin content during the 48 h time period. The minimum inhibitory concentration of neutral formulation was lower than that of free gentamicin (0.25 versus 1 mg/L for P. aeruginosa and 0.5 versus 1 mg/L for K. oxytoca ). The negatively charged formulation exhibited the same bacteriostatic concentration as that of free gentamicin. The minimum bactericidal concentration of neutral liposomes on planktonic bacterial culture was twofold lower than that of free gentamicin, whereas the negatively charged formulations were comparable to free gentamicin. The killing time curve values for the neutral negatively charged formulation against planktonic P. aeruginosa and K. oxytoca were better than those of free gentamicin. Furthermore, liposomal formulations prevent the biofilm-formation ability of these strains better than free gentamicin. In summary, liposomal

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

    Science.gov (United States)

    Tode, V; Voinea, F; Marin, O

    2001-01-01

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

  6. Comparison of efficacy of intraperitoneal instillation of bupivacaine ...

    African Journals Online (AJOL)

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

  7. Gentamicin binds to the megalin receptor as a competitive inhibitor using the common ligand binding motif of complement type repeats

    DEFF Research Database (Denmark)

    Dagil, Robert; O'Shea, Charlotte; Nykjær, Anders

    2013-01-01

    megalin and investigated its interaction with gentamicin. Using NMR titration data in HADDOCK, we have generated a three-dimensional model describing the complex between megalin and gentamicin. Gentamicin binds to megalin with low affinity and exploits the common ligand binding motif previously described...... to megalin is highly similar to gentamicin binding to calreticulin. We discuss the impact of this novel insight for the future structure-based design of gentamicin antagonists....

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

    DEFF Research Database (Denmark)

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

    2016-01-01

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

  9. Protective role of misoprostol in prevention of gentamicin ototoxicity.

    Science.gov (United States)

    Dogan, Murat; Polat, Halil; Yasar, Mehmet; Bayram, Ali; Karatas, Duran; Hira, İbrahim; Kale, Ahmet; Senel, Fatma; Özcan, İbrahim

    2017-05-01

    To demonstrate potential protective effect of misoprostol on cochlear toxicity caused by gentamicin with electrophysiological tests and histopathological studies. The study included 80 ears of 40 rats with normal hearing threshold and DPOAE value in both ears. Animals were assigned into 4 groups. The rats were randomized into 4 groups. Group I (n = 10): Gentamicin, Group II (n = 10): Gentamicin plus misoprostol, Group III (n = 10): Saline; Group IV (n = 10): Misoprostol. All drugs used in the study were given once daily for 15 days. DPOAE and ABR measurements were repeated after drug administration. Subsequently, the rats' cochleae were examined histopathologically. Baseline DPOAE and ABR values were compared to those obtained after drug exposure and cochlear toxicity was evaluated in electrophysiological manner. When At baseline, there were no significant differences in DPOAE responses at frequencies of 1001, 1501, 2002, 3003, 4004, 6006 and 7996 Hz among groups. However In DPOAE test, statistically significant difference was observed between the pre-study basal values and post-study results in groups other than gentamicin + misoprostol group. Additionally, It was found that there was a significant difference in DPOAE response at frequency of 4004 Hz obtained at baseline and after drug exposure according to measurements of epithelial vacuolization in stria vascularis. While ABR threshold values were compared at baseline, there were no significant difference in ABR threshold values of left and right ear between groups. Histopathologically it was also found that there were significant differences measurements of epithelial vacuolization in stria vascularis and inflammation among groups (p misoprostol, a potent antioxidant, has protective effect against cochlear damage, and that may be a safe alternative. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. The impact of storage conditions upon gentamicin coated antimicrobial implants.

    Science.gov (United States)

    Mullins, Nicholas D; Deadman, Benjamin J; Moynihan, Humphrey A; McCarthy, Florence O; Lawrence, Simon E; Thompson, Jonathan; Maguire, Anita R

    2016-12-01

    A systematic approach was developed to investigate the stability of gentamicin sulfate (GS) and GS/poly (lactic-co-glycolic acid) (PLGA) coatings on hydroxyapatite surfaces. The influence of environmental factors (light, humidity, oxidation and heat) upon degradation of the drug in the coatings was investigated using liquid chromatography with evaporative light scattering detection and mass spectrometry. GS coated rods were found to be stable across the range of environments assessed, with only an oxidizing atmosphere resulting in significant changes to the gentamicin composition. In contrast, rods coated with GS/PLGA were more sensitive to storage conditions with compositional changes being detected after storage at 60 °C, 75% relative humidity or exposure to light. The effect of γ-irradiation on the coated rods was also investigated and found to have no significant effect. Finally, liquid chromatography-mass spectrometry analysis revealed that known gentamines C 1 , C 1a and C 2 were the major degradants formed. Forced degradation of gentamicin coatings did not produce any unexpected degradants or impurities.

  11. 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.

  12. Decrease in Shiga toxin expression using a minimal inhibitory concentration of rifampicin followed by bactericidal gentamicin treatment enhances survival of Escherichia coli O157:H7-infected BALB/c mice

    Directory of Open Access Journals (Sweden)

    Abdelnoor Alexander M

    2011-09-01

    Full Text Available Abstract Background Treatment of Escherichia coli O157:H7 infections with antimicrobial agents is controversial due to an association with potentially fatal sequelae. The production of Shiga toxins is believed to be central to the pathogenesis of this organism. Therefore, decreasing the expression of these toxins prior to bacterial eradication may provide a safer course of therapy. Methods The utility of decreasing Shiga toxin gene expression in E. coli O157:H7 with rifampicin prior to bacterial eradication with gentamicin was evaluated in vitro using real-time reverse-transcription polymerase chain reaction. Toxin release from treated bacterial cells was assayed for with reverse passive latex agglutination. The effect of this treatment on the survival of E. coli O157:H7-infected BALB/c mice was also monitored. Results Transcription of Shiga toxin-encoding genes was considerably decreased as an effect of treating E. coli O157:H7 in vitro with the minimum inhibitory concentration (MIC of rifampicin followed by the minimum bactericidal concentration (MBC of gentamicin (> 99% decrease compared to treatment with gentamicin alone (50-75% decrease. The release of Shiga toxins from E. coli O157:H7 incubated with the MIC of rifampicin followed by addition of the MBC of gentamicin was decreased as well. On the other hand, the highest survival rate in BALB/c mice infected with E. coli O157:H7 was observed in those treated with the in vivo MIC equivalent dose of rifampicin followed by the in vivo MBC equivalent dose of gentamicin compared to mice treated with gentamicin or rifampicin alone. Conclusions The use of non-lethal expression-inhibitory doses of antimicrobial agents prior to bactericidal ones in treating E. coli O157:H7 infection is effective and may be potentially useful in human infections with this agent in addition to other Shiga toxin producing E. coli strains.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

  14. Protective effect of ginger on gentamicin-induced apoptosis in testis of rats.

    Science.gov (United States)

    Zahedi, Afshin; Fathiazad, Fatemeh; Khaki, Arash; Ahmadnejad, Behnam

    2012-01-01

    Ginger, the rhizome of Zingiber officinale, is one of the most widely used spices for various foods and as an herbal medicine in Asian countries. It has been shown that ginger has antioxidant power. Gentamicin is an aminoglycoside antibiotic with a very broad spectrum against microbial pathogens, especially the gram-negative. Many studies revealed that gentamicin induces an oxidative stress-status in the testis by increasing free radical formation and lipid peroxidation. The present study was designed to investigate on the effects of Ginger as a natural anioxidant on testis apoptosis after treatment with gentamicin in rats. In order to study the recovery effects of ginger on testis apoptosis after treatment with gentamicin 40 adult Wistar male rats were selected and randomly divided into four groups. Normal salin control (group I) (n=10), gentamicin control (group II), ginger control (group III) and gentamicin + ginger (group IV) each 10 rats. There was observation of negative effect of Gentamicin on testis histology in rats. The results revealed that there was a significant increase in apoptosis in group III when compared with other groups (P<0.05).However, ginger could decrease apoptosis in group IV that received 100mg/kg/rat of Ginger. Regarding the results, it is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections.

  15. Protective Effect of Ginger on Gentamicin-Induced Apoptosis in Testis of Rats

    Directory of Open Access Journals (Sweden)

    Afshin Zahedi

    2012-08-01

    Full Text Available Purpose: Ginger, the rhizome of Zingiber officinale, is one of the most widely used spices for various foods and as an herbal medicine in Asian countries. It has been shown that ginger has antioxidant power. Gentamicin is an aminoglycoside antibiotic with a very broad spectrum against microbial pathogens, especially the gram-negative. Many studies revealed that gentamicin induces an oxidative stress-status in the testis by increasing free radical formation and lipid peroxidation. The present study was designed to investigate on the effects of Ginger as a natural anioxidant on testis apoptosis after treatment with gentamicin in rats. Methods: In order to study the recovery effects of ginger on testis apoptosis after treatment with gentamicin 40 adult Wistar male rats were selected and randomly divided into four groups. Normal salin control (group I (n=10, gentamicin control (group II, ginger control (group III and gentamicin + ginger (group IV each 10 rats. There was observation of negative effect of Gentamicin on testis histology in rats. Results: The results revealed that there was a significant increase in apoptosis in group III when compared with other groups (P<0.05.However, ginger could decrease apoptosis in group IV that received 100mg/kg/rat of Ginger. Conclusion: Regarding the results, it is recommended that administration of ginger with gentamicin might be beneficial in men who receive gentamicin to treat infections.

  16. EXPERIMENTAL CONFIRMATION FOR SELECTION OF IRRADIATION REGIMENS FOR INTRAPERITONEAL PHOTODYNAMIC THERAPY WITH PORPHYRIN AND PHTHALOCYANINE PHOTOSENSITIZERS

    Directory of Open Access Journals (Sweden)

    A. A. Pankratov

    2017-01-01

    Full Text Available Optimized irradiation regimens for intraperitoneal photodynamic therapy with porphyrin and phthalocyanine photosensitizers are determined in in vitro and in vivo studies.The experimental  study on НЕр2 cell line showed that reduce of power density for constant  light dose increased significantly the efficacy of photodynamic therapy (the reduce of power density from 20-80 mW/cm2 to 10 mW/cm2 had the same results (90% cell death for half as much concentration of the photosensitizer.The obtained results were confirmed in vivo in mice with grafted tumor S-37. For light dose of 90 J/cm2  and power density of 25 mW/cm2 none of animals in the experimental  group had total resorption of the tumor. For the same light dose and decrease  of power density to 12 mW/cm2  total tumor resorption was achieved in 34% of animals, 66% of animals died from phototoxic  shock. For twofold decrease  of light dose – to 45 J/cm2  with the same low-intensity power density (12 mW/cm2 we managed total tumor resorption in 100% of animals.In the following studies of optimized irradiation regimen for intrapleural photodynamic therapy the reaction of intact peritoneum of rats on photodynamic exposure was assessed and optimized parameters of laser irradiation, which did not cause necrosis and intense inflammatory reaction of peritoneum, were determined – light dose of 10 J/cm2  with power density of mW/cm2.Thus, the reasonability for use of low-intensity regimens of irradiation for intraperitoneal photodynamic therapy was confirmed experimentally with possibility of high efficacy of treatment without inflammatory reactions of peritoneum.

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    Science.gov (United States)

    Yang, George Pei Cheung

    2017-05-01

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

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

    African Journals Online (AJOL)

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  2. 21 CFR 524.1044b - Gentamicin sulfate, betamethasone valerate otic solution.

    Science.gov (United States)

    2010-04-01

    ... solution. 524.1044b Section 524.1044b Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND... NEW ANIMAL DRUGS § 524.1044b Gentamicin sulfate, betamethasone valerate otic solution. (a) Specifications. Each milliliter of solution contains gentamicin sulfate equivalent to 3 milligrams (mg...

  3. Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application.

    Science.gov (United States)

    Suzuki, Mitsuya; Ushio, Munetaka; Yamasoba, Tatsuya

    2008-07-01

    The present study showed that the molecular signal that promotes the death of cochlear hair cells (HCs) induced by intratympanic gentamicin application is significant before the manifestation of morphological and functional changes. The effect of agents that protect the HCs from aminoglycoside ototoxicity is influenced by the timing of their administration. However, morphological, functional and molecular changes in the cochlea in the early stage following aminoglycoside application have rarely been studied. Therefore, we examined the chronological changes in the cochlea following intratympanic gentamicin application. Small pieces of gelatin sponge soaked with gentamicin (40 mg/ml) were placed on the round window membrane of mature guinea pigs, and the tympanic bulla was filled with gentamicin solution. They were euthanized at 6, 12, 18, 24, and 48 h following gentamicin application. Auditory brainstem responses (ABRs) were measured before gentamicin application and immediately before euthanasia, and the extent of missing and TUNEL-positive HCs was evaluated. ABR thresholds significantly increased 18 h or later following gentamicin application, and the loss of HCs was seen at 24 and 48 h. While functional and morphological changes were not evident until 18 h after gentamicin application, substantial amounts of TUNEL-positive HCs appeared at 12 h.

  4. Relationship between the level of acquired resistance to gentamicin and synergism with amoxicillin in Enterococcus faecalis.

    Science.gov (United States)

    Aslangul, Elisabeth; Ruimy, Raymond; Chau, Françoise; Garry, Louis; Andremont, Antoine; Fantin, Bruno

    2005-10-01

    In enterococci, intrinsic low-level resistance to gentamicin does not abolish synergism with a cell wall-active antibiotic while high-level resistance due to acquired aminoglycoside-modifying enzymes does. To study the impact of intermediate levels of resistance to gentamicin (64 resistant to gentamicin by enzymatic inactivation was used as control. In in vitro killing curves experiments, gentamicin concentrations allowing bactericidal activity and synergism in combination with amoxicillin increased from 4 microg/ml (1/16th the MIC), 16 microg/ml (one-eighth the MIC), 64 microg/ml (one-quarter the MIC), and 256 microg/ml (one-half the MIC) for strains JH2-2, G1-1477, G2-1573 and G3-1688, respectively. As expected, no bactericidal effect of the combination or synergism could be obtained with strain 102. In rabbits with aortic endocarditis caused by strain G1-1477 or G2-1573, combination therapy with amoxicillin and gentamicin was significantly more active than amoxicillin alone (P resistance to gentamicin was not associated with a loss of a beneficial effect of the gentamicin-amoxicillin combination in vivo even though higher concentrations of gentamicin were necessary to achieve in vitro synergism. Therefore, the use of an MIC of 500 microg/ml as a clinical cutoff limit to predict in vivo benefit of the combination remains a simple and effective tool.

  5. Changes of the Serum and Urinary Beta2-Microglobulin in the Gentamicin Treated Patients

    International Nuclear Information System (INIS)

    Kim, S. T.; Shin, Y. T.; Chung, S. I.; Choi, K. W.; Kim, B. K.; Lee, J. S.; Lee, M. H.

    1980-01-01

    Gentamicin is useful to the Gram negative bacterial infection, but its nephrotoxicity is a serious problem and the incidence is probably increasing. The toxicity of gentamicin to the kidney is site-specific to the proximal tubule. In this study, we measured daily peak and trough level of gentamicin, serum creatinine, serum Beta 2 -microglobulin and 24-hr urine Beta 2 -microglobulin in 10 gentamicin treated patients. All the patients had their peak levels of gentamicin in the safe therapeutic range, and their trough level showed no evidence of gentamicin accumulation. There was no patient who showed his daily serum creatinine and Beta 2 -microglobulin rise significantly. But 24-hour urine Beta 2 -microglobulin showed significant rise from basal level(mean 5.8±1.62 X) on the 5th day of gentamicin treatment. Thus, serial monitoring of proximal tubular function with urinary Beta 2 -microglobulin excretion has potential value in the assessment of insults of gentamicin to this site. But clinical significance of raised urinary Beta 2 -microglobulin excretion in relation to the serum creatinine should be further studied.

  6. Gentamicin release from modified acrylic bone cements with lactose and hydroxypropylmethylcellulose.

    Science.gov (United States)

    Virto, M R; Frutos, P; Torrado, Susana; Frutos, G

    2003-01-01

    Modified polymethylmethacrylate (PMMA) bone cements formulations were prepared by including different proportions of gentamicin and release modulators such as lactose or hydroxypropylmethylcellulose (HPMC). Surface aspect, gentamicin release and porosity of these modified formulations were studied by means of scanning electron microscopy (SEM), a specially designed system for the dissolution studies of the bone cements, and mercury intrusion porosimetry. Lactose modified cements presented an irregular surface with numerous hollows and voids due to the lactose dissolution. HPMC cements presented a characteristic laminated and flaky surface. The drug release of lactose formulations was up to four-fold greater (13%) than the commercial bone cement CMW1 Gentamicin one (3%). The amount of gentamicin eluted at the first withdrawn sample ranged from 30% to 60% of total gentamicin released over the assay. Gentamicin release from lactose formulations increased as lactose percentage was increased which agree with the porosity results. Nevertheless, the use of release modulator HPMC increased porosity, but did not produce an increase in the gentamicin release. HPMC dissolution creates a surrounding sticky and viscous medium similar to a gel that makes the gentamicin release from the cement matrix difficult. Copyright 2002 Elsevier Science Ltd.

  7. Effects of gentamicin on the recovery of renal function after unilateral hydronephrosis

    Energy Technology Data Exchange (ETDEWEB)

    Seki, Nobumitsu [Ehime Univ., Shigenobu (Japan). School of Medicine

    2002-06-01

    Urinary tract infection is one of complications in hydronephrosis, and antibiotics such as gentamicin are indicated for the treatment. However, gentamicin is known to cause drug-induced nephropathy. Using a rat kidney model, we investigated the effects of gentamicin treatment on the functional recovery from unilateral hydronephrosis. Quantitative separate renal function study by means of Technetium-99m DMSA renoscintigraphy revealed that contralateral kidney was affected by the treatment right after the release of complete ureteral obstruction. Moreover, in the case of incomplete ureteral obstruction, bilateral kidneys were affected by the treatment. Morphological studies using in situ DNA3' -end labeling and immunohistochemical methods showed that regeneration in the bilateral kidney followed gentamicin treatment right after the release. These results suggest that we should take account of separate renal function failure after gentamicin administration in the perihydronephrotic periods. (author)

  8. Intraperitoneal fipronil effects on liver histopathological, biochemistry and morphology in Caspian kutum, Rutilus frisii kutum (Kamenskii, 1901

    Directory of Open Access Journals (Sweden)

    R. Alijani Ardeshir

    2017-12-01

    Full Text Available Fipronil is a relatively new insecticide in agriculture with health and environmental effects. This is the first report studying effect of fipronil on fish administered via intraperitoneal route. Intraperitoneal LD50  of fipronil in 16.3 g Caspian kutum, Rutilus frisii kutum, fingerlings was determined using a total of 133 fish in 19 tanks (7 fish/tank including one control and 6 treatment groups (300, 450, 550, 650, 750, 850 mg/kg. Fish were injected intraperitoneally and monitored at 96 h. The LD50 of fipronil was 632 mg/kg in Caspian kutum. Sub-lethal test doses of 10, 20, and 30% of the LD50 at 96 h were used to assess the effect of fipronil on the fish’s liver.  The blood plasma of 90 fish were used (18 at each test dose and in controls on days 7 and 14 for biochemistry. The hepatosomatic index (HSI of the livers were obtained and histopathology done on the same days. Pyknosis, sinusoid dilation and vacuolization were common histological changes, and these changes became more severe in a time and dose dependent manner. This dependence was also observed for HSI and the liver biochemical test (alanine and aspartate transaminase. Liver histological alterations showed that fipronil can be a potential factor in liver carcinoma.

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

    Science.gov (United States)

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

    2014-10-01

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

  10. Severity of gentamicin's nephrotoxic effect on patients with infective endocarditis: a prospective observational cohort study of 373 patients

    DEFF Research Database (Denmark)

    Buchholtz, Kristine; Larsen, Carsten T; Hassager, Christian

    2009-01-01

    BACKGROUND: Gentamicin is often used to treat infective endocarditis (IE). Gentamicin is highly effective, but its applicability is reduced by its nephrotoxic effect. The aim of this study was to quantify the nephrotoxic effect of gentamicin and the association between the nephrotoxic effect...

  11. The influence of ultrasound on the release of gentamicin from antibiotic-loaded acrylic beads and bone cements

    NARCIS (Netherlands)

    Ensing, GT; Hendriks, JGE; Jongsma, JE; van Horn, [No Value; van der Mei, HC; Busscher, HJ

    2005-01-01

    Gentamicin-loaded acrylic beads are loosely placed in infected bone cavities, whereas gentamicin-loaded acrylic bone cement is used as a mechanical filler in bone to anchor prosthetic components. Both drug delivery systems are used to decrease infection rates by gentamicin release. The objective of

  12. Immunotherapeutic modulation of intraperitoneal adhesions by Asparagus racemosus.

    Directory of Open Access Journals (Sweden)

    Rege N

    1989-10-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  14. Evaluating synergy between marbofloxacin and gentamicin in Pseudomonas aeruginosa strains isolated from dogs with otitis externa.

    Science.gov (United States)

    Jerzsele, Ákos; Pásztiné-Gere, Erzsébet

    2015-03-01

    The aim of this study was to determine antimicrobial susceptibility of Pseudomonas aeruginosa strains to marbofloxacin and gentamicin, and investigate the possible synergistic, additive, indifferent or antagonistic effects between the two agents. P. aeruginosa strains can develop resistance quickly against certain antibiotics if used alone, thus the need emerges to find synergistic combinations. A total of 68 P. aeruginosa strains isolated from dogs were examined. In order to describe interactions between marbofloxacin and gentamicin the checkerboard microdilution method was utilized. The MICs (minimum inhibitory concentrations) for marbofloxacin and gentamicin were in the range 0.25-64 mg/L and 0.25-32 mg/L, respectively. The combination of marbofloxacin and gentamicin was more effective with a MIC range of 0.031-8 mg/L and a MIC90 of 1 mg/L, compared to 16 mg/L for marbofloxacin alone and 8 mg/L for gentamicin alone. The FIC (fractional inhibitory concentration) indices ranged from 0.0945 (pronounced synergy) to 1.0625 (indifference). Synergy between marbofloxacin and gentamicin was found in 33 isolates. The mean FIC index is 0.546, which represents a partial synergistic/additive effect close to the full synergy threshold. In vitro results indicate that marbofloxacin and gentamicin as partially synergistic agents may prove clinically useful in combination therapy against P. aeruginosa infections. Although marbofloxacin is not used in the human practice, the interactions between fluoroquinolones and aminoglycosides may have importance outside the veterinary field.

  15. Comparison of Giemsa Staining, Intraperitoneal Injection and Oral

    Directory of Open Access Journals (Sweden)

    Sajad Rashidi

    2014-02-01

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

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

    International Nuclear Information System (INIS)

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

    1995-01-01

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

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

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

    International Nuclear Information System (INIS)

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

    2014-01-01

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

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

    International Nuclear Information System (INIS)

    Syme, A M; McQuarrie, S A; Middleton, J W; Fallone, B G

    2003-01-01

    A simple model has been developed to investigate the dosimetry of micrometastases in the peritoneal cavity during intraperitoneal targeted liposomal radioimmunotherapy. The model is applied to free-floating tumours with radii between 0.005 cm and 0.1 cm. Tumour dose is assumed to come from two sources: free liposomes in solution in the peritoneal cavity and liposomes bound to the surface of the micrometastases. It is assumed that liposomes do not penetrate beyond the surface of the tumours and that the total amount of surface antigen does not change over the course of treatment. Integrated tumour doses are expressed as a function of biological parameters that describe the rates at which liposomes bind to and unbind from the tumour surface, the rate at which liposomes escape from the peritoneal cavity and the tumour surface antigen density. Integrated doses are translated into time-dependent tumour control probabilities (TCPs). The results of the work are illustrated in the context of a therapy in which liposomes labelled with Re-188 are targeted at ovarian cancer cells that express the surface antigen CA-125. The time required to produce a TCP of 95% is used to investigate the importance of the various parameters. The relative contributions of surface-bound radioactivity and unbound radioactivity are used to assess the conditions required for a targeted approach to provide an improvement over a non-targeted approach during intraperitoneal radiation therapy. Using Re-188 as the radionuclide, the model suggests that, for microscopic tumours, the relative importance of the surface-bound radioactivity increases with tumour size. This is evidenced by the requirement for larger antigen densities on smaller tumours to affect an improvement in the time required to produce a TCP of 95%. This is because for the smallest tumours considered, the unbound radioactivity is often capable of exerting a tumouricidal effect before the targeting agent has time to accumulate

  20. Is Penicillin plus Gentamicin Synergistic against Clinical Group B Streptococcus isolates?: A in-vitro Study.

    Directory of Open Access Journals (Sweden)

    Corinne Ruppen

    2016-10-01

    Full Text Available Group B Streptococcus (GBS is increasingly causing invasive infections in nonpregnant adults. Elderly patients and those with comorbidities are at increased risk. On the basis of previous studies focusing on neonatal infections, penicillin plus gentamicin is recommended for infective endocarditis (IE and periprosthetic joint infections (PJI in adults. The purpose of this study was to investigate whether a synergism with penicillin and gentamicin is present in GBS isolates that caused IE and PJI. We used 5 GBS isolates, two clinical strains and three control strains, including one displaying high-level gentamicin resistance (HLGR. The results from the checkerboard and time-kill assays (TKAs were compared. For TKAs, antibiotic concentrations for penicillin were 0.048 and 0.2 mg/L, and for gentamicin 4 mg/L or 12.5 mg/L. In the checkerboard assay, the median fractional inhibitory concentration indices (FICIs of all isolates indicated indifference. TKAs for all isolates failed to demonstrate synergism with penicillin 0.048 or 0.2 mg/L, irrespective of gentamicin concentrations used. Rapid killing was seen with penicillin 0.048 mg/L plus either 4 mg/L or 12.5 mg/L gentamicin, from 2 h up to 8 h hours after antibiotic exposure. TKAs with penicillin 0.2 mg/L decreased the starting inoculum below the limit of quantification within 4 h to 6 h, irrespective of the addition of gentamicin. Fast killing was seen with penicillin 0.2 mg/L plus 12.5 mg/L gentamicin within the first 2 h. Our in vitro results indicate that the addition of gentamicin to penicillin contributes to faster killing at low penicillin concentrations, but only within the first few hours. Twenty-four hours after antibiotic exposure, PEN alone was bactericidal and synergism was not seen.

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

    International Nuclear Information System (INIS)

    Wahl, R.L.; Fisher, S.

    1987-01-01

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

  2. Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

    Science.gov (United States)

    Nazarali, A J; Baker, G B; Coutts, R T; Pasutto, F M

    1983-01-01

    Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    International Nuclear Information System (INIS)

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

    2006-01-01

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

  5. High intra-abdominal pressure enhances the penetration and antitumor effect of intraperitoneal cisplatin on experimental peritoneal carcinomatosis.

    Science.gov (United States)

    Esquis, Philippe; Consolo, David; Magnin, Guy; Pointaire, Philippe; Moretto, Philippe; Ynsa, Maria Dolores; Beltramo, Jean-Luc; Drogoul, Carole; Simonet, Michel; Benoit, Laurent; Rat, Patrick; Chauffert, Bruno

    2006-07-01

    To investigate the role of increased intra-abdominal pressure (IAP) on the intratumoral accumulation and the antitumor effect of intraperitoneal cisplatin in rats with advanced peritoneal carcinomatosis. To evaluate the tolerance of IAP in pigs, as it is a large animal with a body size equivalent to humans. To investigate if an active convection, driven by a positive IAP, increases cisplatin penetration and antitumor effectiveness in a model of advanced peritoneal carcinomatosis in rats. BDIX rats with macroscopic peritoneal tumors received cisplatin administered as intravenous injection (IV), conventional intraperitoneal injection (IP), or sustained intraperitoneal injection of cisplatin given in a large volume of solvent for maintaining IAP for 1 hour. Platinum tissue concentration was measured by atomic absorption spectroscopy (AAS), and platinum distribution into the tumor nodules was assessed by the particular-induced x-ray emission (PIXE) method. The antitumor effect was assessed in a survival experiment. The hemodynamic, local, and systemic tolerance of IAP, with or without cisplatin, was evaluated in Large White pigs. The maximum tolerated IAP was 22 mm Hg for 1 hour in nonventilated rats. IAP, in comparison with IV or conventional IP injections, resulted in the increased concentration and depth of diffusion of platinum into diaphragm and peritoneal tumor nodules. Consequently, IAP treatment induced an extended survival of rats treated at an advanced stage of carcinomatosis. In 7 50- to 70-kg ventilated pigs, a 40-mm Hg IAP was well tolerated when maintained stable for 2 hours. Renal failure occurred in pigs receiving a total dose of 200 and 400 mg of cisplatin with IAP, but a dose of 100 mg was well tolerated. Intraperitoneal chemotherapy with increased IAP, in comparison with conventional IP or IV chemotherapy, improved the tumor accumulation and the antitumor effect of cisplatin in rats bearing advanced peritoneal carcinomatosis. In preclinical

  6. Gentamicin modified chitosan film with improved antibacterial property and cell biocompatibility.

    Science.gov (United States)

    Liu, Yang; Ji, Peihong; Lv, Huilin; Qin, Yong; Deng, Linhong

    2017-05-01

    Gentamicin modified chitosan film (CS-GT) was produced using a three-step procedure comprising: (i) the chitosan solution was air-dried to form a chitosan (CS) film, (ii) using citric acid to generate the amide and carboxyl groups on the surface of CS, (iii) the CS with surface carboxyl groups was modified by grafting of gentamicin. After modification, this CS-GT film has excellent hydrophilicity and biocompatibility. It is very evident that the gentamicin grafting treatment significantly improves the antibacterial properties of the CS film. Our preliminary results suggest that this novel gentamicin modified chitosan film, which can be prepared in large quantities and at low cost, should have potential application in biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    1994-01-01

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

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

    Science.gov (United States)

    Kataria, Hanish; Singh, Vinod Prem

    2017-12-01

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

  9. Comparison Between the Polymyxins and Gentamicin in Preventing Endotoxin-Induced Intravascular Coagulation and Leukopenia

    Science.gov (United States)

    Corrigan, James J.; Bell, Bobbie M.

    1971-01-01

    Three antimicrobial agents were evaluated as to their ability to neutralize the toxic effects of endotoxin in rabbits. These consisted of two cyclic polypeptides, polymyxin B sulfate and colymycin M (sodium colistimethate), and an aminoglycoside, gentamicin sulfate. Polymyxin B regularly prevented endotoxin-induced leukopenia, thrombocytopenia, and disseminated intravascular coagulation. Colymycin M had similar activity but was not as effective as polymyxin B. Gentamicin demonstrated no neutralizing ability in this study. PMID:4343409

  10. Effect of cyclooxygenase inhibitors on gentamicin-induced nephrotoxicity in rats

    Directory of Open Access Journals (Sweden)

    Hosaka E.M.

    2004-01-01

    Full Text Available The frequent use of nonsteroidal anti-inflammatory drugs (NSAID in combination with gentamicin poses the additional risk of nephrotoxic renal failure. Cyclooxygenase-1 (COX-1 is the main enzyme responsible for the synthesis of renal vasodilator prostaglandins, while COX-2 participates predominantly in the inflammatory process. Both are inhibited by non-selective NSAID such as indomethacin. Selective COX-2 inhibitors such as rofecoxib seem to have fewer renal side effects than non-selective inhibitors. The objective of the present study was to determine whether the combined use of rofecoxib and gentamicin can prevent the increased renal injury caused by gentamicin and indomethacin. Male Wistar rats (250-300 g were treated with gentamicin (100 mg/kg body weight, ip, N = 7, indomethacin (5 mg/kg, orally, N = 7, rofecoxib (1.4 mg/kg, orally, N = 7, gentamicin + rofecoxib (100 and 1.4 mg/kg, respectively or gentamicin + indomethacin (100 and 5 mg/kg, respectively, N = 8 for 5 days. Creatinine clearance and alpha-glutathione-S-transferase concentrations were used as markers of renal injury. Animals were anesthetized with ether and sacrificed for blood collection. The use of gentamicin plus indomethacin led to worsened renal function (0.199 ± 0.019 ml/min, as opposed to the absence of a nephrotoxic effect of rofecoxib when gentamicin plus rofexicob was used (0.242 ± 0.011 ml/min. These results indicate that COX-2-selective inhibitors can be used as an alternative treatment to conventional NSAID, especially in situations in which risk factors for nephrotoxicity are present.

  11. Cell-specific accumulation patterns of gentamicin in the guinea pig cochlea.

    Science.gov (United States)

    Heinrich, Ulf-Rüdiger; Schmidtmann, Irene; Strieth, Sebastian; Helling, Kai

    2015-08-01

    Intratympanic gentamicin therapy has become a popular treatment modality for Ménière's disease (MD) through controlled elimination of vertigo spells caused by the balance organ. However, the known ototoxic properties of aminoglycosides lead to cochlear damage. In order to gain more information about cellular preferences for aminoglycoside accumulation within the cochlea, gentamicin was immuno histochemically localized by light microscopy in male guinea pigs 1 and 7 days after intratympanic application (n = 8 ears/incubation time). Differences in the gentamicin-specific cellular storage capacities were quantified by determination of the local immuno staining intensities. Gentamicin was detected in every cochlear cell type, but with spatiotemporal variability. One day after application, an intense staining reaction was found in all cell types except the spiral ganglion cells and the stria vascularis. Six days later, gentamicin staining intensities were additionally reduced in the nerve fibers and the spiral ligament. Statistic analysis revealed strong cellular associations in respect to aminoglycoside accumulation. Furthermore, associations with recorded hearing losses were identified comparing the cellular gentamicin content in the organ of Corti, in the stria vascularis, in the spiral ganglion cells and in fibrocytes of the Limbus. In the lateral wall, clear differences in cellular gentamicin accumulation were found between type I fibrocytes of the spiral ligament compared with basal and intermediate cells of the stria vascularis. This finding was unexpected as these three cell types belong to a well-developed gap-junction system which normally enables unhampered cell communication. Cellular differences in local gentamicin storage capacities, transport processes and inherent diffusion barriers are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Characterisation, in vitro release study, and antibacterial activity of montmorillonite-gentamicin complex material

    International Nuclear Information System (INIS)

    Rapacz-Kmita, A.; Bućko, M.M.; Stodolak-Zych, E.; Mikołajczyk, M.; Dudek, P.; nd Department of Surgery, Kopernika 21, 31-501 Krakow (Poland))" data-affiliation=" (Jagiellonian University, Medical College, 2nd Department of Surgery, Kopernika 21, 31-501 Krakow (Poland))" >Trybus, M.

    2017-01-01

    The present paper concerns the potential use of montmorillonite as a drug carrier and focusses on the intercalation of the studied clay with gentamicin (an aminoglycoside antibiotic) at various temperatures (20, 50 and 80 °C). The experiments were performed to identify the temperature required for the optimum intercalation of gentamicin into the interlayer of montmorillonite. The structural and microstructural properties of gentamicin and the potential for introducing it between smectite clay layers were investigated by means of X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopic techniques, and SEM with EDS analysis. Additionally, the in vitro drug release behaviour of the montmorillonite-gentamicin complex and its antibacterial activity against Escherichia coli (E. coli) bacteria was investigated. Based on these studies, the impact of temperature on the intercalation of the drug between layers of smectite was evaluated. It was found that an intercalation temperature of 50 °C resulted in the highest shift in the position of principle peak d (001) as measured by XRD, suggesting, that the greatest amount of gentamicin had been introduced into the interlayer space of montmorillonite at this temperature. Subsequently, the montmorillonite-gentamicin complex material obtained at 50 °C revealed the greatest capacity for killing E. coli bacteria during an in vitro test. - Highlights: • A novel montmorillonite-gentamicin hybrid materials was prepared as potential drug carrier. • Optimal conditions for the intercalation of gentamicin into the interlayer space of montmorillonite were tested. • The MMT-G complex material obtained at 50 °C revealed the greatest capacity for killing E. coli during the inhibitory zone test. • Modulating drug delivery was monitored and confirmed in in vitro drug release study.

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

    OpenAIRE

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

    1996-01-01

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

  14. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

    Science.gov (United States)

    Sarabia-Sainz, Andre-i; Sarabia-Sainz, Hector Manuel; Ramos-Clamont Montfort, Gabriela; Mata-Haro, Veronica; Guzman-Partida, Ana María; Guzman, Roberto; Garcia-Soto, Mariano; Vazquez-Moreno, Luz

    2015-01-01

    The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88) was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1) galactose) was used as the microsphere matrix (MS-Lac) and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3) were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections. PMID:26389896

  15. K88 Fimbrial Adhesin Targeting of Microspheres Containing Gentamicin Made with Albumin Glycated with Lactose

    Directory of Open Access Journals (Sweden)

    Andre-i Sarabia-Sainz

    2015-09-01

    Full Text Available The formulation and characterization of gentamicin-loaded microspheres as a delivery system targeting enterotoxigenic Escherichia coli K88 (E. coli K88 was investigated. Glycated albumin with lactose (BSA-glucose-β (4-1 galactose was used as the microsphere matrix (MS-Lac and gentamicin included as the transported antibiotic. The proposed target strategy was that exposed galactoses of MS-Lac could be specifically recognized by E. coli K88 adhesins, and the delivery of gentamicin would inhibit bacterial growth. Lactosylated microspheres (MS-Lac1, MS-Lac2 and MS-Lac3 were obtained using a water-in-oil emulsion, containing gentamicin, followed by crosslinking with different concentrations of glutaraldehyde. Electron microscopy displayed spherical particles with a mean size of 10–17 µm. In vitro release of gentamicin from MS-Lac was best fitted to a first order model, and the antibacterial activity of encapsulated and free gentamicin was comparable. MS-Lac treatments were recognized by plant galactose-specific lectins from Ricinus communis and Sophora japonica and by E. coli K88 adhesins. Results indicate MS-Lac1, produced with 4.2 mg/mL of crosslinker, as the best treatment and that lactosylated microsphere are promising platforms to obtain an active, targeted system against E. coli K88 infections.

  16. Concentrations of gentamicin in bronchial secretions after intramuscular and endotracheal administration.

    Science.gov (United States)

    Odio, W; Van Laer, E; Klastersky, J

    1975-07-01

    A crossover study was performed in five adult tracheotomized patients without respiratory tract disease to investigate the tracheobronchial kinetics of intramuscularly and endotracheally administered gentamicin in the absence of infection. Although intramuscular injection of 2 mg/kg of gentamicin yielded adequate levels in the serum, the concentrations in the bronchial secretions of noninfected patients were not adequate to inhibit strains of Pseudomonas aeruginosa isolated from other patients with clinical infections. Conversely, endotracheally administered gentamicin resulted in high and sustained concentrations in the bronchial secretions that were many times superior to the minimum bactericidal concentration of gentamicin against Pseudomonas aeruginosa. Gentamicin administered by aerosols resulted in concentrations within the bronchial secretions and sputum that were adequate to kill more than 90 per cent of the strains of Pseudomonas aeruginosa isolated in this hosopital. These studies suggest that endotracheally administered gentamicin might prove to be an adequate adjunct for the treatment of severe Pseudomonas infection of the tracheobronchial tract, particularly in the absence of foreight bodies and abnormalities of structure or function.

  17. Radiation sensitivity of Salmonella isolates relative to resistance to ampicillin, chloramphenicol or gentamicin

    International Nuclear Information System (INIS)

    Niemira, Brendan A.; Lonczynski, Kelly A.; Sommers, Christopher H.

    2006-01-01

    Antibiotic resistance of inoculated bacteria is a commonly used selective marker. Bacteria resistant to the antibiotic nalidixic acid have been shown to have an increased sensitivity to irradiation. The purpose of this research was to screen a collection of Salmonella isolates for antibiotic resistance and determine the association, if any, of antibiotic resistance with radiation sensitivity. Twenty-four clinical isolates of Salmonella were screened for native resistance to multiple concentrations of ampicillin (Amp), chloramphenicol (Chl), or gentamicin (Gm). Test concentrations were chosen based on established clinical minimum inhibitory concentration (MIC) levels, and isolates were classified as either sensitive or resistant based on their ability to grow at or above the MIC. Salmonella cultures were grown overnight at (37 o C) in antibiotic-amended tryptic soy broth (TSB). Native resistance to Gm was observed with each of the 24 isolates (100%). Eight isolates (33%) were shown to be resistant to Amp, while seven isolates (29%) were shown to be resistant to Chl. In separate experiments, Salmonella cultures were grown overnight (37 o C) in TSB, centrifuged, and the cell pellets were re-suspended in phosphate buffer. The samples were then gamma irradiated at doses up to 1.0 kGy. The D 10 values (the ionizing radiation dose required to reduce the viable number of microorganisms by 90%) were determined for the 24 isolates and they ranged from 0.181 to 0.359 kGy. No correlation was found between the D 10 value of the isolate and its sensitivity or resistance to each of the three antibiotics. Resistance to Amp or Chl is suggested as appropriate resistance marker for Salmonella test strains to be used in studies of irradiation

  18. Radiation sensitivity of Salmonella isolates relative to resistance to ampicillin, chloramphenicol or gentamicin

    Science.gov (United States)

    Niemira, Brendan A.; Lonczynski, Kelly A.; Sommers, Christopher H.

    2006-09-01

    Antibiotic resistance of inoculated bacteria is a commonly used selective marker. Bacteria resistant to the antibiotic nalidixic acid have been shown to have an increased sensitivity to irradiation. The purpose of this research was to screen a collection of Salmonella isolates for antibiotic resistance and determine the association, if any, of antibiotic resistance with radiation sensitivity. Twenty-four clinical isolates of Salmonella were screened for native resistance to multiple concentrations of ampicillin (Amp), chloramphenicol (Chl), or gentamicin (Gm). Test concentrations were chosen based on established clinical minimum inhibitory concentration (MIC) levels, and isolates were classified as either sensitive or resistant based on their ability to grow at or above the MIC. Salmonella cultures were grown overnight at (37 °C) in antibiotic-amended tryptic soy broth (TSB). Native resistance to Gm was observed with each of the 24 isolates (100%). Eight isolates (33%) were shown to be resistant to Amp, while seven isolates (29%) were shown to be resistant to Chl. In separate experiments, Salmonella cultures were grown overnight (37 °C) in TSB, centrifuged, and the cell pellets were re-suspended in phosphate buffer. The samples were then gamma irradiated at doses up to 1.0 kGy. The D10 values (the ionizing radiation dose required to reduce the viable number of microorganisms by 90%) were determined for the 24 isolates and they ranged from 0.181 to 0.359 kGy. No correlation was found between the D10 value of the isolate and its sensitivity or resistance to each of the three antibiotics. Resistance to Amp or Chl is suggested as appropriate resistance marker for Salmonella test strains to be used in studies of irradiation.

  19. Gentamicin coated iron oxide nanoparticles as novel antibacterial agents

    Science.gov (United States)

    Bhattacharya, Proma; Neogi, Sudarsan

    2017-09-01

    Applications of different types of magnetic nanoparticles for biomedical purposes started a long time back. The concept of surface functionalization of the iron oxide nanoparticles with antibiotics is a novel technique which paves the path for further application of these nanoparticles by virtue of their property of superparamagnetism. In this paper, we have synthesized novel iron oxide nanoparticles surface functionalized with Gentamicin. The average size of the particles, concluded from the HR-TEM images, came to be around 14 nm and 10 nm for unmodified and modified nanoparticles, respectively. The magnetization curve M(H) obtained for these nanoparticles are typical of superparamagnetic nature and having almost zero values of coercivity and remanance. The release properties of the drug coated nanoparticles were studied; obtaining an S shaped profile, indicating the initial burst effect followed by gradual sustained release. In vitro investigations against various gram positive and gram negative strains viz Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus subtilis indicated significant antibacterial efficiency of the drug-nanoparticle conjugate. The MIC values indicated that a small amount like 0.2 mg ml-1 of drug capped particles induce about 98% bacterial death. The novelty of the work lies in the drug capping of the nanoparticles, which retains the superparamagnetic nature of the iron oxide nanoparticles and the medical properties of the drug simultaneously, which is found to extremely blood compatible.

  20. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection

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    Mario Negrette-Guzmán

    2013-01-01

    Full Text Available Sulforaphane (SFN, an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress.

  1. Sulforaphane Attenuates Gentamicin-Induced Nephrotoxicity: Role of Mitochondrial Protection

    Science.gov (United States)

    Huerta-Yepez, Sara; Medina-Campos, Omar Noel; Zatarain-Barrón, Zyanya Lucía; Hernández-Pando, Rogelio; Torres, Ismael; Tapia, Edilia; Pedraza-Chaverri, José

    2013-01-01

    Sulforaphane (SFN), an isothiocyanate naturally occurring in Cruciferae, induces cytoprotection in several tissues. Its protective effect has been associated with its ability to induce cytoprotective enzymes through an Nrf2-dependent pathway. Gentamicin (GM) is a widely used antibiotic; nephrotoxicity is the main side effect of this compound. In this study, it was investigated if SFN is able to induce protection against GM-induced nephropathy both in renal epithelial LLC-PK1 cells in culture and in rats. SFN prevented GM-induced death and loss of mitochondrial membrane potential in LLC-PK1 cells. In addition, it attenuated GM-induced renal injury (proteinuria, increases in serum creatinine, in blood urea nitrogen, and in urinary excretion on N-acetyl-β-D-glucosaminidase, and decrease in creatinine clearance and in plasma glutathione peroxidase activity) and necrosis and apoptosis in rats. The apoptotic death was associated with enhanced active caspase-9. Caspase-8 was unchanged in all the studied groups. In addition, SFN was able to prevent GM-induced protein nitration and decrease in the activity of antioxidant enzymes catalase and glutathione peroxidase in renal cortex. In conclusion, the protective effect of SFN against GM-induced acute kidney injury could be associated with the preservation in mitochondrial function that would prevent the intrinsic apoptosis and nitrosative stress. PMID:23662110

  2. 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.

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

    Science.gov (United States)

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

    2018-02-06

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

  4. Efficacy of neutral and negatively charged liposome-loaded gentamicin on planktonic bacteria and biofilm communities

    Directory of Open Access Journals (Sweden)

    Alhariri M

    2017-09-01

    Full Text Available Moayad Alhariri,1 Majed A Majrashi,2 Ali H Bahkali,3 Faisal S Almajed,4 Ali O Azghani,5 Mohammad A Khiyami,2 Essam J Alyamani,2 Sameera M Aljohani,6 Majed A Halwani1 1Nanomedicine Department, King Abdullah International Medical Research Center (KAIMRC, King Saud bin Abdulaziz University for Health Sciences, 2National Centre for Biotechnology, Life Sciences and Environment Research Institute, King Abdulaziz City for Science and Technology (KACST, 3Botany and Microbiology Department, College of Science, King Saud University, 4Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 5Department of Biology, The University of Texas at Tyler, Tyler, TX, USA; 6College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, Riyadh, Saudi Arabia Abstract: We investigated the efficacy of liposomal gentamicin formulations of different surface charges against Pseudomonas aeruginosa and Klebsiella oxytoca. The liposomal gentamicin formulations were prepared by the dehydration–rehydration method, and their sizes and zeta potential were measured. Gentamicin encapsulation efficiency inside the liposomal formulations was determined by microbiologic assay, and stability of the formulations in biologic fluid was evaluated for a period of 48 h. The minimum inhibitory concentration and the minimum bactericidal concentration were determined, and the in vitro time kill studies of the free form of gentamicin and liposomal gentamicin formulations were performed. The activities of liposomal gentamicin in preventing and reducing biofilm-forming P. aeruginosa and K. oxytoca were compared to those of free antibiotic. The sizes of the liposomal formulations ranged from 625 to 806.6 nm in diameter, with the zeta potential ranging from

  5. Activity of daptomycin alone and in combination with rifampin and gentamicin against Staphylococcus aureus assessed by time-kill methodology.

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C

    2007-04-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 microg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin.

  6. In vitro synergy of baicalein and gentamicin against vancomycin-resistant Enterococcus.

    Science.gov (United States)

    Chang, Ping Chin; Li, Hua Yu; Tang, Hung Jen; Liu, Jien Wei; Wang, Jhi Joung; Chuang, Yin Ching

    2007-02-01

    Little is known about the possible synergism of baicalein, a bioactive flavone of Scutellariae radix (a Chinese herb), when used in conjunction with other antimicrobial agents against vancomycin-resistant Enterococcus (VRE). This in vitro study examined the possible synergism of the combination of baicalein and gentamicin against VRE. Minimal inhibitory concentrations (MICs) of baicalein as well as gentamicin were determined against 39 clinical isolates of VRE by the agar dilution method. Synergistic activities were determined using the checkerboard method based on the fractional inhibitory concentration indices and also the time-kill method. Further time-kill studies were conducted with these two agents against one randomly chosen clinical isolate, VRE-096. Minimal concentrations inhibiting 50% (MIC(50)) and 90% (MIC(90)) of isolates for baicalein and gentamicin were all >256 microg/mL. Synergism between baicalein and gentamicin was demonstrated against four clinical isolates of VRE (VRE-70, VRE-940, VRE-096 and VRE-721). When approximately 5 x 10(5) colony-forming units/mL of VRE-096 was incubated with both baicalein at a concentration of 32 microg/mL (1/8 x MIC) and gentamicin at a concentration of 128 microg/mL (1/2 x MIC), there was an inhibitory effect against VRE that persisted for 48 h. At 48 h, the combination of baicalein and gentamicin at these respective concentrations resulted in a reduction of growth by approximately 2 orders of magnitude compared to that for the starting inoculum and by 3 orders of magnitude compared to that for baicalein alone, the more active single agent. This study demonstrated that baicalein and gentamicin can act synergistically in inhibiting VRE in vitro.

  7. Effect of Peritoneal Lavage with Clindamycin-Gentamicin Solution on Post-Operative Pain and Analytic Acute-Phase Reactants after Laparoscopic Sleeve Gastrectomy.

    Science.gov (United States)

    Ruiz-Tovar, Jaime; Llavero, Carolina; Muñoz, Jose Luis; Zubiaga, Lorea; Diez, Maria

    2016-06-01

    Peritoneal lavage has been proposed to remove bacterial contamination and other materials promoting bacterial proliferation and pro-inflammatory cytokines that may enhance local inflammation. The aims of this study were to evaluate the effects of peritoneal lavage with physiologic saline or an antibiotic solution (clindamycin-gentamicin) on post-operative pain and analytic acute-phase reactants and to determine the microbiologic impact of both irrigations on peritoneal contamination in patients undergoing laparoscopic sleeve gastrectomy (LSG) as a bariatric procedure. The patients were randomized into two groups: Those undergoing an intra-abdominal lavage with physiologic saline (Group 1; n = 40) and those undergoing a similar lavage with a gentamicin-clindamycin solution (Group 2; n = 40). Peritoneal contamination, post-operative pain, and analytic acute-phase reactants 24 h after surgery were investigated. The median pain score 24 h after surgery was 3.5 in Group 1 and 1.5 in Group 2 (p = 0.021). The glucose concentration (mean difference 33.1 mg/dL; p = 0.004), aspartate aminotransferase (AST) concentration (mean difference 41.8 U/L; p = 0.009), alanine aminotransferase (ALT) concentration (mean difference 34.2 U/L; p = 0.029), white blood cell count (mean difference 1930/mm(3); p = 0.029); C-reactive protein concentration (mean difference 27.3 mg/L; p = 0.036), and serum lactic acid concentration (mean difference 0.34 mg/L; p = 0.049) were significantly higher in Group 1. Peritoneal contamination also was significantly higher in Group 1 (17.5% vs 0; p = 0.006). Intra-peritoneal irrigation with a gentamicin and clindamycin solution in patients undergoing LSG leads to a reduction in post-operative pain and peritoneal contamination, less alteration of acute-phase reactants, lower blood glucose concentration, a smaller increase in liver enzymes, and a shorter hospital stay.

  8. CELL RESPONSE TO INTRAPERITONEAL PDMS/HAP COMPOSITE IMPLANT

    Directory of Open Access Journals (Sweden)

    Perica Vasiljević

    2005-07-01

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

  9. Neutron-Activatable Nanoparticles for Intraperitoneal Radiation Therapy.

    Science.gov (United States)

    Hargrove, Derek; Lu, Xiuling

    2017-01-01

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

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

    Science.gov (United States)

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

    1987-04-01

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

  11. The development of polymeric pellicles with gentamicine sulfate for therapeutic correction of cervical erosion (pseudoerosion

    Directory of Open Access Journals (Sweden)

    T. M. Litvinenko

    2014-08-01

    Full Text Available Introduction.Cervical erosionsoccur in 12-15%gynaecological diseases. Erosion is a damage of epithelialmucous membrane or skin. Therapy of patients with cervical erosionsis based on selection of pathogeneticsubstantiative method of treatment. Bathes and irrigations with 20% protargol, alum, carbolic acid, potassium permanganate are used. But some authors admit the destructive influence of these procedures. Using of tampons with 10% sintomycine emulsion, cod liver oil, sea-buckthorn oil,kalanchoe sap, propolis, vagotil, cigerol, galantamine also doesn’t give desirable result. Recently polymeric pellicleswith antibacterial substances are widely used. The most perspective in this route are aminoglycoside antibiotics. That is why we chose gentamicine sulfate (broad-spectrum aminoglycoside antibiotic. The aim of study is the development of the optimal composition of vaginal pellicleswith gentamicine sulfate for gynaecological practice, scientifically substantiation of excipients: polymeric base and plasticizer. Results and discussion.Polymeric bases and plasticizers influence on gentamicine sulfate releasing from polimericpellicleshas been studied. Research on choice of optimal composition has been carried out by two-factor experiment plan. The next bases and plasticizers have been used: methylcellulose, sodium carboxymethylcellulose, soluble biopolymer, gelatin; glycerine, propylenglycol, polyethylene glycol, twin 80. Gentamicine sulfate content was 80 mg in one pellicle. Gentamicine sulfate releasing from polimericpellicleshas been investigated by the Kruvchinsky method, concentration of active substance has been detected after 45 min. As a result it has been established that base makes essential influence on the gentamicine sulfate releasing (Fexp.52,88>Ftabl. 3,9. The best plasticizer is glycerin and the most optimal base is gelatin. So the optimal composition for vaginal films has been chosen: Gentamicine sulfate0,08 g Glycerin0,7 g Gelatin0

  12. Alteration of renal excretion pathways in gentamicin-induced renal injury in rats.

    Science.gov (United States)

    Ma, Yan-Rong; Luo, Xuan; Wu, Yan-Fang; Zhang, Tiffany; Zhang, Fan; Zhang, Guo-Qiang; Wu, Xin-An

    2018-02-20

    The kidney plays a major part in the elimination of many drugs and their metabolites, and drug-induced kidney injury commonly alters either glomerular filtration or tubular transport, or both. However, the renal excretion pathway of drugs has not been fully elucidated at different stages of renal injury. This study aimed to evaluate the alteration of renal excretion pathways in gentamicin (GEN)-induced renal injury in rats. Results showed that serum cystatin C, creatinine and urea nitrogen levels were greatly increased by the exposure of GEN (100 mg kg -1 ), and creatinine concentration was increased by 39.7% by GEN (50 mg kg -1 ). GEN dose-dependently upregulated the protein expression of rOCT1, downregulated rOCT2 and rOAT1, but not affected rOAT2. Efflux transporters, rMRP2, rMRP4 and rBCRP expressions were significantly increased by GEN(100), and the rMATE1 level was markedly increased by GEN(50) but decreased by GEN(100). GEN(50) did not alter the urinary excretion of inulin, but increased metformin and furosemide excretion. However, GEN(100) resulted in a significant decrease of the urinary excretion of inulin, metformin and p-aminohippurate. In addition, urinary metformin excretions in vivo were significantly decreased by GEN(100), but slightly increased by GEN(50). These results suggested that GEN(50) resulted in the induction of rOCTs-rMATE1 and rOAT3-rMRPs pathway, but not changed the glomerular filtration rate, and GEN(100)-induced acute kidney injury caused the downregulated function of glomerular filtration -rOCTs-rMATE1 and -rOAT1-rMRPs pathway. Copyright © 2018 John Wiley & Sons, Ltd.

  13. Bactericidal Effect of Pterostilbene Alone and in Combination with Gentamicin against Human Pathogenic Bacteria

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    Wee Xian Lee

    2017-03-01

    Full Text Available The antibacterial activity of pterostilbene in combination with gentamicin against six strains of Gram-positive and Gram-negative bacteria were investigated. The minimum inhibitory concentration and minimum bactericidal concentration of pterostilbene were determined using microdilution technique whereas the synergistic antibacterial activities of pterostilbene in combination with gentamicin were assessed using checkerboard assay and time-kill kinetic study. Results of the present study showed that the combination effects of pterostilbene with gentamicin were synergistic (FIC index < 0.5 against three susceptible bacteria strains: Staphylococcus aureus ATCC 25923, Escherichia coli O157 and Pseudomonas aeruginosa 15442. However, the time-kill study showed that the interaction was indifference which did not significantly differ from the gentamicin treatment. Furthermore, time-kill study showed that the growth of the tested bacteria was completely attenuated with 2 to 8 h treatment with 0.5 × MIC of pterostilbene and gentamicin. The identified combinations could be of effective therapeutic value against bacterial infections. These findings have potential implications in delaying the development of bacterial resistance as the antibacterial effect was achieved with the lower concentrations of antibacterial agents.

  14. Intramammary treatment with gentamicin in lactating cows with clinical and subclinical mastitis

    Directory of Open Access Journals (Sweden)

    Thamires Martins

    2016-04-01

    Full Text Available Abstract The study evaluated the microbiological profile of milk samples collected before and after mastitis treatment with gentamicin and investigated biofilms production and antimicrobial susceptibility of Staphylococcus spp. isolated. The presence of gentamicin residues in milk after the recommended withdrawal period was also evaluated. Antimicrobial residues were analyzed by Delvotest® SP NT over a period of 12 days beginning after 24 hours the last gentamicin application. Some of Staphylococcus spp. isolates were biofilm producers (19.05%. Staphylococcus spp. showed high levels of resistance to neomycin (16.95%, penicillin G (10.17%, and ampicillin (10.17%. Multidrug resistance to all antibiotics tested was observed in 1.69% of the Staphylococcus spp. isolates. Among 1440 mammary quarter milk samples 24.95% presented gentamicin residues after the withdrawal period. Gentamicin residues were also detected in 3.8% of samples from calibrated glass recorder jar (n=383 4.1 days after treatment. The indiscriminate use of antibiotics may lead to the emergence of multidrug-resistant strains as well as increasing the risk of presence of residues of these drugs in milk. These problems affect the milk quality and may become a public health problem.

  15. Intestinal transport of gentamicin with a novel, glycosteroid drug transport agent

    Science.gov (United States)

    Axelrod, H. R.; Kim, J. S.; Longley, C. B.; Lipka, E.; Amidon, G. L.; Kakarla, R.; Hui, Y. W.; Weber, S. J.; Choe, S.; Sofia, M. J.

    1998-01-01

    PURPOSE: The objective was to investigate the ability of a glycosteroid (TC002) to increase the oral bioavailability of gentamicin. METHODS: Admixtures of gentamicin and TC002 were administered to the rat ileum by injection and to dogs by ileal or jejunal externalized ports, or PO. Bioavailability of gentamicin was determined by HPLC. 3H-TC002 was injected via externalized cannulas into rat ileum or jejunum, or PO and its distribution and elimination was determined. The metabolism of TC002 in rats was evaluated by solid phase extraction and HPLC analysis of plasma, urine and feces following oral or intestinal administration. RESULTS: The bioavailability of gentamicin was substantially increased in the presence of TC002 in both rats and dogs. The level of absorption was dependent on the concentration of TC002 and site of administration. Greatest absorption occurred following ileal orjejunal administration. TC002 was significantly more efficacious than sodium taurocholate, but similar in cytotoxicity. TC002 remained primarily in the GI tract following oral or intestinal administration and cleared rapidly from the body. It was only partly metabolized in the GI tract, but was rapidly and completely converted to its metabolite in plasma and urine. CONCLUSIONS: TC002 shows promise as a new drug transport agent for promoting intestinal absorption of polar molecules such as gentamicin.

  16. General Tritium Labelling of Gentamicin C by catalytic hydrogen exchange Reaction with Tritiated Water

    International Nuclear Information System (INIS)

    Suarez, C.; Diaz, D.; Paz, D.

    1991-01-01

    Gentamicin C was labelled with tritium by means of a PtO2 catalyzed hydrogen exchange reaction. Under the conditions of the exchange (100 mg of gentamicin, basic form, 0,3 ml H2O-3H, and 50 mg of prereduced PtO2) the radiochemical yield was 0,24, 0,38 and 0,48 % at 120 degree celsius, for 8, 16 and 24 hours respectively. Chemical yield for purified gentamicin was about 60 %. Purification was accomplished with a cellulose column eluted with the lower phase of chloroform-methanol 17 % ammonium hydroxide (2:1:1, v/v) . Chemical purity, determined by HPLC, was 96,5 % and radiochemical one was 95. Main exchange degradation products show biological activity. (Author) 12 refs

  17. Radioimmunoassay, acetylating radio-enzymatic assay, and microbioassay of gentamicin: a comparative study

    International Nuclear Information System (INIS)

    Stevens, P.; Young, L.S.; Hewitt, W.L.

    1975-01-01

    Gentamicin is an aminoglycoside antibiotic widely used to treat gram-negative bacillary infections. Because it has a low therapeutic index, monitoring of serum levels may help to insure adequacy of dosage and avoid toxicity. Microbiological assays are relatively slow and can be complicated by the presence of other antimicrobials. Radioimmunoassay (RIA) and acetylating radio-enzymatic assay (ARA) are new methods for gentamicin assay which offer the following advantages: rapidity (less than 3 hours); no interference by other antibiotics; RIA is extremely sensitive and ARA is versatile (being useful in the measurement of other aminoglycosides). Correlation coefficients determined by linear regression analysis of assays on 36 patient samples performed in duplicate on 2 different days demonstrated no significant difference in measurement of gentamicin by each of the methods. Factors such as numbers of specimens, cost, and time involved will affect the decision of the method to be applied in individual laboratories. (U.S.)

  18. Magnetically assisted intraperitoneal drug delivery for cancer chemotherapy.

    Science.gov (United States)

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

    2018-11-01

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

  19. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Energy Technology Data Exchange (ETDEWEB)

    Jain-Gupta, Neeta [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Pothayee, Nipon; Pothayee, Nikorn [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Tyler, Ronald; Caudell, David L. [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States); Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S. [Virginia Polytechnic Institute and State University, Macromolecules and Interfaces Institute (United States); Sriranganathan, Nammalwar, E-mail: nathans@vt.edu [Virginia-Maryland Regional College of Veterinary Medicine, Virginia Polytechnic Institute and State University, Department of Biomedical Sciences and Pathobiology (United States)

    2013-11-15

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30–32 weight percentage of gentamicin. The zeta potential changed from −39 to −13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log{sub 10}), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log{sub 10}). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B.melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  20. Efficacies of gentamicin-loaded magnetite block ionomer complexes against chronic Brucella melitensis infection

    Science.gov (United States)

    Jain-Gupta, Neeta; Pothayee, Nipon; Pothayee, Nikorn; Tyler, Ronald; Caudell, David L.; Balasubramaniam, Sharavanan; Hu, Nan; Davis, Richey M.; Riffle, Judy S.; Sriranganathan, Nammalwar

    2013-11-01

    Anionic copolymers can enable intracellular delivery of cationic drugs which otherwise cannot cross cell membrane barriers. We tested the efficacy of gentamicin-loaded magnetite block ionomer complexes (MBICs) against intracellular Brucella melitensis. Anionic block copolymers were used to coat nanomagnetite through adsorption of a portion of anions on the particle surfaces, then the remaining anions were complexed with 30-32 weight percentage of gentamicin. The zeta potential changed from -39 to -13 mV after encapsulation of the drug with complementary charge. The gentamicin-loaded MBICs had intensity average hydrodynamic diameters of 62 nm, while the polymer-coated nanomagnetite particles without drug were 34 nm in size. No toxicity as measured by a MTS assay was observed upon incubation of the MBICs with J774A.1 murine macrophage-like cells. Confocal microscopic images showed that the MBICs were taken up by the macrophages and distributed in the cell cytoplasm and endosomal/lysosomal compartments. Upon treatment with gentamicin-loaded MBICs (3.5 Log10), B. melitensis-infected macrophages showed significantly higher clearance of Brucella compared to the treatment with free g (0.9 Log10). Compared to doxycycline alone, a combination of doxycycline and gentamicin (either free or encapsulated in MBICs) showed significantly higher clearance of B. melitensis from chronically infected mice. Histopathological examination of kidneys from the MBICs-treated mice revealed multifocal infiltration of macrophages containing intracytoplasmic iron (MBICs) in peri-renal adipose. Although MBICs showed similar efficacy as free gentamicin against Brucella in mice, our strategy presents an effective way to deliver higher loads of drugs intracellularly and ability to study the bio-distribution of drug carriers.

  1. Determination of vancomycin and gentamicin clearance in an in vitro, closed loop dialysis system.

    Science.gov (United States)

    Jang, Soo Min; Cardone, Katie E; Nolin, Thomas D; Mason, Darius L; Grabe, Darren W

    2014-12-20

    The purpose of this study was to evaluate the feasibility of utilizing an in-vitro, closed loop hemodialysis system as a method to assess drug clearance. Secondarily, this study tested the influence of variables (blood flow rate, dialysate flow rate, and type of filter) in the hemodialysis procedure on the clearance of vancomycin and gentamicin. An in-vitro, closed loop hemodialysis system was constructed. The vancomycin (30 mg/L) and gentamicin (25 mg/L) were added to a simulated blood system (SBS). Four conditions (C1-C4) were tested by defining the filter (Polyflux 170H or F180) and the blood and dialysate flow rates (BFR and DFR). All hemodialysis sessions were 3 hours in length and each condition was completed in duplicate. Dialysate effluent was collected in a 50 gallon polyethylene drum. Samples were collected (in duplicate) from the SBS and the dialysate effluent at baseline and at the end of the hemodialysis session. Samples were analyzed for vancomycin and gentamicin with an ultrahigh performance liquid chromatography/tandem mass spectrometry method. A total of eight 3-hour hemodialysis sessions were conducted. For all tested conditions (C1-C4), vancomycin was undetectable in the SBS at the end of dialysis. However, total vancomycin recovery in the dialysis effluent was 85±18%, suggesting that up to 15% may have adsorbed to the dialysis filter or tubing. Gentamicin clearance from SBS was >98% in all tested conditions. Average gentamicin recovery in the dialysate effluent was 99±15%. Both vancomycin and gentamicin were readily removed by high-flux hemodialysis under all conditions studied. No significant differences in drug clearance were observed between conditions used in this in vitro study. The clinical implications of changing these hemodialysis parameters are unknown.

  2. Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats

    Directory of Open Access Journals (Sweden)

    Lakhera Abhijeet

    2015-06-01

    Full Text Available Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies.

  3. Auditory function after continuous infusion of gentamicin to high-risk newborns

    DEFF Research Database (Denmark)

    Colding, H; Andersen, E A; Prytz, S

    1989-01-01

    Audiometry was performed at four years of age in 69 of 105 surviving children who had received continuous intravenous infusion of gentamicin during neonatal intensive care. A hearing loss of 20 dB was found in 2 of them (3%), corresponding to that shown in other studies of survivors following...... neonatal intensive care. Free field audiometry performed in another 7 children and questionnaires returned from 13 of the remaining 29 gave no suspicion of hearing loss. Thus there is no indication that continuous 24 hours intravenous infusion of gentamicin causes more hearing impairment than intermittent...

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

    Science.gov (United States)

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

    2006-03-01

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

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

    DEFF Research Database (Denmark)

    Elgqvist, Jörgen; Andersson, Håkan; Jensen, Holger

    2010-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Marcella L.B. Carneiro

    2015-01-01

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

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

    Science.gov (United States)

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

    2011-06-18

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

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

    International Nuclear Information System (INIS)

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

    1985-01-01

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

  9. Refinement of intraperitoneal injection of sodium pentobarbital for euthanasia in laboratory rats (Rattus norvegicus).

    Science.gov (United States)

    Zatroch, Katie K; Knight, Cameron G; Reimer, Julie N; Pang, Daniel S J

    2017-02-21

    The Canadian Council on Animal Care and American Veterinary Medical Association classify intraperitoneal (IP) pentobarbital as an acceptable euthanasia method in rats. However, national guidelines do not exist for a recommended dose or volume and IP euthanasia has been described as unreliable, with misinjections leading to variable success in ensuring a timely death. The aims of this study were to assess and improve efficacy and consistency of IP euthanasia. In a randomized, blinded study, 51 adult female Sprague-Dawley rats (170-495 g) received one of four treatments: low-dose low-volume (LL) IP pentobarbital (n = 13, 200 mg/kg pentobarbital), low-dose high-volume (LH) IP pentobarbital (n = 14, 200 mg/kg diluted 1:3 with phosphate buffered saline), high-dose high-volume (HH, n = 14, 800 mg/kg pentobarbital), or saline. Times to loss of righting reflex (LORR) and cessation of heartbeat (CHB) were recorded. To identify misinjections, necropsy examinations were performed on all rats. Video recordings of LL and HH groups were analyzed for pain-associated behaviors. Between-group comparisons were performed with 1-way ANOVA and Games-Howell post hoc tests. Variability in CHB was assessed by calculating the coefficient of variation (CV). The fastest euthanasia method (CHB) was HH (283.7 ± 38.0 s), compared with LL (485.8 ± 140.7 s, p = 0.002) and LH (347.7 ± 72.0 s, p = 0.039). Values for CV were: HH, 13.4%; LH, 20.7%; LL, 29.0%. LORR time was longest in LL (139.5 ± 29.6 s), compared with HH (111.6 ± 19.7 s, p = 0.046) and LH (104.2 ± 19.3 s, p = 0.01). Misinjections occurred in 17.0% (7/41) of euthanasia attempts. Pain-associated behavior incidence ranged from 36% (4/11, LL) to 46% (5/11, HH). These data illustrate refinement of the IP pentobarbital euthanasia technique. Both dose and volume contribute to speed of death, with a dose of 800 mg/kg (HH) being the most effective method. An increase in volume alone does not significantly reduce variability. The

  10. In vitro the differences of inflammatory and oxidative reactions due to sulfur mustard induced acute pulmonary injury underlying intraperitoneal injection and intratracheal instillation in rats.

    Science.gov (United States)

    Yu, Dan; Bei, Yuan-Yuan; Li, Yuan; Han, Wei; Zhong, Yu-Xu; Liu, Fei; Zhao, Yu-Ling; Zhu, Xiao-Ji; Zhao, Jian

    2017-06-01

    This study was to investigate the differences of inflammatory reaction and oxidative stress due to sulfur mustard (SM)-induced acute pulmonary injury via two ways in rats. In intraperitoneal and tracheal SM groups, injected intraperitoneally and instilled intratracheally with 0.1mL diluted SM (0.96 LD 50 =8mg/kg) and SM (0.98 LD 50 =2mg/kg) were administered in rats. In bronchoalveolar lavage fluid, serum, and alveolar septum, lactate dehydrogenase, glutathione peroxidase, tumor necrosis factor-α, interleukin-1β, interleukin-6, C-reactive protein, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, l-selectin, r-glutamyl transpeptidase, thiobarbituric acid reactive substances levels as well as the expression of CD4, CD20, CD68, 8-hydroxy deoxyguanosine, nuclear factor-E2-related factor 2, and heme oxygenase-1 measured by ELISA, immune scatter turbidimetry and immunohistochemical method in the intraperitoneal SM group were increased at each time-point compared with the tracheal SM groups, respectively. These data demonstrated an increased inflammatory reaction and oxidative stress indices in rat via intraperitoneal injection under similar SM LD 50 doses. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. 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.

  12. Population pharmacokinetics and relationship between demographic and clinical variables and pharmacokinetics of gentamicin in neonates

    NARCIS (Netherlands)

    Stolk, L M L; Degraeuwe, P L J; Nieman, F H M; de Wolf, M C; de Boer, A|info:eu-repo/dai/nl/075097346

    Population pharmacokinetic parameter estimates were calculated from 725 routine plasma gentamicin concentrations obtained in 177 neonates of 24 to 42 weeks' gestational age in their first week of life. Kel increases and V/W decreases with increasing gestational age. Almost identical results were

  13. Administration of gentamicin and ampicillin by continuous intravenous infusion to newborn infants during parenteral nutrition

    DEFF Research Database (Denmark)

    Colding, H; Andersen, G E

    1982-01-01

    Gentamicin and ampicillin were dissolved in an L-amino acid solution especially prepared for newborn infants and infused intravenously over 24 h in 7 babies with serious neonatal surgical problems. Serum concentrations of the antibiotics were maintained rather constant and well above the minimal...

  14. Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia coli in a rabbit model.

    Science.gov (United States)

    Xie, Zongping; Cui, Xu; Zhao, Cunju; Huang, Wenhai; Wang, Jianqiang; Zhang, Changqing

    2013-07-01

    The treatment of osteomyelitis induced by Gram-negative bacilli is rarely reported in the literature. This study established a rabbit tibia model of osteomyelitis induced by the Gram-negative bacillus Escherichia coli. Using this model, pellets composed of a chitosan-bonded mixture of borate bioactive glass and gentamicin were evaluated in vitro and in vivo for the treatment of osteomyelitis induced by Escherichia coli. Our results showed that the pellets in phosphate-buffered saline released gentamicin continuously over 26 days. Without the simultaneous use of a systemic antibiotic, the implantation of the gentamicin-loaded pellets into the osteomyelitis region of the tibia resulted in the eradication of 81.82% of infections, as determined by microbiological, histological and radiographic evaluation, and supported the ingrowth of new bone into the tibia defects after 6 weeks of implantation. The results indicate that the gentamicin-loaded borate bioactive glass implant, combining sustained drug release with the ability to support new bone formation, could provide a method for treating osteomyelitis induced by Gram-negative bacilli.

  15. Microbubble-Mediated Ultrasound Enhances the Lethal Effect of Gentamicin on Planktonic Escherichia coli

    Directory of Open Access Journals (Sweden)

    Han-Xiao Zhu

    2014-01-01

    Full Text Available Previous research has found that low-intensity ultrasound enhanced the lethal effect of gentamicin on planktonic E. coli. We aimed to further investigate whether microbubble-mediated low-intensity ultrasound could further enhance the antimicrobial efficacy of gentamicin. The planktonic E. coli (ATCC 25922 was distributed to four different interventions: control (GCON, microbubble only (GMB, ultrasound only (GUS, and microbubble-mediated ultrasound (GMUS. Ultrasound was applied with 100 mW/cm2 (average intensity and 46.5 KHz, which presented no bactericidal activity. After 12 h, plate counting was used to estimate the number of bacteria, and bacterial micromorphology was observed with transmission electron microscope. The results showed that the viable counts of E. coli in GMUS were decreased by 1.01 to 1.42 log10 CFU/mL compared with GUS (P<0.01. The minimal inhibitory concentration (MIC of gentamicin against E. coli was 1 μg/mL in the GMUS and GUS groups, lower than that in the GCON and GMB groups (2 μg/mL. Transmission electron microscopy (TEM images exhibited more destruction and higher thickness of bacterial cell membranes in the GMUS than those in other groups. The reason might be the increased permeability of cell membranes for gentamicin caused by acoustic cavitation.

  16. Continuous intravenous infusion of ampicillin and gentamicin during parenteral nutrition in 88 newborn infants

    DEFF Research Database (Denmark)

    Colding, H; Møller, S; Andersen, G E

    1982-01-01

    Ampicillin and gentamicin were dissolved once a day in an L-amino acid solution especially prepared for parenteral nutrition of newborn infants and infused continuously to 88 infants in whom septicaemia was suspected or had been proved. The mean dosages were 162 and 5.3 mg/kg per 24 hours...

  17. A novel inner ear monitoring system for evaluating ototoxicity of gentamicin eardrops in guinea pigs.

    Science.gov (United States)

    Yang, Ting-Hua; Liu, Shing-Hwa; Young, Yi-Ho

    2010-06-01

    Although most studies have identified damage in the cochlea and semicircular canals as the primary sites of aminoglycoside toxicity, little attention has been devoted to the toxic effects on the otolithic organs. This study aimed to assess the toxic effect of gentamicin eardrops on the inner ear end organs via a novel inner ear monitoring system combined with morphological examination. Prospective study. Guinea pigs were treated with 50 microL saline (n = 10) and 50 microL gentamicin (40 mg/mL; n = 10) on the right and left round window membranes, respectively. An inner ear monitoring system, including auditory brainstem response (ABR), caloric, ocular vestibular-evoked myogenic potential (oVEMP), and cervical VEMP (cVEMP) tests, was used to assess ototoxicity in guinea pigs at 2 weeks after treatment. The animals were then sacrificed for morphological study via confocal microscopy. Normal results in ABR, caloric, cVEMP, and oVEMP tests were shown in all saline-treated ears, whereas elevated ABR threshold and absent responses in caloric, oVEMP, and cVEMP tests were noted in all gentamicin-treated ears. The cochlear and vestibular explants harvested from the gentamicin-treated ears revealed substantial loss of hair cells. The inner ear monitoring system, including ABR, caloric, oVEMP, and cVEMP tests, might help to evaluate toxicity information of the topical eardrops or agents on the inner ear end organs, including cochlea, semicircular canals, utricle, and saccule.

  18. Lack of protection against gentamicin ototoxicity by auditory conditioning with noise

    Directory of Open Access Journals (Sweden)

    Alex Strose

    2014-10-01

    Full Text Available INTRODUCTION: Auditory conditioning consists of the pre-exposure to low levels of a potential harmful agent to protect against a subsequent harmful presentation. OBJECTIVE: To confirm if conditioning with an agent different from the used to cause the trauma can also be effective. METHOD: Experimental study with 17 guinea pigs divided as follows: group Som: exposed to 85 dB broadband noise centered at 4 kHz, 30 minutes a day for 10 consecutive days; group Cont: intramuscular administration of gentamicin 160 mg/kg a day for 10 consecutive days; group Expt: conditioned with noise similarly to group Som and, after each noise presentation, received gentamicin similarly to group Cont. The animals were evaluated by distortion product otoacoustic emissions (DPOAEs, brainstem auditory evoked potentials (BAEPs and scanning electron microscopy. RESULTS: The animals that were conditioned with noise did not show any protective effect compared to the ones that received only the ototoxic gentamicin administration. This lack of protection was observed functionally and morphologically. CONCLUSION: Conditioning with 85 dB broadband noise, 30 min a day for 10 consecutive days does not protect against an ototoxic gentamicin administration of 160 mg/kg a day for 10 consecutive days in the guinea pig.

  19. Hyaluronic acid derivatives and its polyelectrolyte complexes with gentamicin as a delivery system for antibiotics

    NARCIS (Netherlands)

    ter Boo, Gert-Jan A.; Richards, Robert G.; Moriarty, Thomas F.; Grijpma, Dirk W.; Eglin, David

    2017-01-01

    Repeated administration of gentamicin (Gen) is often necessary to have efficacious pharmacokinetics in both infection prophylaxis and treatment. In order to increase the half-time of Gen sulfate and minimize the dosage, the antibiotic can be grafted to polymers as a prodrug or encapsulated within

  20. Hyaluronic acid derivatives and its polyelectrolyte complexes with gentamicin as a delivery system for antibiotics

    NARCIS (Netherlands)

    ter Boo, G.A.; Richards, R.G.; Moriarty, T.F.; Grijpma, Dirk W.; Eglin, D.

    2016-01-01

    Repeated administration of gentamicin (Gen) is often necessary to have efficacious pharmacokinetics in both infection prophylaxis and treatment. In order to increase the half-time of Gen sulfate and minimize the dosage, the antibiotic can be grafted to polymers as a prodrug or encapsulated within

  1. Gentamicin bladder instillations decrease symptomatic urinary tract infections in neurogenic bladder patients on intermittent catheterization.

    Science.gov (United States)

    Cox, Lindsey; He, Chang; Bevins, Jack; Clemens, J Quentin; Stoffel, John T; Cameron, Anne P

    2017-09-01

    This study aimed to determine if gentamicin bladder instillations reduce the rate of symptomatic urinary tract infection (UTI) in neurogenic bladder (NGB) patients on intermittent self-catheterization (ISC) who have recurrent UTIs. Secondary aims were to examine the effects of intravesical gentamicin on the organism resistance patterns. We retrospectively reviewed our prospective NGB database. Inclusion criteria were NGB patients performing ISC exclusively for bladder drainage with clinical data available for six months before and six months after initiating prophylactic intravesical gentamicin instillations. Symptomatic UTIs were defined as symptoms consistent with UTI plus the need for antibiotic treatment. Twenty-two patients met inclusion criteria; etiology of NGB was 63.6% spinal cord injury, 13.6% multiple sclerosis. Median time since injury/diagnosis was 14 years and 6/22 (27.3%) had undergone urological reconstruction. Patients had fewer symptomatic UTI's (median 4 vs. 1 episodes; pbladder instillations decrease symptomatic UTI episodes and reduce oral antibiotics in patients with NGB on ISC who were suffering from recurrent UTIs. Antibiotic resistance decreased while on gentamicin instillations.

  2. Intraperitoneal radioimmunotherapy for ovarian cancer: pharmacokinetics, toxicity, and efficacy of I-131 labeled monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    Stewart, J.S.; Hird, V.; Snook, D.; Sullivan, M.; Hooker, G.; Courtenay-Luck, N.; Sivolapenko, G.; Griffiths, M.; Myers, M.J.; Lambert, H.E.

    1989-02-01

    Thirty-six patients with ovarian cancer were treated with intraperitoneal I-131 labeled monoclonal antibodies to tumor associated antigens. The activity of I-131 administered was increased from 20 mCi to 158 mCi and the pharmacokinetics and toxicity evaluated. Five patients who had developed HAMA (Human Antimouse Antibodies) were retreated, and the pharmacokinetics and toxicity of the first and second treatment compared. Patients receiving their first therapy (HAMA negative), had a maximum of 25% (range 19.8-39.8%) of the injected activity in their circulation. This was accompanied by severe marrow suppression at I-131 activities over 120 mCi. The 5 HAMA positive patients had only 5% injected activity in the systemic circulation (range 3.8-6%), with rapid urinary excretion and neglible marrow suppression. In 31 patients with assessable disease there were no responses in 8 patients with gross disease (nodules greater than 2 cms), partial responses in 2 out of 15 patients with nodules less than 2 cms, and complete responses in 3 out of 6 patients with microscopic disease. The non specific radiation dose to the peritoneal cavity was estimated to be less than 500 cGy by lithium fluoride TLD, and could not be expected to account for the responses seen.

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

    Science.gov (United States)

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

    2013-06-01

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

  4. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

    Directory of Open Access Journals (Sweden)

    H.D.C. Francescato

    2012-03-01

    Full Text Available Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H2S is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG, an inhibitor of endogenous H2S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8 were injected with 40 mg/kg gentamicin (im twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg-1·day-1, ip. Control rats (N = 6 were treated with saline or PAG only (N = 4. Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H2S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87 mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00] in the renal cortex. These changes were associated with increased H2S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein-1·h-1 compared to control (21.12 ± 1.63 and PAG (11.44 ± 3.08. Treatment with PAG reduced this increase (171.60 ± 18.34, the disturbances in plasma creatinine levels [2.20 (1.92; 4.60 mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H2S formation.

  5. Effect of endogenous hydrogen sulfide inhibition on structural and functional renal disturbances induced by gentamicin

    Energy Technology Data Exchange (ETDEWEB)

    Francescato, H.D.C.; Chierice, J.R.A.; Marin, E.C.S. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Cunha, F.Q. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Costa, R.S. [Departamento de Patologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Silva, C.G.A.; Coimbra, T.M. [Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil)

    2012-02-17

    Animal models of gentamicin nephrotoxicity present acute tubular necrosis associated with inflammation, which can contribute to intensify the renal damage. Hydrogen sulfide (H{sub 2}S) is a signaling molecule involved in inflammation. We evaluated the effect of DL-propargylglycine (PAG), an inhibitor of endogenous H{sub 2}S formation, on the renal damage induced by gentamicin. Male Wistar rats (N = 8) were injected with 40 mg/kg gentamicin (im) twice a day for 9 days, some of them also received PAG (N = 8, 10 mg·kg{sup −1}·day{sup −1}, ip). Control rats (N = 6) were treated with saline or PAG only (N = 4). Twenty-four-hour urine samples were collected one day after the end of these treatments, blood samples were collected, the animals were sacrificed, and the kidneys were removed for quantification of H{sub 2}S formation and histological and immunohistochemical studies. Gentamicin-treated rats presented higher sodium and potassium fractional excretion, increased plasma creatinine [4.06 (3.00; 5.87) mg%] and urea levels, a greater number of macrophages/monocytes, and a higher score for tubular interstitial lesions [3.50 (3.00; 4.00)] in the renal cortex. These changes were associated with increased H{sub 2}S formation in the kidneys from gentamicin-treated rats (230.60 ± 38.62 µg·mg protein{sup −1}·h{sup −1}) compared to control (21.12 ± 1.63) and PAG (11.44 ± 3.08). Treatment with PAG reduced this increase (171.60 ± 18.34), the disturbances in plasma creatinine levels [2.20 (1.92; 4.60) mg%], macrophage infiltration, and score for tubular interstitial lesions [2.00 (2.00; 3.00)]. However, PAG did not interfere with the increase in fractional sodium excretion provoked by gentamicin. The protective effect of PAG on gentamicin nephrotoxicity was related, at least in part, to decreased H{sub 2}S formation.

  6. Oral and intraperitoneal LD/sub 50/ of thymoquinone, an active principle of nigella sativa, in mice and rats

    International Nuclear Information System (INIS)

    Ali, A.A.; Aziz, A.

    2008-01-01

    Thymoquinone is the major active principle of Nigella sativa (N. sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone. The present study was carried out to determine LD/sub 50/ of thymoquinone both in mice and rats, orally as well as intraperitoneall, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined. The LD/sub 50/ in mice after intraperitoneal injection was determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD/sub 50/ in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6-69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8- 1118.8, 95% confidence intervals). The LD/sub 50/ values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals. (author)

  7. Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes▿

    Science.gov (United States)

    Christensen, Ellen G.; Gram, Lone; Kastbjerg, Vicky G.

    2011-01-01

    The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agents. The purpose of the present study was to determine if sublethal biocide concentrations affected antibiotic susceptibility in L. monocytogenes. Exposure of L. monocytogenes strains EGD and N53-1 to sublethal concentrations of Incimaxx DES (containing peroxy acids and hydrogen peroxide) and Triquart Super (containing quaternary ammonium compound) in four consecutive cultures did not alter the frequency of antibiotic-tolerant isolates, as determined by plating on 2× the MIC for a range of antibiotics. Exposure of eight strains of L. monocytogenes to 1 and 4 μg/ml triclosan did not alter triclosan sensitivity. However, all eight strains became resistant to gentamicin (up to 16-fold increase in MIC) after exposure to sublethal triclosan concentrations. Gentamicin-resistant isolates of strains N53-1 and 4446 were also resistant to other aminoglycosides, such as kanamycin, streptomycin, and tobramycin. Gentamicin resistance remained at a high level also after five subcultures without triclosan or gentamicin. Aminoglycoside resistance can be caused by mutations in the target site, the 16S rRNA gene. However, such mutations were not detected in the N53-1-resistant isolates. A combination of gentamicin and ampicillin is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan. PMID:21746948

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-02-29

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

  10. Naringin ameliorates gentamicin-induced nephrotoxicity and associated mitochondrial dysfunction, apoptosis and inflammation in rats: Possible mechanism of nephroprotection

    Energy Technology Data Exchange (ETDEWEB)

    Sahu, Bidya Dhar [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Tatireddy, Srujana [National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037 (India); Koneru, Meghana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Borkar, Roshan M. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Kumar, Jerald Mahesh [CSIR-Centre for Cellular and Molecular Biology (CCMB), Hyderabad 500 007 (India); Kuncha, Madhusudana [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Srinivas, R. [National Centre for Mass Spectrometry, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India); Shyam Sunder, R. [Faculty of Pharmacy, Osmania University, Hyderabad 500 007 (India); Sistla, Ramakrishna, E-mail: sistla@iict.res.in [Medicinal Chemistry and Pharmacology Division, Indian Institute of Chemical Technology (IICT), Hyderabad 500 007 (India)

    2014-05-15

    Gentamicin-induced nephrotoxicity has been well documented, although its underlying mechanisms and preventive strategies remain to be investigated. The present study was designed to investigate the protective effect of naringin, a bioflavonoid, on gentamicin-induced nephrotoxicity and to elucidate the potential mechanism. Serum specific renal function parameters (blood urea nitrogen and creatinine) and histopathology of kidney tissues were evaluated to assess the gentamicin-induced nephrotoxicity. Renal oxidative stress (lipid peroxidation, protein carbonylation, enzymatic and non-enzymatic antioxidants), inflammatory (NF-kB [p65], TNF-α, IL-6 and MPO) and apoptotic (caspase 3, caspase 9, Bax, Bcl-2, p53 and DNA fragmentation) markers were also evaluated. Significant decrease in mitochondrial NADH dehydrogenase, succinate dehydrogenase, cytochrome c oxidase and mitochondrial redox activity indicated the gentamicin-induced mitochondrial dysfunction. Naringin (100 mg/kg) treatment along with gentamicin restored the mitochondrial function and increased the renal endogenous antioxidant status. Gentamicin induced increased renal inflammatory cytokines (TNF-α and IL-6), nuclear protein expression of NF-κB (p65) and NF-κB-DNA binding activity and myeloperoxidase (MPO) activity were significantly decreased upon naringin treatment. In addition, naringin treatment significantly decreased the amount of cleaved caspase 3, Bax, and p53 protein expression and increased the Bcl-2 protein expression. Naringin treatment also ameliorated the extent of histologic injury and reduced inflammatory infiltration in renal tubules. U-HPLS-MS data revealed that naringin co-administration along with gentamicin did not alter the renal uptake and/or accumulation of gentamicin in kidney tissues. These findings suggest that naringin treatment attenuates renal dysfunction and structural damage through the reduction of oxidative stress, mitochondrial dysfunction, inflammation and apoptosis in

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

    Science.gov (United States)

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

    1996-11-01

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

  12. Novel gentamicin resistance genes in Campylobacter isolated from humans and retail meats in the USA.

    Science.gov (United States)

    Zhao, Shaohua; Mukherjee, Sampa; Chen, Yuansha; Li, Cong; Young, Shenia; Warren, Melissa; Abbott, Jason; Friedman, Sharon; Kabera, Claudine; Karlsson, Maria; McDermott, Patrick F

    2015-05-01

    To understand the molecular epidemiology of gentamicin-resistant Campylobacter and investigate aminoglycoside resistance mechanisms. One-hundred-and-fifty-one gentamicin-resistant Campylobacter isolates from humans (n = 38 Campylobacter jejuni; n = 41, Campylobacter coli) and retail chickens (n = 72 C. coli), were screened for the presence of gentamicin resistance genes by PCR and subtyped using PFGE. A subset of the isolates (n = 41) was analysed using WGS. Nine variants of gentamicin resistance genes were identified: aph(2″)-Ib, Ic, Ig, If, If1, If3, Ih, aac(6')-Ie/aph(2″)-Ia and aac(6')-Ie/aph(2″)-If2. The aph(2″)-Ib, Ic, If1, If3, Ih and aac(6')-Ie/aph(2″)-If2 variants were identified for the first time in Campylobacter. Human isolates showed more diverse aminoglycoside resistance genes than did retail chicken isolates, in which only aph(2″)-Ic and -Ig were identified. The aph(2″)-Ig gene was only gene shared by C. coli isolates from human (n = 27) and retail chicken (n = 69). These isolates displayed the same resistance profile and similar PFGE patterns, suggesting that contaminated retail chicken was probably the source of human C. coli infections. Human isolates were genetically diverse and generally more resistant than the retail chicken isolates. The most frequent co-resistance was to tetracycline (78/79, 98.7%), followed by ciprofloxacin/nalidixic acid (46/79, 58.2%), erythromycin and azithromycin (36/79, 45.6%), telithromycin (32/79, 40.5%) and clindamycin (18/79, 22.8%). All human and retail meat isolates were susceptible to florfenicol. This study demonstrated that several new aminoglycoside resistance genes underlie the recent emergence of gentamicin-resistant Campylobacter, and that, in addition to contaminated retail chicken, other sources have also contributed to gentamicin-resistant Campylobacter infections in humans. Published by Oxford University Press on behalf of the British Society for Antimicrobial

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

    NARCIS (Netherlands)

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

    1991-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Hyun Sin In

    2014-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-10-15

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

  16. A comparison of trimethoprim-sulfamethoxazole plus nystatin with gentamicin plus nystatin in the prevention of infections in acute leukemia.

    Science.gov (United States)

    Wade, J C; Schimpff, S C; Hargadon, M T; Fortner, C L; Young, V M; Wiernik, P H

    1981-04-30

    Fifty-three profoundly granulocytopenic patients with relapsed acute leukemia who were undergoing reinduction chemotherapy were prospectively randomized to receive either trimethoprim-sulfamethoxazole plus nystatin or gentamicin plus nystatin for prevention of infections. The acquisition of new organisms per patient during the total study period was similar in both groups. Thirty-five symptomatic infections (five of which were bacteremias) occurred in patients receiving trimethoprim-sulfamethoxazole plus nystatin, whereas 31 infections (eight bacteremias) occurred in patients receiving gentamicin plus nystatin. Four deaths related to infection occurred in patients taking trimethoprim-sulfamethoxazole, and eight occurred in patients taking gentamicin. We conclude that trimethoprim-sulfamethoxazole plus nystatin was approximately as effective as gentamicin plus nystatin for prophylaxis against infection in relapsed acute leukemia. Furthermore, side effects were fewer and compliance was better with trimethoprim-sulfamethoxazole plus nystatin.

  17. Tritium Labeled Gentamicin C: II.- Bioradiactive Degradation Products of Gentamicin by Catalytic H2O-3H Exchange Reaction; Getamicina C Tritiada: II.- Productos de Degradacion Radiactivos y Bioactivos en el Intercambio Catalitico con H2O-3H

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.; Diaz, A.; Paz, D.; Jimeno, M. L.

    1992-07-01

    The main bio radioactive degradation products from catalytic hydrogen exchange of gentamicin C, (C1 + C2 + Cla) in basic form, are generated by N-demethylation in 3{sup -}N and 6-N positions. Their structures were confirmed by 1HNMR and 13CNMR. These derivatives were fractionated by chromatography on silica gel. Antibacterial activities were similar to those of the parent antibiotics. Tritium exchange, under vacuum or nitrogen, is highly increased (4:1) when gentamicin are in basic form. In contrast with gentamicin sulfate, hydrolytic sub products as gramine, genta mines, garosamine and purpurosamines are practically absent. To properly optimize the exchange process, the composition of the gentamicin C complex must be taken into account. The exchange decreases in the order C2 > C1> Cla. Because of 6'-N-demethyl gentamicin C1 is C2, the radiochemical yield of C2 appears enhanced in the H2O-3H exchange of a mixture of them. Radioactivity distribution among the components and subunits of these three gentamicin were studied by strong and mild hydrolysis, and by methanolysis. (Author) 18 refs.

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

    OpenAIRE

    van Dijk, Peter R.

    2015-01-01

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

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

    Science.gov (United States)

    2015-12-08

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

  20. Respiratory and intraperitoneal infection of mice with encephalomyocarditis cirus

    International Nuclear Information System (INIS)

    Bogaerts, W.J.C.; Durville-van der Oord, B.J.

    1975-01-01

    The relationships governing host resistance to viraliinfection were evaluated in mice following respiratory or peritoneal infection with three strains of encephalomyocarditis virus, which were antigenically similar but differed in virulence. The contribution of non-specific resistance to the overall defense of the host was assessed in mice that had received 450 R of X-radiation prior to viral infection. Survival time correlated with the degree of attenuation of the virus strains and was not influenced by sublethal X-irradiation and route of inoculation, provided that the viral dose was expressed in LD 50 units

  1. Histological Evidence of Nephroprotective Effect of Ashwagandha (Withania somnifera Root Extract against Gentamicin Induced Nephrotoxicity in Rats

    Directory of Open Access Journals (Sweden)

    Sadia Choudhury Shimmi

    2014-01-01

    Full Text Available Background: Kidney damage can occur due to exposure to nephrotoxic drugs, chemicals, toxins and infectious agents, ultimately leading to renal failure, management of which is a great challenge. So, efforts have been focused on traditional and herbal medicines for the treatment of renal failure. Ashwagandha (Withania somnifera may have free radical scavenging activity and can be used for the prevention and treatment of kidney damage. Objective: To observe the histological evidence of nephroprotective effect of Ashwagandha root against gentamicin induced nephrotoxicity in rats. Materials and Methods: This study was done in the department of Physiology, Sir Salimullah Medical College, Dhaka. A total number of 31 male Wistar albino rats were acclimatized for 14 days. Then, these were divided into two groups, control group consisted of 18 rats (Group A and Ashwagandha pretreated and gentamicin-treated group consisted of 13 rats (Group B. Control group was again subdivided into baseline control and gentamicin-treated control groups (A1 and A2 ─ each group contained 9 rats. All the animals received basal diet for 22 consecutive days. In addition to this, animals of Group A2 received gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day and animals of Group B received Ashwagandha root extract (500 mg/kg body weight/day orally for 22 consecutive days and gentamicin subcutaneously (100 mg/kg body weight/day from 15th to 22nd day. All the animals were sacrificed on 23rd day. Then kidney samples were collected and histology was done by using standard laboratory procedure. Results: Histological examination of kidney revealed abnormal histological findings in 100% of gentamicin-treated rats. But 92.31% of rats in Ashwagandha pretreated and gentamicin-treated group showed almost normal structure and 7.69% showed mild histological changes. Conclusion: Ashwagandha root may have some nephroprotective effect against gentamicin induced

  2. Preparative purification of gentamicin components using high-speed counter-current chromatography coupled with electrospray mass spectrometry.

    Science.gov (United States)

    Inoue, Koichi; Hattori, Yasuko; Horie, Masakazu; Hino, Tomoaki; Oka, Hisao

    2011-06-01

    We developed a useful and preparative method based on high-speed counter-current chromatography with mass spectrometry (HSCCC/MS) to purify gentamicin C1a, C2/2a and C1 from standard powder. The analytes were purified on the HSCCC model CCC-1000 (multi-layer coil planet centrifuge) with a volatile two-phase solvent system composed of n-butanol/10% aqueous ammonia solution (50:50, v/v) and detected on an LCMS-2020EV quadrupole mass spectrometer fitted with an electrospray ionization (ESI) source system in positive ionization following scan mode (m/z 100-500). The HSCCC/ESI-MS peaks indicated that gentamicin C1a (m/z 450: [M+H](+)), C2/2a (m/z 464: [M+H](+)) and C1 (m/z 478: [M+H](+)) have the peak resolution values of 1.3 and 1.7 from 30 mg of loaded gentamicin powder. The HSCCC yielded 3.9 mg of gentamicin C1a, 12.6 mg of gentamicin C2/2a and 12.0 mg of gentamicin C1. These purified substances were analyzed by LC/MS with scan positive-mode. Based on the LC/MS chromatograms and spectra of the fractions, analytes were estimated to be over 95% pure. These gentamicin isomers of C1a, C2/2a and C1 were evaluated for their antibacterial activities. The overall results indicate that this approach of HSCCC/MS is a powerful technique for the purification of gentamicin components. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin

    Science.gov (United States)

    Floquet, Célia; Hatin, Isabelle; Rousset, Jean-Pierre; Bidou, Laure

    2012-01-01

    The efficiency of translation termination depends on the nature of the stop codon and the surrounding nucleotides. Some molecules, such as aminoglycoside antibiotics (gentamicin), decrease termination efficiency and are currently being evaluated for diseases caused by premature termination codons. However, the readthrough response to treatment is highly variable and little is known about the rules governing readthrough level and response to aminoglycosides. In this study, we carried out in-depth statistical analysis on a very large set of nonsense mutations to decipher the elements of nucleotide context responsible for modulating readthrough levels and gentamicin response. We quantified readthrough for 66 sequences containing a stop codon, in the presence and absence of gentamicin, in cultured mammalian cells. We demonstrated that the efficiency of readthrough after treatment is determined by the complex interplay between the stop codon and a larger sequence context. There was a strong positive correlation between basal and induced readthrough levels, and a weak negative correlation between basal readthrough level and gentamicin response (i.e. the factor of increase from basal to induced readthrough levels). The identity of the stop codon did not affect the response to gentamicin treatment. In agreement with a previous report, we confirm that the presence of a cytosine in +4 position promotes higher basal and gentamicin-induced readthrough than other nucleotides. We highlight for the first time that the presence of a uracil residue immediately upstream from the stop codon is a major determinant of the response to gentamicin. Moreover, this effect was mediated by the nucleotide itself, rather than by the amino-acid or tRNA corresponding to the −1 codon. Finally, we point out that a uracil at this position associated with a cytosine at +4 results in an optimal gentamicin-induced readthrough, which is the therapeutically relevant variable. PMID:22479203

  4. Punica granatum improves renal function in gentamicin-induced nephropathy in rats via attenuation of oxidative stress.

    Science.gov (United States)

    Mestry, Snehal N; Gawali, Nitin B; Pai, Sarayu A; Gursahani, Malvika S; Dhodi, Jayesh B; Munshi, Renuka; Juvekar, Archana R

    2018-03-16

    Gentamicin is widely used as an antibiotic for the treatment of gram negative infections. Evidences indicates that oxidative stress is involved in gentamicin-induced nephrotoxicity. In Ayurvedic medicine, Punica granatum Linn. is considered as 'a pharmacy unto itself". It has been claimed in traditional literature, to treat various kidney ailments due to its antioxidant potential. To explore the possible mechanism of action of methanolic extract of P.granatum leaves (MPGL) in exerting a protective effect on gentamicin-induced nephropathy. Animals were administered with gentamicin (80 mg/kg/day i.m.) and simultaneously with MPGL (100, 200 and 400 mg/kg p.o.) or metformin (100 mg/kg p.o.) for 8 days. A satellite group was employed in order to check for reversibility of nephrotoxic effects post discontinuation of gentamicin administration. At the end of the study, all the rats were sacrificed and serum-urine parameters were investigated. Antioxidant enzymes and tumor necrosis factor alpha (TNF-α) levels were determined in the kidney tissues along with histopathological examination of kidneys. Increase in serum creatinine, urea, TNF-α, lipid peroxidation along with fall in the antioxidant enzymes activity and degeneration of tubules, arterioles as revealed by histopathological examination confirmed the manifestation of nephrotoxicity caused due to gentamicin. Simultaneous administration of MPGL and gentamicin protected kidneys against nephrotoxic effects of gentamicin as evidenced from normalization of renal function parameters and amelioration of histopathological changes. Data suggests that MPGL attenuated oxidative stress associated renal injury by preserving antioxidant enzymes, reducing lipid peroxidation and inhibiting inflammatory mediators such as TNF-α. Copyright © 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Published by Elsevier B.V. All rights reserved.

  5. Treatment of infectious arthritis of the radiocarpal joint of cattle with gentamicin-impregnated collagen sponges

    International Nuclear Information System (INIS)

    Hirsbrunner, G.; Steiner, A.

    1998-01-01

    Gentamicin-impregnated collagen sponges were used successfully in the treatment of chronic septic arthritis of the radiocarpal joint in two cattle. Both animals were moderately to severely lame and refractory to systemic antibiotics, and one of them was refractory to joint lavage and local antibiotics. The clinical diagnosis was confirmed by radiography and arthrocentesis. Arthroscopy was performed under general anaesthesia and, after debridement and lavage of the joint, gentamicin-impregnated collagen sponges were placed intra-articularly. Synovial fluid was sampled at 10 and 20 days after surgery and radiographs were taken three months (case 1) and two months (case 2) after surgery. The infection was eliminated from both animals and they recovered without residual lameness

  6. Gentamicin susceptibility in Escherichia coli related to the genetic background: problems with breakpoints

    DEFF Research Database (Denmark)

    Jakobsen, L.; Sandvang, D.; Jensen, Vibeke Frøkjær

    2007-01-01

    In total, 120 Escherichia coli isolates positive for one of the gentamicin resistance (GEN(R)) genes aac(3)-II, aac(3)-IV or ant(2 '')-I were tested for gentamicin susceptibility by the agar dilution method. Isolates positive for aac(3)-IV or ant(2 '')-I had an MIC distribution of 8-64 mg....../L, whereas isolates positive for aac(3)-II had MICs of 32 to > 512 mg/L, suggesting a relationship between the distribution of MICs and the specific GEN(R) mechanism. The MIC distribution, regardless of the GEN(R) mechanism, was 8 - > 512 mg/L, which supports the clinical breakpoint of MIC > 4 mg/L suggested...

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

    International Nuclear Information System (INIS)

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

    2010-01-01

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

  8. Heterogeneity of plasmids determining high-level resistance to gentamicin in clinical isolates of Streptococcus faecalis.

    OpenAIRE

    Zervos, M J; Mikesell, T S; Schaberg, D R

    1986-01-01

    Between November 1981 and October 1984, 48 of 3,458 clinical isolates of Streptococcus faecalis at the University of Michigan Hospital showed high-level (greater than 2,000 micrograms/ml) resistance to gentamicin, as well as to all other clinically available aminoglycosides. Thirteen percent of clinical isolates in the University of Michigan Hospital currently demonstrate this level of resistance. Transfer of resistance to a plasmid-free streptococcal recipient was observed in filter matings ...

  9. Management of intractable Ménière's disease after intratympanic injection of gentamicin.

    Science.gov (United States)

    Rah, Yoon C; Han, Jae J; Park, Jaehong; Choi, Byung Y; Koo, Ja-Won

    2015-04-01

    1) To evaluate the efficacy of, and problems with, intratympanic gentamicin injection (ITG) in medically intractable definite Ménière's disease (MD) and secondary endolymphatic hydrops (EH); and 2) to review the vestibular status and treatment options of intractable vertigo even after ITG. Retrospective case review and survey. 780 patients with definite MD and secondary EH were enrolled. Long-term outcomes and problems of applied treatment options including ITG and exploratory tympanotomy and gentamicin application (ETG) were analyzed. Of the 780 patients, 95 patients received ITG. Class A and B control of vertigo was achieved in 85 (89.5%) patients; two patients were class C and eight patients were class F (ETG: 6; labyrinthectomy: 1; vestibular neurectomy: 1). Among seven patients who received ETG including 1 patient who skipped ITG due to chronic otitis media, five patients improved to class A, showing a 71.4% success rate; and labyrinthectomies were performed subsequently in the two remaining patients. Vertigo was controlled (class A) in all the patients who received labyrinthectomies (n = 4) or vestibular neurectomy (n = 1). Eight patients (8.4%) experienced more than 10 dB worsening, and two patients (2.1%) progressed to bilateral Ménière's disease. ITG failed to control vertigo in 10.5% of cases. ETG may be a reasonable option to facilitate the delivery of gentamicin into the inner ear by direct application of gentamicin over the round window and the oval window. Labyrinthectomy and vestibular neurectomy still have roles in the era of ITG. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  10. Sildenafil Ameliorates Gentamicin-Induced Nephrotoxicity in Rats: Role of iNOS and eNOS

    Directory of Open Access Journals (Sweden)

    Mohamed A. Morsy

    2014-01-01

    Full Text Available Gentamicin, an aminoglycoside antibiotic, is used for the treatment of serious Gram-negative infections. However, its usefulness is limited by its nephrotoxicity. Sildenafil, a selective phosphodiesterase-5 inhibitor, was reported to prevent or decrease tissue injury. The aim of this study is to evaluate the potential protective effects of sildenafil on gentamicin-induced nephrotoxicity in rats. Male Wistar rats were injected with gentamicin (100 mg/kg/day, i.p. for 6 days with and without sildenafil. Sildenafil administration resulted in nephroprotective effect in gentamicin-intoxicated rats as it significantly decreased serum creatinine and urea, urinary albumin, and renal malondialdehyde and nitrite/nitrate levels, with a concomitant increase in renal catalase and superoxide dismutase activities compared to gentamicin-treated rats. Moreover, immunohistochemical examination revealed that sildenafil treatment markedly reduced inducible nitric oxide synthase (iNOS expression, while expression of endothelial nitric oxide synthase (eNOS was markedly enhanced. The protective effects of sildenafil were verified histopathologically. In conclusion, sildenafil protects rats against gentamicin-induced nephrotoxicity possibly, in part, through its antioxidant activity, inhibition of iNOS expression, and induction of eNOS production.

  11. Effects of the antibiotics Gentamicin on the postembryonic development of Chrysomya putoria (Diptera: Calliphoridae).

    Science.gov (United States)

    Ferraz, Adriana C P; Dallavecchia, Daniele L; Silva, Débora C; Figueiredo, Adriana L; Proença, Barbara; Silva-Filho, Renato G; Aguiar, Valéria M

    2014-01-01

    We evaluate the effects the antibiotic Gentamicin on the development of Chrysomya putoria (Wiedemann, 1818). Third-generation, first-instar larvae were reared in a climatic chamber on 60 g of homogenate + agar 65% and were treated with three concentrations of Gentamicin: 4.44 mg/ml, 13.33 mg/ml, and 66.66 mg/ml. The control consisted of distilled water. The relationships between mean body mass of mature larvae (measured after diet abandonment, in batches of five individuals), duration of larval and pupal stages, and overall duration of development were analyzed. The actual sex ratio was compared against the expected using the chi square. None of the parameters measured differed significantly among the four treatments, with one exception: when Gentamicin concentration was 13.33 mg/ml, larval viability differed significantly from the control. All larvae from all treatments were considered normal. We conclude that the antibiotic did not significantly alter the development of C. putoria (Wiedemann) (Diptera: Calliphoridae). © The Author 2014. Published by Oxford University Press on behalf of the Entomological Society of America.

  12. Gentamicin volume of distribution as a power function of body weight.

    Science.gov (United States)

    Keller, F

    1989-01-01

    Gentamicin volume of distribution (V) was related to body weight (W) in 183 obese, normal weight and infant patients as reported in five published studies. In contrast to the usually postulated simple proportionality (V = bW) a linear function was found (V = a + bW) with an intercept (a = 2.5 +/- 0.49) significantly different from zero (P = 0.0001) and a slope (b = 0.19 +/- 0.10) significantly different (P = 0.0001) from the mean factor of proportion (b = 0.35 +/- 0.19). As compared with the linear function, a power function (V = 0.57 W 0.79) approximated even more closely the dependence of gentamicin volume on body weight (r = 0.94 vs r = 0.81). The difference between both functions was more than 50% only for body weight less than 5 kg. It is concluded that the relation between gentamicin volume of distribution and body weight is non-linear. PMID:2590606

  13. Chromosomally and Extrachromosomally Mediated High-Level Gentamicin Resistance in Streptococcus agalactiae.

    Science.gov (United States)

    Sendi, Parham; Furitsch, Martina; Mauerer, Stefanie; Florindo, Carlos; Kahl, Barbara C; Shabayek, Sarah; Berner, Reinhard; Spellerberg, Barbara

    2016-01-04

    Streptococcus agalactiae (group B Streptococcus [GBS]) is a leading cause of sepsis in neonates. The rate of invasive GBS disease in nonpregnant adults also continues to climb. Aminoglycosides alone have little or no effect on GBS, but synergistic killing with penicillin has been shown in vitro. High-level gentamicin resistance (HLGR) in GBS isolates, however, leads to the loss of a synergistic effect. We therefore performed a multicenter study to determine the frequency of HLGR GBS isolates and to elucidate the molecular mechanisms leading to gentamicin resistance. From eight centers in four countries, 1,128 invasive and colonizing GBS isolates were pooled and investigated for the presence of HLGR. We identified two strains that displayed HLGR (BSU1203 and BSU452), both of which carried the aacA-aphD gene, typically conferring HLGR. However, only one strain (BSU1203) also carried the previously described chromosomal gentamicin resistance transposon designated Tn3706. For the other strain (BSU452), plasmid purification and subsequent DNA sequencing resulted in the detection of plasmid pIP501 carrying a remnant of a Tn3 family transposon. Its ability to confer HLGR was proven by transfer into an Enterococcus faecalis isolate. Conversely, loss of HLGR was documented after curing both GBS BSU452 and the transformed E. faecalis strain from the plasmid. This is the first report showing plasmid-mediated HLGR in GBS. Thus, in our clinical GBS isolates, HLGR is mediated both chromosomally and extrachromosomally. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  14. Quality and Clinical Outcomes Associated with a Gentamicin Use System Change for Managing Chorioamnionitis.

    Science.gov (United States)

    Sauberan, Jason B; Choi, Brittney; Paradyse, Alexander R; Le, Jennifer

    2017-11-09

    Chorioamnionitis is an intra-amniotic infection with serious maternal and neonatal complications. Clinical studies suggest antibiotic administration before delivery reduces the risk of complications compared to after delivery. Our center implemented a standardized intrapartum gentamicin computerized provider order entry and dosage form dispensing system intended to improve treatment initiation efficiency in hospitalized obstetric patients. The primary objective of this retrospective study was to determine if these system changes were associated with decreased time from gentamicin ordering to administration in patients with chorioamnionitis. A secondary objective was to compare clinical outcomes before and after system changes. Classification and regression tree (CART) analyses was applied to identify key predictors. Results demonstrated a trend towards reduced time to administration in the post-implementation group. Clinical outcomes were not altered. CART analysis revealed that post-implementation assignment and length of membrane rupture predicted shorter time to gentamicin initiation. This study suggests that the specific system changes we implemented were safe and improved efficiency, but additional changes are needed to have a clinically significant impact.

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

    Science.gov (United States)

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

    2007-01-01

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

  16. Activity of Daptomycin Alone and in Combination with Rifampin and Gentamicin against Staphylococcus aureus Assessed by Time-Kill Methodology▿ †

    Science.gov (United States)

    Credito, Kim; Lin, Gengrong; Appelbaum, Peter C.

    2007-01-01

    The synergistic effects of daptomycin plus gentamicin or rifampin were tested against 50 Staphylococcus aureus strains, with daptomycin MICs ranging between 0.25 and 8 μg/ml. Daptomycin sub-MICs combined with gentamicin concentrations lower than the MIC yielded synergy in 34 (68%) of the 50 strains. Daptomycin combined with rifampin yielded synergy in one vancomycin-intermediate S. aureus strain only, and virtually all synergy occurred between daptomycin and gentamicin. PMID:17220402

  17. Extracellular gentamicin reduces the activity of connexin hemichannels and interferes with purinergic Ca2+ signaling in HeLa cells

    Science.gov (United States)

    Figueroa, Vania A.; Retamal, Mauricio A.; Cea, Luis A.; Salas, José D.; Vargas, Aníbal A.; Verdugo, Christian A.; Jara, Oscar; Martínez, Agustín D.; Sáez, Juan C.

    2014-01-01

    Gap junction channels (GJCs) and hemichannels (HCs) are composed of protein subunits termed connexins (Cxs) and are permeable to ions and small molecules. In most organs, GJCs communicate the cytoplasm of adjacent cells, while HCs communicate the intra and extracellular compartments. In this way, both channel types coordinate physiological responses of cell communities. Cx mutations explain several genetic diseases, including about 50% of autosomal recessive non-syndromic hearing loss. However, the possible involvement of Cxs in the etiology of acquired hearing loss remains virtually unknown. Factors that induce post-lingual hearing loss are diverse, exposure to gentamicin an aminoglycoside antibiotic, being the most common. Gentamicin has been proposed to block GJCs, but its effect on HCs remains unknown. In this work, the effect of gentamicin on the functional state of HCs was studied and its effect on GJCs was reevaluated in HeLa cells stably transfected with Cxs. We focused on Cx26 because it is the main Cx expressed in the cochlea of mammals where it participates in purinergic signaling pathways. We found that gentamicin applied extracellularly reduces the activity of HCs, while dye transfer across GJCs was not affected. HCs were also blocked by streptomycin, another aminoglycoside antibiotic. Gentamicin also reduced the adenosine triphosphate release and the HC-dependent oscillations of cytosolic free-Ca2+ signal. Moreover, gentamicin drastically reduced the Cx26 HC-mediated membrane currents in Xenopus laevis oocytes. Therefore, the extracellular gentamicin-induced inhibition of Cx HCs may adversely affect autocrine and paracrine signaling, including the purinergic one, which might partially explain its ototoxic effects. PMID:25237294

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

    Directory of Open Access Journals (Sweden)

    Lana Bijelic

    2012-01-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  20. Effects of Korean red ginseng extract on acute renal failure induced by gentamicin and pharmacokinetic changes by metformin in rats.

    Science.gov (United States)

    Lee, Yu Kyung; Chin, Young-Won; Choi, Young Hee

    2013-09-01

    Korean red ginseng is one of the best selling dietary supplements and its individual constituents enhance renal function. Acute renal failure (ARF) is a predisposing complication of diabetes mellitus as a result of combination drug therapy. The combination of antibiotic-antidiabetic drugs can entail toxicities and drug interactions because of the antibiotic resistance in patients with severe bacterial infection. Currently, gentamicin-metformin combination therapy is commonly prescribed for treating bacterial infections and diabetes, even though both drugs are mainly excreted via the kidney. Thus, this study was designed to investigate whether a Korean red ginseng extract (KRG) prevents renal impairment and pharmacokinetic changes by metformin in rats with renal failure induced by gentamicin. The in vivo pharmacokinetics and in vitro hepatic/intestinal metabolism of metformin were assessed using control (CON), control with Korean red ginseng extract (KRG-CON), acute renal failure induced by gentamicin (ARF), and ARF with Korean red ginseng (KRG-ARF) rats. Pharmacokinetic changes of metformin did not occur in KRG-ARF rats because KRG reduce the renal accumulation of gentamicin compared to ARF rats. Thus, KRG seemed to prevent acute renal failure induced by gentamicin treatment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. In vitro bioactivity, cytocompatibility, and antibiotic release profile of gentamicin sulfate-loaded borate bioactive glass/chitosan composites.

    Science.gov (United States)

    Cui, Xu; Gu, Yifei; Li, Le; Wang, Hui; Xie, Zhongping; Luo, Shihua; Zhou, Nai; Huang, Wenhai; Rahaman, Mohamed N

    2013-10-01

    Borate bioactive glass-based composites have been attracting interest recently as an osteoconductive carrier material for local antibiotic delivery. In the present study, composites composed of borate bioactive glass particles bonded with a chitosan matrix were prepared and evaluated in vitro as a carrier for gentamicin sulfate. The bioactivity, degradation, drug release profile, and compressive strength of the composite carrier system were studied as a function of immersion time in phosphate-buffered saline at 37 °C. The cytocompatibility of the gentamicin sulfate-loaded composite carrier was evaluated using assays of cell proliferation and alkaline phosphatase activity of osteogenic MC3T3-E1 cells. Sustained release of gentamicin sulfate occurred over ~28 days in PBS, while the bioactive glass converted continuously to hydroxyapatite. The compressive strength of the composite loaded with gentamicin sulfate decreased from the as-fabricated value of 24 ± 3 MPa to ~8 MPa after immersion for 14 days in PBS. Extracts of the soluble ionic products of the borate glass/chitosan composites enhanced the proliferation and alkaline phosphatase activity of MC3T3-E1 cells. These results indicate that the gentamicin sulfate-loaded composite composed of chitosan-bonded borate bioactive glass particles could be useful clinically as an osteoconductive carrier material for treating bone infection.

  2. Decreased Expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT in Gentamicin-induced Nephropathy

    Science.gov (United States)

    Bae, Woo Kyun; Lee, JongUn; Park, Jeong Woo; Bae, Eun Hui; Ma, Seong Kwon; Kim, Suhn Hee

    2008-01-01

    The present study was aimed to determine whether there is an altered regulation of tubular transporters in gentamicin-induced nephropathy. Sprague-Dawley male rats (200~250 g) were subcutaneously injected with gentamicin (100 mg/kg per day) for 7 days, and the expression of tubular transporters was determined by immunoblotting and immunohistochemistry. The mRNA and protein expression of OAT was also determined. Gentamicin-treated rats exhibited significantly decreased creatinine clearance along with increased plasma creatinine levels. Accordingly, the fractional excretion of sodium increased. Urine volume was increased, while urine osmolality and free water reabsorption were decreased. Immunoblotting and immunohistochemistry revealed decreased expression of Na+/K+-ATPase, NHE3, NBC1, and AQP1 in the kidney of gentamicin-treated rats. The expression of OAT1 and OAT3 was also decreased. Gentamicin-induced nephropathy may at least in part be causally related with a decreased expression of Na+/K+-ATPase, NHE3, NBC1, AQP1 and OAT. PMID:19967075

  3. Formulation design and in vitro physicochemical characterization of surface modified self-nanoemulsifying formulations (SNEFs) of gentamicin.

    Science.gov (United States)

    Umeyor, Chukwuebuka; Attama, Anthony; Uronnachi, Emmanuel; Kenechukwu, Franklin; Nwakile, Calistus; Nzekwe, Ifeanyi; Okoye, Eric; Esimone, Charles

    2016-01-30

    Self-nanoemulsifying formulations (SNEFs) structured with PEG 4000 as PEGylated SNEFs, were formulated after solubility studies using rational blends of soybean oil, a combination of Kolliphor(®) EL and Kolliphor(®) P188 as surfactants, and Transcutol(®) HP as co-surfactant, and evaluated for oral delivery of gentamicin. Incorporation of gentamicin and PEG 4000 reduced the initial area of nanoemulsion of the ternary phase diagrams produced by water titration method using oil, surfactant mixture and co-surfactant. Emulsion droplets were in the nanometer scale ranging from 80-210 nm. FT-IR study revealed that gentamicin structure remained intact in all formulations, and SEM micrographs showed spherical globules. Zeta potentials of SNEFs were in the range of -25.4 to -42.5 mV, and showed a stable system with minor flips in electrostatic charges. There was high in vitro diffusion-dependent permeation of gentamicin from the SNEFs. Results obtained in this work showed that oral delivery of gentamicin was improved by formulation as surface modified SNEFs. Copyright © 2015 Elsevier B.V. All rights reserved.

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

    Science.gov (United States)

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

    2008-06-01

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

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

    Directory of Open Access Journals (Sweden)

    Wei Huang

    2017-09-01

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

  6. Co-delivery of ibuprofen and gentamicin from nanoporous anodic titanium dioxide layers.

    Science.gov (United States)

    Pawlik, Anna; Jarosz, Magdalena; Syrek, Karolina; Sulka, Grzegorz D

    2017-04-01

    Although single-drug therapy may prove insufficient in treating bacterial infections or inflammation after orthopaedic surgeries, complex therapy (using both an antibiotic and an anti-inflammatory drug) is thought to address the problem. Among drug delivery systems (DDSs) with prolonged drug release profiles, nanoporous anodic titanium dioxide (ATO) layers on Ti foil are very promising. In the discussed research, ATO samples were synthesized via a three-step anodization process in an ethylene glycol-based electrolyte with fluoride ions. The third step lasted 2, 5 and 10min in order to obtain different thicknesses of nanoporous layers. Annealing the as-prepared amorphous layers at the temperature of 400°C led to obtaining the anatase phase. In this study, water-insoluble ibuprofen and water-soluble gentamicin were used as model drugs. Three different drug loading procedures were applied. The desorption-desorption-diffusion (DDD) model of the drug release was fitted to the experimental data. The effects of crystalline structure, depth of TiO 2 nanopores and loading procedure on the drug release profiles were examined. The duration of the drug release process can be easily altered by changing the drug loading sequence. Water-soluble gentamicin is released for a long period of time if gentamicin is loaded in ATO as the first drug. Additionally, deeper nanopores and anatase phase suppress the initial burst release of drugs. These results confirm that factors such as morphological and crystalline structure of ATO layers, and the procedure of drug loading inside nanopores, allow to alter the drug release performance of nanoporous ATO layers. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Gentamicin-Eluting Titanium Dioxide Nanotubes Grown on the Ultrafine-Grained Titanium.

    Science.gov (United States)

    Nemati, Sima Hashemi; Hadjizadeh, Afra

    2017-08-01

    Titanium (Ti)-based materials is the most appropriate choices for the applications as orthopedic and dental implants. In this regard, ultrafine-grained (UFG) titanium with an enhanced mechanical properties and surface energy has attracted more attention. Titanium dioxide (TiO 2 ) nanotubes grown on the titanium could enhance bone bonding, cellular response and are good reservoirs for loading drugs and antibacterial agents. This article investigates gentamicin loading into and release from the TiO 2 nanotubes, grown on the UFG compared to coarse-grained (CG) titanium substrate surfaces. Equal Channel Angular Pressing (ECAP) was employed to produce the UFG structure titanium. TiO 2 nanotubes were grown by the anodizing technique on both UFG and CG titanium substrate surfaces. Scanning electron microscopy (SEM) imaging confirmed TiO 2 nanotube growth on the surface. The UV-vis spectroscopy analysis results show that the amount of gentamicin load-release in the anodized UFG titanium sample is higher than that of CG one which can be explained in terms of thicker TiO 2 nanotube arrays layer formed on UFG sample. Moreover, the anodized UFG titanium samples released the drug in a longer time than CG (1 day for the UFG titanium vs. 3 h for the CG one). Regarding wettability analysis, anodized UFG titanium sample showed more enhanced hydrophilicity than CG counterpart. Therefore, the significantly smaller grain size of pure titanium provided by the ECAP technique coupled with appropriate subsequent anodization treatment not only offers a good combination of biocompatibility and adequate mechanical properties but also it provides a delayed release condition for gentamicin.

  8. Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular  Salmonella model

    Directory of Open Access Journals (Sweden)

    Ashish Ranjan

    2009-12-01

    Full Text Available Ashish Ranjan1, Nikorn Pothayee2,3, Mohammed N Seleem2, Ronald D Tyler Jr4, Bonnie Brenseke4, Nammalwar Sriranganathan2,4, Judy S Riffle2,3, Ramanathan Kasimanickam11Department of Large Animal Clinical Sciences, 2Institute for Critical Technology and Applied Science, 3Macromolecules and Interfaces Institute, 4Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, VAAbstract: Pluronic based core-shell nanostructures encapsulating gentamicin were designed in this study. Block copolymers of (PAA–+Na-b-(PEO-b-PPO-b-PEO-b-PAA– +Na were blended with PAA– Na+ and complexed with the polycationic antibiotic gentamicin to form nanostructures. Synthesized nanostructures had a hydrodynamic diameter of 210 nm, zeta potentials of –0.7 (±0.2, and incorporated ~20% by weight of gentamicin. Nanostructures upon co-incubation with J774A.1 macrophage cells showed no adverse toxicity in vitro. Nanostructures administered in vivo either at multiple dosage of 5 µg g–1 or single dosage of 15 µg g–1 in AJ-646 mice infected with Salmonella resulted in significant reduction of viable bacteria in the liver and spleen. Histopathological evaluation for concentration-dependent toxicity at a dosage of 15 µg g–1 revealed mineralized deposits in 50% kidney tissues of free gentamicin-treated mice which in contrast was absent in nanostructure-treated mice. Thus, encapsulation of gentamicin in nanostructures may reduce toxicity and improve in vivo bacterial clearance.Keywords: gentamicin, core-shell nanostructures, Salmonella

  9. 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

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

    Directory of Open Access Journals (Sweden)

    Anne-Laure Zilber

    2016-03-01

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

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

    NARCIS (Netherlands)

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

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

  12. 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

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

    NARCIS (Netherlands)

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

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2006-01-01

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

  16. 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.

  17. 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...

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Joji Kitayama

    2014-01-01

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

  20. Tebal Struktur Histologis Duodenum Ayam Pedaging yang Diberi Kombinasi Tylosin dan Gentamicin

    Directory of Open Access Journals (Sweden)

    I Gede Gilang Ikra Raditya

    2013-12-01

    Usaha ternak broiler, sejak tahun 1998 semakin menonjol perannya dalam mempersempit kesenjangan terhadap meningkatnya kebutuhan akan daging. Daging ayam broiler dipilih sebagai salah satu alternatif, karena kita tahu bahwa ayam broiler sangat efisen diproduksi. Tujuan dilakukan penelitian ini adalah untuk mengetahui tebal struktur histologis duodenum ayam yang diberi kombinasi tylosin dan gentamicin. Metode yang dipakai pada penelitian ini menggunakan 32 ayam pedaging yang di bagi dalam 4 kelompok yang di mana masing masing kelompok terbagi atas 8 ayam. Hasil penelitian ini sendiri adalah ketebalan struktur histologis duodenum pada kontrol (P0 rata-rata 7,2 ?m, perlakuan P1 rata-rata 7,2 ?m, perlakuan P2 rata-rata adalah 7,6 ?m, dan perlakuan P3 rata-rata adalah 7,9 ?m. P3 lebih tebal dari P2 dan P2 lebih besar dari P1 dan P0. Kesimpulan dari penelitian ini adalah kombinasi tylosin dan gentamicin ini efektif untuk menyeimbangkan flora normal yang ada di dalam duodenum sehingga membuat pertumbuhan ayam menjadi sempurna.

  1. Camel Milk Beneficial Effects on Treating Gentamicin Induced Alterations in Rats

    Directory of Open Access Journals (Sweden)

    Abdulrahman K. Al-Asmari

    2014-01-01

    Full Text Available The potential effect of camel milk (CM against gentamicin (GM induced biochemical changes in the rat serum was evaluated. Four groups of six albino rats were used for control, CM fed, injected with GM(i.p., and then fed and injected with GM. The results showed that the administration of GM significantly altered the levels of aspartate aminotransferase (AST, alanine aminotransferase (ALT, alkaline phosphatase (ALP, and lactate dehydrogenase (LDH activity in rat serum. CM restored these parameters to almost their normal range in group IV. Additionally, the present study showed that injection of rats with gentamicin caused an increase in malondialdehyde (MDA and myeloperoxidase (MPO activity while the antioxidant enzymes like superoxide dismutase (SOD and glutathione s-transferase (GST activity decreased significantly (P≤0.05. Administration of CM significantly (P≤0.05 inhibited the formation of MDA and activity of MPO and upregulated the antioxidant enzymes (SOD and GST activity. The overall findings of this study demonstrated that pretreatment with CM gave protection against GM induced hepatic damage possibly by inhibiting oxidative stress and inflammation, and hence camel milk can be identified as a new therapeutic agent.

  2. Measurement of total phospholipids in urine of patients treated with gentamicin.

    Science.gov (United States)

    Saunders, D A; Begg, E J; Kirkpatrick, C M; Yeo, J; Graham, G G; Bailey, R R

    1997-04-01

    The excretion of phospholipids in urine may be a marker of the early renal toxicity of the aminoglycoside antibiotics. Urinary phospholipids are formed in myeloid bodies which develop in the lysosomes of proximal tubules during treatment with the aminoglycosides, and overflow into the urine. Published assays were modified in order to measure the total phospholipid concentrations in human urine. Phospholipids were extracted from freeze-dried urine samples, digested in concentrated sulphuric acid, and the inorganic phosphorus content determined by complexing with ammonium molybdate and measuring the absorbance at 820 nm. Ten septicaemic patients treated with gentamicin for 5-7 days had significantly higher urine phospholipid concentrations than 10 healthy untreated control subjects (P < 0.0001). There was a negative linear relationship between phospholipid excretion and creatinine clearance (r2 = 0.71). In 34 patients with acute pyelonephritis, increased phospholipid concentrations were observed prior to treatment compared with healthy controls (P < 0.001) and did not alter during treatment with gentamicin. However, the phospholipid concentrations decreased significantly after treatment was completed (P < 0.03). These studies suggest that urinary phospholipids may indicate early aminoglycoside toxicity but with poor specificity, as many of the infections being treated may themselves be associated with phospholipiduria.

  3. Application of Box-Behnken design to prepare gentamicin-loaded calcium carbonate nanoparticles.

    Science.gov (United States)

    Maleki Dizaj, Solmaz; Lotfipour, Farzaneh; Barzegar-Jalali, Mohammad; Zarrintan, Mohammad-Hossein; Adibkia, Khosro

    2016-09-01

    The aim of this research was to prepare and optimize calcium carbonate (CaCO3) nanoparticles as carriers for gentamicin sulfate. A chemical precipitation method was used to prepare the gentamicin sulfate-loaded CaCO3 nanoparticles. A 3-factor, 3-level Box-Behnken design was used for the optimization procedure, with the molar ratio of CaCl2: Na2CO3 (X1), the concentration of drug (X2), and the speed of homogenization (X3) as the independent variables. The particle size and entrapment efficiency were considered as response variables. Mathematical equations and response surface plots were used, along with the counter plots, to relate the dependent and independent variables. The results indicated that the speed of homogenization was the main variable contributing to particle size and entrapment efficiency. The combined effect of all three independent variables was also evaluated. Using the response optimization design, the optimized Xl-X3 levels were predicted. An optimized formulation was then prepared according to these levels, resulting in a particle size of 80.23 nm and an entrapment efficiency of 30.80%. It was concluded that the chemical precipitation technique, together with the Box-Behnken experimental design methodology, could be successfully used to optimize the formulation of drug-incorporated calcium carbonate nanoparticles.

  4. Radiation doses to the tissues of rat from tritiated thymidine administered by three different routes

    International Nuclear Information System (INIS)

    Takeda, Hiroshi; Iwakura, Tetsuo; Mabuchi, Yasuo.

    1984-01-01

    Biological behaviour of tritiated thymidine were investigated in rat over 120 days after oral, intraperitoneal or intravenous administration and the absorbed doses to different tissues were estimated. The result of present study revealed that the absorbed dose from tritiated thymidine varied with the route of administration. Among the three routes of administration, intraperitoneal injection gave the highest dose to all of the tissues examined. A significant difference due to the route of administration was found in spleen and small intestine, where the doses were, respectively, 3.3 and 4.5 times higher after intraperitoneal injection than after oral ingestion. The difference was substantially dependent on the dose value from non-volatile tritium which would be incorporated into DNA. Present observation suggests that the radiation hazards of tritiated thymidine differ depending on the route of entry into the body. (author)

  5. Role of somatostatin receptor-2 in gentamicin-induced auditory hair cell loss in the Mammalian inner ear.

    Directory of Open Access Journals (Sweden)

    Yves Brand

    Full Text Available Hair cells and spiral ganglion neurons of the mammalian auditory system do not regenerate, and their loss leads to irreversible hearing loss. Aminoglycosides induce auditory hair cell death in vitro, and evidence suggests that phosphatidylinositol-3-kinase/Akt signaling opposes gentamicin toxicity via its downstream target, the protein kinase Akt. We previously demonstrated that somatostatin-a peptide with hormone/neurotransmitter properties-can protect hair cells from gentamicin-induced hair cell death in vitro, and that somatostatin receptors are expressed in the mammalian inner ear. However, it remains unknown how this protective effect is mediated. In the present study, we show a highly significant protective effect of octreotide (a drug that mimics and is more potent than somatostatin on gentamicin-induced hair cell death, and increased Akt phosphorylation in octreotide-treated organ of Corti explants in vitro. Moreover, we demonstrate that somatostatin receptor-1 knockout mice overexpress somatostatin receptor-2 in the organ of Corti, and are less susceptible to gentamicin-induced hair cell loss than wild-type or somatostatin-1/somatostatin-2 double-knockout mice. Finally, we show that octreotide affects auditory hair cells, enhances spiral ganglion neurite number, and decreases spiral ganglion neurite length.

  6. Development of a standardized susceptibility test for Campylobacter with quality control ranges for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem

    DEFF Research Database (Denmark)

    McDermott, P. F.; Bodeis, S. M.; Aarestrup, Frank Møller

    2004-01-01

    -control (QC) strain. Minimal inhibitory concentration (MIC) QC ranges were determined for two incubation time/temperature combinations: 36degreesC for 48 hr and 42degreesC for 24 hr. Quality-control ranges were determined for ciprofloxacin, doxycycline, erythromycin, gentamicin, and meropenem. For all...

  7. Clinical consequences of increased ciprofloxacin and gentamicin resistance in patients with Escherichia coli bacteraemia in the Netherlands

    NARCIS (Netherlands)

    Cranendonk, Duncan R.; van der Valk, Marc; Langenberg, M. L.; van der Meer, Jan T. M.

    2012-01-01

    Background: Escherichia coli is a common cause of bacteraemia and is increasingly resistant to ciprofloxacin and gentamicin. The primary objective of this study was to investigate how often this leads to inadequate initial antimicrobial treatment. Secondary goals were to determine factors associated

  8. Erosion of the Silicone Peritoneal Dialysis Catheter with the Use of Gentamicin Cream at the Exit Site.

    Science.gov (United States)

    Gardezi, Ali I; Schlageter, Karen W; Foster, Dawn M; Astor, Brad C; Chan, Micah R; Waheed, Sana

    Infection remains the leading complication of peritoneal dialysis (PD). Topical mupirocin and gentamicin are frequently used to prevent infections. Mupirocin ointment has been reported to cause damage to both polyurethane and silicone PD catheters. Gentamicin cream has not been associated with physical damage to catheters.A 64-year-old woman on PD developed relapsing peritonitis with Staphylococcus epidermidis. Because of a drainage problem and white discoloration at the exit site, which is known as " frosting," she underwent catheter exchange. The catheter was found to be fractured within the area of frosting. Four more patients with frosting of the catheter were identified. On further questioning, it was recognized that they were applying excessive amounts of gentamicin cream directly on the catheter surface rather than at the exit site. All patients in the program were educated about the correct method of topical antibiotic application. After the change in practice, no further cases of catheter frosting were identified.Polyurethane catheters can undergo oxidation, mineralization, and environmental stress cracking, leading to physical damage such frosting, ballooning, and fracture. Polyethylene glycol, a component of the mupirocin ointment base, is thought to cause plasticization of polyurethane, reducing its tensile strength. Similar damage has been observed in silicone catheters. Previous reports have not found gentamicin cream to cause that type of damage. We observed that excessive amounts of cream applied directly to the catheter surface can damage it. Damage did not recur once patients had been educated about the proper method of application.

  9. Collagen implant with gentamicin sulphate as an option to treat a neuroischaemic diabetic foot ulcer: Case report.

    Science.gov (United States)

    Costa Almeida, C E

    2016-01-01

    The ischaemic diabetic foot is associated with a faster evolving atherosclerosis affecting preferentially the bellow knee arteries. This distal ischemia associated with a wide distribution of multiple stenosis and occlusions throughout lower limb arteries, makes revascularization very hard or even impossible. This represents a major factor responsible for non-healing diabetic foot ulcer. In these cases all efforts should be made to find treatment alternatives that can promote ulcer healing. Male patient with neuroischaemic diabetic foot ulcer with exposure tendon, without possibility for endovascular or surgical revascularization, was treated unsuccessfully with prostaglandin and several types of dressings for 7 months. Skin graft failed. Weekly dressings with collagen implant impregnated with gentamicin sulphate were then started and continued in an outpatient setting. Evolution was very positive, with 99% of epithelisation in 9 months. No pain or infection since the beginning of this treatment. Successful treatment of a neuroischaemic diabetic foot ulcer rests with the possibility of increasing the perfusion to the foot. Whether or not a revascularization procedure is possible will set the tone for the ensuing treatment. Using collagen implant with gentamicin sulphate, collagen is delivered to the wound bed helping in the granulation tissue formation, will increase microcirculation, and topic gentamicin will decrease bacterial load, exudate and proteases production, increasing cicatrisation. In neuroischaemic diabetic foot ulcer weekly dressings with collagen implant impregnated with gentamicin sulphate can be a good option for ulcer healing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Neamin as an immunogen for the development of a generic ELISA detecting gentamicin, kanamycin and neomycin in milk

    NARCIS (Netherlands)

    Loomans, E.E.M.G.; Wiltenburg, van J.; Koets, M.; Amerongen, van A.

    2003-01-01

    A broad-specific ELISA using one antibody preparation for the detection of gentamicin, kanamycin, and neomycin in milk is reported for the first time. For the immunization of rabbits, neamin was used as the generic hapten on the basis of the facts that it is a two-ring fragment of neomycin and, in

  11. In vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against Pseudomonas aeruginosa.

    OpenAIRE

    Watanakunakorn, C

    1983-01-01

    The in vitro activity of ceftriaxone alone and in combination with gentamicin, tobramycin, and amikacin against 50 Pseudomonas aeruginosa strains was studied by the broth dilution method and the time-kill curve method. The majority of the P. aeruginosa strains tested were resistant to ceftriaxone. Combining ceftriaxone with the aminoglycosides resulted in synergism, antagonism, or indifference.

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

    Science.gov (United States)

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

    2014-01-01

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

  13. An experimental design approach to the preparation of pegylated polylactide-co-glicolide gentamicin loaded microparticles for local antibiotic delivery

    Energy Technology Data Exchange (ETDEWEB)

    Dorati, Rossella; DeTrizio, Antonella; Genta, Ida; Grisoli, Pietro; Merelli, Alessia [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy); Tomasi, Corrado [IENI CNR Lecco Unit, Via Promessi Sposi 29, 23900, Lecco (Italy); Conti, Bice, E-mail: bice.conti@unipv.it [Department of Drug Sciences, Viale Taramelli 12, University of Pavia, 27100, Pavia (Italy)

    2016-01-01

    The present paper takes into account the DOE application to the preparation process of biodegradable microspheres for osteomyelitis local therapy. With this goal gentamicin loaded polylactide-co-glycolide-co-polyethyleneglycol (PLGA-PEG) microspheres were prepared and investigated. Two preparation protocols (o/w and w/o/w) with different process conditions, and three PLGA-PEG block copolymers with different compositions of lactic and glycolic acids and PEG, were tested. A Design Of Experiment (DOE) screening design was applied as an approach to scale up manufacturing step. The results of DOE screening design confirmed that w/o/w technique, the presence of salt and the 15%w/v polymer concentration positively affected the EE% (72.1–97.5%), and span values of particle size distribution (1.03–1.23), while salt addition alone negatively affected the yield process. Process scale up resulted in a decrease of gentamicin EE% that can be attributed to the high volume of water used to remove PVA and NaCl residues. The results of in vitro gentamicin release study show prolonged gentamicin release up to three months from the microspheres prepared with salt addition in the dispersing phase; the behavior being consistent with their highly compact structure highlighted by scanning electron microscopy analysis. The prolonged release of gentamicin is maintained even after embedding the biodegradable microspheres into a thermosetting composite gel made of chitosan and acellular bovine bone matrix (Orthoss® granules), and the microbiologic evaluation demonstrated the efficacy of the gentamicin loaded microspheres on Escherichia coli. The collected results confirm the feasibility of the scale up of microsphere manufacturing process and the high potential of the microparticulate drug delivery system to be used for the local antibiotic delivery to bone. - Highlights: • To get a more effective therapy for the prevention and treatment of osteomyelitis. • To exploit the local

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Science.gov (United States)

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

    1999-10-01

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

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

    Science.gov (United States)

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

    2013-04-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

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

  18. The effects of CoenzymeQ10 on gentamicin induced nephrotoxicity

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    Zeinab Hameidi Zad

    2016-10-01

    Full Text Available Abstract Background: Gentamicin (GM is one the aminoglycoside antibiotics which isroutinelyused to treatinfections gram-negative, either alone or insynergistic withbeta-lactamantibioticsused. However, frequent useleads toserious side effectssuch asrenal toxicity, ototoxicity. Coenzyme Q10 has antioxidant, anti-inflammatory and vasodilatory properties. According to these properties of Coenzyme Q10 and tissue damage mechanism in GM induced-nephrotoxicity, in this study, the effects of these two substances for the co-treatment and post -treatment on renal injury induced by gentamicin were investigated. Materials and Methods: Experiments has been done on 77 male Wistar rats in weight range of 200 to 250 g. Animals were divided randomly into 5 groups of 7 numbers. Renal nephrotoxicity induced by i.p injection of gentamicin (100mg/kg Therapeutic effect of coenzyme Q10 (10mg/kgin the two protocols co-treatment and post-treatmentwas investigated.The animals after the last injectionon the ninth day of co-treatment andthe seventeenth day of post-treatmentwere placed into individual metabolic cages so as to collection urine and urine volume was measured gravimetrically. Afteranesthesia, systolic blood pressure and renal blood flow was measured. Then blood sampling was done. Amount of urea, creatinin, sodium, potassium and osmolarity was measured in plasma and urine samples. Left kidney, for doing histological experiments in 10% buffered formaldehyde and right kidney for biochemical experiments in fluid nitrogen was preserved. Results: Co-treatment with Coenzyme Q10 significantly decreased fractional excretion of sodium (6.37±1.33 %; p<0.001 and decreased fractional excretion of potassium(219.14±83.8 %; p<0.001 MDA levels (2.13 ±0.24µmol/gkw; p<0.001, and significantly increased renal blood flow (6.38 ±0.1ml/min: p<0.01 and FRAP levels (24.44±0.42mmol/gkw; p<0.001. Post-treatment with coenzyme Q10 significantly decreased fractional excretion of sodium

  19. 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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-01-01

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

  2. ASPECTOS CLÍNICOS DA INFUSÃO INTRAPERITONEAL EM BOVINOS

    Directory of Open Access Journals (Sweden)

    Wilmar Sachetin Marçal

    2015-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Rashid Alijani Ardeshir

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

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

    International Nuclear Information System (INIS)

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

    2005-01-01

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

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

    Science.gov (United States)

    Azaïs, H; Mordon, S; Collinet, P

    2017-04-01

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

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

    International Nuclear Information System (INIS)

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

    1984-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-04-01

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

  8. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile

    Directory of Open Access Journals (Sweden)

    Bronckers Antonius LJJ

    2006-02-01

    Full Text Available Abstract Background Polymethyl-methacrylate (PMMA beads releasing antibiotics are used extensively to treat osteomyelitis, but require surgical removal afterwards because they do not degrade. Methods As an alternative option, this report compares the in vitro gentamicin release profile from clinically used, biodegradable carrier-materials: six injectable cements and six granule-types. Cement cylinders and coated granules containing 3% gentamicin were submerged in dH2O and placed in a 48-sample parallel drug-release system. At regular intervals (30, 90, 180 min. and then every 24 h, for 21 days, the release fluid was exchanged and the gentamicin concentration was measured. The activity of released gentamicin was tested on Staphylococcus aureus. Results All combinations showed initial burst-release of active gentamicin, two cements had continuous-release (17 days. The relative release of all cements (36–85% and granules (30–62% was higher than previously reported for injectable PMMA-cements (up to 17% and comparable to other biodegradable carriers. From the cements residual gentamicin could be extracted, whereas the granules released all gentamicin that had adhered to the surface. Conclusion The high release achieved shows great promise for clinical application of these biodegradable drug-carriers. Using the appropriate combination, the required release profile (burst or sustained may be achieved.

  9. Risk of hearing loss in children exposed to gentamicin for the treatment of sepsis in young infancy: A community based cohort study in pakistan

    International Nuclear Information System (INIS)

    Iftikhar, U.; Ali, S.A.; Tikmani, S.S.; Zaidi, A.K.; Azam, S.I.; Saleem, S.

    2013-01-01

    Objective: To determine the safety of gentamicin when used in a community setting to treat neonatal sepsis. Methods: The study was conducted in peri-urban areas of Karachi from September 2009 to April 2010. The exposed group consisted of children 6 months to 3 years of age who were treated for sepsis during 0-2 months of age in the community, with a regimen that included gentamicin for at least five days. The control group included children from the same area who never received gentamicin. The outcome measure was hearing loss, which was assessed by Brainstem Evoked Response Audiometry. Results: Of the 255 children enrolled, 125 (49%) received gentamicin, while 130 (51%) were not exposed to gentamicin. Children in the gentamicin exposed group were not at increased risk for hearing loss compared to controls (n=30; 30.9% vs. n=33; 31.4%, RR 0.98; 95% CI: 0.60-1.61). Children with history of ear discharge (RR 1.7) and children with family history of deafness (RR 2.0) were more at risk for having hearing loss. Conclusion: No association was found between hearing loss and gentamicin exposure in a community setting for the management of sepsis in the first two months of life. (author)

  10. Median lethal dose (LD 50 ) evaluation of some polyherbal ...

    African Journals Online (AJOL)

    The polyherbal preparations reported here are traditionally used in Northern Nigeria for the treatment of wide range of illnesses. The aim of this study was to evaluate the acute toxicity potential of 70% ethanol extracts of forty polyherbal products by determining their median lethal dose (LD50) estimates intraperitoneally and ...

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

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    Neha Dabral

    Full Text Available 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.

  12. 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.

  13. Effect of Catechins, Green tea Extract and Methylxanthines in Combination with Gentamicin Against Staphylococcus aureus and Pseudomonas aeruginosa - Combination therapy against resistant bacteria -

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    Bibi Sedigheh Fazly Bazzaz

    2016-12-01

    Full Text Available Objectives: Bacterial resistant infections have become a global health challenge and threaten the society’s health. Thus, an urgent need exists to find ways to combat resistant pathogens. One promising approach to overcoming bacterial resistance is the use of herbal products. Green tea catechins, the major green tea polyphenols, show antimicrobial activity against resistant pathogens. The present study aimed to investigate the effect of catechins, green tea extract, and methylxanthines in combination with gentamicin against standard and clinical isolates of Staphylococcus aureus (S. aureus and the standard strain of Pseudomonas aeruginosa (P. aeruginosa. Methods: The minimum inhibitory concentration (MIC and the minimum bactericidal concentration (MBC values of different agents against bacterial strains were determined. The interactions of green tea extract, epigallate catechin, epigallocatechin gallate, two types of methylxanthine, caffeine, and theophylline with gentamicin were studied in vitro by using a checkerboard method and calculating the fraction inhibitory concentration index (FICI. Results: The MICs of gentamicin against bacterial strains were in the range of 0.312 - 320 μg/mL. The MIC values of both types of catechins were 62.5 - 250 μg/ mL. Green tea extract showed insufficient antibacterial activity when used alone. Methylxanthines had no intrinsic inhibitory activity against any of the bacterial strains tested. When green tea extract and catechins were combined with gentamicin, the MIC values of gentamicin against the standard strains and a clinical isolate were reduced, and synergistic activities were observed (FICI < 1. A combination of caffeine with gentamicin did not alter the MIC values of gentamicin. Conclusion: The results of the present study revealed that green tea extract and catechins potentiated the antimicrobial action of gentamicin against some clinical isolates of S. aureus and standard P. aeruginosa strains

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

    Science.gov (United States)

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

    2015-11-01

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

  15. The effect of gentamicin-induced readthrough on a novel premature termination codon of CD18 leukocyte adhesion deficiency patients.

    Directory of Open Access Journals (Sweden)

    Amos J Simon

    2010-11-01

    Full Text Available Leukocyte adhesion deficiency 1 (LAD1 is an inherited disorder of neutrophil function. Nonsense mutations in the affected CD18 (ITB2 gene have rarely been described. In other genes containing such mutations, treatments with aminoglycoside types of antibiotics (e.g., gentamicin were reported to partially correct the premature protein termination, by induction of readthrough mechanism.Genetic analysis was performed on 2 LAD1 patients. Expression, functional and immunofluorescence assays of CD18 in the patients were used to determine the in-vivo and in-vitro effects of gentamicin-induced readthrough. A theoretical modeling of the corrected CD18 protein was developed to predict the protein function.We found a novel premature termination codon, C562T (R188X, in exon 6 of the CD18 gene that caused a severe LAD1 phenotype in two unrelated Palestinian children. In-vivo studies on these patients' cells after gentamicin treatment showed abnormal adhesion and chemotactic functions, while in-vitro studies showed mislocalization of the corrected protein to the cytoplasm and not to the cell surface. A theoretical modeling of the corrected CD18 protein suggested that the replacement of the wild type arginine by gentamicin induced tryptophan at the position of the nonsense mutation, although enabled the expression of the entire CD18 protein, this was not sufficient to stabilize the CD18/11 heterodimer at the cell surface.A novel nonsense mutation in the CD18 gene causing a complete absence of CD18 protein and severe LAD1 clinical phenotype is reported. Both in vivo and in vitro treatments with gentamicin resulted in the expression of a corrected full-length dysfunctional or mislocalized CD18 protein. However, while the use of gentamicin increased the expression of CD18, it did not improve leukocyte adhesion and chemotaxis. Moreover, the integrity of the CD18/CD11 complex at the cell surface was impaired, due to abnormal CD18 protein and possibly lack of CD11a

  16. Effect of intraperitoneal and incisional port site lidocaine on pain relief after gynecological laparoscopic surgery: A randomized controlled study

    Directory of Open Access Journals (Sweden)

    Nahla W. Shady

    2018-03-01

    Conclusions: This study clearly depicts that incisional and intraperitoneal infiltration of lidocaine is an easy, safe, inexpensive, and noninvasive method that provides good analgesia during the early post-operative period and also provides early recovery from laparoscopic surgery.

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

    Science.gov (United States)

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

    2014-06-01

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

  18. 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.

  19. intraperitoneal infiltration of ropivacaine for post-operative analgesia in open cholecystectomy

    International Nuclear Information System (INIS)

    Ahmed, A.; Ahmed, M.

    2017-01-01

    Objective: To assess the role of Intraperitoneal infiltration of Ropivacaine for post-op analgesia in open cholecystectomy in a low resource setting. Study Design: Randomized controlled trial. Place and Duration of Study: Study was conducted at department of Anesthesia, Scouts Hospital Chitral, from Jul 2014 to Jun 2016. Material and Methods: After taking approval from hospital ethical committee, total 126 patients were divided randomly in two groups. Group I (study group) was given intraperitoneal ropivacaine and group II (control group) was given routine standard analgesia. After complete recovery, pain was measure on VAS score (1-10) at 1 hour, 6 hour and 24 hour in all patients. Patients having pain score of 4 or more were managed with nalbuphine 5 mg IV bolus. Data was analyzed by SPSS version 16. Results: The comparison of pain score (after 1, 6and 24 hours of surgery), showed that study group had significantly (p-value<0.05) less mean pain score as compared with placebo group. Significant rate of nausea/vomiting was observed (p-value<0.05) higher (62%) in placebo group as compared with (38%) in study group. Statistically there was no significant difference (p-value>0.05) between groups on the basis of mean age (47.89 ± 8.56 vs. 48.75 ± 9.36), gender (Females 70% vs. 68%), duration of the surgery (88.54 ± 12.34 minutes vs. 91.70 ± 13.50 minutes) and American society of anesthesiologist (ASA) grades in study and placebo group patients respectively. Conclusion: Intraperitoneal ropivacaine infiltration helped in reducing the post op pain significantly in open cholecystectomy. (author)

  20. Ny behandling af peritoneal karcinose fra kolorektal cancer. Cytoreduktiv kirurgi og hyperterm intraperitoneal kemoterapi

    DEFF Research Database (Denmark)

    Iversen, Lene Hjerrild; Rasmussen, Peter C; Laurberg, Søren

    2007-01-01

    Peritoneal carcinomatosis (PC) is commonly seen in colorectal cancer and is uniformly fatal. Cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIIC) is a new treatment in strictly selected patients with PC. CS includes peritonectomy procedures and resection...... of infiltrated viscera leaving no macroscopic tumor thicker than 2.5 mm behind. Peritoneal perfusion with mitomycin C at a temperature of 40 degrees -41 degrees C is performed at the end of surgery. The postoperative morbidity and mortality rates are 20%-30% and 4%-8% respectively. Median survival is 1-2 years...

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

    Science.gov (United States)

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

    2015-11-01

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

  2. Fosfomycin Addition to Poly(D,L-Lactide Coating Does Not Affect Prophylaxis Efficacy in Rat Implant-Related Infection Model, But That of Gentamicin Does.

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    Anil Gulcu

    Full Text Available Gentamicin is the preferred antimicrobial agent used in implant coating for the prevention of implant-related infections (IRI. However, the present heavy local and systemic administration of gentamicin can lead to increased resistance, which has made its future use uncertain, together with related preventive technologies. Fosfomycin is an alternative antimicrobial agent that lacks the cross-resistance presented by other classes of antibiotics. We evaluated the efficacy of prophylaxis of 10% fosfomycin-containing poly(D,L-lactide (PDL coated K-wires in a rat IRI model and compared it with uncoated (Control 1, PDL-coated (Control 2, and 10% gentamicin-containing PDL-coated groups with a single layer of coating. Stainless steel K-wires were implanted and methicillin-resistant Staphylococcus aureus (ATCC 43300 suspensions (103 CFU/10 μl were injected into a cavity in the left tibiae. Thereafter, K-wires were removed and cultured in tryptic soy broth and then 5% sheep blood agar mediums. Sliced sections were removed from the tibiae, stained with hematoxylin-eosin, and semi-quantitatively evaluated with X-rays. The addition of fosfomycin into PDL did not affect the X-ray and histopathological evaluation scores; however, the addition of gentamicin lowered them. The addition of gentamicin showed a protective effect after the 28th day of X-ray evaluations. PDL-only coating provided no protection, while adding fosfomycin to PDL offered a 20% level protection and adding gentamicin offered 80%. Furthermore, there were 103 CFU level growths in the gentamicin-added group, while the other groups had 105. Thus, the addition of fosfomycin to PDL does not affect the efficacy of prophylaxis, but the addition of gentamicin does. We therefore do not advise the use of fosfomycin as a single antimicrobial agent in coating for IRI prophylaxis.

  3. Hydrogels of Poly(acrylamide-co-acrylic acid): In-vitro Study on Release of Gentamicin Sulfate

    OpenAIRE

    Thakur, A.; Wanchoo, R. K.; Singh, P.

    2012-01-01

    Poly(acrylamide-co-acrylic acid) hydrogels, poly(AAm-co-AAc), were synthesized by free radical polymerization in solution using N,N’-methylenebisacrylamide (MBAAm) as the crosslinker. The structural parameters and the swelling behavior of the synthesized hydrogels were investigated for varying nominal crosslinking ratio and composition of the hydrogels. The use of hydrogels for drug release was investigated with gentamicin sulfate (GS) as the model drug. The drug release from hydrogels was in...

  4. Electrochemical oxidation of drug residues in water by the example of tetracycline, gentamicin and Aspirin {sup trademark}

    Energy Technology Data Exchange (ETDEWEB)

    Weichgrebe, D.; Danilova, E.; Rosenwinkel, K.H. [Inst. of Water Quality and Waste Management, Univ. of Hannover, Hannover (Germany); Vedenjapin, A.; Baturova, M. [Inst. of Organic Chemistry, Russian Academy of Science, Moscow (Russian Federation)

    2003-07-01

    The electrochemical oxidation as a method to destroy drug residues like Aspirin {sup trademark}, tetracycline or gentamicin in water was investigated with C-Anode (modified by manganese oxides) and Pt Anode. The mechanism of Aspirin {sup trademark} and tetracycline oxidation and the influence of the biocide effect was observed using GC-MS and three different microbiological tests. In general the biological availability increases with progressive oxidation of the antibiotics. (orig.)

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

    Directory of Open Access Journals (Sweden)

    Alleyassin A

    2007-08-01

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

  6. Effect of intraperitoneal injection of sulodexide on peritoneal function and albumin leakage in continuous ambulatory peritoneal dialysis patients.

    Science.gov (United States)

    Guedri, Yosra; Damma, K Najla; Toumi, Melek; Sahtout, Wissal; Azzabi, Awatef; Mrabet, Sinda; Nouira, Safa; Saidane, Dalila; Amor, Samira; Belarbia, Anis; Zellama, Dorsaf; Achour, Abdellatif

    2016-01-01

    Peritoneal protein loss is one of the inevitable consequences during continuous ambulatory peritoneal dialysis (CAPD). Our objective was to study the effect of sulodexide on the protein loss and efficiency of dialysis. This study included six patients receiving CAPD treated with sulodexide at the dose of 600 IU/day given by intraperitoneal injection for 10 days. Clinical and biologic parameters were assessed before starting the treatment (D0 and after 10 days of treatment (D10. We also evaluated the benefit of therapy persisting 20 days after the end of treatment (D30. The sulodexide administration produced a significant improvement of the peritoneal function as determined by a significant increase in the following ratios measured at the 4 th h of dwell time on D0 and D30: dialysate-to plasma (D/P) creatinine from 0.63 ± 1.45 to 0.85 ± 0.073 (P = 0.028) and D/P urea from 0.63 ± 0.15 to 79 ± 0.2 (P = 0.048). A significant decrease of albumin leakage was observed, which was 0.90 ± 0.40 g/L at baseline, 0.67 ± 0.36 g/L on the 10 th day, and 0.43 ± 0.22g/L 20 days after the end of treatment. Within 10-day treatment period, use of sulodexide resulted in a reduction in the peritoneal loss of albumin, in addition to improvement of the quality of dialysis and the residual renal function among these patients.

  7. Intraperitoneal Gemcitabine Chemotherapy Treatment for Patients with Resected Pancreatic Cancer: Rationale and Report of Early Data

    Directory of Open Access Journals (Sweden)

    Paul H. Sugarbaker

    2011-01-01

    Full Text Available Currently, the surgical management of pancreas cancer is recognized around the world as inadequate. Despite a potentially curative R0 resection, long-term survival is rare. There is a strong rationale for the use of chemotherapy in the operating room to reduce local-regional of recurrent/progressive disease. Gemcitabine monotherapy administered by an intraperitoneal route in the operating room with hyperthermia and then for long-term treatment postoperatively has a pharmacologic basis in that the exposure of peritoneal surfaces to intraperitoneal gemcitabine is approximately 200–500 times the exposure that occurs within the plasma. A standardized treatment with intraoperative and long-term chemotherapy that is well tolerated would greatly facilitate further improvements in pancreas cancer treatment and may lead the way to an evolution of more successful treatment strategies of this dread disease. The aim of this paper is to present the early data on a protocol in progress in patients with resected pancreatic cancer.

  8. 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.

  9. Experimental intraperitoneal infusion of OK-432 in rats: Evaluation of peritoneal complications and pathology

    International Nuclear Information System (INIS)

    Kim, Dong Wook; Kim, Hak Jin; Lee, Jun Woo

    2010-01-01

    Purpose: OK-432 is known to be a potent sclerosant of cystic lesions. The purpose of this study was to evaluate both its safety and pathologic effects after the infusion of OK-432 into the peritoneal cavity of rats. Materials and methods: Twenty male rats were used in this study. Twelve rats were infused intraperitoneally with 0.2 Klinishe Einheit of OK-432 melted in 2 mL of normal saline (group 1: the treated group); four rats each were infused intraperitoneally with 0.5 mL of 99% ethanol (group 2) and normal saline (group 3), and served as the control groups. An abdominal ultrasonographic examination was performed both before and after the infusions in all rats. Three rats in group 1 and one rat in each of groups 2 and 3 were sacrificed each week following the infusion. Gross and microscopic evaluations of the peritoneum and abdominal cavity were performed on each rat. Results: In group 1, the abdomen was clear on gross inspection and the peritoneum was unremarkable on microscopic examination. In group 2, mild-to-moderate peritoneal adhesions were revealed grossly, and inflammation and fibrosis of the peritoneum were demonstrated microscopically. In group 3, no specific abnormalities were noted on gross or microscopic examinations. Conclusion: Leakage or abnormal infusion of OK-432 solution into the peritoneal cavity during sclerotherapy of intra-abdominal or retroperitoneal cystic lesions does not result in any significant complications.

  10. Current status and future prospects of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) clinical trials in ovarian cancer.

    Science.gov (United States)

    Cowan, Renee A; O'Cearbhaill, Roisin E; Zivanovic, Oliver; Chi, Dennis S

    2017-08-01

    The natural history of advanced-stage epithelial ovarian cancer is one of clinical remission after surgery and platinum/taxane-based intravenous (IV) and/or intraperitoneal (IP) chemotherapy followed by early or late recurrence in the majority of patients. Prevention of progression and recurrence remains a major hurdle in the management of ovarian cancer. Recently, many investigators have evaluated the use of normothermic and hyperthermic intraoperative IP drug delivery as a management strategy. This is a narrative review of the current status of clinical trials of hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) in ovarian cancer and the future directions for this treatment strategy. The existing studies on HIPEC in patients with epithelial ovarian cancer are mostly retrospective in nature, are heterogeneous with regards to combined inclusion of primary and recurrent disease and lack unbiased data. Until data are available from evidence-based trials, it is reasonable to conclude that surgical cytoreduction and HIPEC is a rational and interesting, though still investigative, approach in the management of epithelial ovarian cancer, whose use should be employed within prospective clinical trials.

  11. 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.

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

    International Nuclear Information System (INIS)

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

    1979-01-01

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

  13. Gentamicin rapidly inhibits mitochondrial metabolism in high-frequency cochlear outer hair cells.

    Directory of Open Access Journals (Sweden)

    Heather C Jensen-Smith

    Full Text Available Aminoglycosides (AG, including gentamicin (GM, are the most frequently used antibiotics in the world and are proposed to cause irreversible cochlear damage and hearing loss (HL in 1/4 of the patients receiving these life-saving drugs. Akin to the results of AG ototoxicity studies, high-frequency, basal turn outer hair cells (OHCs preferentially succumb to multiple HL pathologies while inner hair cells (IHCs are much more resilient. To determine if endogenous differences in IHC and OHC mitochondrial metabolism dictate differential sensitivities to AG-induced HL, IHC- and OHC-specific changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH fluorescence during acute (1 h GM treatment were compared. GM-mediated decreases in NADH fluorescence and succinate dehydrogenase activity were observed shortly after GM application. High-frequency basal turn OHCs were found to be metabolically biased to rapidly respond to alterations in their microenvironment including GM and elevated glucose exposures. These metabolic biases may predispose high-frequency OHCs to preferentially produce cell-damaging reactive oxygen species during traumatic challenge. Noise-induced and age-related HL pathologies share key characteristics with AG ototoxicity, including preferential OHC loss and reactive oxygen species production. Data from this report highlight the need to address the role of mitochondrial metabolism in regulating AG ototoxicity and the need to illuminate how fundamental differences in IHC and OHC metabolism may dictate differences in HC fate during multiple HL pathologies.

  14. Curcumin Attenuates Gentamicin-Induced Kidney Mitochondrial Alterations: Possible Role of a Mitochondrial Biogenesis Mechanism

    Directory of Open Access Journals (Sweden)

    Mario Negrette-Guzmán

    2015-01-01

    Full Text Available It has been shown that curcumin (CUR, a polyphenol derived from Curcuma longa, exerts a protective effect against gentamicin- (GM- induced nephrotoxicity in rats, associated with a preservation of the antioxidant status. Although mitochondrial dysfunction is a hallmark in the GM-induced renal injury, the role of CUR in mitochondrial protection has not been studied. In this work, LLC-PK1 cells were preincubated 24 h with CUR and then coincubated 48 h with CUR and 8 mM GM. Treatment with CUR attenuated GM-induced drop in cell viability and led to an increase in nuclear factor (erythroid-2-related factor 2 (Nrf2 nuclear accumulation and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α cell expression attenuating GM-induced losses in these proteins. In vivo, Wistar rats were injected subcutaneously with GM (75 mg/Kg/12 h during 7 days to develop kidney mitochondrial alterations. CUR (400 mg/Kg/day was administered orally 5 days before and during the GM exposure. The GM-induced mitochondrial alterations in ultrastructure and bioenergetics as well as decrease in activities of respiratory complexes I and IV and induction of calcium-dependent permeability transition were mostly attenuated by CUR. Protection of CUR against GM-induced nephrotoxicity could be in part mediated by maintenance of mitochondrial functions and biogenesis with some participation of the nuclear factor Nrf2.

  15. Synergistic effects of the combination of galangin with gentamicin against methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Lee, Young-Seob; Kang, Ok-Hwa; Choi, Jang-Gi; Oh, You-Chang; Chae, Hee-Sung; Kim, Jong Hak; Park, Hyun; Sohn, Dong Hwan; Wang, Zheng-Tao; Kwon, Dong-Yeul

    2008-06-01

    The antimicrobial killing activity toward methicillin-resistant Staphylococcus aureus (MRSA) has been a serious emerging global issue. New effective antimicrobials and/or new approaches to settle this issue are urgently needed. The oriental herb, Alpinia officinarum, has been used in Korea for several hundreds of years to treat various infectious diseases. As it is well known, one of the active constituents of Alpinia officinarum is galangin. Against the 17 strains, the minimum inhibitory concentrations (MICs) of galangin (GAL) were in the range of 62.5 ~ 125 microg/ml, and the MICs of gentamicin (GEN) ranged from 1.9 microg/ml to 2,000 microg/ml. The fractional inhibitory concentrations (FICs) of GAL, in combination with GEN, against 3 test strains were 0.4, 3.9, and 250 microg/ml, and were all 15.62 microg/ml in GEN. The FIC index showed marked synergism in the value range of 0.19 to 0.25. By determining time-kill curves, also confirmed the low synergism of the GAL and GEN combination against 4 h, 8 h, 12 h, and 24 h cultured MRSA. The time-kill study results indicated a low synergistic effect against 3 test strains. Thus, the mixture of GAL and GEN could lead to the development of new combination antibiotics against MRSA infection.

  16. Gentamicin coating of nanotubular anodized titanium implant reduces implant-related osteomyelitis and enhances bone biocompatibility in rabbits

    Directory of Open Access Journals (Sweden)

    Liu D

    2017-07-01

    Full Text Available Denghui Liu,1,* Chongru He,2,* Zhongtang Liu,2 Weidong Xu2 1Department of Orthopedics, the 113 Military Hospital, Ningbo, 2Department of Orthopedics, Changhai Hospital Affiliated to the Second Military Medical University, Shanghai, People’s Republic of China *These authors contributed equally to this work Abstract: Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G through in vivo study in ­rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G, nanotubular anodized titanium uncoated with gentamicin (NTATi and titanium uncoated with gentamicin (Ti. The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively (P<0.05. Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively (P<0.01. The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti

  17. Gentamicin-loaded poly(lactic-co-glycolic acid) microparticles for the prevention of maxillofacial and orthopedic implant infections

    Energy Technology Data Exchange (ETDEWEB)

    Flores, Claudia [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Degoutin, Stephanie [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Chai, Feng [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Raoul, Gwenael [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Hornez, Jean-Chritophe [Laboratoire des Matériaux Céramiques et Procédés Associés (LMCPA), Université de Valenciennes, 59300 Valenciennes (France); Martel, Bernard [Univ. Lille, 59000 Lille (France); UMET, Ingénierie des Systèmes Polymères, Université de Lille 1, 59655 Villeneuve d' Ascq (France); Siepmann, Juergen [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Ferri, Joel [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France); Service Chirurgie Maxillo-Faciale, CHRU de Lille, 59000 Lille (France); Blanchemain, Nicolas, E-mail: nicolas.blanchemain@univ-lille2.fr [Univ. Lille, 59000 Lille (France); INSERM U1008, Controlled Drug Delivery Systems and Biomaterials, 59000 Lille (France)

    2016-07-01

    Trauma and orthopedic surgery can cause infections as any open surgical procedures. Such complications occur in only1 to 5% of the cases, but the treatment is rather complicated due to bacterial biofilm formation and limited drug access to the site of infection upon systemic administration. An interesting strategy to overcome this type of complications is to prevent bacterial proliferation and biofilm formation via the local and controlled release of antibiotic drugs from the implant itself. Obviously, the incorporation of the drug into the implant should not affect the latter's biological and mechanical properties. In this context, we optimized the preparation process for gentamicin-loaded poly(lactic-co-glycolic acid) (PLGA) microparticles, which can be incorporated in the macropores of calcium phosphate-based bone substitutes. Microparticles were prepared using a double emulsion solvent extraction/evaporation technique. The processing parameters were optimized in order to provide an average microparticle size of about 60 μm, allowing for incorporation inside the macropores (100 μm) of the hydroxyapatite scaffold. Gentamicin-loaded PLGA microparticles showed a sustained release for 25–30 days and a rapid antibacterial activity due to a burst effect, the extent of which was controlled by the initial loading of the microparticles. SEM pictures revealed a highly porous microparticle structure, which can help to reduce the micro environmental pH drop and autocatalytic effects. The biological evaluation showed the cytocompatibility and non-hemolytic property of the microparticles, and the antibacterial activity against Staphylococcus aureus under the given conditions. - Highlights: • The optimization of microparticle preparation parameters allows to obtain a size compatible with the bone substitute porosity • PDL% has a direct impact on the burst effect, a control release of gentamicin was obtained • The incorporation of microparticles into the

  18. Multiwall carbon nanotubes chemically modified carbon paste electrodes for determination of gentamicin sulfate in pharmaceutical preparations and biological fluids.

    Science.gov (United States)

    Khalil, M M; Abed El-Aziz, G M

    2016-02-01

    This article focused on the construction and characteristics of novel and sensitive gentamicin carbon paste electrodes which are based on the incorporation of multiwall carbon nanotubes (MWCNTs) which improve the characteristics of the electrodes. The electrodes were constructed based on gentamicin-phosphotungstate (GNS-PTA) called CPE1, gentamicin-phosphomolybdate (GNS-PMA) called CPE2, GNS-PTA+ MWMCNTs called MWCPE1, and GNS-PMA+ MWMCNTs called MWCPE2. The constructed electrodes, at optimum paste composition, exhibited good Nernstian response for determination of gentamicin sulfate (GNS) over a linear concentration range from 2.5×10(-6) to 1×10(-2), 3.0×10(-6) to 1×10(-2), 4.9×10(-7) to 1×10(-2) and 5.0×10(-7) to 1×10(-2)molL(-1), with lower detection limit 1×10(-6), 1×10(-6), 1.9×10(-7) and 2.2×10(-7)molL(-1), and with slope values of 29.0±0.4, 29.2±0.7, 31.2±0.5 and 31.0±0.6mV/decade for CPE1, CPE2, MWCPE1 and MWCPE2, respectively. The response of electrodes is not affected by pH in the range 3-8 for CPE1 and CPE2 and in the range 2.5-8.5 for MWCPE1 and MWCPE2. The results showed fast dynamic response time (about 8-5s) and long lifetime (more than 2months) for all electrodes. The sensors showed high selectivity for gentamicin sulfate (GNS) with respect to a large number of interfering species. The constructed electrodes were successfully applied for determination of GNS in pure form, its pharmaceutical preparations and biological fluids using standard addition and potentiometric titration methods with high accuracy and precision. Published by Elsevier B.V.

  19. Gentamicin versus ceftriaxone for the treatment of gonorrhoea (G-TOG trial): study protocol for a randomised trial.

    Science.gov (United States)

    Brittain, Clare; Childs, Margaret; Duley, Lelia; Harding, Jan; Hepburn, Trish; Meakin, Garry; Montgomery, Alan A; Tan, Wei; Ross, Jonathan D C

    2016-11-24

    Gonorrhoea is a common sexually transmitted infection which causes genital pain and discomfort; in women it can also lead to pelvic inflammatory disease and infertility, and in men to epididymo-orchitis. Current treatment is with ceftriaxone, but there is increasing evidence of antimicrobial resistance which is reducing its effectiveness against gonorrhoea. A small, but increasing, number of patients have already been found to have highly resistant strains of gonorrhoea which has been associated with clinical failure. This trial aims to determine whether gentamicin is not clinically worse than ceftriaxone in the treatment of gonorrhoea. This is a blinded, two-arm, multicentre, noninferiority randomised trial. Patients are eligible if they are aged 16-70 years with a diagnosis of genital, pharyngeal and/or rectal gonorrhoea. Exclusion criteria are: known concurrent sexually transmitted infection(s) (excluding chlamydia); bacterial vaginosis and/or Trichomonas vaginalis infection; contraindications or an allergy to gentamicin, ceftriaxone, azithromycin or lidocaine; pregnancy or breastfeeding; complicated gonorrhoeal infection; weight under 40 kg; use of ceftriaxone, gentamicin or azithromycin within the preceding 28 days. Randomisation is to receive a single intramuscular injection of either gentamicin or ceftriaxone, all participants receive 1 g oral azithromycin as standard treatment. The estimated sample size is 720 participants (noninferiority limit 5%). The primary outcome is clearance of Neisseria gonorrhoeae at all infected sites by a negative Nucleic Acid Amplification Test, 2 weeks post treatment. Secondary outcomes include clinical resolution of symptoms, frequency of adverse events, tolerability of therapy, relationship between clinical effectiveness and antibiotic minimum inhibitory concentration for N. gonorrhoeae, and cost-effectiveness. The options for future treatment of gonorrhoea are limited. Results from this randomised trial will demonstrate

  20. Exame do fluido peritoneal e hemograma de eqüinos submetidos à laparotomia e infusão intraperitoneal de carboximetilcelulose Peritoneal fluid exam and hemogram of horses submited to laparotomy and carboxymethylcellulose intraperitoneal infusion

    Directory of Open Access Journals (Sweden)

    Marco Aurélio Ferreira Lopes

    1999-03-01

    Full Text Available A aplicação intraperitoneal de carboximetilcelulose (CMC tem sido utilizada na prevenção de aderências peritoneais em animais e em humanos. Os objetivos deste trabalho foram avaliar a resposta do peritônio ao trauma cirúrgico e à aplicação de CMC e estudar como se processa a metabolização da CMC. Dezenove eqüinos mestiços foram submetidos à laparotomia, quando se produziram lesões no jejuno distal por abrasão da serosa e isquemia. Nos 9 eqüinos do grupo tratamento, antes da síntese da parede abdominal, foi instilada, na cavidade peritoneal, uma solução estéril de CMC, a 1% na dose de 7ml/kg. Nos eqüinos do grupo controle, nenhum medicamento foi aplicado na cavidade peritoneal. Após a cirurgia, colheram-se sangue e fluido peritoneal em 9 momentos: 4 horas após o fim da cirurgia, nos 3 primeiros dias pós-operatórios, pela manhã e a cada 48 horas nos dias subseqüentes (no 5º, 7º, 9º, 11º e 13º dias pós-operatórios. Os exames laboratoriais demonstraram que todos os animais desenvolveram inflamação peritoneal. Entretanto, nos animais do grupo tratamento, esta inflamação foi mais intensa e com um curso mais longo. Observou-se também que a excreção da CMC ocorreu por fagocitose.Intraperitoneal application of carboxymethylcellulose (CMC has been used for peritoneal adhesions prevention in animals and humans. The objectives of this research was to study the peritoneal response to surgical trauma and application of CMC and also to study how CMC excretion occurs. Nineteen healthy mixed breed horses were submited to laparotomy to produce lesions in distal jejunum by serosal abrasion and ischemia. In the nine horses of the treatment group, 7ml/kg of a 1% CMC sterile solution were instilated in peritoneal cavity before abdominal wall syntesis. No medication was instiled in peritoneal cavitiy of the control group horses. After surgery, blood and peritoneal fluid were colected in 9 postoperative moments: 4 hours after

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

    Directory of Open Access Journals (Sweden)

    A.B. Carregaro

    2005-04-01

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

  2. In vivo effects of synthetic cannabinoids JWH-018 and JWH-073 and phytocannabinoid Δ9-THC in mice: inhalation versus intraperitoneal injection.

    Science.gov (United States)

    Marshell, R; Kearney-Ramos, T; Brents, L K; Hyatt, W S; Tai, S; Prather, P L; Fantegrossi, W E

    2014-09-01

    Human users of synthetic cannabinoids (SCBs) JWH-018 and JWH-073 typically smoke these drugs, but preclinical studies usually rely on injection for drug delivery. We used the cannabinoid tetrad and drug discrimination to compare in vivo effects of inhaled drugs with injected doses of these two SCBs, as well as with the phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC). Mice inhaled various doses of Δ(9)-THC, JWH-018 or JWH-073, or were injected intraperitoneally (IP) with these same compounds. Rectal temperature, tail flick latency in response to radiant heat, horizontal bar catalepsy, and suppression of locomotor activity were assessed in each animal. In separate studies, mice were trained to discriminate Δ(9)-THC (IP) from saline, and tests were performed with inhaled or injected doses of the SCBs. Both SCBs elicited Δ(9)-THC-like effects across both routes of administration, and effects following inhalation were attenuated by pretreatment with the CB1 antagonist/inverse agonist rimonabant. No cataleptic effects were observed following inhalation, but all compounds induced catalepsy following injection. Injected JWH-018 and JWH-073 fully substituted for Δ(9)-THC, but substitution was partial (JWH-073) or required relatively higher doses (JWH-018) when drugs were inhaled. These studies demonstrate that the SCBs JWH-018 and JWH-073 elicit dose-dependent, CB1 receptor-mediated Δ(9)-THC-like effects in mice when delivered via inhalation or via injection. Across these routes of administration, differences in cataleptic effects and, perhaps, discriminative stimulus effects, may implicate the involvement of active metabolites of these compounds. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2012-02-01

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

  4. Closed-Loop Insulin Delivery Using a Subcutaneous Glucose Sensor and Intraperitoneal Insulin Delivery

    Science.gov (United States)

    Renard, Eric; Place, Jerome; Cantwell, Martin; Chevassus, Hugues; Palerm, Cesar C.

    2010-01-01

    OBJECTIVE Attempts to build an artificial pancreas by using subcutaneous insulin delivery from a portable pump guided by an subcutaneous glucose sensor have encountered delays and variability of insulin absorption. We tested closed-loop intraperitoneal insulin infusion from an implanted pump driven by an subcutaneous glucose sensor via a proportional-integral-derivative (PID) algorithm. RESEARCH DESIGN AND METHODS Two-day closed-loop therapy (except for a 15-min premeal manual bolus) was compared with a 1-day control phase with intraperitoneal open-loop insulin delivery, according to randomized order, in a hospital setting in eight type 1 diabetic patients treated by implanted pumps. The percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was the primary end point. RESULTS During the closed-loop phases, the mean ± SEM percentage of time spent with blood glucose in the 4.4–6.6 mmol/l range was significantly higher (39.1 ± 4.5 vs. 27.7 ± 6.2%, P = 0.05), and overall dispersion of blood glucose values was reduced among patients. Better closed-loop glucose control came from the time periods excluding the two early postprandial hours with a higher percentage of time in the 4.4–6.6 mmol/l range (46.3 ± 5.3 vs. 28.6 ± 7.4, P = 0.025) and lower mean blood glucose levels (6.9 ± 0.3 vs. 7.9 ± 0.6 mmol/l, P = 0.036). Time spent with blood glucose <3.3 mmol/l was low and similar for both investigational phases. CONCLUSIONS Our results demonstrate the feasibility of intraperitoneal insulin delivery for an artificial β-cell and support the need for further study. Moreover, according to a semiautomated mode, the features of the premeal bolus in terms of timing and amount warrant further research. PMID:19846796

  5. The Treatment of Possible Severe Infection in Infants: An Open Randomized Safety Trial of Parenteral Benzylpenicillin and Gentamicin Versus Ceftriaxone in Infants <60 days of Age in Malawi.

    Science.gov (United States)

    Molyneux, Elizabeth M; Dube, Queen; Banda, Francis M; Chiume, Msandeni; Singini, Isaac; Mallewa, Macpherson; Schwalbe, Edward C; Heyderman, Robert S

    2017-12-01

    The World Health Organization recommends benzylpenicillin and gentamicin as antimicrobial treatment for infants with sepsis in low-income settings, and ceftriaxone or cefotaxime as an alternative. In a meta-analysis from 13 low-income settings, Staphylococcus aureus, Klebsiella spp. and Escherichia coli accounted for 55% of infants with sepsis. In a review of bacterial meningitis, resistance to third generation cephalosporins was >50% of all isolates, and 44% of Gram-negative isolates were gentamicin resistant. However, ceftriaxone may cause neonatal jaundice, and gentamicin may cause deafness. Therefore, we compared parenteral benzylpenicillin plus gentamicin with ceftriaxone as first-line treatment, assessing outcome and adverse events. This was an open randomized trial carried out in the Queen Elizabeth Central Hospital, Blantyre, Malawi, from 2010 to 2013. Infants ceftriaxone. Adverse events and outcomes were recorded until 6 months post discharge. Three-hundred forty-eight infants were included in analyses. Outcome in the benzylpenicillin and gentamicin and ceftriaxone groups was similar; deaths were 13.7% and 16.5% and sequelae were 14.5% and 11.2%, respectively. More infants in the penicillin/gentamicin group required phototherapy: 15% versus 5%, P = 0.03. Thirteen (6%) survivors had bilateral hearing loss. There was no difference between the treatment groups. By 6 months post discharge, 11 more infants had died, and 17 more children were found to have sequelae. Ceftriaxone and gentamicin are safe for infants in our setting. Infants should receive long-term follow-up as many poor outcomes occurred after hospital discharge.

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

    Science.gov (United States)

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

    2014-01-01

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

  7. Effect of intraperitoneal electronic identification on productive performance of Sardinian suckling lambs

    Directory of Open Access Journals (Sweden)

    I.L. Solinas

    2010-01-01

    Full Text Available The electronic identification could represent a further step to improve the traceability of meat, considering that, starting from the 1st of January 2008, this method will be compulsory in the whole EU (Reg. CE n. 21/2004. The “Agnello di Sardegna” is a Protected Geographic Identification product (Provv. 13/03/2001 and it has to match up a series of requirements, such as the identification of animals in 20 days time from birth. In a previous work, Pinna et al. (2004 showed the results of a survey carried out for the development of the intraperitoneal identification systems in lambs. In the present work, the effects on the main productive in vivo and post mortem performance are taken into account.

  8. Presumptive intraperitoneal envenomation resulting in hemoperitoneum and acute abdominal pain in a dog.

    Science.gov (United States)

    Istvan, Stephanie A; Walker, Julie M; Hansen, Bernard D; Hanel, Rita M; Marks, Steven L

    2015-01-01

    To describe the clinical features, diagnostic findings, treatment, and outcome of a dog with acute abdominal pain and hemoperitoneum secondary to a presumptive intraperitoneal (IP) snakebite. A 10-month-old castrated male mixed-breed dog was evaluated for suspected snake envenomation. The dog presented recumbent and tachycardic with signs of severe abdominal pain. Two cutaneous puncture wounds and hemoperitoneum were discovered during evaluation. Ultrasonographic examination revealed communication of the wounds with the peritoneal cavity. The dog was treated with supportive care, parenteral analgesia, packed red blood cell and fresh frozen plasma transfusions, crotalid antivenom, and placement of an IP catheter to provide local analgesia. The dog recovered fully and was discharged 5 days after initial presentation. To our knowledge, this is the first report of IP envenomation accompanied by hemorrhage treated with continuous IP analgesia in the veterinary literature. © Veterinary Emergency and Critical Care Society 2015.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    R. V. Pavlov

    2006-01-01

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

  11. Is Palliative Laparoscopic Hyperthermic Intraperitoneal Chemotherapy Effective in Patients with Malignant Hemorrhagic Ascites?

    Science.gov (United States)

    de Mestier, Louis; Volet, Julien; Scaglia, Elodie; Msika, Simon; Kianmanesh, Reza; Bouché, Olivier

    2012-01-01

    Malignant hemorrhagic ascites may complicate the terminal evolution of digestive cancers with peritoneal carcinomatosis. It has a bad influence on prognosis and may severely impair patients’ quality of life. Palliative laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to treat debilitating malignant ascites. Two cases of peritoneal carcinomatosis causing hemorrhagic ascites and severe anemia that needed iterative blood transfusions are reported. These patients were treated by laparoscopic HIPEC (mitomycin C and cisplatin with an inflow temperature of 43°C), resulting in cessation of peritoneal bleeding. No postoperative complication or relapse of ascites occurred during the following months. No more blood transfusion was needed. Laparoscopic HIPEC might be an effective and safe therapeutic option to consider in patients with malignant hemorrhagic ascites. PMID:22679405

  12. Intraperitoneal Calcitriol for Treatment of Severe Hyperparathyroidism in Children with Chronic Kidney Disease: A Therapy Forgotten.

    Science.gov (United States)

    Chanchlani, Rahul; Ackerman, Susan; Piva, Elizabeth; Harvey, Elizabeth

    Active Vitamin D sterols such as calcitriol and alfacalcidol are quite effective in the treatment of mineral bone disease secondary to chronic kidney disease. However, some children on peritoneal dialysis (PD) are resistant to oral formulations of active Vitamin D, and use of an intravenous formulation in such patients is inconvenient. In these children, intraperitoneal (IP) calcitriol has been shown to be effective in the treatment of secondary hyperparathyroidism. However, its use has declined. We report 2 children, aged 1 and 9.5 years, on chronic cycler PD with severe secondary hyperparathyroidism refractory to oral active Vitamin D who were successfully treated with IP calcitriol for a period of 12 and 4 months, respectively. We also discuss the published literature on the efficacy of IP calcitriol for treatment of secondary hyperparathyroidism and specific considerations for its use in PD patients. Copyright © 2016 International Society for Peritoneal Dialysis.

  13. Use of intraperitoneal xenon-133 for imaging of intestinal strangulation in small bowel obstruction. [Rats; Dogs

    Energy Technology Data Exchange (ETDEWEB)

    Bulkley, G.B.; Gharagozloo, F.; Alderson, P.O.; Horn, S.D.; Zuidema, G.D.

    1981-01-01

    Intraperitoneal xenon-133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay inexternally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponsed to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction.

  14. Use of intraperitoneal xenon-133 for imaging of intestinal strangulation in small bowel obstruction

    International Nuclear Information System (INIS)

    Bulkley, G.B.; Gharagozloo, F.; Alderson, P.O.; Horn, S.D.; Zuidema, G.D.

    1981-01-01

    Intraperitoneal xenon-133 dissolved in saline solution was evaluated for the detection of early strangulation in a reproducible model of segmental intestinal obstruction in rats and dogs. There was a highly significant delay inexternally detected isotope washout from animals with strangulated loops compared with normal, sham operated and simple (nonstrangulated) obstruction control groups. Corresponding anterior abdominal gamma camera images showed marked retention of isotope at 1 hour in the strangulation obstruction groups and the sites of this activity corresponsed to the location of the ischemic loops. Blinded readings of these images by nuclear radiologists showed this method to be highly accurate for the detection of strangulation in these animal models. This method should be directly applicable to patients with intestinal obstruction

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

    Directory of Open Access Journals (Sweden)

    Jae Hee Chung

    Full Text Available Polyethylene glycol (PEG-3350 is the most frequently used lavage solution for bowel cleansing prior to colonoscopy or elective surgery because its large molecular weight means that it is poorly absorbed. However, if it leaks into the peritoneal cavity, complications may arise. Few published studies have assessed the absorption, distribution, metabolism and excretion of PEG. Moreover, no published clinical data regarding complications due to the intra-peritoneal leakage of PEG-3350 could be found. We report on an elderly patient who developed the poisoning caused by leaking of PEG-3350 during bowel preparation. It resulted in severe metabolic acidosis, hypernatremia, hyperosmolality and a high anion gap, but it was effectively treated with early continuous renal replacement therapy after surgery.

  16. Bactericidal activity of penicillin, ceftriaxone, gentamicin and daptomycin alone and in combination against Aerococcus urinae.

    Science.gov (United States)

    Hirzel, Cédric; Hirzberger, Lea; Furrer, Hansjakob; Endimiani, Andrea

    2016-09-01

    Aerococcus urinae can cause severe infections (bacteraemia and endocarditis) that are associated with high mortality. However, data on the bactericidal and synergistic activity for clinically implemented antibiotics are scarce. Time-kill analyses were performed on two clinical isolates (AU1 and AU2) and the reference strain ATCC 700306 for penicillin (PG), ceftriaxone (CRO), gentamicin (GEN), daptomycin (DAP) and their combinations. AU1 and AU2 were CRO-resistant (MICs, 2 µg/mL) and ATCC 700306 was high-level GEN-resistant (MIC, 512 µg/mL), whereas all strains were PG- and DAP-susceptible (MICs, ≤0.125 and ≤1 µg/mL, respectively). CFU counts were determined at various time points from 0 to 48 h. All experiments were performed at 0.5×, 1×, 2× and 4× MIC. PG and CRO were not bactericidal for all strains, whereas DAP exhibited bactericidal activity at all concentrations for AU2 and ATCC 700306. The combination of PG or CRO with GEN was bactericidal for AU1 and AU2 at antibiotic concentrations ≥1× MIC. Bactericidal synergism was detected for PG or CRO combined with GEN in the two clinical isolates. PG plus CRO showed non-bactericidal synergism for ATCC 700306. DAP with GEN was synergistic at 1× MIC for AU1, whereas the killing activity of DAP was too pronounced to detect potential synergism in AU2. The combination of PG or CRO with GEN is synergistic and bactericidal. Moreover, these in vitro data suggest that DAP may represent a potential bactericidal treatment alternative against A. urinae. This finding could be important for the treatment of patients with a β-lactam allergy or renal insufficiency. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  17. Efficacy of ciprofloxacin-gentamicin combination therapy in murine bubonic plague.

    Directory of Open Access Journals (Sweden)

    Nadine Lemaître

    Full Text Available Potential benefits of combination antibiotic therapy for the treatment of plague have never been evaluated. We compared the efficacy of a ciprofloxacin (CIN and gentamicin (GEN combination therapy with that of each antibiotic administered alone (i against Yersinia pestis in vitro and (ii in a mouse model of bubonic plague in which animals were intravenously injected with antibiotics for five days, starting at two different times after infection (44 h and 56 h. In vitro, the CIN+GEN combination was synergistic at 0.5x the individual drugs' MICs and indifferent at 1x- or 2x MIC. In vivo, the survival rate for mice treated with CIN+GEN was similar to that observed with CIN alone and slightly higher than that observed for GEN alone 100, 100 and 85%, respectively when treatment was started 44 h post challenge. 100% of survivors were recorded in the CIN+GEN group vs 86 and 83% in the CIN and GEN groups, respectively when treatment was delayed to 56 h post-challenge. However, these differences were not statistically significant. Five days after the end of treatment, Y. pestis were observed in lymph nodes draining the inoculation site (but not in the spleen in surviving mice in each of the three groups. The median lymph node log(10 CFU recovered from persistently infected lymph nodes was significantly higher with GEN than with CIN (5.8 vs. 3.2, p = 0.04 or CIN+GEN (5.8 vs. 2.8, p = 0.01. Taken as the whole, our data show that CIN+GEN combination is as effective as CIN alone but, regimens containing CIN are more effective to eradicate Y. pestis from the draining lymph node than the recommended GEN monotherapy. Moreover, draining lymph nodes may serve as a reservoir for the continued release of Y. pestis into the blood - even after five days of intravenous antibiotic treatment.

  18. Experimental gentamicin nephrotoxicity and agents that modify it: a mini-review of recent research.

    Science.gov (United States)

    Ali, Badreldin H; Al Za'abi, Mohammed; Blunden, Gerald; Nemmar, Abderrahim

    2011-10-01

    The aminoglycoside antibiotic gentamicin (GM) is still widely used against infections by Gram-positive and Gram-negative aerobic bacteria. Its therapeutic efficacy, however, is limited by renal impairment that occurs in up to 30% of treated patients. The drug may accumulate in epithelial tubular cells causing a range of effects starting with loss of the brush border in epithelial cells and ending in overt tubular necrosis, activation of apoptosis and massive proteolysis. GM also causes cell death by generation of free radicals, phospholipidosis, extracellular calcium-sensing receptor stimulation and energetic catastrophe, reduced renal blood flow and inflammation. Many drugs have been shown to either ameliorate or potentiate GM nephrotoxicity. This article aims at updating the literature that has been published in the past decade on the effects of agents that either ameliorate or augment the nephrotoxicity of this aminoglycoside. Notable among the new ameliorating procedures are gene therapy, such as intravenous cell therapy with serum amyloid A protein-programmed cells, and the use of some novel antioxidant agents and oils of natural origin. These include, for example, green tea, garlic saffron, grape seed extracts as well as sesame and oleanolic oils. Agents that may augment GM nephrotoxicity include indomethacin, cyclosporin, uric acid and the Ca(++) -channel blocker verapamil. Most of the nephroprotective agents mentioned here have not been tested in large controlled clinical trials. Because of their relative safety and effectiveness, antioxidant agents seem to be good candidates for testing in humans. © 2011 The Authors. Basic & Clinical Pharmacology & Toxicology © 2011 Nordic Pharmacological Society.

  19. Intraperitoneal Hydrocortisone plus Bupivacaine versus Bupivacaine alone for Pain Relief after Laparoscopic Cholecystectomy

    Directory of Open Access Journals (Sweden)

    Mahesh Sharma

    2016-11-01

    Full Text Available Introduction: Laparoscopic cholecystectomy has been the gold standard in the treatment of gallstones since last decades. Beside several benefits of laparoscopic cholecystectomy compared with open surgery, postoperative pain is still a frequent melancholy.  Hence, pain management is utmost regarding patients' comfort. The main objective of the study was to compare the effect of intraperitoneal hydrocortisone plus bupivacaine with bupivacaine alone on pain relief following laparoscopic cholecystectomy.   Methods: A randomized study was conducted from December 2015 to August 2015 that included 100 patients aged 20 to 60 years of both genders who were found to have symptomatic gallstones and were scheduled for elective laparoscopic cholecystectomy at Lumbini Medical College. Patients randomly received 100 mg hydrocortisone plus 100 mg bupivacaine in 200 ml normal saline (group A or 100 mg bupivacaine in 200 ml normal saline (group B into the peritoneum. Post-operative abdominal and shoulder pain were evaluated using Visual Analog Score (VAS. The patients were also followed up for postoperative analgesic requirements, and recovery variables. Data were collected, tabulated and analyzed statistically using SPSS version 19.   Results: Total number of patients in this study were 100. Age and gender among both groups were comparable. VAS scores for pain was significantly lower for group A as compared to group B at 0, 2, 4, 6, 12, and 24 hours. Time of oral intake in hrs for liquids and solids was statistically significant in Group A compared to Group B. Rescue analgesic requirement was also significantly low in Group A compared to Group B. Hospital stay in both group were comparable.   Conclusion: Combination of hydrocortisone plus bupivacaine can relieve pain after laparoscopic cholecystectomy better compared to bupivacaine alone when administered intraperitoneally.

  20. Formation of adhesion after intraperitoneal application of TiMesh: experimental study on a rodent model.

    Science.gov (United States)

    Delibegovic, Samir; Koluh, Anhel; Cickusic, Elmir; Katica, Muhamed; Mustedanagic, Jasminka; Krupic, Ferid

    2016-10-01

    After laparoscopic repair of an incisive hernia, intraperitoneal prosthetic mesh, as a foreign material, is a strong stimulus for the development of adhesion, which may be the cause of serious complications. This experimental study compared three different meshes and their ability to prevent the formation of adhesion and shrinkage. Ninety rats were divided randomly into three groups: in Group 1 Proceed mesh was implanted, in Group 2 Ultrapro mesh was implanted, and in Group 3 TiMesh was implanted. Mesh samples were fixed as an intraabdominal mesh in the upper part of the abdomen. Ten animals from each group were sacrificed on days 7, 28 and 60 post-surgery. After opening the abdomen, the formation of adhesion was assessed according to the Surgical Membrane Study Group (SMSG) score, the percentage of shrinkage of the mesh was established and inflammatory reaction scored. The SMSG score for adhesion was statistically significantly higher on all the postoperative days in the Proceed and Ultrapro mesh groups than in the TiMesh group which caused milder inflammatory reaction on 60th day than others meshes. The size of the mesh after 7 days was statistically significantly smaller in the Proceed and Ultrapro groups than in the TiMesh group, but after 60 days it was statistically significantly larger than in the TiMesh group. The least formation of adhesion was noted in the TiMesh group, in which the highest level of shrinkage was noticed after 28 and 60 days. TiMesh has advantages over the other meshes studied, but a larger size mesh may be recommended for intraperitoneal application.

  1. Laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) for refractory malignant ascites in patients unsuitable for cytoreductive surgery.

    Science.gov (United States)

    Valle, S J; Alzahrani, N A; Alzahrani, S E; Liauw, W; Morris, D L

    2015-11-01

    Malignant ascites (MA) is the abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal dissemination of their disease and is associated with a short life expectancy. The most common clinical feature is a progressive increase of abdominal distention resulting in pain, discomfort, anorexia and dyspnoea. Currently, no treatment is established standard of care due to limited efficacy or considerable toxicity. The objective was to examine the efficacy of laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) in the palliation of refractory MA in patients who were unsuitable for cytoreductive surgery. From May 2009 to June 2015, 12 patients with MA due to their peritoneal malignancy were treated with laparoscopic HIPEC. The time between operation and repeat paracentesis, in-hospital data, and the proportion of patients that did not require repeat paracentesis was analyzed. One patient (8%) was admitted to ICU for 1 day. The mean operating time and hospital stay was 149.3 min (range 79-185) and 4.6 days (range 2-11) respectively. Neither high-grade morbidity nor mortality was observed. The median OS was 57 days. In our experience, a complete and definitive disappearance of MA was observed in 83% of patients. Two patients (17%) developed recurrent MA 124 days and 283 days post-HIPEC. Laparoscopic HIPEC is a beneficial treatment for the management and palliation of refractory MA and results in an excellent clinical and radiological resolution in patients with a complete resolution observed in selected patients. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  2. Intraperitoneal mesh devices for small midline hernias: mesh behavior in a porcine model.

    Science.gov (United States)

    Reynvoet, E; Chiers, K; Van Overbeke, I; Troisi, R; Berrevoet, F

    2015-12-01

    Although clinical data on long-term efficacy are lacking, the use of self-expanding devices for intraperitoneal placement in the management of small midline hernias has been popularized. In the present experimental study, two different devices were investigated regarding tissue ingrowth, adhesion formation and solid mesh placement. Two devices of 4.3 cm diameter, one ePTFE-containing small pore polypropylene mesh (PP/ePTFE) and a multi-layered large-pore polypropylene patch with an oxidized cellulose anti-adhesive barrier (PP/ORC), both containing a self-deployment system, were placed intraperitoneally at the linea alba of 24 female pigs. A first laparoscopy was performed to evaluate mesh positioning against the abdominal wall. 1 (n = 6), 2 (n = 6), 4 (n = 6) and 12 weeks (n = 6) later, mesh appearance was inspected and adhesion formation was assessed. All meshes were excised for histological evaluation. Folding of the patch was more frequently observed at PP/ePTFE, yet no excessive cupping was noticed. Adhesions predominantly presented at short-term evaluation. Overall adhesion formation at all samples was significantly more extensive for PP/ORC (p = 0.048). Massive shrinkage was observed for PP/ORC: after a 12-week period 22% residual surface was preserved, compared to 83% for PP/ePTFE (p < 0.001). While at short-term inflammatory reaction was comparable, at long-term PP/ORC induced a significant more pronounced inflammatory and foreign body reaction. Although a strong deployment system provides adequate initial placement, shrinkage and excessive adhesion formation are much more prominent in the large-pore multi-layered restorbable devices compared to the ePTFE patch. This might influence long-term clinical outcome and caution seems warranted.

  3. Intraperitoneal xenon for the detection of early intestinal ischemia: effect of ascites, adhesions, and misdirected injections

    International Nuclear Information System (INIS)

    Gharagozloo, F.; Bulkley, G.B.; LaFrance, N.; Zuidema, G.D.

    1983-01-01

    Significant delay in the washout of intraperitoneal xenon ( 133 Xe) in rats and dogs with decreased splanchnic blood flow (bowel strangulation, superior mesenteric artery and vein occlusion) has been previously demonstrated as the basis for radionuclide imaging to detect early (prenecrotic) intestinal ischemia. In this study, the effect of ascites, adhesions, and misdirected injections on the validity of this technique is evaluated. Xenon-133 (0.6 mCi) in 3 ml saline was injected into the peritoneal cavity of anesthetized rats and the washout of gamma activity monitored externally for 90 min. Gamma camera images were obtained at 30-min intervals. After 60 min, only 12 +/- 2% of injected activity remained in the controls. Sham option (13 +/- 1%) and simple obstruction (12 +/- 2) had been previously shown not to significantly slow washout, but segmental strangulation had done so dramatically (32 +/- 2%, P less than 0.0001). In these experiments, ascitic fluid (Ringer's lactate) in volumes of 10 ml (13 +/- 1%), 20 ml (13 +/- 1%), and 40 ml (13 +/- 1%), did not significantly slow washout in nonischemic rats. Sixty and eighty milliliters produced very tense ascites and slight but significant delay in washout (14 +/- 1%, 17 +/- 1%, respectively, P less than 0.05). Moderate (11 +/- 1%) and severe (11 +/- 1%) adhesions produced by serosal scarification did not delay washout nor affect imaging. Injections of isotope intentionally misdirected into the abdominal wall (32 +/- 2%), bowel wall (18 +/- 1%), and bowel lumen (19 +/- 2%), each significantly (P less than 0.001) slowed washout. However, such misdirected injections were easily recognizable as such on the 1-min gamma camera images and could thereby be excluded as artifactual. It is concluded that the intraperitoneal xenon technique is not invalidated by mild to moderate ascites nor by moderate to severe adhesions

  4. Intraperitoneal xenon for the detection of early intestinal ischemia: effect of ascites, adhesions, and misdirected injections

    Energy Technology Data Exchange (ETDEWEB)

    Gharagozloo, F.; Bulkley, G.B.; LaFrance, N.; Zuidema, G.D.

    1983-06-01

    Significant delay in the washout of intraperitoneal xenon (/sup 133/Xe) in rats and dogs with decreased splanchnic blood flow (bowel strangulation, superior mesenteric artery and vein occlusion) has been previously demonstrated as the basis for radionuclide imaging to detect early (prenecrotic) intestinal ischemia. In this study, the effect of ascites, adhesions, and misdirected injections on the validity of this technique is evaluated. Xenon-133 (0.6 mCi) in 3 ml saline was injected into the peritoneal cavity of anesthetized rats and the washout of gamma activity monitored externally for 90 min. Gamma camera images were obtained at 30-min intervals. After 60 min, only 12 +/- 2% of injected activity remained in the controls. Sham option (13 +/- 1%) and simple obstruction (12 +/- 2) had been previously shown not to significantly slow washout, but segmental strangulation had done so dramatically (32 +/- 2%, P less than 0.0001). In these experiments, ascitic fluid (Ringer's lactate) in volumes of 10 ml (13 +/- 1%), 20 ml (13 +/- 1%), and 40 ml (13 +/- 1%), did not significantly slow washout in nonischemic rats. Sixty and eighty milliliters produced very tense ascites and slight but significant delay in washout (14 +/- 1%, 17 +/- 1%, respectively, P less than 0.05). Moderate (11 +/- 1%) and severe (11 +/- 1%) adhesions produced by serosal scarification did not delay washout nor affect imaging. Injections of isotope intentionally misdirected into the abdominal wall (32 +/- 2%), bowel wall (18 +/- 1%), and bowel lumen (19 +/- 2%), each significantly (P less than 0.001) slowed washout. However, such misdirected injections were easily recognizable as such on the 1-min gamma camera images and could thereby be excluded as artifactual. It is concluded that the intraperitoneal xenon technique is not invalidated by mild to moderate ascites nor by moderate to severe adhesions.

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

    Science.gov (United States)

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

    2017-12-01

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

  6. Cefazolin-Gentamicin versus Vancomycin-Ceftazidime Eye Drops for Bacterial Corneal Ulcers; a Randomized Clinical Trial

    Directory of Open Access Journals (Sweden)

    Ali-Reza Dehghani

    2009-01-01

    Full Text Available

    PURPOSE: To compare the efficacy of topical cefazolin-gentamicin versus vancomycin-ceftazidime for treatment of bacterial corneal ulcers. METHODS: This randomized double-masked clinical trial was performed on consecutive patients with bacterial corneal ulcers referred to Feiz Hospital, Isfahan, Iran from 2004 to 2005. Patients were randomly assigned to cefazolin-gentamicin or vancomycin-ceftazidime eye drops in a masked fashion. Outcome measures included time for resolution of stromal infiltration, re-epithelization of the epithelial defect, and clearance of anterior chamber inflammation as well as culture results and complications. RESULTS: The study included 89 eyes of 89 patients with bacterial corneal ulcers consisting of 57 (64% male and 32 (36% female subjects. Specimens were culture-negative in 46% of cases. Forty-one eyes received cefazolin-gentamicin and 48 eyes were treated with vancomycin-ceftazidime. Time for resolution of stromal infiltration was 17.7±4.3 days versus 13.8±3.6 days (P=0.04, time to complete re-epithelization was 13.2±3.1 days versus 9.6±2.7 days (P=0.01 and time for clearing of the anterior chamber was 11.6±2.9 days versus 8.1±2.3 days (P

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

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Ring-Larsen, H; Lassen, N A

    1983-01-01

    Albumin-kinetics and haemodynamic studies were performed in 20 patients with decompensated liver cirrhosis in order to improve the knowledge on genesis and perpetuation of hepatic ascites, especially with respect to determinants of intraperitoneal protein. A positive relationship was found between...... the plasma-to-peritoneal transport rate of albumin (index of 'lymph-imbalance') and the mass of intraperitoneal albumin (rlog = 0.82, P less than 0.001), indicating a significant role of 'lymph-imbalance' to sequestration of protein in the peritoneal cavity. Ascitic fluid albumin concentration...

  8. Presión intraperitoneal y ultrafiltración conseguida con diferentes volúmenes intraperitoneales

    Directory of Open Access Journals (Sweden)

    Lucila Fernández Arroyo

    Full Text Available En condiciones fisiológicas el abdomen actúa como una cavidad cerrada cuya presión aumenta de forma proporcional al volumen que contiene. El valor normal de la presión hidrostática intraperitoneal está alrededor de 0 y en pacientes en diálisis peritoneal con volúmenes intraperitoneales de 2 litros puede estar en torno a 12±2 cmH2O. Realizamos un estudio multicéntrico cuantitativo, descriptivo, longitudinal y prospectivo, que incluía a 42 pacientes en programa de diálisis peritoneal con el fin de examinar la presión intraperitoneal y la ultrafiltración conseguida al infundir diferentes volúmenes de líquido de diálisis. Se hicieron dos intercambios consecutivos el primero con 2500 ml y el segundo con 1500 ml con líquido de diálisis con glucosa 2,3% y permanencia de 120 minutos en cada intercambio. De los 42 pacientes el 71,5% eran hombres, con una edad de 59.31±12.23 años y con un índice de masa corporal de 27.01±4.46. La presión intraperitoneal con volumen intraperitoneal 0 fue de 8.2±4.1; con volumen intraperitoneal 2500 ml la presión fue de 13.8±4.4 y la ultrafiltración de 131±206; con volumen intraperitoneal de 1500 ml la presión fue de 11.2±4.2 y la ultrafiltración de 192±145. La ultrafiltración con respecto a la infusión fue del 5,2%±8,2% con volumen de 2500 ml y del 12,8%±9,6% con volumen de 1500 ml. Podemos describir un aumento de la presión intraperitoneal al aumentar el volumen intraperitoneal, al mismo tiempo hemos observado una mayor ultrafiltración con volúmenes más bajos que implicaban a su vez cifras menores de presión.

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Ziyad Binkhathlan

    2017-09-01

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

  11. Experimental infection with Klebsiella pneumoniae and its gentamicin therapy in guinea pigs 60Co irradiated with 4 Gy

    International Nuclear Information System (INIS)

    Kallay, Z.; Trnovec, T.; Durisova, M.; Mazurova, E.; Navarova, J.; Plskova, M.; Kettner, M.

    1982-01-01

    Sublethal irradiation was used to suppress the immunity response of the organism. Following the development of infection with Klebsiella pneumoniae the therapeutical effect was compared of intramuscular administration and of inhalation of gentamicin. Intramuscular administration was statistically significant for reducing the mortality of infected guinea pigs as against non-treated animals at days 7 to 10 after irradiation. Administration by inhalation had the same effect between days 12 and 25 after irradiation. The weight and blood counts of the animals were observed during the experiment. (M.D.)

  12. A randomized, blinded, multicenter trial of a gentamicin vancomycin gel (DFA-02) in patients undergoing abdominal surgery.

    Science.gov (United States)

    Bennett-Guerrero, Elliott; Berry, Scott M; Bergese, Sergio D; Fleshner, Phillip R; Minkowitz, Harold S; Segura-Vasi, Alvaro M; Itani, Kamal M F; Henderson, Karen W; Rackowski, Felicia P; Aberle, Laura H; Stryjewski, Martin E; Corey, G Ralph; Allenby, Kent S

    2017-06-01

    SI is a significant medical problem. DFA-02 is an investigational bioresorbable modified release gel consisting of both gentamicin (16.8 mg/mL) and vancomycin (18.8 mg/mL). A Phase 2a study, where the drug was applied during surgical incision closure, suggested safety and tolerability but was not designed to assess its efficacy. In a Phase 2b randomized, blinded trial patients undergoing abdominal, primarily colorectal, surgery were randomized (4:1:1) to one of three study arms: DFA-02, matching placebo gel, or standard of care (SOC) involving irrigation of the wound with normal saline. The DFA-02 and placebo gel groups received up to 20 mL of study drug inserted above the fascia during wound closure, and were treated in a double-blind manner; the SOC group was treated in a single-blind manner. The primary endpoint was SSI (adjudicated centrally by a blinded committee) through postoperative day 30. Overall, 445 subjects (intention-to-treat) were randomized at 35 centers with 425 subjects completing the study and being evaluable. There were 67 SSIs (15.8%): 64.2% superficial, 7.5% deep, and 28.4% organ space. The incidence of SSI was not statistically significantly different between the DFA-02 and the placebo gel/SOC arms combined, 42/287 = 14.6% vs 25/138 = 18.1% (p = 0.36), respectively. Rehospitalization within 30 days was also similar between study groups (DFA-02 28.6%, placebo gel 21.4%, SOC 27.3%). In this multicenter, blinded, randomized trial with central adjudication, the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Patients undergoing abdominal surgery were randomized to one of three study arms: DFA-02 gel consisting of both gentamicin and vancomycin, matching placebo gel, or standard of care (SOC). Of 425 patients completing the study at 35 sites the gentamicin/vancomycin gel was not associated with a significant reduction in SSI. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. A Cassette Containing Thiostrepton, Gentamicin Resistance Genes, and dif sequences Is Effective in Construction of Recombinant Mycobacteria.

    Science.gov (United States)

    Mugweru, Julius; Makafe, Gaelle; Cao, Yuanyuan; Zhang, Yang; Wang, Bangxing; Huang, Shaobo; Njire, Moses; Chhotaray, Chiranjibi; Tan, Yaoju; Li, Xinjie; Liu, Jianxiong; Tan, Shouyong; Deng, Jiaoyu; Zhang, Tianyu

    2017-01-01

    The genetic manipulation of Mycobacterium tuberculosis genome is limited by the availability of selection markers. Spontaneous resistance mutation rate of M. tuberculosis to the widely used kanamycin is relatively high which often leads to some false positive transformants. Due to the few available markers, we have created a cassette containing thiostrepton resistance gene ( tsr ) for selection in M. tuberculosis and M. bovis BCG, and gentamicin resistance gene ( aacC1 ) for Escherichia coli and M. smegmatis mc 2 155, flanked with dif sequences recognized by the Xer system of mycobacteria. This cassette adds to the limited available selection markers for mycobacteria.

  14. Dose limits

    International Nuclear Information System (INIS)

    Fitoussi, L.

    1987-12-01

    The dose limit is defined to be the level of harmfulness which must not be exceeded, so that an activity can be exercised in a regular manner without running a risk unacceptable to man and the society. The paper examines the effects of radiation categorised into stochastic and non-stochastic. Dose limits for workers and the public are discussed

  15. General Tritium Labelling of Gentamicin C by catalytic hydrogen exchange Reaction with Tritiated Water; Marcado general con tritio de la Gentamicina C por intercambio catalitico con agua triatiada

    Energy Technology Data Exchange (ETDEWEB)

    Suarez, C.; Diaz, D.; Paz, D.

    1991-07-01

    Gentamicin C was labelled with tritium by means of a PtO2 catalyzed hydrogen exchange reaction. Under the conditions of the exchange (100 mg of gentamicin, basic form, 0,3 ml H2O-3H, and 50 mg of prereduced PtO2) the radiochemical yield was 0,24, 0,38 and 0,48 % at 120 degree celsius, for 8, 16 and 24 hours respectively. Chemical yield for purified gentamicin was about 60 %. Purification was accomplished with a cellulose column eluted with the lower phase of chloroform-methanol 17 % ammonium hydroxide (2:1:1, v/v) . Chemical purity, determined by HPLC, was 96,5 % and radiochemical one was 95. Main exchange degradation products show biological activity. (Author) 12 refs.

  16. Update on new medicinal applications of gentamicin: Evidence-based review

    Directory of Open Access Journals (Sweden)

    Changhua Chen

    2014-02-01

    Full Text Available Gentamicin (GM was discovered in 1963 and was introduced into parenteral usage in 1971. Since then, GM has been widely used in medicinal applications. The Food and Drug Administration of the United States approved the routine prescription of GM to treat the following infectious disorders: infection due to Klebsiella pneumoniae, Escherichia coli, Serratia marcescens, Citrobacter spp., Enterobacteriaceae spp., Pseudomonas spp.; Staphylococcus infectious disease; bacterial meningitis; bacterial sepsis of newborns; bacterial septicemia; infection of the eye, bone, skin and/or subcutaneous tissue; infective endocarditis; peritoneal dialysis–associated peritonitis due to Pseudomonas and other gram-negative organisms; peritonitis due to gastrointestinal tract infections; respiratory tract infections; and urinary tract infectious disease. GM is an old antibiotic and is used widely beyond its FDA-labeled indications as follows: actinomycotic infection; Staphylococcus saprophyticus bacteremia with pyelonephritis; appendicitis; cystic fibrosis; diverticulitis; adjunct regimen for febrile neutropenia; female genital infection; uterine infection; postnatal infection; necrotizing enterocolitis in fetus or newborn; osteomyelitis; pelvic inflammatory disease; plague; gonorrhea; tularemia; prophylaxis of post-cholecystectomy infection, transrectal prostate biopsy, and post–tympanostomy-related infection; malignant otitis externa; and intratympanically or transtympanically for Ménière's disease. GM is also used in combination regimens, such as with beta-lactam antibiotics to treat mixed infection and with bacteriophage to treat Staphylococcus aureus infections. It is also added to medical materials, such as GM-loaded cement spacers for osteomyelitis and prosthetic joint–associated infections. Overall, there are many medicinal applications for GM. To reduce the development of GM-resistant bacteria and to maintain its effectiveness, GM should be used

  17. La presión intraperitoneal en diálisis peritoneal

    Directory of Open Access Journals (Sweden)

    Vicente Pérez Díaz

    2017-11-01

    Full Text Available La medida de la presión intraperitoneal en diálisis peritoneal es muy sencilla y aporta claros beneficios terapéuticos. Sin embargo, su monitorización todavía no se ha generalizado en las unidades de diálisis peritoneal de adultos. Esta revisión pretende divulgar su conocimiento y la utilidad de su medida. Se realiza en decúbito antes de iniciar el drenaje de un intercambio manual con bolsa en Y, elevando la bolsa de drenaje y midiendo la altura que alcanza la columna de líquido desde la línea medio-axilar. Los valores habituales son 10 a 16 cmH2O y nunca debe superar los 18 cmH2O. Aumenta de 1 a 3 cmH2O por litro de volumen intraperitoneal sobre valores basales que dependen del índice de masa corporal y varía con la postura y la actividad física. Su aumento provoca malestar, alteraciones del sueño y de la respiración, y se ha relacionado con la aparición de fugas de líquido, hernias, hidrotórax, reflujo gastroesofágico y peritonitis por gérmenes intestinales. Menos conocida y valorada es su capacidad para disminuir la eficacia de la diálisis contrarrestando, sobre todo, la ultrafiltración y, en menor grado, el aclaramiento de solutos. Por su facilidad de medida y potencial utilidad, debería ser uno de los factores que investigar en los fallos de ultrafiltración, pues su elevación podría contribuir a ellos en algunos pacientes. Aunque todavía no se menciona en las guías de actuación en diálisis peritoneal, sus claros beneficios justifican su inclusión entre las mediciones periódicas que considerar para la prescripción y seguimiento de la diálisis peritoneal.

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

    Science.gov (United States)

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

    2017-12-01

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

  19. A low-dose regimen of cisplatin before high-dose cisplatin potentiates ototoxicity.

    Science.gov (United States)

    Harrison, Ryan T; DeBacker, J Riley; Bielefeld, Eric C

    2015-02-01

    Cochlear preconditioning with low doses of kanamycin or noise can reduce susceptibility to noise- and ototoxic drug-induced hearing loss. The current study was undertaken to investigate whether a preconditioning regimen of low-dose cisplatin would alter susceptibility to ototoxicity induced by a single large dose of cisplatin. In vivo study using an animal model. Twenty-six Fischer 344/NHsd rats were used in the study. The low-dose regimen consisted of cisplatin (2 or 3 mg/kg) given every 2 weeks by intraperitoneal injection. Control animals received injections of saline on the same schedule as the cisplatin injections. Four injections were done in total. Following the preconditioning interval, seven of the animals were sacrificed for hair cell analyses. The remaining 19 animals were exposed to 12 mg/kg cisplatin by intraperitoneal infusion to induce cochlear injury. Auditory brainstem response (ABR) thresholds were measured 3 days after cisplatin, and the cochleae from the 19 animals were harvested and analyzed. Statistical analyses revealed no threshold shifts, but mild outer hair cell losses, after the low-dose regimen. ABR threshold shifts in the rats exposed to the 12 mg/kg cisplatin dose were significantly higher at day 3 in the animals that underwent preconditioning with low-dose cisplatin. Outer hair cell losses were also greater in the preconditioned animals. Preconditioning with low-dose cisplatin, using the protocol applied in the current experiment, created potentiation of cisplatin ototoxicity, rather than protection from it. There are numerous possible explanations for this effect that should be considered. NA. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  20. Quality of life after cytoreductive surgery plus early intraperitoneal postoperative chemotherapy for pseudomyxoma peritonei: A prospective study

    DEFF Research Database (Denmark)

    Jess, Per; Iversen, Lene Hjerrild; Nielsen, Mette B

    2008-01-01

    PURPOSE: The modern treatment of pseudomyxoma peritonei is cytoreductive surgery plus intraperitoneal chemotherapy resulting in a survival of up to 70 percent after 20 years. The goal of this study was to investigate the impact on quality of life of this very aggressive treatment, which has not b...

  1. 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)

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

    NARCIS (Netherlands)

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-09-07

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

  4. Work Environment in the Operating Room during Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy : Factors Influencing Choice of Protective Equipment

    OpenAIRE

    Näslund Andréasson, Sara

    2011-01-01

    Peritoneal carcinomatosis (PC) is a common metastatic manifestation of both gastrointestinal and gynecological malignancies. Curative modes of treatment are cytoreductive surgery (CRS) combined with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC). Surgeons and operating room (OR) staff attending these procedures are exposed to chemotherapy and electrocautery smoke. Heated chemotherapy (HIPEC) may vaporize and become inhaled by those administering it and, moreover, large quant...

  5. Influence of intraperitoneal therapy with mitomycin C adsorbed on activated carbon on anastomotic and wound healing in rats

    NARCIS (Netherlands)

    Jansen, M; Jansen, PL; Fass, J; Langejurgen, E; Forsch, S; Tietze, L; Schumpelick, [No Value

    In an effort to prevent intraperitoneal dissemination of gastric carcinoma, local chemotherapy with mitomycin C adsorbed to activated carbon (MMC-CH) has been implemented. Results of clinical studies showed improved survival and a reduced systemic toxicity after the use of prophylactic treatment

  6. Determinants of virulence and of resistance to ceftiofur, gentamicin, and spectinomycin in clinical Escherichia coli from broiler chickens in Québec, Canada.

    Science.gov (United States)

    Chalmers, Gabhan; Cormier, Ashley C; Nadeau, Marie; Côté, Geneviève; Reid-Smith, Richard J; Boerlin, Patrick

    2017-05-01

    Antimicrobials are frequently used for the prevention of avian colibacillosis, with gentamicin used for this purpose in Québec until 2003. Ceftiofur was also used similarly, but voluntarily withdrawn in 2005 due to increasing resistance. Spectinomycin-lincomycin was employed as a replacement, but ceftiofur use was partially reinstated in 2007 until its definitive ban by the poultry industry in 2014. Gentamicin resistance frequency increased during the past decade in clinical Escherichia coli isolates from broiler chickens in Québec, despite this antimicrobial no longer being used. Since this increase coincided with the use of spectinomycin-lincomycin, co-selection of gentamicin resistance through spectinomycin was suspected. Therefore, relationships between spectinomycin, gentamicin, and ceftiofur resistance determinants were investigated here. The distribution of 13 avian pathogenic E. coli virulence-associated genes and their association with spectinomycin resistance were also assessed. A sample of 586 E. coli isolates from chickens with colibacillosis in Québec between 2009 and 2013 was used. The major genes identified for resistance to ceftiofur, gentamicin, and spectinomycin were bla CMY , aac(3)-VI, and aadA, respectively. The aadA and aac(3)-VI genes were strongly associated and shown to be located on a modified class 1 integron. The aadA and bla CMY genes were negatively associated, but when present together, were generally located on the same plasmids. No statistical positive association was observed between aadA and virulence genes, and virulence genes were only rarely detected on plasmids encoding spectinomycin resistance. Thus, the use of spectinomycin-lincomycin may likely select for gentamicin but not ceftiofur resistance, nor for any of the virulence-associated genes investigated. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. [Study on TGF beta 1, TGF beta 2, TGF beta 3 expression in the chick basilar papilla following gentamicin toxicity].

    Science.gov (United States)

    Li, H; Wang, J

    1998-10-01

    The beta-type transforming growth factors (TGF beta s) are secreted proteins, which play an important role in regulation of cell proliferation and differentiation in the embryonic inner ear. In order to probe into the effect of TGF beta s on the hair cell regeneration, expression of TGF beta 1, TGF beta 2 and TGF beta 3 proteins were examined by using immunohistochemistry in the chicken basilar papilla during hair cell regeneration following gentamicin ototoxicity. Ten-day-old chickens received daily subcutaneous injection of gentamicin sulfate 50 mg/kg of ten consecutive days. The animals were allowed to survive 1,3,7,14,21 and 28 days before sacrifice and preparation for examination of the expression of TGF beta 1, TGF beta 2 and TGF beta 3 proteins. Immunostaining results demonstrated that TGF beta 2 and TGF beta 3 proteins were observed in the damaged region of basilar papilla. TGF beta 2 and TGF beta 3 proteins positive cells were limited to the lumenal nuclear layer within the damaged region. TGF beta 1 protein positive cell was not found in our study. These results indicated that TGF beta 2 and TGF beta 3 proteins might play a role in regulating proliferation of the supporting cells immigrated into the lumenal nuclear layer during hair cell regeneration.

  8. Gentamicin-attenuated Leishmania infantum vaccine: protection of dogs against canine visceral leishmaniosis in endemic area of southeast of Iran.

    Science.gov (United States)

    Daneshvar, Hamid; Namazi, Mohammad Javad; Kamiabi, Hossein; Burchmore, Richard; Cleaveland, Sarah; Phillips, Stephen

    2014-04-01

    An attenuated line of Leishmania infantum (L. infantum H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A vaccine trial was conducted using 103 naive dogs from a leishmaniosis non-endemic area (55 vaccinated and 48 unvaccinated) brought into an endemic area of southeast Iran. No local and/or general indications of disease were observed in the vaccinated dogs immediately after vaccination. The efficacy of the vaccine was evaluated after 24 months (4 sandfly transmission seasons) by serological, parasitological analyses and clinical examination. In western blot analysis of antibodies to L. infantum antigens, sera from 10 out of 31 (32.2%) unvaccinated dogs, but none of the sera from vaccinated dogs which were seropositive at >100, recognized the 21 kDa antigen of L. infantum wild-type (WT). Nine out of 31 (29%) unvaccinated dogs, but none of vaccinated dogs, were positive for the presence of Leishmania DNA. One out of 46 (2.2%) vaccinated dogs and 9 out of 31 (29%) unvaccinated dogs developed clinical signs of disease. These results suggest that gentamicin-attenuated L. infantum induced a significant and strong protective effect against canine visceral leishmaniosis in the endemic area.

  9. Comparison of E-test with other conventional susceptibility testing methods for ciprofloxacin and gentamicin against gram negative enteric bacilli.

    Science.gov (United States)

    Ogbolu, D O; Terry-Alli, O A; Daini, O A; Olabiyi, F A; Igharo, E A

    2012-06-01

    Increasing antibiotic resistance in Gram negative bacteria has led to the need for a faster and reliable method for determining antimicrobial susceptibility testing. In a resource poor setting like ours, it's also important to look for methods that will be clinically and economically beneficial to the patient. This study was aimed at evaluating the Epsilometer test (E-test) and conventional methods for determining antimicrobial susceptibility of isolates of Gram-negative enteric bacteria to ciprofloxacin and gentamicin. Disc diffusion, E-test, broth dilution and agar dilution methods were performed on 54 bacterial isolates. Using the E-test, 88.9% of bacterial isolates were resistant to ciprofloxacin, 92.6% were resistant using broth microdilution, 96.3% were resistant using agar dilution and 72.2% were resistant using disc diffusion. Minimum inhibitory concentration (MIC50) of isolates for gentamicin showed significant difference for all the techniques (p 0.05). Both E-test and broth dilution methods showed high levels of agreement (p > 0.05), there were low levels of agreement between E-test and agar dilution method (p < 0.05), especially at MIC50. The E-test can therefore be considered a reliable method to determine antimicrobial susceptibility testing and it gives results which are at least as accurate as those obtained by the broth dilution method.

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

    Directory of Open Access Journals (Sweden)

    Xinhe Wang

    2015-07-01

    Full Text Available The prion hypothesis postulates that the infectious agent in transmissible spongiform encephalopathies (TSEs is an unorthodox protein conformation based agent. Recent successes in generating mammalian prions in vitro with bacterially expressed recombinant prion protein provide strong support for the hypothesis. However, whether the pathogenic properties of synthetically generated prion (rec-Prion recapitulate those of naturally occurring prions remains unresolved. Using end-point titration assay, we showed that the in vitro prepared rec-Prions have infectious titers of around 104 LD50/μg. In addition, intraperitoneal (i.p. inoculation of wild-type mice with rec-Prion caused prion disease with an average survival time of 210-220 days post inoculation. Detailed pathological analyses revealed that the nature of rec-Prion induced lesions, including spongiform change, disease specific prion protein accumulation (PrP-d and the PrP-d dissemination amongst lymphoid and peripheral nervous system tissues, the route and mechanisms of neuroinvasion were all typical of classical rodent prions. Our results revealed that, similar to naturally occurring prions, the rec-Prion has a titratable infectivity and is capable of causing prion disease via routes other than direct intra-cerebral challenge. More importantly, our results established that the rec-Prion caused disease is pathogenically and pathologically identical to naturally occurring contagious TSEs, supporting the concept that a conformationally altered protein agent is responsible for the infectivity in TSEs.

  11. Indications for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in elderly patients with peritoneal malignancy.

    Science.gov (United States)

    Kitai, Toshiyuki; Yamanaka, Kenya; Miyauchi, Yuya; Kawashima, Masahiro

    2017-06-01

    A combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is effective for some peritoneal malignancies. However, the indications for elderly patients remain unclear, with substantial postoperative morbidity and mortality being problematic. Clinical data were analyzed in 42 patients undergoing CRS + HIPEC for peritoneal malignancy. The primary tumor was located in the appendix in 32 cases and elsewhere in 10 cases. Operative results and survival data were compared between patients aged ≥70 and Elderly patients had a higher peritoneal cancer index (32.0 vs. 21.5), higher CA19-9 level (189.0 vs. 28.1), and higher frequency of grade 4-5 complications (5/9 vs. 2/26) than the younger patients. Grade 4-5 respiratory failure occurred in three elderly patients. There was a significant difference of postoperative survival between the elderly patients and younger patients, with 5-year survival rates being 41.3 and 74.2%, respectively (p = 0.0166). The poor prognosis of elderly patients was related to the higher frequency of grade 4-5 complications. Elderly patients were referred for treatment with more advanced disease than younger patients. An age ≥70 years was associated with more frequent grade 4-5 complications and worse survival. Performing CRS + HIPEC in elderly patients should be considered carefully due to the risk of severe complications, especially respiratory failure.

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

    Directory of Open Access Journals (Sweden)

    Martin Hübner

    2017-01-01

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

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

    International Nuclear Information System (INIS)

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

    2004-01-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2012-06-01

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

  17. Intraperitoneal microdialysis in the postoperative surveillance after surgery for necrotizing enterocolitis: a preliminary report.

    Science.gov (United States)

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

    2011-02-01

    The aim of the present pilot study was to evaluate the safety and clinical application of intraperitoneal microdialysis (MD) in preterm infants operated on for necrotizing enterocolitis (NEC). Fourteen infants underwent MD. Two were excluded from analysis: 1 because of catheter malfunction and 1 because of fatal outcome immediately after surgery. The median MD time was 122 hours. Samples were collected every 4 hours, and the concentration of glucose, lactate, pyruvate, and glycerol was measured. Three infants were reoperated on: 2 because of recurrent NEC and 1 because of ileal stenosis. In the 2 cases with recurrent NEC, changes in MD variables were found. Another had a prolonged postoperative period owing to diffuse fecal peritonitis. The values of MD normalized along with the return of bowel function. In 8 infants, the postoperative course was uncomplicated. The results of peritoneal MD in patients with complications were significantly different from those with an uncomplicated course (lactate/pyruvate ratio and glucose concentration). Peritoneal MD is a safe procedure and an applicable method in surveillance of the metabolic and inflammatory changes in the peritoneal cavity after surgery for NEC. Larger series are needed to evaluate the clinical significance and use of this method. Copyright © 2011 Elsevier Inc. All rights reserved.

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

    DEFF Research Database (Denmark)

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

    2004-01-01

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

  19. 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.

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

    Science.gov (United States)

    Rosa, P; Clementi, F

    1983-01-01

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

  2. Subcutaneous versus subcutaneous and intraperitoneal local anaesthetic in the management of post appendicectomy pain

    International Nuclear Information System (INIS)

    Qureshi, K.Z.; Gondal, Z.I.; Raza, A.

    2014-01-01

    To compare the efficacy of subcutaneous only and combined subcutaneous and peritoneal infiltration of 0.5% bupivacaine during appendicectomy for the management of early post operative pain. Study Design: Randomized controlled study. Place and Duration of Study: Department of Surgery, CMH Kohat from 13th December 2007 to 20th December 2008. Patients and Methods: Sixty patients of a cute appendicitis, divided into two groups of 30 each, were included in the study. Group A was given 0.5% bupivacaine subcutaneously, whereas group B was given the anaesthetic subcutaneously as well as intraperitoneally during appendectomy. Results: In group A, 24 (80%) were VAS (visual analoguescoring) 3 (uncomfortable) and 6 (20%) were VAS 2 (mild pain) whereas in study group B, 11 (36.6%) were VAS 3, 19 (63.3%) were VAS 2 and 19 (63.3%) were VAS 2 during 1st 12 hrs postoperatively (p=0.001). In 12-24 hrs post operatively, 15 (50%) patients were VAS 3 in group A and same number was VAS 2 and in group B, only 3 (10%) were in VAS 3 and 27 (90%) were VAS 2 (p=0.001). Conclusion: A combination of subcutaneous and peritoneal infiltration with bupivacaine is superior in relieving post appendectomy pain so patients require less dosage of analgesics in early post operative period along with early mobilization. (author)

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

    International Nuclear Information System (INIS)

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

    1997-01-01

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

  4. Incidence and predictors of postoperative delirium after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Plas, Matthijs; Hemmer, Patrick H J; Been, Lukas B; van Ginkel, Robert J; de Bock, Geertruida H; van Leeuwen, Barbara L

    2018-02-01

    Incidence of, and baseline characteristics associated with delirium in patients after cytoreduction surgery-hyperthermic intraperitoneal chemotherapy (CRS-HIPEC), were subject of investigation. The study was conducted among a consecutive series of prospectively included patients who underwent CRS-HIPEC at the University Medical Center Groningen, Groningen, the Netherlands, between February 2006 and January 2015. A chart-based instrument for delirium during hospitalization was used to identify patients with symptoms of delirium who were not diagnosed by a psychiatrist during admission. Uni- and multivariate logistic regression analyses were performed. Data of 136 patients were included in the analysis. Median age was 60 years (range: 18-76) and 50 (37%) patients were male. During hospitalization, 38 (28%) patients were diagnosed with delirium. Factors that differed significantly between the patients with and without delirium by univariate analysis were included in multivariate analysis. Multivariate analysis showed that after adjustment for age and complications other than delirium, having three or more organs resected and the CRP serum levels were independent predictors for delirium (OR: 3.97; 95% 1.24-12.76; OR: 1.01; 95% 1-1.01, respectively). This report shows an incidence of 28% of delirium, occurring after CRS-HIPEC and suggests a role for systemic inflammation in the development of postoperative delirium. © 2017 Wiley Periodicals, Inc.

  5. Multiwall carbon nanotubes chemically modified carbon paste electrodes for determination of gentamicin sulfate in pharmaceutical preparations and biological fluids

    Energy Technology Data Exchange (ETDEWEB)

    Khalil, M.M., E-mail: magdy_mmagdy@yahoo.com; Abed El-aziz, G.M., E-mail: Gamal_abedelaziz@yahoo.com

    2016-02-01

    This article focused on the construction and characteristics of novel and sensitive gentamicin carbon paste electrodes which are based on the incorporation of multiwall carbon nanotubes (MWCNTs) which improve the characteristics of the electrodes. The electrodes were constructed based on gentamicin-phosphotungstate (GNS-PTA) called CPE{sub 1}, gentamicin-phosphomolybdate (GNS-PMA) called CPE{sub 2}, GNS-PTA + MWMCNTs called MWCPE{sub 1}, and GNS-PMA + MWMCNTs called MWCPE{sub 2}. The constructed electrodes, at optimum paste composition, exhibited good Nernstian response for determination of gentamicin sulfate (GNS) over a linear concentration range from 2.5 × 10{sup −6} to 1 × 10{sup −2}, 3.0 × 10{sup −6} to 1 × 10{sup −2}, 4.9 × 10{sup −7} to 1 × 10{sup −2} and 5.0 × 10{sup −7} to 1 × 10{sup −2} mol L{sup −1}, with lower detection limit 1 × 10{sup −6}, 1 × 10{sup −6}, 1.9 × 10{sup −7} and 2.2 × 10{sup −7} mol L{sup −1}, and with slope values of 29.0 ± 0.4, 29.2 ± 0.7, 31.2 ± 0.5 and 31.0 ± 0.6 mV/decade for CPE{sub 1}, CPE{sub 2}, MWCPE{sub 1} and MWCPE{sub 2}, respectively. The response of electrodes is not affected by pH in the range 3–8 for CPE{sub 1} and CPE{sub 2} and in the range 2.5–8.5 for MWCPE{sub 1} and MWCPE{sub 2}. The results showed fast dynamic response time (about 8–5 s) and long lifetime (more than 2 months) for all electrodes. The sensors showed high selectivity for gentamicin sulfate (GNS) with respect to a large number of interfering species. The constructed electrodes were successfully applied for determination of GNS in pure form, its pharmaceutical preparations and biological fluids using standard addition and potentiometric titration methods with high accuracy and precision. - Graphical abstract: The incorporation of MWCNTs in paste composition improves the characteristics of the MWCPE electrodes which show better responses in terms of sensitivity, Nernstian slope, linear range, faster

  6. Cimento ósseo com gentamicina no tratamento da infecção óssea: estudo da eluição in vitro Bone cement and gentamIcin in the treatment of bone infection: background and in vitro study

    Directory of Open Access Journals (Sweden)

    Matheus Lemos Azi

    2010-01-01

    Full Text Available OBJETIVO: Determinar as características de eluição da gentamicina. MÉTODO: 480mg de gentamicina foram adicionadas a 40g de cimento ósseo. Dez corpos de teste semelhantes foram produzidos e imersos individualmente em solução salina tamponada por 28 dias. Amostras dos dias 1, 2, 7, 14, 21 e 28 foram analisadas pelo método de imunofluorescência polarizada. RESULTADO: A maior parte da gentamicina foi liberada do cimento nas primeiras 24 horas. Uma queda gradual se deu do 2° ao 14° dia. No 28° dia, a maior parte das amostras não apresentava mais níveis detectáveis do antibiótico. CONCLUSÃO: A mistura liberou quantidades elevadas e em doses terapêuticas do antibiótico de forma previsível ate o décimo quarto dia.OBJECTIVE: To determine the elution characteristics of the antibiotic (gentamicin mixed with bone cement. METHODS: 480mg of gentamicin was added to 40g of bone cement. Ten specimens were immersed in buffered saline solution for 28 days. Samples of days 1, 2, 7, 14, 21 and 28 were analyzed by the fluorescence polarization immunoassay method. RESULTS: Most of the gentamicin was eluted from the cement in the first 24 hours. A gradual downslide occurred between days 2 and 14. By the 28th day, there was no trace of the antibiotic. CONCLUSION: The mixture released high amounts of the antibiotic in a predictable (therapeutic manner during at least fourteen days.

  7. 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.

  8. Controllable dose

    International Nuclear Information System (INIS)

    Alvarez R, J.T.; Anaya M, R.A.

    2004-01-01

    With the purpose of eliminating the controversy about the lineal hypothesis without threshold which found the systems of dose limitation of the recommendations of ICRP 26 and 60, at the end of last decade R. Clarke president of the ICRP proposed the concept of Controllable Dose: as the dose or dose sum that an individual receives from a particular source which can be reasonably controllable by means of any means; said concept proposes a change in the philosophy of the radiological protection of its concern by social approaches to an individual focus. In this work a panorama of the foundations is presented, convenient and inconveniences that this proposal has loosened in the international community of the radiological protection, with the purpose of to familiarize to our Mexican community in radiological protection with these new concepts. (Author)

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

    Science.gov (United States)

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

    2018-04-03

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

  10. Intraperitoneal bupivacaine with or without incisional bupivacaine for postoperative analgesia in dogs undergoing ovariohysterectomy.

    Science.gov (United States)

    Kalchofner Guerrero, Karin S; Campagna, Ivo; Bruhl-Day, Rodolfo; Hegamin-Younger, Cecilia; Guerrero, Tomas G

    2016-09-01

    Intraperitoneal (IP) bupivacaine provides postoperative analgesia in dogs undergoing ovariohysterectomy (OHE) alone or in combination with incisional (INC) bupivacaine. This study investigated whether the combination of INC and IP bupivacaine is superior to IP bupivacaine alone. Prospective, randomized, blinded clinical study. Thirty-nine privately owned dogs undergoing OHE, aged 25 ± 23 months and weighing 11.8 ± 5.7 kg. Dogs were premedicated with acepromazine (0.05 mg kg(-1) ) and morphine (0.5 mg kg(-1) ) intramuscularly (IM); anaesthesia was induced with propofol and maintained with isoflurane in oxygen. Carprofen (4 mg kg(-1) ) was administered subcutaneously (SC) after intubation. Bupivacaine (3 mg kg(-1) ) IP was administered before complete closure of the linea alba to all dogs. Dogs were randomly assigned into two groups: group B received bupivacaine (n = 20; 1 mg kg(-1) ) and group S received saline (n = 19; 0.2 mL kg(-1) ) INC as a subcutaneous 'splash' before skin closure. Postoperative analgesia was assessed with a dynamic interactive visual analogue scale, the short form of the Glasgow Composite Pain Scale, and mechanical nociceptive threshold (MNT) measurement at 0.5, 1, 2, 4, 6, 8, 12 and 20 hours after surgery by one blinded observer. Parametric data were tested using t-test; nonparametric data were analysed using the two-sample Wilcoxon test (p Bupivacaine IP and carprofen SC after morphine IM did provide satisfactory postoperative analgesia in dogs undergoing OHE with the anaesthetic protocol used. There appears to be no clinical advantage to adding bupivacaine INC. Neither protocol could prevent the development of primary hyperalgesia. © 2016 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesia and Analgesia.

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

    Science.gov (United States)

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

    2017-05-25

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

  12. Unresectability during open surgical exploration in planned cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

    Science.gov (United States)

    Yong, Zachary Zihui; Tan, Grace Hwei Ching; Wong, Joelle Fui Sze; Lim, Cindy; Soo, Khee Chee; Teo, Melissa Ching Ching

    2016-12-01

    Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy are the treatment of choice for selected patients with peritoneal metastasis. Despite a stringent selection process, some patients were found to be unresectable only at surgery, which leads to disappointment and poor utilisation of limited infrastructural resources. This study aims to determine the pre-operative factors associated with unresectability in planned CRS and HIPEC. Retrospective analysis of 172 consecutive patients eligible for CRS and HIPEC at the National Cancer Centre Singapore from April 2004 to May 2014 was performed. Pre-operative factors (clinical presentation, disease factors, and investigation findings) between the unresectable (13%) and the successful groups (87%) were compared. Patient demographics between the two cohorts were comparable. In terms of clinical presentation, the unresectable group was more likely to present with bloating (p = .00), altered bowel habits (p = .04), abdominal distension (p = .00), palpable abdominal masses (p = .00) and palpable pouch of Douglas nodules (p = .00). Differences were also noted in disease factors with the unresectable group having more high-grade tumours (p = .01), inadequate initial resections (p = .01), progression through chemotherapy (p = .00) and shorter median disease-free intervals (p = .03). In addition, investigations in the unresectable group revealed more patients with elevated tumour markers (p = .01), thrombocytosis (p = .00) and computed tomography findings of ascites (p = .00), omental thickening (p = .00), lymphadenopathy (p = .02) and small bowel disease (p = .00). Significant factors associated with unresectability that were identified in our study could potentially create a new treatment algorithm and refine current selection process to exclude patients at risk of unresectability in planned CRS and HIPEC.

  13. 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.

  14. Base Excess as a Predictor of Complications in Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

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

    2017-09-01

    Base excess is important in assessing metabolic status. Postoperative management in patients undergoing cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancies can be a challenge, and we therefore sought to investigate perioperative predictors of overall morbidity in CRS/HIPEC patients at our institution. Patients who underwent CRS/HIPEC from 2012 to 2016 were identified retrospectively from a prospectively collected institutional database. Patient demographics and perioperative variables were obtained and the comprehensive complication index (CCI) was calculated for each patient in order to assess perioperative morbidity. Stepwise linear regression analyses were performed, with CCI as the outcome variable. A total of 72 CRS/HIPEC patients had recorded base excesses in the first 48 h postoperatively. Mean immediate postoperative base excess was -6.0 mmol/L (interquartile range [IQR] -8 to -4.1), mean delta base excess at 48 h was +4.3 mmol/L (IQR +2.1 to +6.2), and mean CCI was 25.2 (IQR 8.7-36.7). On multivariate analysis, delta base excess was the only significant predictor of CCI, demonstrating a protective effect (p = 0.001). In patients who experienced less than the mean delta base excess of +4.3 mmol/L, lower delta base excess was an independent predictor of complications (p < 0.001). Delta base excess is an independent predictor of morbidity in patients undergoing CRS/HIPEC. A delta base excess of greater than +4.3 mmol/L at 48 h may be an appropriate goal for resuscitation of CRS/HIPEC patients in the immediate postoperative period. Standardized protocols to correct the base deficit in CRS/HIPEC patients during the early postoperative period can potentially help mitigate perioperative morbidity.

  15. The Comprehensive Complication Index: a New Measure of the Burden of Complications After Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

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

    2018-03-01

    Cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) are complex surgeries with multiple comorbidities. The Clavien-Dindo classification (CDC) is the most commonly used method to report surgical morbidity, but limits it to the highest-grade complication. The Comprehensive Complication Index (CCI) is a score ranging from 0 to 100, calculated using all 30-day complications and their treatment after abdominal surgery. The aim of this study is to assess the CCI's validity in the HIPEC patient population. A review of our institutional cytoreduction database from 2009 to 2015 was undertaken. Patient demographics, pathology, Peritoneal Carcinomatosis Index (PCI), complications and their treatments, and length of stay (LOS) were reviewed. The CCI was calculated for each patient. Linear regression was used to assess whether the CCI and CDC were predictors of LOS. Of 157 patients reviewed, 110 (70.1%) underwent HIPEC. The majority were female (77, 66.9%), and the mean age was 53.7 years. Mean PCI was 13.2 [interquartile range (IQR) 7-18]. Median CDC was grade 2 (IQR 0-2), and only 9.8% had CDC of grade 4 or higher. Mean CCI was 21.4, while the median was 20.9 (IQR 0-30.8). Mean LOS was 16.2 days, while the median was 11 days (IQR 8-15 days). The CCI strongly correlated with LOS with coefficient of 0.46 [95% confidence interval (CI) 0.38-0.54, p = 0.000]. The CCI is an adequate tool to capture all complications and their overall burden in patients having undergone HIPEC. This study shows that the CCI can predict LOS and could be used to quantify and compare the burden of multiple complications.

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2017-08-26

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

  18. Efficacy of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in the management of malignant ascites.

    Science.gov (United States)

    Randle, Reese W; Swett, Katrina R; Swords, Douglas S; Shen, Perry; Stewart, John H; Levine, Edward A; Votanopoulos, Konstantinos I

    2014-05-01

    In peritoneal surface disease, accumulation of malignant ascites represents a difficult problem to treat, with adverse impact on quality of life. The role of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in controlling malignant ascites is not well defined. A retrospective analysis of a prospectively maintained database of 1,000 procedures was performed. Type of malignancy, resolution of ascites, duration and agent of chemoperfusion, performance status, resection status, morbidity, mortality, and survival were reviewed. Ascites was found in 299 patients (310 procedures) either before or during exploration. A total of 142 (46 %) procedures were performed for appendiceal primary disease, 53 (17 %) colorectal, 20 (6 %) gastric, 45 (15 %) mesothelioma, and 26 (8 %) ovarian. A total of 288 (93 %) patients had resolution of ascites by 3 months' follow-up. In patients with ascites, complete cytoreduction was obtained in 15 versus 59 % when ascites was not present (p < 0.001). In the group of patients who had their ascites controlled, 243 of 288 (84 %) had resection with residual macroscopic disease (R2 status). Twenty-two patients (7 %) had persistent ascites at 3 months' follow-up, 19 (86 %) of whom had an R2 resection. Univariate analysis revealed that type of primary disease, resection status, duration or agent of chemoperfusion, and performance status did not predict failure. CRS-HIPEC is effective in controlling ascites in 93 % of patients with malignant ascites, even when a complete cytoreduction is not feasible. Ascites is predictive of incomplete cytoreduction and worse overall survival. Although complete cytoreduction remains the goal of this procedure, HIPEC can provide palliative value in selected patients with malignant ascites.

  19. Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study.

    Science.gov (United States)

    Coccolini, Federico; Campanati, Luca; Catena, Fausto; Ceni, Valentina; Ceresoli, Marco; Jimenez Cruz, Jorge; Lotti, Marco; Magnone, Stefano; Napoli, Josephine; Rossetti, Diego; De Iaco, Pierandrea; Frigerio, Luigi; Pinna, Antonio; Runnebaum, Ingo; Ansaloni, Luca

    2015-01-01

    Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC. This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease. Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months. CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.

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

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    Ariputra -

    2015-07-01

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

  1. Hybrid NOTES transvaginal intraperitoneal onlay mesh in abdominal wall hernias: an alternative to traditional laparoscopic procedures.

    Science.gov (United States)

    Descloux, Alexandre; Pohle, Sebastian; Nocito, Antonio; Keerl, Andreas

    2015-12-01

    Abdominal wall hernias are increasingly treated by laparoscopic placement of an intraperitoneal onlay mesh (IPOM). We present an alternative technique for women: the laparoscopic-assisted transvaginal IPOM. Before surgery, all patients underwent a gynecological examination. The patients agreed to IPOM repair via a transvaginal approach, and written informed consent for surgery was obtained. Pneumoperitoneum was established with a Veress needle at the umbilicus. This access was subsequently dilated to 5 mm (VersaStep), and a 5-mm laparoscope was inserted. Under laparoscopic view, the transvaginal trocars (12-mm VersaStep and 5-mm flexible accesses) were safely inserted after lifting the uterus with a uterus manipulator. After preparation of the falciform ligament, the ligamentum teres and the preperitoneal fat, a lightweight composite mesh was introduced through the transvaginal access and fixed with absorbable tacks using the double-crown technique. From September 2011 to December 2012, we performed six laparoscopic-assisted transvaginal IPOM procedures (one epigastric, three umbilical, two combined epigastric and umbilical hernias; all were primary hernias). In the initial phase, only patients with small or medium primary abdominal wall hernia were selected (max. 3 cm diameter). Median hospital stay was 3 days (range 2-6 days). One minor complication occurred perioperatively (second-degree skin burn to the labia majora). At 1-year follow-up, we identified one recurrence in a high-risk patient with a body mass index higher than 35 kg/m(2). No infection and no mortality were observed. Although no final conclusion can be made regarding the presumed non-inferiority of this technique in terms of recurrence and mesh infection compared with traditional laparoscopic IPOM, laparoscopic-assisted transvaginal IPOM is a feasible alternative to treat abdominal wall hernias.

  2. Splenectomy Increases Postoperative Complications Following Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

    Science.gov (United States)

    Dagbert, Francois; Thievenaz, Remy; Decullier, Evelyne; Bakrin, Naoual; Cotte, Eddy; Rousset, Pascal; Vaudoyer, Delphine; Passot, Guillaume; Glehen, Olivier

    2016-06-01

    Complete cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) is increasingly performed on patients with peritoneal carcinomatosis of various origins. Splenectomy often is required in these patients to achieve complete tumor removal. Although splenectomy has been associated with increased morbidity in many major abdominal surgeries, its effect in patients undergoing CRS + HIPEC is unknown. The purpose of this study was to evaluate the impact of splenectomy during CRS + HIPEC on postoperative outcomes. We retrospectively identified 39 patients who underwent CRS + HIPEC with splenectomy during a 3-year study period from a prospective database. We compared them to case controls (CRS + HIPEC without splenectomy) that were matched for the complexity of the procedure. We evaluated the complication rate and outcomes of patients in each group. During the study period, splenectomy was performed in 32 % of patients undergoing CRS + HIPEC procedure. Patients in the splenectomy group experienced more grade 3-4 complications than patients in the control group (59 vs. 35.9 %, p = 0.041) as well as more pulmonary complications (41 vs. 7.7 %, p = 0.0006). Multivariate analysis identified splenectomy as the only predictor of overall major complications (odds ratio = 2.57, 95 % confidence interval = 1.03-6.40). Mortality was similar in both groups. Splenectomy increases major complication rate in patients undergoing CRS + HIPEC and efforts should be made to preserve the spleen during the surgery.

  3. Efeito vasomotor após intoxicação aguda com bupivacaína e levobupivacaína via intraperitoneal em ratos, analisado por imagem infravermelha digital

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    Angelo Manoel Grande Carstens

    2011-04-01

    Full Text Available JUSTIFICATIVA E OBJETIVOS: O estudo do efeito vasomotor dos anestésicos locais (AL é de suma importância para a análise da ocorrência de efeitos cardiotóxicos, neurotóxicos e interações medicamentosas. Com a finalidade de encontrar um fármaco mais seguro do que a bupivacaína racêmica, o presente estudo teve por objetivo a análise por imagem infravermelha digital do efeito vasomotor da intoxicação aguda da bupivacaína e da levobupivacaína via intraperitoneal em ratos. MÉTODO: Utilizaram-se 30 ratos machos da linhagem Wistar, alocados em três grupos (n = 10 e submetidos a uma injeção intraperitoneal de AL. No Grupo C (Controle, foi realizada injeção intraperitoneal de soro fisiológico 0,9% 1 mL. No Grupo B (bupivacaína, injeção intraperitoneal de bupivacaína racêmica a 0,5% (R50-S50, dose de 20 mg.kg-1 de peso. No Grupo L (levobupivacaína, injeção intraperitoneal de levobupivacaína a 0,5%, excesso enantiomérico (S75-R25 em dose de 20 mg.kg-1 de peso. Procedeu-se à filmagem termográfica contínua desde o momento da pré-injeção até 30 minutos após a injeção. Os resultados das filmagens foram analisados em forma gráfica, verificando-se a temperatura máxima de cada rato e a temperatura média do sistema que abrigava o animal. RESULTADOS: Os resultados da análise gráfica revelaram que não houve diferença entre o Grupo L e o Grupo C, e a temperatura média permaneceu estável durante todo o experimento em ambos os grupos. No Grupo B, houve um fenômeno de aumento de temperatura após a injeção intraperitoneal de bupivacaína. CONCLUSÕES: Os resultados demonstraram que o efeito vasomotor da toxicidade aguda da levobupivacaína foi semelhante ao Grupo C com soro fisiológico, por meio de estudos macroscópicos por filmagem digital infravermelha, e que houve alterações vasomotoras (vasoconstrição com a intoxicação por bupivacaína em relação ao Grupo C e em relação ao Grupo L.

  4. Effect of local hemostatics on bone induction in rats: a comparative study of bone wax, fibrin-collagen paste, and bioerodible polyorthoester with and without gentamicin

    DEFF Research Database (Denmark)

    Solheim, E; Pinholt, E M; Bang, G

    1992-01-01

    evaluated by light microscopy and 85Sr uptake analyses. Non-absorbable bone wax of 88% beeswax and absorbable bovine fibrin-collagen paste both significantly inhibited osteoinduction, whereas a bioerodible polyorthoester drug delivery system with or without 4% gentamicin did not. Bone wax was not absorbed...

  5. Peritoneal carcinomatosis: patients selection, perioperative complications and quality of life related to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

    Directory of Open Access Journals (Sweden)

    Schlitt Hans J

    2009-01-01

    Full Text Available Abstract Background Peritoneal tumor dissemination arising from colorectal cancer, appendiceal cancer, gastric cancer, gynecologic malignancies or peritoneal mesothelioma is a common sign of advanced tumor stage or disease recurrence and mostly associated with poor prognosis. Methods and results In the present review article preoperative workup, surgical technique, postoperative morbidity and mortality rates, oncological outcome and quality of life after CRS and HIPEC are reported regarding the different tumor entities. Conclusion Cytoreductive surgery (CRS and hyperthermic intraperitoneal chemotherapy (HIPEC provide a promising combined treatment strategy for selected patients with peritoneal carcinomatosis that can improve patient survival and quality of life. The extent of intraperitoneal tumor dissemination and the completeness of cytoreduction are the leading predictors of postoperative patient outcome. Thus, consistent preoperative diagnostics and patient selection are crucial to obtain a complete macroscopic cytoreduction (CCR-0/1.

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

    DEFF Research Database (Denmark)

    Eriksen, J.R.; Bech, J.I.; Linnemann, D.

    2008-01-01

    ) test). There was no significant difference in the formation of fibrosis or inflammation between the different meshes or fixation methods. All samples showed significant foreign-body reaction with giant cells. CONCLUSION: Our results suggest that the laparoscopic fixation of an intraperitoneal mesh...... chronic) pain after LVHR. Therefore, non-invasive and patient-friendly mesh fixation methods must be considered. The present study was designed to investigate the technical applicability, safety and effect of Tisseel((R)) for intraperitoneal mesh fixation. METHODS: Nine 40-kg Danish Landrace female pigs...... and the mesh-tissue samples were tested for strength of ingrowth (peel test), adhesion formation, mesh shrinkage and examined for histological alterations. RESULTS: No meshes were displaced from their initial position at autopsy, but we observed two cases of mesh folding that could have resulted in hernia...

  7. Development of Schistosoma incognitum in mice upon intraperitoneal inoculation with irradiated schistosomula

    International Nuclear Information System (INIS)

    Bhilegaonkar, N.G.; Sahasrabudhe, V.K.

    1987-01-01

    As a prelude to the study of the immunizing potential of gamma-irradiated Schistosoma incognitum schistosomula, experiments were conducted to study the effect of different doses of gamma irradiation (1,3,5 and 10 kr) on the development and survival of S. incognitum in mice, and its attendant pathology. The present experiments suggested that 3 and 5 kr irradiation doses can be safely used for irradiating schistosomula for immunization experiments in mice as the worms will not mature and therefore no harm will be caused which is mainly due to the eggs. (author). 7 refs

  8. The Impact of 0.9% NaCl on Mesothelial Cells After Intraperitoneal Lavage During Surgical Procedures.

    Science.gov (United States)

    Cwaliński, Jarosław; Bręborowicz, Andrzej; Połubińska, Alicja

    2016-01-01

    Normal saline gained wide popularity in abdominal surgery as a basic compound used in intraoperative drainage of the peritoneal cavity. However, recent studies have revealed that saline solution is not quite biocompatible with the intraperitoneal enviroment and may promote peritoneal adhesions. The aim of the study was to evaluate the function and viability of human mesothelial cells cultured in vitro in 0.9% NaCl solution from intraperitoneal lavage carried out during laparoscopic cholecytectomies. The study included 40 consecutive patients suffering from gallstones who underwent laparoscopic cholecystectomy. Fluid was collected after intraperitoneal lavage during the surgical procedures. The samples obtained were used as a medium for in vitro incubation of primary human mesothelial cells. After 24 h the synthesis of interleukin 6 (IL-6), plasminogen activator inhibitor (PAI) and tissue plasminogen activator (tPA), as well as the index of cell proliferation were assessed in all the experimental groups. All the mesothelium cell cultures treated with fluid samples obtained ex vivo were characterized by elevated levels of IL-6. The highest concentrations of PAI-1 were found in groups of cells exposed to fluid with bile; similarly, tPA synthesis was extremely elevated in groups treaded with fluid containing bile and small amounts of hemolyzed blood. In contrast, cell proliferation was exceedingly high in 2 groups of cells placed in a standard culture medium and in 0.9% NaCl solution. Normal saline introduced into the abdominal cavity modifies the biological and physicochemical conditions of the intraperitoneal environment. The impact of 0.9% NaCl on mesothelial cells is manifested in destabilized tissue regeneration, which supposedly initiates adhesion formation.

  9. Light-microscopic immunocytochemistry for Gentamicin and its use for studying uptake of the drug in kidney

    DEFF Research Database (Denmark)

    Fujiwara, Kunio; Shin, Masashi; Matsunaga, Hayato

    2009-01-01

    Gentamicin (GM) is a widely used antibiotic but shows renal toxicity. We produced a serum against GM (anti-GM) conjugated to bovine serum albumin with N-(gamma-maleimidobutyryloxy)succinimide. The antiserum was monospecific for GM and did not cross-react with the analog streptomycin, tobramycin......, kanamycin, or amikacin. The antiserum also detected glutaraldehyde-fixed GM, and this enabled us to develop an immunocytochemical method for detecting the uptake of GM in rat kidney. Twelve hours after a single intravenous administration of GM, immunocytochemistry revealed that GM accumulated in the S1, S2......, and S3 segments of the proximal tubules, as well as in the distal tubules and collecting ducts. By 12 h after injection, the drug was detected in cytoplasmic granules of the proximal tubule cells. However, early (1 h) after injection, drug accumulation was detected in the microvilli of these cells...

  10. Genotypic characterization of gentamicin and cephalosporin resistant Escherichia coli isolates from blood cultures in a Norwegian university hospital 2011–2015

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    Øyvind Andreas Fladberg

    2017-11-01

    Full Text Available Abstract Background Cephalosporin resistance in clinical E. coli isolates is increasing internationally. The increase has been caused by virulent and often multidrug-resistant clones, especially the extended spectrum β-lactamase (ESBL producing E. coli clone O25b-ST131. Methods In Norway, recommended empirical treatment of sepsis consists of gentamicin and penicillin combined, or a broad-spectrum cephalosporin. To investigate if increased gentamicin and cephalosporins resistance rates in our hospital could be caused by specific clones, we conducted a retrospective study on E. coli blood culture isolates from 2011 through 2015. All E. coli isolates non-susceptible to gentamicin and/or third-generation cephalosporins were genotyped using multiple-locus variable-number of tandem repeat analysis (MLVA and compared with antibiotic susceptible isolates. The frequency of the most common genes causing ESBL production (bla CTX-M, bla ampC was examined by Real-Time PCR. Results A total of 158 cephalosporin and/or gentamicin resistant and 97 control isolates were differentiated into 126 unique MLVA types. Of these, 31% of the isolates belonged to a major MLVA cluster consisting of 41% of the gentamicin resistant and 35% of the cephalosporin resistant isolates. The majority (65/80 isolates of this MLVA cluster contained MLVA types associated with the E. coli O25b-ST131 clone. Genes encoding CTX-M enzyme phylogroups 1 and 9 occurred in 65% and 19% of cephalosporin resistant isolates, respectively, whereas bla ampC-CIT was identified in 3%. Conclusion No local E. coli bacteraemia clone was identified. Antibiotic resistance was dispersed over a variety of genotypes. However, association with the international E. coli O25b-ST131 clone was frequent and may be an important driver behind increased resistance rates. Monitoring and preventing dissemination of these resistant clones are important for continued optimal treatment.

  11. Better Clinical Efficiency of TILs for Malignant Pleural Effusion and Ascites than Cisplatin Through Intrapleural and Intraperitoneal Infusion.

    Science.gov (United States)

    Chu, Hongjin; Du, Fengcai; Gong, Zhaohua; Lian, Peiwen; Wang, Zhixin; Li, Peng; Hu, Baohong; Chi, Cheng; Chen, Jian

    2017-08-01

    To evaluate the clinical efficiency of tumor-infiltrating lymphocytes (TILs) compared to cisplatin for malignant pleural effusion and ascites through intrapleural and intraperitoneal infusion. Thirteen patients with malignant pleural effusion and ascites were divided into a TIL-treated group and a cisplatin-treated group. Patients were given TILs or cisplatin, through intrapleural and intraperitoneal infusion respectively, after drainage of the malignant serous effusion by thoracentesis or abdominocentesis. The overall response rate and disease control rate of the TIL-treated group (33.33% and 83.33%) were higher than that of the cisplatin-treated group (28.57% and 71.43%). The progression-free survival for the TIL-treated group was significantly longer (p=0.002) and better than that of the cisplatin-treated group (66.67% vs. 28.57%). Quality of life apparently improved in the TIL-treated group and was clearly higher than that in the cisplatin-treated group. The use of TILs has a better clinical efficiency for malignant pleural effusion and ascites than cisplatin through intrapleural and intraperitoneal infusion without severe adverse effects. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

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

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    Kana Bavesh D

    2007-12-01

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

  13. Efficacy of port-site and intraperitoneal application of bupivacaine in reducing early post-laparoscopic cholecystectomy pain

    International Nuclear Information System (INIS)

    Ahmad, J.; Khan, Z.A.; Khan, A.

    2015-01-01

    The aim of this study was to assess the analgesic efficacy of Bupivacaine application at port-site and intraperitoneal infiltration in patients with laparoscopic cholecystectomy. Study Design: Randomized Controlled Clinical Trial. Place and Duration: The study was conducted at Rehman Medical Institute (RMI) Peshawar, Pakistan from June 2009 to June 2012. Materials and Methods: Patients who underwent elective laparoscopic cholecystectomy during the study period were included in the study. Eighty patients were randomized into two groups, study group and control group. The study group received 40 ml of 0.25% bupivacaine intraoperatively as intraperitoneal infiltration and local infiltration at the port sites. Pain assessment was done using visual analogue pain score (VAS) of 0-10 at fixed intervals during the first 24 hours post surgery. Results: The mean VAS score in the study group was less as compared to the control group throughout the 24 hours assessment period, however this difference was statistically significant (p<0.001) only during the first three assessments at 1 hour, 4 hours and 8 hours post surgery. The analgesia requirement was also significantly (p<0.001) decreased in the study group. Conclusion: Port site and intraperitoneal application of local anesthetic bupivacaine significantly reduced pain during the first 8 hours post surgery and total analgesia requirement was also significantly reduced. It is a simple and easily applicable technique which increases patient comfort and can be safely used to decrease post operative pain in patients undergoing laparoscopic cholecystectomy. (author)

  14. A new survival model for hyperthermic intraperitoneal chemotherapy (HIPEC) in tumor-bearing rats in the treatment of peritoneal carcinomatosis

    International Nuclear Information System (INIS)

    Pelz, Joerg OW; Doerfer, Joerg; Hohenberger, Werner; Meyer, Thomas

    2005-01-01

    Cytoreduction followed by hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival in patients with peritoneal carcinomatosis of colorectal origin. Animal models are important in the evaluation of new treatment modalities. The purpose of this study was to devise an experimental setting which can be routinely used for the investigation of HIPEC in peritoneal carcinomatosis. A new peritoneal perfusion system in tumor bearing rats were tested. For this purpose CC531 colon carcinoma cells were implanted intraperitoneally in Wag/Rija rats. After 10 days of tumor growth the animals were randomized into three groups of six animals each: group 1: control (n = 6), group 2: HIPEC with mitomycin C in a concentration of 15 mg/m 2 (n = 6), group III: mitomycin C i.p. as monotherapy in a concentration of 10 mg/m 2 (n = 6). After 10 days, total tumor weight and the extent of tumor spread, as classified by the modified Peritoneal Cancer Index (PCI), were assessed by autopsy of the animals. No postoperative deaths were observed. Conjunctivitis, lethargy and loss of appetite were the main side effects in the HIPEC group. No severe locoregional or systemic toxity was observed. All control animals developed massive tumor growth. Tumor load was significantly reduced in the treatment group and was lowest in group II. The combination of hyperthermia with MMC resulted in an increased tumoricidal effect in the rat model. The presented model provides an opportunity to study the mechanism and effect of hyperthermic intraperitoneal chemotherapy and new drugs for this treatment modality

  15. Evaluation of Gentamicin and Lidocaine Release Profile from Gum Acacia-crosslinked-poly(2-hydroxyethylmethacrylate)-carbopol Based Hydrogels.

    Science.gov (United States)

    Singh, Baljit; Dhiman, Abhishek

    2017-01-01

    No doubt, the prevention of infection is an indispensable aspect of the wound management, but, simultaneous wound pain relief is also required. Therefore, herein this article, incorporation of antibiotic agent 'gentamicin' and pain relieving agent 'lidocaine' into hydrogel wound dressings, prepared by using acacia gum, carbopol and poly(2-hydroxyethylmethacrylate) polymers, has been carried out. The hydrogels were evaluated as a drug carrier for model drugs gentamicin and lidocaine. Synthesis of hydrogel wound dressing was carried out by free radical polymerization technique. The drug loading was carried out by swelling equilibrium method and gel strength of hydrogels was measured by a texture analyzer. Porous microstructure of the hydrogel was observed in cryo-SEM images. The hydrogel showed mesh size 37.29 nm, cross-link density 2.19× 10-5 mol/cm3, molecular weight between two cross-links 60.25× 10-3 g/mol and gel strength 0.625±0.112 N in simulated wound fluid. It is concluded that the pH of swelling medium has influenced the network structure of hydrogel i.e., molecular weight of the polymer chain between two neighboring cross links, crosslink density and the corresponding mesh size. A good correlation was established between gel strength and network parameters. Cryo-SEM images showed porous morphology of hydrogels. These hydrogels were found to be biodegradable and antimicrobial in nature. Drug release occurred through Fickian diffusion mechanism and release profile was best fitted in first order model. Overall it is concluded that modification in GA has led to formation of a porous hydrogels for wound dressing applications. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Dose and dose rate monitor

    International Nuclear Information System (INIS)

    Novakova, O.; Ryba, J.; Slezak, V.; Svobodova, B.; Viererbl, L.

    1984-10-01

    The methods are discussea of measuring dose rate or dose using a scintillation counte. A plastic scintillator based on polystyrene with PBD and POPOP activators and coated with ZnS(Ag) was chosen for the projected monitor. The scintillators were cylindrical and spherical in shape and of different sizes; black polypropylene tubes were chosen as the best case for the probs. For the counter with different plastic scintillators, the statistical error 2σ for natural background was determined. For determining the suitable thickness of the ZnS(Ag) layer the energy dependence of the counter was measured. Radioisotopes 137 Cs, 241 Am and 109 Cd were chosen as radiation sources. The best suited ZnS(Ag) thickness was found to be 0.5 μm. Experiments were carried out to determine the directional dependence of the detector response and the signal to noise ratio. The temperature dependence of the detector response and its compensation were studied, as were the time stability and fatigue manifestations of the photomultiplier. The design of a laboratory prototype of a dose rate and dose monitor is described. Block diagrams are given of the various functional parts of the instrument. The designed instrument is easiiy portable, battery powered, measures dose rates from natural background in the range of five orders, i.e., 10 -2 to 10 3 nGy/s, and allows to determine a dose of up to 10 mGy. Accouracy of measurement in the energy range of 50 keV to 1 MeV is better than +-20%. (E.S.)

  17. Intraperitoneal P-32 for adjuvant and consolidative therapy in ovarian carcinoma

    International Nuclear Information System (INIS)

    Condra, Kellie S.; Mendenhall, William M.; Morgan, Linda S.; Freeman, Debra E.; Marcus, Robert B.; Hagan, Michael P.

    1996-01-01

    Purpose/Objective: To determine the role of intraperitoneal radioactive chromic phosphate (P-32) in the treatment of patients with ovarian carcinoma. Survival results, patterns of recurrence, and treatment morbidity are reported for patients treated adjuvantly after primary surgery and for patients treated with the intent of consolidation after second-look laparotomy. Materials and Methods: Between 1976 and 1993, 25 patients with ovarian carcinoma were treated with 15 mCi P-32 as adjuvant therapy and 43 patients received P-32 as consolidation after second-look laparotomy. The majority of patients (13 of 19) treated adjuvantly had high-risk early-stage disease (IAG 3, IBG 2-3, IC) or more advanced stages (6 patients). Thirty-nine patients received consolidative P-32 after negative second-look laparotomy (35 Stage II-IV and 4 Stage I) and 4 Stage III patients were treated after positive second-look laparotomy. All patients had 2-year minimum follow-up (median, 7.9 years). Results: Ten-year abdominal control and cause-specific survival rates for adjuvant P-32 were 83% and 82%, respectively. For patients treated with consolidative P-32, 5-year abdominal control and cause-specific survival rates were 65% and 78%, respectively. The 5-year cause-specific survival rate for 35 patients with Stage II-IV disease treated with consolidative P-32 after negative second-look laparotomy was 81%. A component of peritoneal failure was the primary mode of recurrence (15 of 22 failures). Four patients required surgical intervention for small-bowel obstruction. No patients died of treatment-related complications. Conclusion: P-32 is well tolerated with acceptable toxicity. In comparing our results to the literature, adjuvant P-32 appears to offer improved cause-specific survival compared with observation alone and equivalent cause-specific survival compared with adjuvant chemotherapy. Consolidative P-32 after negative second-look laparotomy resulted in improved 5-year cause

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

    Science.gov (United States)

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

    2014-01-01

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

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

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    R. Azarfarin

    2006-05-01

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

  20. Is extended antibiotic prophylaxis necessary after penetrating trauma to the thoracolumbar spine with concomitant intraperitoneal injuries?

    Science.gov (United States)

    Pasupuleti, Latha V; Sifri, Ziad C; Mohr, Alicia M

    2014-02-01

    Prolonged courses of broad-spectrum antibiotics are often cited as standard care for the prevention of infectious complications in thoracolumbar or sacral (TLS) fractures following penetrating abdominal trauma. Perforation of a hollow viscus in addition to a TLS fracture is believed to be associated with a high incidence of spine infection. Because over use of antibiotics is associated with an increasing prevalence of multi-drug-resistant organisms, this study seeks to define the actual risk of infection of the spine and need for antibiotics in patients with TLS fractures and intraperitoneal injuries following penetrating trauma. A retrospective review of 67 patients with penetrating abdominal trauma and concomitant TLS fracture was performed. Demographics, level of TLS fracture, associated spinal cord injury (SCI), need for operative intervention, presence of concomitant hollow viscus injury, and type and duration of antibiotic coverage were collected. In addition, associated infectious complications were reviewed. Spine infections were defined as spinal or paraspinal abscess, osteomyelitis of the spine, or meningitis. Intraabdominal infections were defined with imaging studies or positive peritoneal cultures. Sixty-seven patients (mean age of 27 ± 9 years) had an exploratory laparotomy and one or more TLS fractures. Four patients died within 24 h and were excluded from further study. Thirty-eight patients (60%) had one or more hollow viscus injuries, 13 (21%) had solid organ injuries alone and 12 (19%) had a non-therapeutic laparotomy. All patients received perioperative antibiotics; 92% received 48 h or less of antibiotic prophylaxis and 62% received only 24 h of antibiotics. In one patient with an isolated solid organ injury there was a spine infection (1%). In this study, 92% of patients received antibiotics for 48 h or less with no increased incidence of spine infections. Bacterial colonization of the vertebrae was not higher in patients with penetrating

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

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    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

  2. On the effects of the Fusarium toxin deoxynivalenol (DON) administered per os or intraperitoneal infusion to sows during days 63 to 70 of gestation.

    Science.gov (United States)

    Goyarts, Tanja; Brüssow, Klaus-Peter; Valenta, Hana; Tiemann, Ute; Jäger, Kathrin; Dänicke, Sven

    2010-05-01

    Six pregnant sows of 180.6 ± 5.6 kg were fed either a Fusarium-contaminated (4.42 mg DON and 48.3 µg ZON per kg, DON per os, n = 3) or a control diet (0.15 mg DON and 5 µg ZON/kg) in the period of days 63 and 70 of gestation. On day 63 of gestation, sows fed the control diet were implanted with an intraperitoneal osmotic minipump (delivery rate of 10 µL/h, for 7 days) containing 50 mg pure (98%) DON in 2 ml 50% DMSO (DON ip, n = 3). Frequent plasma samples were taken to estimate the kinetics after oral and ip DON exposure. The intended continuous delivery of DON by the intraperitoneal minipump could not be shown, as there was a plasma peak (Cmax) of 4.2-6.4 ng DON/mL either immediately (sow IP-2+3) or 2.5 h (sow IP-1) after implantation of the pump followed by a one-exponential decline with a mean half-time (t1/2) of 1.75-4.0 h and only negligible DON plasma concentrations after 12 h. Therefore, the DON ip exposure has to be regarded as one single dose 1 week before termination of experiment. The DON per os sows showed a mean basis level (after achieving a steady state) of DON plasma concentration of about 6-8 ng/mL, as also indicated by the plasma DON concentration at the termination of the experiment. On day 70, caesarean section was carried out, the fetuses were killed immediately after birth, and samples of plasma, urine, and bile were taken to analyze the concentration of DON and its metabolite de-epoxy-DON. At necropsy there were no macroscopic lesions observed in any organ of either sows or piglets. Histopathological evaluation of sows liver and spleen revealed no alterations. The proliferation rate of peripheral blood mononuclear cells (PBMC) with or without stimulation was not affected by the kind of DON treatment. The exposure of pregnant sows at mid-gestation (days 63-70, period of organogenesis) to a Fusarium toxin-contaminated diet (4.42 mg DON and 0.048 mg ZON per kg) or pure DON via intraperitoneal osmotic minipump

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

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    Ahmet Oktay Cihan

    2011-01-01

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

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

    Czech Academy of Sciences Publication Activity Database

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

    2001-01-01

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

  5. Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

    Science.gov (United States)

    Paquette, Jay; Olmstead, Mary C; Olmstead, Mary

    2005-12-01

    Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems interact, this study investigated whether ultra-low dose naltrexone also influences cannabinoid-induced antinociception. Separate groups of Long-Evans rats were tested for antinociception following an injection of vehicle, a sub-maximal dose of the cannabinoid agonist WIN 55 212-2, naltrexone (an ultra-low or a high dose) or a combination of WIN 55 212-2 and naltrexone doses. Tail-flick latencies were recorded for 3 h, at 10-min intervals for the first hour, and at 15-min intervals thereafter. Ultra-low dose naltrexone elevated WIN 55 212-2-induced tail flick thresholds without extending its duration of action. This enhancement was replicated in animals receiving intraperitoneal or intravenous injections. A high dose of naltrexone had no effect on WIN 55 212-2-induced tail flick latencies, but a high dose of the cannabinoid 1 receptor antagonist SR 141716 blocked the elevated tail-flick thresholds produced by WIN 55 212-2+ultra-low dose naltrexone. These data suggest a mechanism of cannabinoid-opioid interaction whereby activated opioid receptors that couple to Gs-proteins may attenuate cannabinoid-induced antinociception and/or motor functioning.

  6. Utilização de gentamicina no tratamento de neonatos atendidos em uma maternidade pública da região metropolitana de Belo Horizonte, Minas Gerais (1999 Gentamicin utilization for treating neonates at a public maternity in Belo Horizonte, Minas Gerais (1999

    Directory of Open Access Journals (Sweden)

    Maria Auxiliadora Parreiras Martins

    2005-03-01

    Full Text Available A gentamicina é um antimicrobiano de baixo custo amplamente utilizado no tratamento da septicemia neonatal. Entretanto, existe um risco potencial de oto e nefrotoxicidade. Neste trabalho, buscou-se caracterizar o recém-nascido hospitalizado em uso de gentamicina e avaliar o cumprimento do protocolo de tratamento adotado em uma Instituição pública de Belo Horizonte, Minas Gerais. Trata-se de um estudo transversal incluindo 63 recém-nascidos atendidos em uma maternidade pública no período de agosto, outubro e dezembro de 1999. Essa maternidade é referência na assistência à gestação e ao parto de alto risco em Minais Gerais. A maioria dos recém-nascidos foi prematura (85,7% e de baixo peso (90,5%. Apenas dois (3,2% casos de septicemia foram confirmados por hemocultura. O protocolo adotado preconiza a administração de doses de 2,5 mg/kg a intervalos de 24 horas para neonatos com peso inferior a 1200 g e 12 horas para aqueles com peso superior a esse. Observou-se que o esquema terapêutico foi adotado em 96,7% dos casos. Contudo, constatou-se uma utilização por tempo superior ao recomendado, frente à hemocultura negativa, em mais de 70,0% dos casos.Gentamicin is a low cost antimicrobian commonly used in the treatment of neonatal sepsis. Nevertheless, there is a potential risk of oto and nephrotoxicity. The objectives of the study were to characterize the hospitalized neonate in use of gentamicin and to evaluate the follow-up of the dosing protocol adopted. It is a cross sectional study of a total of 63 neonates who received assistence at a public maternity in August, October and December, 1999. It is a Brazilian public institution which plays a role of reference in the high risk pregnancy and delivery. Most patients were premature (85.7% and low birth weight (90.5%. Only two (3.2% sepse cases were confirmed by hemoculture. The protocol adopted recommends doses of 2.5mg/kg with a 24 hour dosing interval for neonates weighing less

  7. Distribution of the hallucinogens N,N-dimethyltryptamine and 5-methoxy-N,N-dimethyltryptamine in rat brain following intraperitoneal injection: application of a new solid-phase extraction LC-APcI-MS-MS-isotope dilution method.

    Science.gov (United States)

    Barker, S A; Littlefield-Chabaud, M A; David, C

    2001-02-10

    A method for the solid-phase extraction (SPE) and liquid chromatographic-atmospheric pressure chemical ionization-mass spectrometric-mass spectrometric-isotope dilution (LC-APcI-MS-MS-ID) analysis of the indole hallucinogens N,N-dimethyltryptamine (DMT) and 5-methoxy DMT (or O-methyl bufotenin, OMB) from rat brain tissue is reported. Rats were administered DMT or OMB by the intraperitoneal route at a dose of 5 mg/kg and sacrificed 15 min post treatment. Brains were dissected into discrete areas and analyzed by the methods described as a demonstration of the procedure's applicability. The synthesis and use of two new deuterated internal standards for these purposes are also reported.

  8. Experimental autoimmune encephalomyelitis (EAE): lesion visualization on a 3 tesla Clinical whole-body system after intraperitoneal contrast injection

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    Heckl, S.; Naegele, T.; Klose, U. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Herrmann, M.; Gaertner, S.; Weissert, R. [Dept. of Neurology, Medical School, Univ. of Tuebingen (Germany); Schick, F. [Dept. of Radiology, Medical School, Univ. of Tuebingen (Germany); Kueker, W. [Dept. of Neuroradiology, Medical School, Univ. of Tuebingen (Germany); Dept. of Neuroradiology, Radcliffe Infirmary, Oxford, England (United Kingdom)

    2004-11-01

    Purpose: To investigate the intravital visibility of CNS lesions in rats with experimental autoimmune encephalomyelitis (EAE), the animal correlate of multiple sclerosis, using a 3-Tesla (T) wholebody MR system. Materials and Methods: Three healthy Dark Agouti (DA) rats and 16 DA rats with clinical signs of EAE were examined on a 3T whole body-system using a normal wrist coil. In total, 25 examinations were preformed using T2- and T1-weighted images in transverse and sagittal orientation with a slice thickness of 2 mm or 1 mm (voxel size up to 0.2 x 0.2 x 1 mm). Sedation was achieved by intraperitoneal injection of ketamine and xylazine. In addition, T1-weighted images were obtained after the instillation of 1.0 ml of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) (0.5 mmol/ml) into the peritoneal cavity. Results: T2- and T1-weighted images of the brain and spinal cord with high spatial and contrast resolution could be obtained in all animals. The anatomical details of the olfactory bulb glomeruli, cerebellum foliae, ventricles and corpus callosum were clearly visible. The EAE lesions presented as hyperintense area in T2-weighted images and could be demonstrated in all clinically affected animals by MRI and histologically verified. In total, the 16 affected rats had 28 cerebral and 2 spinal cord lesions (range 1 to 4, median 2). Contrast enhancement was noted in 12 animals and ranked as severe in ten and moderate in two cases. No adverse effects were noted due to sedation or intraperitoneal contrast injection. Conclusions: The intravital demonstration of cerebral and spinal cord EAE lesions in rats is possible on a 3T whole-body MR scanner using a normal wrist coil. Intraperitoneal injection of ketamine/xylazine and contrast agent is an easy, safe and effective procedure in rats. (orig.)

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

    Science.gov (United States)

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

    2014-07-01

    The purpose of this study was to examine changes of thermoregulation, neurotransmitters in the preoptic area and anterior hypothalamus (PO/AH), which is the thermoregulatory center, and endurance exercise performance after the intraperitoneal injection of caffeine in rats. Core body temperature (Tcore), oxygen consumption (VO₂) and tail skin temperature (Ttail) were measured. A microdialysis probe was inserted in the PO/AH, and samples for the measurements of extracellular dopamine (DA), noradrenaline (NA) and serotonin (5-HT) levels were collected. During the rest experiment, 1 h after baseline collections in the chamber (23 °C), the rats were intraperitoneally injected with saline, or 3 mg kg(-1) or 10 mg kg(-1) caffeine. The duration of the test was 4 h. During the exercise experiment, baseline collections on the treadmill were obtained for 1 h. One hour before the start of exercise, rats were intraperitoneally injected with either 10 mg kg(-1) caffeine (CAF) or saline (SAL). Animals ran until fatigue at a speed of 18 m min(-1), at a 5% grade, on the treadmill in a normal environment (23 °C). At rest, 3 mg kg(-1) caffeine did not influence Tcore, Ttail, VO₂, extracellular DA, NA and 5-HT. 10 mg kg(-1) caffeine caused significant increases in Tcore, VO₂, Ttail and extracellular DA in the PO/AH. In addition, 10 mg kg(-1) caffeine increased the run time to fatigue (SAL: 104.4 ± 30.9 min, CAF: 134.0 ± 31.1 min, pcaffeine and exercise increased Tcore, VO₂, Ttail and extracellular DA in the PO/AH. NA increased during exercise, while neither caffeine nor exercise changed 5-HT. These results indicate that caffeine has ergogenic and hyperthermic effects, and these effects may be related to changes of DA release in the brain. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Pediatric Obesity: Pharmacokinetic Alterations and Effects on Antimicrobial Dosing.

    Science.gov (United States)

    Natale, Stephanie; Bradley, John; Nguyen, William Huy; Tran, Tri; Ny, Pamela; La, Kirsten; Vivian, Eva; Le, Jennifer

    2017-03-01

    Limited data exist for appropriate drug dosing in obese children. This comprehensive review summarizes pharmacokinetic (PK) alterations that occur with age and obesity, and these effects on antimicrobial dosing. A thorough comparison of different measures of body weight and specific antimicrobial agents including cefazolin, cefepime, ceftazidime, daptomycin, doripenem, gentamicin, linezolid, meropenem, piperacillin-tazobactam, tobramycin, vancomycin, and voriconazole is presented. PubMed (1966-July 2015) and Cochrane Library searches were performed using these key terms: children, pharmacokinetic, obesity, overweight, body mass index, ideal body weight, lean body weight, body composition, and specific antimicrobial drugs. PK studies in obese children and, if necessary, data from adult studies were summarized. Knowledge of PK alterations stemming from physiologic changes that occur with age from the neonate to adolescent, as well as those that result from increased body fat, become an essential first step toward optimizing drug dosing in obese children. Excessive amounts of adipose tissue contribute significantly to body size, total body water content, and organ size and function that may modify drug distribution and clearance. PK studies that evaluated antimicrobial dosing primarily used total (or actual) body weight (TBW) for loading doses and TBW or adjusted body weight for maintenance doses, depending on the drugs' properties and dosing units. PK studies in obese children are imperative to elucidate drug distribution, clearance, and, consequently, the dose required for effective therapy in these children. Future studies should evaluate the effects of both age and obesity on drug dosing because the incidence of obesity is increasing in pediatric patients. © 2017 Pharmacotherapy Publications, Inc.

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

    Directory of Open Access Journals (Sweden)

    Costa Wilson L

    2012-09-01

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

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

    Science.gov (United States)

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

    2012-09-19

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

  13. Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ko Eun [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Eun Young [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Chang Seong; Choi, Joon Seok; Bae, Eun Hui; Ma, Seong Kwon [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Kyung Keun [Department of Pharmacology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Lee, Jong Un [Department of Physiology, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of); Kim, Soo Wan, E-mail: skimw@chonnam.ac.kr [Department of Internal Medicine, Chonnam National University Medical School, Gwangju 501-757 (Korea, Republic of)

    2013-05-10

    Highlights: •MSP/RON system is activated in rat kidney damaged by gentamicin. •MSP inhibits GM-induced cellular apoptosis and inflammation in HK-2 cells. •MSP attenuates GM-induced activation of MAPKs and NF-κB pathways in HK-2 cells. -- Abstract: The present study aimed to investigate whether macrophage-stimulating protein (MSP) treatment attenuates renal apoptosis and inflammation in gentamicin (GM)-induced tubule injury and its underlying molecular mechanisms. To examine changes in MSP and its receptor, recepteur d’origine nantais (RON) in GM-induced nephropathy, rats were injected with GM for 7 days. Human renal proximal tubular epithelial (HK-2) cells were incubated with GM for 24 h in the presence of different concentrations of MSP and cell viability was measured by MTT assay. Apoptosis was determined by flow cytometry of cells stained with fluorescein isothiocyanate-conjugated annexin V protein and propidium iodide. Expression of Bcl-2, Bax, caspase-3, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS), nuclear factor-kappa B (NF-κB), IκB-α, and mitogen-activated protein kinases (MAPKs) was analyzed by semiquantitative immunoblotting. MSP and RON expression was significantly greater in GM-treated rats, than in untreated controls. GM-treatment reduced HK-2 cell viability, an effect that was counteracted by MSP. Flow cytometry and DAPI staining revealed GM-induced apoptosis was prevented by MSP. GM reduced expression of anti-apoptotic protein Bcl-2 and induced expression of Bax and cleaved caspase 3; these effects and GM-induced expression of COX-2 and iNOS were also attenuated by MSP. GM caused MSP-reversible induction of phospho-ERK, phospho-JNK, and phospho-p38. GM induced NF-κB activation and degradation of IκB-α; the increase in nuclear NF-κB was blocked by inhibitors of ERK, JNK, p-38, or MSP pretreatment. These findings suggest that MSP attenuates GM-induced inflammation and apoptosis by inhibition of the MAPKs

  14. Development of a modified gentamicin protection assay to investigate the interaction between Campylobacter jejuni and Acanthamoeba castellanii ATCC 30010.

    Science.gov (United States)

    Dirks, Brian P; Quinlan, Jennifer J

    2014-05-01

    Campylobacter jejuni is one of the leading causes of diarrheal illness worldwide. It is persistent in the environment and on poultry despite its microaerophilic nature and sensitivity to dessication and pH. Studies have demonstrated that C. jejuni co-incubated with Acanthamoeba spp. may be protected from harmful environmental factors. Research in this area, however has included a range of different methodologies for co-incubation, recovery of bacteria and amoebae, and verification of internalization. In this study a modified gentamicin protection assay (mGPA) was developed with a standardized co-incubation procedure. The mGPA addresses limitations of the traditional GPA by providing quantification of the rate of internalization, or lack of internalization, of C. jejuni by Acanthamoeba castellanii. The mGPA described here utilizes tubes instead of cell culture plates allowing for determination of exact numbers of A. castellanii and C. jejuni to be co-incubated prior to addition to tubes. Additionally, the mGPA allows for the incorporation of C. jejuni-only controls to determine the fate of C. jejuni throughout the assay in the absence of A. castellanii. Using the mGPA it was determined that on average 1.6×10(5) C. jejuni (or 0.006% of initial 1×10(9) inoculum) survive the assay in the absence of A. castellanii. Additionally, results obtained with the mGPA demonstrated that while co-incubation with amoebae sometimes (56% of co-incubations) provided a protective effect for C. jejuni, in other cases it did not provide any protective effect (39% of co-incubations), and in at least one case there was a statistically significant higher recovery of C. jejuni in controls when compared to C. jejuni co-incubated with amoebae. The modified gentamicin protection assay described here allows better quantification of the rate and incidence of internalization of bacteria by amoebae. Use of the standardized mGPA developed here with varying environmental parameters and/or strains

  15. JBP485 improves gentamicin-induced acute renal failure by regulating the expression and function of Oat1 and Oat3 in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Xinjin [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Meng, Qiang; Liu, Qi; Wang, Changyuan; Sun, Huijun; Peng, Jinyong; Ma, Xiaochi [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China); Kaku, Taiichi [Japan Bioproducts Industry Co. Ltd., Tomigaya, Shibuya-ku, Tokyo (Japan); Liu, Kexin, E-mail: kexinliu@dlmedu.edu.cn [Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, Dalian (China); Provincial Key Laboratory for Pharmacokinetics and Transport, Dalian Medical University, Liaoning (China)

    2013-09-01

    We investigated the effects of JBP485 (an anti-inflammatory dipeptide and a substrate of OAT) on regulation of the expression and function of renal Oat1 and Oat3, which can accelerate the excretion of accumulated uremic toxins (e.g. indoxyl sulfate) in the kidney to improve gentamicin-induced ARF in rats. JBP485 caused a significant decrease in the accumulation of endogenous substances (creatinine, blood urea nitrogen and indoxyl sulfate) in vivo, an increase in the excretion of exogenous compounds (lisinopril and inulin) into urine, and up-regulation of the expressions of renal Oat1 and Oat3 in the kidney tissues and slices via substrate induction. To determine the effect of JBP485 on the accelerated excretion of uremic toxins mediated by Oat1 and Oat3, the mRNA and protein expression levels of renal basolateral Oats were assessed by quantitative real-time PCR, western blot, immunohistochemical analysis and an immunofluorescence method. Gentamicin down-regulated the expression of Oats mRNA and protein in rat kidney, and these effects were reversed after administration of JBP485. In addition, JBP485 caused a significant decrease in MPO and MDA levels in the kidney, and improved the pathological condition of rat kidney. These results indicated that JBP485 improved acute renal failure by increasing the expression and function of Oat1 and Oat3, and by decreasing overoxidation of the kidney in gentamicin-induced ARF rats. - Highlights: • JBP485 could up-regulate function and expression of Oat1 and Oat3 in kidney. • Effects of JBP485 on ARF are mediated by stimulating excretion of uremic toxins. • JBP485 protected against gentamicin-induced ARF by decreasing MPO and MDA.

  16. Study the therapeutic mechanism of Amomum compactum in gentamicin-induced acute kidney injury rat based on a back propagation neural network algorithm.

    Science.gov (United States)

    Wang, Xiye; Chen, Hongmei; Chang, Chun; Jiang, Mingyang; Wang, Xiulan; Xu, Liang

    2017-